Factors influencing osteoradionecrosis progression during hyperbaric oxygen therapy: A case study

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Various therapeutic approaches, including hyperbaric oxygen therapy (HBOT), are utilized in managing ORN. This study aims to evaluate the role of HBOT in ORN management and to identify predictive factors influencing the evolution of head and neck ORN after HBOT. Methods This retrospective study includes 46 patients who received HBOT for head and neck ORN between 2017 and 2020. The patients were divided into two groups: Group 1 (n=36) included those with regression or stabilization of ORN, while Group 2 (n=10) comprised patients with worsening lesions. We performed a statistical study in order to identify factors influencing ORN progression under treatment. Results ORN affected the mandible in 93.5% of patients, the maxilla in 2 cases, and the skull base in 4 cases. All patients received HBOT, with an average of 44.65 sessions. Pre-operative HBOT was administered in 17% of cases, and post-operative HBOT was given in 42% of cases. After at least 20 sessions, ORN regressed in 33% of cases, stabilized in 45%, and worsened in 22%. Analysis of factors influencing ORN progression on the univariate study revealed significant associations with high blood pressure (p=0.046), larger tumor size (p=0.004), advanced tumor stages (p=0.048), mean radiation dose (p=0.002), delays between dental care and radiotherapy (p=0.045), and the location of ORN within the mandible (p=0.049). Additionally, the number of HBOT sessions significantly affected ORN evolution, with more sessions correlating with better outcomes (p=0.001). In the multivariate analysis, variables such as the average interval between dental care and radiotherapy (p=0.043) as well as the number of HBOT sessions (p=0.040) emerged as significant influencers of ORN evolution. Conclusion Our study provides valuable insights into the management of ORN by identifying key predictors that influence the post-therapeutic evolution of head and neck ORN after HBOT. 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F1000Research 2025, 13 :1225 ( https://doi.org/10.12688/f1000research.155112.2 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. Close Copy Citation Details Export Export Citation Sciwheel EndNote Ref. Manager Bibtex ProCite Sente EXPORT Select a format first Track Share ▬ ✚ Clinical Practice Article Revised Factors influencing osteoradionecrosis progression during hyperbaric oxygen therapy: A case study [version 2; peer review: 1 approved, 2 approved with reservations] Sameh Mezri https://orcid.org/0000-0002-6889-4181 1,2 , Chaima Zitouni https://orcid.org/0009-0000-2279-3038 1,2 , Khadija Bahrini 1,3 , Mounir Haggui 1,4 , Wiem Boughzala 1,2 , Hedi Gharsallah 1,5 Sameh Mezri https://orcid.org/0000-0002-6889-4181 1,2 , Chaima Zitouni https://orcid.org/0009-0000-2279-3038 1,2 , [...] Khadija Bahrini 1,3 , Mounir Haggui 1,4 , Wiem Boughzala 1,2 , Hedi Gharsallah 1,5 PUBLISHED 02 Jan 2025 Author details Author details 1 University of Tunis El Manar, Rommana, Tunis, 1068, Tunisia 2 ENT department, Military hospital of Tunis, Montfleury, Tunis, 1008, Tunisia 3 Research Unit UR17DN05, Military hospital of Tunis, Montfleury, Tunis, 1008, Tunisia 4 Emergency department, Military hospital of Tunis, Montfleury, Tunis, 1008, Tunisia 5 Department of hyperbaric oxygen therapy, Military Hospital of Tunis, Montfleury, Tunis, 1008, Tunisia Sameh Mezri Roles: Conceptualization Chaima Zitouni Roles: Writing – Original Draft Preparation, Writing – Review & Editing Khadija Bahrini Roles: Formal Analysis Mounir Haggui Roles: Supervision Wiem Boughzala Roles: Investigation Hedi Gharsallah Roles: Resources OPEN PEER REVIEW DETAILS REVIEWER STATUS Abstract Introduction Although relatively uncommon, osteoradionecrosis (ORN) remains a serious complication following radiotherapy. Various therapeutic approaches, including hyperbaric oxygen therapy (HBOT), are utilized in managing ORN. This study aims to evaluate the role of HBOT in ORN management and to identify predictive factors influencing the evolution of head and neck ORN after HBOT. Methods This retrospective study includes 46 patients who received HBOT for head and neck ORN between 2017 and 2020. The patients were divided into two groups: Group 1 (n=36) included those with regression or stabilization of ORN, while Group 2 (n=10) comprised patients with worsening lesions. We performed a statistical study in order to identify factors influencing ORN progression under treatment. Results ORN affected the mandible in 93.5% of patients, the maxilla in 2 cases, and the skull base in 4 cases. All patients received HBOT, with an average of 44.65 sessions. Pre-operative HBOT was administered in 17% of cases, and post-operative HBOT was given in 42% of cases. After at least 20 sessions, ORN regressed in 33% of cases, stabilized in 45%, and worsened in 22%. Analysis of factors influencing ORN progression on the univariate study revealed significant associations with high blood pressure (p=0.046), larger tumor size (p=0.004), advanced tumor stages (p=0.048), mean radiation dose (p=0.002), delays between dental care and radiotherapy (p=0.045), and the location of ORN within the mandible (p=0.049). Additionally, the number of HBOT sessions significantly affected ORN evolution, with more sessions correlating with better outcomes (p=0.001). In the multivariate analysis, variables such as the average interval between dental care and radiotherapy (p=0.043) as well as the number of HBOT sessions (p=0.040) emerged as significant influencers of ORN evolution. Conclusion Our study provides valuable insights into the management of ORN by identifying key predictors that influence the post-therapeutic evolution of head and neck ORN after HBOT. READ ALL READ LESS Keywords Osteoradionecrosis, Radiotherapy, Hyperbaric oxygen therapy, Head and neck Corresponding Author(s) Chaima Zitouni ( [email protected] ) Close Corresponding author: Chaima Zitouni Competing interests: No competing interests were disclosed. Grant information: The author(s) declared that no grants were involved in supporting this work. Copyright: © 2025 Mezri S et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. How to cite: Mezri S, Zitouni C, Bahrini K et al. Factors influencing osteoradionecrosis progression during hyperbaric oxygen therapy: A case study [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2025, 13 :1225 ( https://doi.org/10.12688/f1000research.155112.2 ) First published: 14 Oct 2024, 13 :1225 ( https://doi.org/10.12688/f1000research.155112.1 ) Latest published: 02 Jan 2025, 13 :1225 ( https://doi.org/10.12688/f1000research.155112.2 ) Revised Amendments from Version 1 We have made several important revisions to improve the quality and clarity of the manuscript. The section on antimicrobials was expanded to include detailed information on the types of antibiotics used and their duration of administration, along with a discussion on how hyperbaric oxygen therapy (HBOT) may enhance their effectiveness. To address the role of bacterial testing, we added a new section emphasizing the significance of anaerobic bacteria in osteoradionecrosis (ORN) and the relevance of HBOT in managing these infections. The introduction was thoroughly expanded, incorporating additional references to provide a more comprehensive overview of the current state of knowledge and to clearly identify the knowledge gap that this study aims to address. To improve the results section, a demographic data table was added to enhance the clarity and presentation of the findings. Additionally, the data analysis was adjusted to account for potential confounders, such as age and gender, using regression analysis to ensure the robustness of the results. The discussion section was also significantly improved by including an explanation of the biological plausibility of the factors influencing ORN progression, such as hypertension, and how these factors may contribute to disease mechanisms. These revisions were made to ensure that the manuscript provides a more detailed and scientifically rigorous account of the study, while addressing key issues to improve its clarity and impact. We have made several important revisions to improve the quality and clarity of the manuscript. The section on antimicrobials was expanded to include detailed information on the types of antibiotics used and their duration of administration, along with a discussion on how hyperbaric oxygen therapy (HBOT) may enhance their effectiveness. To address the role of bacterial testing, we added a new section emphasizing the significance of anaerobic bacteria in osteoradionecrosis (ORN) and the relevance of HBOT in managing these infections. The introduction was thoroughly expanded, incorporating additional references to provide a more comprehensive overview of the current state of knowledge and to clearly identify the knowledge gap that this study aims to address. To improve the results section, a demographic data table was added to enhance the clarity and presentation of the findings. Additionally, the data analysis was adjusted to account for potential confounders, such as age and gender, using regression analysis to ensure the robustness of the results. The discussion section was also significantly improved by including an explanation of the biological plausibility of the factors influencing ORN progression, such as hypertension, and how these factors may contribute to disease mechanisms. These revisions were made to ensure that the manuscript provides a more detailed and scientifically rigorous account of the study, while addressing key issues to improve its clarity and impact. See the authors' detailed response to the review by Busra Yilmaz See the authors' detailed response to the review by Atsushi Shudo See the authors' detailed response to the review by Amaliya Amaliya READ REVIEWER RESPONSES Introduction Head and neck cancers rank seventh in the world, with an incidence of 890,000 new cases. 1 Their management typically involves surgery, radiotherapy (RT), and chemotherapy. Despite advancements in techniques, external RT often leads to complications, including osteoradionecrosis (ORN). ORN is defined as progressive bone destruction, occurring spontaneously or following trauma, with mucosal ulceration exposing irradiated bone, persisting for 3 to 6 months without healing, excluding tumor recurrence. 2 Although relatively uncommon, ORN remains a serious complication, significantly affecting patients’ quality of life often leading to chronic pain, infections, and functional impairments in the affected areas. 3 The pathophysiology of ORN remains poorly understood, despite extensive research. It is believed to result from the interplay between radiation-induced damage to the vasculature, impaired healing, and an inflammatory response. However, there is still no clear consensus on the exact mechanisms behind its development. 4 Various therapeutic approaches are utilized in the treatment of ORN. They include antibiotics, hyperbaric oxygen therapy (HBOT), the PENTOCLO protocol, and conservative surgery. Among these, HBOT has garnered significant attention due to its potential to enhance tissue healing and reduce bone damage by improving oxygen supply to irradiated tissues. 5 Several studies have evaluated the role of HBOT in managing ORN, with varying results. However, the optimal treatment protocol, including the duration and frequency of HBOT sessions, remains a topic of debate. Moreover, there is limited research identifying predictive factors that influence the outcomes of ORN treatment, particularly concerning the progression of the condition following HBOT. While some studies have shown promising results, the role of HBOT in combination with other treatments and its impact on long-term outcomes remains underexplored. Our study aims to evaluate the role of HBOT in ORN management and describe predictive factors influencing post-therapeutic evolution of head and neck ORN. By addressing the current gaps in knowledge, we hope to provide insights that could lead to more effective and personalized treatment strategies for ORN patients. Methods The cohort study This is a retrospective study conducted at the HBOT Department of the Military Hospital of Tunis over a period of 4 years, from January 1, 2017, to December 31, 2020. The study included patients who met the following criteria: - Treated with HBOT for head and neck ORN - Completed at least 20 HBOT sessions - Had a complete medical record - Were available for follow-up evaluations for at least six months after the end of the therapy All cases with recurrent loco-regional tumor and who received discontinued or irregular HBOT sessions were excluded from this study. For this study, we developed a specialized data collection tool called a case report form (CRF). This form was used to document various aspects of each patient’s case, including their demographics, clinical examination, laboratory results, imaging, treatment, and follow-up. ORN was classified into four grades according to the LENT/SOMA (Late Effects of Normal Tissues/Subjective Objective Management Analytic) classification. 6 Grade 1: Normal bone appearance or debatable modifications Grade 2: Bone lysis or condensation Grade 3: Bone sequestration Grade 4: Bone fracture OHB protocol HBOT sessions were conducted in a multiplace hyperbaric chambers type HAUX-STARMED 2400. The HBOT protocol included 3 steps: ➢ Step 1: Compression phase: Around 0.1 ATA (Atmosphere Absolute) and the Compression rate was adjusted based on patient’s tolerance. ➢ Step 2: Plateau phase: in this phase patients received 100% oxygen using facial mask for 60 and or 90 minutes with 5-minute air breaks every 25 minutes. ➢ Step 3: decompression phase: this step is slow typically around 0.1 ATA/min. Patients were followed up during and following HBOT therapy. Clinical and imaging evolution of injuries was recorded. Radiological examinations, if needed, were performed after at least 40 HBOT sessions. However, if the hyperbaric medicine specialist noticed any signs of worsening condition after 20 HBOT sessions, CT scans were ordered earlier. In our study, only CT was used for radiological control. ORN injuries were assessed clinically and by imaging following HBOT treatment. Thereby lesion evolution was classified into three categories: - Regression: Clinically and/or radiologically confirmed the disappearance of functional and radiological signs - Stabilization: It involves partial healing of the ORN with no progression of bone necrosis. Functional signs are moderate. - Worsening or Aggravation: Progressive worsening of the ORN characterized by the persistence of functional and radiological signs. There is no bone healing and the ORN was progressed to a more severe stage. Statistical analysis Statistical analyses were performed using SPSS version 22.0. Categorical variables were reported as percentages, and their significance was assessed using Fisher’s exact test or chi-square tests. Quantitative variables were presented as mean (standard deviation) or median ± interquartile range (IQR25%, 75%). Normality was tested using the Kolmogorov-Smirnov test. An unpaired t-test was used to compare two groups when continuous variables were normally distributed. For continuous variables that were not normally distributed, a two-tailed unpaired Mann-Whitney U test was applied. Both univariate and multivariate analyses were conducted to evaluate the effectiveness of HBOT on ORN patients. The cases were divided into two groups: Group 1 (n=36) included patients with regression or stabilization, and Group 2 (n=10) included patients with worsening signs of injury after HBOT ( Figure 1 ). Differences were considered significant if p ≤ 0.05. Figure 1. Diagram of patient recruitment, exclusions, and study groups. Ethics statement This study was approved by the Ethics Committee of the Military Hospital of Tunis, under decision number 81/2024/CLPP, dated July 22, 2024. The study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki ( https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/ ). Results Demographic characteristics of the cohort study ( Table 4 ) This study included 46 patients. The average age of patients was 58 ± 13.9 years, with the majority of patients (61%) aged between 31 and 65 years old. Fifty-two percent were female, and 48% were male. Two-thirds of the patients had diabetes and 59% were smokers. Radiotherapy treatment All patients had undergone RT for head and neck malignancies, primarily nasopharyngeal carcinoma (67%) ( Table 1 ). Table 1. Tumor histological type and location. Tumor histological type and location Number of patients Undifferentiated carcinoma of nasopharyngeal type (UCNT) 31 Squamous cell carcinoma of the mandible 2 Gingival squamous cell carcinoma 1 Squamous cell carcinoma of the palate 1 Squamous cell carcinoma of the tonsil 1 Lymphoma with tonsillar localization 1 Squamous cell carcinoma of the tongue 1 Mucoepidermoid carcinoma of the parotid gland 1 Squamous cell carcinoma of the external auditory canal 1 Cutaneous squamous cell carcinoma 1 Breast ductal carcinoma with metastatic cervical lymph nodes 5 The mean tumor size was 29.67 mm. RT was conventional in 40 cases, cobalt-60 2D dimensional in two cases, three-dimensional in one case, and Intensity-Modulated Radiation Therapy (IMRT) in three cases; with a mean radiation dose of 48.7 Gy. The association with chemotherapy was noted in thirty cases, accounting for 65% of the cases. Prior to radiotherapy, all patients received comprehensive dental care, including professional cleaning and fluoride treatments. Among these patients, 67% required tooth extractions. Twelve patients used the custom fluoride tray correctly. Patients were also educated on proper oral hygiene practices during and after radiation therapy, emphasizing brushing techniques, fluoride toothpaste, and the importance of regular dental follow-ups. The interval between dental care and the start of RT ranged from one month to 48 months, with a median of two months. Osteoradionecrosis diagnosis ORN typically occurred due to dental extractions (83% of cases) or surgical procedures (15%). The median time from RT to ORN onset was 6 years, while from dental care to ORN onset was 36 months. Common clinical symptoms included pain (100% of patients) and mastication difficulties (98%). Trismus was present in all patients, with varying degrees of severity. Dental mobility was observed in 33% of cases. We also noted the presence of bone exposure ( Figure 2 ) in 6 cases, bone sequestration in 15 cases, or bone fracture in 9 cases. The presence of a cutaneous fistula ( Figure 3 ) was noted in 39% of cases. In four cases, there was pus discharge through the fistula. Figure 2. Exposure of the mandibular bone. Figure 3. Cutaneous fistula in osteoradionecrosis. We performed panoramic radiograph (76%), cone beam imaging (11%), computed tomography (CT scan) (80%), and magnetic resonance imaging (MRI) (28%). Imaging revealed the following grades of ORN according to the LENT/SOMA classification: Grade 2 (43% of cases), Grade 3 (37%), and Grade 4 (20%). ORN was predominantly mandibular (40 patients), affecting various regions such as the horizontal branch (27 patients) ( Figure 4 ), mandibular angle (10 patients), and ascending branch (3 patients). Other locations included the maxilla (2 cases) and the skull base (4 cases) ( Figure 5 ). Figure 4. Osteoradionecrosis of the left mandible. CT scan showing osteoradionecrosis of the horizontal branch of the left mandible complicated by sequestra (star) and mandibulo-cutaneous fistula (yellow arrow). A: Sagittal section. B: Frontal section. C: 3D reconstruction. Figure 5. Osteoradionecrosis of the temporal bone. A and B: Coronal section showing of a CT-scan showing bilateral lytic erosion of the tympanic bone (star) and thickening of the walls of the external auditory canal. The anatomopathological examination was performed in one case due to delayed alveolar consolidation and diagnostic doubt for differential diagnosis. It concluded with fibro-inflammatory chronic scarring remodeling, displaying features of ORN without specific granuloma or signs of malignancy. A bacteriological examination with culture was performed in four cases, yielding negative results in three cases and identifying polymicrobial flora in one case. Treatment of osteoradionecrosis The therapeutic management of ORN included topical antibacterial mouthwash prescribed to all patients. All patients received analgesic treatment based on their pain intensity. Antibiotic therapy was initiated in 89% of cases. In all cases, it was empirical. In about 70% of cases, the treatment was primarily based on amoxicillin and clavulanic acid (89%). The average duration of the treatment was 6 weeks. Surgical treatment was performed in 36 patients, predominantly involving sequestrectomy (94% of cases). Mandibulectomy with mandibular reconstruction using flaps was conducted in 6% of cases. HBOT was provided to all patients, with a mean of 44.65 sessions. HBOT sessions preceded ORN surgery in 17% of cases and were indicated after surgery in 42% of cases. Complications of HBOT were observed in two patients, including middle ear barotrauma, necessitating transient discontinuation of therapy. Evolution of ORN lesions was evaluated clinically after 20 HBOT sessions and radiologically after 40 sessions. Results showed regression in 33% of cases, stabilization in 45%, and progression or aggravation in 22% ( Figure 6 ). Figure 6. Evolution of osteoradionecrosis based on the number of hyperbaric oxygen therapy sessions. Risk factors associated with osteoradionecrosis aggravation In the univariate study ( Table 2 ), age and sex did not show statistical significance in influencing ORN progression. However, among comorbidities, hypertension was significantly associated with worsened ORN evolution. Table 2. Univariate study of factors influencing the post-therapeutic evolution of osteoradionecrosis. 1st group (%) 2 nd group (%) p Age groups < 31 1 (3) 2 (20) 0.148 [31- 65] 21 (58) 5 (50) ≥65 14 (39) 3 (30) Gender Male 19 (53) 3 (30) 0.202 Female 17 (47) 7 (70) Diabetes Yes 23 (64) 7 (70) 0.720 No 13 (36) 3 (30) High blood pressure Yes 20 (56) 2 (20) 0.046 No 16 (44) 8 (80) Smoking Yes 20 (56) 5 (50) 0.755 No 16 (44) 5 (50) Tumor site Nasopharynx 22 9 0.997 Mouth 8 0 Breasts 4 1 External auditory canal 1 0 Skin 1 0 Mean tumor size 27.9 mm 36 mm 0.004 Tumor stage T2 13 (95) 1 (11) 0.048 T3 8 (36) 7 (78) T4 1 (4) 1 (11) Type of RT Conventional RT 30 (83) 10 (100) 0.590 IMRT 3 (8) 0 3D RT 1 (3) 0 2D cobalt-60 RT 2 (6) 0 Mean radiation dose 42 68 0.021 Chemotherapy Yes 22 (61) 8 (80) 0.267 No 14 (39) 2 (20) The average interval between dental care (before RT) and RT 5.46 months 1.6 months 0.045 Dental extraction after RT Yes 29 (81) 9 (90) 0.486 No 7 (19) 1 (10) Location of the ORN Horizontal branch of the mandible 22 (74) 5 (50) 0.049 Mandibular angle 5 (17) 5 (50) Ascending ramus of the mandible 3 (10) Radiological signs Bone lysis 15 (42) 5 (50) 0.686 Bone sequestrum 13 (36) 4 (40) Bone fracture 8 (22) 1 (10) Antibiotic therapy Yes 32(89) 9(90) 0.920 No 4(11) 1(10) Average number of HBOT sessions 49.11 28.6 0.001 Surgery after RT Yes 7 (20) 1 (10) 0.466 No 28 (80) 9 (90) Type of surgery Sequestrectomy 28 (93) 6 (100) 0.515 Mandibular reconstruction with flap 2 (7) 0 Interval between HBOT and surgery Before 4 2 0.359 Simultaneously 13 2 After 13 2 Our study also revealed that larger tumor size and advanced tumor stages correlated with worse outcomes, while tumor location did not statistically influence ORN evolution. The type of radiotherapy did not statistically influence the progression of ORN lesions, nor did its association with chemotherapy. Higher radiation therapy doses statistically influenced ORN evolution. Delays between dental care (before RT) and RT were associated with worse ORN evolution, while dental care after RT did not significantly influence it. The location of ORN within the mandible significantly influenced lesion evolution, but radiological signs did not. The use of antibiotics did not statistically influence the progression of ORN lesions. HBOT significantly influenced ORN evolution, with more sessions correlating with better outcomes. We observed that the progression of lesions in patients who underwent surgery was not influenced by the timing of surgery, whether it was before, concurrent with, or after HBOT therapy. The type of surgical treatment did not statistically influence lesion evolution. In the multivariate analysis ( Table 3 ), variables such as the average interval between dental care (before RT) and RT and the number of HBOT sessions emerged as significant influencers of ORN evolution. Specifically, extending the delay between dental care and RT by one month correlated with a sevenfold enhancement in ORN lesion evolution. Furthermore, each additional ten HBOT sessions were linked with a tenfold improvement in ORN lesion evolution. Table 3. Multivariate study of factors influencing the post-therapeutic evolution of osteoradionecrosis. P OR 95% confidence interval for EXP(B) Lower value Upper value High blood pressure 0.623 1.803 0.172 18.923 Tumor mean size 0.778 1.022 0.878 1.189 Mean radiation dose 0.193 1.055 0.973 1.145 The average interval between dental care before RT and RT 0.043 7.055 1.067 46.649 Dental extraction after RT 0.121 6.159 0.618 61.371 Location of the ORN 0.909 Average number of HBO sessions 0.040 1.041 1.021 1.062 Table 4. Demographic and clinical characteristics of study participants. Characteristic Total (n = 46) % Mean Age (years) 58 ± 13.9 - Gender - Female - Male 24 22 52% 48% Diabetes 30 65% Smoking 27 59% High blood pressure 22 48% Discussion In 1973, Mainous et al. 7 first proposed HBOT as a treatment for ORN. Subsequent studies have highlighted the significant benefits of HBOT in managing ORN, primarily due to its ability to deliver hyper-concentrated oxygen levels, up to 20 times higher than normal conditions. HBOT facilitates increased oxygen diffusion in hypoxic tissues, stimulates osteogenesis and mucosal tissue epithelialization, promotes collagen synthesis and osteoblast proliferation in irradiated tissues, enhances the expression of Vascular Endothelial Growth Factor (VEGF) leading to angiogenesis, improves tissue oxygen perfusion, and exerts a bactericidal and bacteriostatic effect against various pathogens. These mechanisms collectively underscore the therapeutic potential of HBOT in the management of ORN. 8 Several studies have reported healing rates ranging from zero to 100%. 9 – 14 However, comparing these results is challenging due to the variability of protocols applied and the variability in case indications (varying severity of ORN cases). Many authors have demonstrated improvement in ORN with HBOT. 15 – 17 Besides its therapeutic effect on ORN lesions, HBOT can help improve patients’ quality of life by reducing pain, promoting wound healing, and lowering the risk of infectious complications. 18 However, Annane et al. 19 halted their trial due to a significantly better healing rate in the placebo group (32%) compared to the HBOT group (19%). The main criticisms of this trial were the monomodal use of HBOT in treating his patients and the lack of strict and clear criteria for defining ORN and its severity. According to recommendations established by medical organizations such as the Undersea and Hyperbaric Medical Society (UHMS) 18 and the Tenth European Consensus Conference on Hyperbaric Medicine, 20 HBOT is recommended for treating symptomatic ORN cases or as an adjunct treatment to surgical intervention in order to enhance wound healing, reduce infection risk, and promote tissue healing after reconstructive or debridement surgery. According to the UHMS, to achieve these effects, the recommended pressure should be equal to or greater than 1.4 atmospheres (atm). However, all current indications approved by the UHMS require patients to breathe nearly 100% oxygen in a pressurized chamber at a minimum pressure of 2 ATA. 18 However, results appear controversial and inconclusive. Thus, at the limit of our literature search, only one randomized clinical trial has been published, with other studies mainly consisting of cohort studies of varying quality. A study by Annane et al. 19 examined the efficacy of HBOT in the treatment of ORN and found that patients who received a higher number of HBOT sessions had higher healing rates. A meta-analysis by Bennett et al. (2016) 21 also examined the results of several studies on HBOT in the treatment of ORN. They found that healing rates were higher in patients who received a higher number of HBOT sessions, although the results varied depending on the healing criteria used in the different studies. Marx et al. 22 reported healing rates of up to 85% in patients who received more than 20 HBOT sessions. This was applicable to our study where a minimum of 20 sessions was indicated for our patients, although.patient compliance during this extended treatment plays a critical role in achieving optimal outcomes. The combination of HBOT and surgical treatment has been addressed in the literature. Several authors have reported ORN healing rates of 15% to 45% with HBOT alone and 20% to 90% when HBOT was combined with surgery. 23 – 25 However, these studies lack precision with somewhat heterogeneous groups. In a recently published multicenter randomized trial in 2021, Forner et al. 26 reported a significantly better healing rate in the HBOT-surgery group (surgical treatment preceded by 30 HBOT sessions and followed by 10 HBOT sessions) at 70% (21/30) compared to 51% (18/35) in the surgery-only group. HBOT was associated with improved healing rates, regardless of ORN severity. It also reduced the severity of xerostomia and dysphagia and improved total unstimulated salivary flow. However, despite the most supported multimodal approach to ORN management being the combination of HBOT and surgery, due to the divergent conclusions of the literature, establishing standardized protocols for HBOT use in parallel with surgery seems compromised. Broad-spectrum antibiotics such as penicillins, metronidazole, and clindamycin are commonly used in ORN due to their effectiveness against anaerobic bacteria often involved. 27 Aas et al. 28 used culture-independent molecular techniques to identify 59 bacterial species in ORN specimens, with anaerobes predominating and 27% of the bacteria being uncultivable, highlighting the complexity of microbial involvement in ORN and the need for comprehensive clinical management. There is no consensus on the duration of antibiotic treatment for ORN. 27 HBOT demonstrates a synergistic effect when combined with various antibiotics. It exerts bactericidal and bacteriostatic effects on anaerobic bacteria by promoting the generation of free oxygen radicals. It also enhances the bacterial-killing efficacy of leukocytes in hypoxic wounds by elevating tissue oxygen levels. 29 The evolution of ORN under treatment can be influenced by several factors. Oh et al., 14 studied factors influencing ORN evolution, collecting 114 patients treated for ORN over a 16-year period. They were divided into two groups: group 1 of 47 patients treated with conservative treatment (sequestrectomy, debridement, and/or HBOT) and group 2 of 67 patients treated with immediate intervention or after failure of conservative treatment. Patients whose ORN was associated with an early-stage tumor or extraction before irradiation responded favorably to conservative treatment. However, patients with advanced primary tumors, who continued to smoke and drink after RT, who received palliative RT or a radiation dose exceeding 60Gy, and who had oro-cutaneous fistulas, pathological fractures, swelling, or trismus responded poorly to conservative treatment. In these latter cases, radical resection of the affected tissue proved useful. Smoking induces vasoconstriction and oxidative damage, reducing oxygen supply to irradiated tissues and impairing healing. 30 Similarly, alcohol contributes to systemic inflammation and immune suppression. 31 Hypertension can exacerbate ORN due to its association with vascular dysfunction, which reduces microvascular density and perfusion in irradiated tissues. This condition worsens hypoxia, delaying healing and promoting fibrosis. Hypertension-induced chronic inflammation and oxidative stress further compromise tissue repair mechanisms. 32 Larger tumors and advanced staging necessitate higher doses of RT, leading to greater damage to surrounding healthy tissues. Mandibular bone, in particular, is vulnerable to radiation-induced hypoxia and fibrosis due to dense cortical bone and limited vascular supply; which are primary drivers of ORN progression. 33 The onset time of ORN relative to RT is a factor influencing the evolution of ORN lesions. This notion was supported by Oh et al., 14 who reported that patients whose ORN occurred within 12 months after RT had a higher resolution rate with conservative treatment than patients whose ORN occurred after 12 months. Beumer et al. 34 reported that ORN occurring after a dose of 70 Gy did not systematically respond to conservative treatment measures, thus requiring non-conservative treatment. At these levels, there is significant cytotoxicity to osteoblasts and endothelial cells, leading to impaired bone remodeling and microvascular obliteration. 35 Also, the overall dose and the distribution of that dose across the mandible are key factors. While IMRT can reduce the maximum dose to the mandible, the risk of ORN is still significantly influenced by the total dose delivered to specific mandibular regions. Doses in the range of 35–73 Gy, rather than a single point dose, are crucial in determining the likelihood of ORN development. 36 In the same study, the authors reported that ORN occurring due to irritation from dental prostheses or extraction before irradiation respond more effectively to conservative treatment than ORN occurring due to dental disease, either spontaneously or in association with post-irradiation extraction. The latter often requires a radical approach; this result was refuted by Oh et al. 14 Tooth extractions should be performed based on pre-radiotherapy dental assessments to remove infected, non-restorable, or periodontally compromised teeth, as these are at higher risk for infection and subsequent ORN. 37 A tooth extraction should ideally occur at least two weeks before radiotherapy. 33 In a retrospective study conducted by De Felice 38 published in 2016, comparing resolved ORN and unresolved ORN, no factor was identified as influencing the resolution or progression of ORN during logistic regression. In our study, the evolution of ORN lesions was influenced by the presence of hypertension, tumor size, T and N stages, RT dose, dental care delays relative to RT, ORN location within the mandible, and HBOT sessions. During logistic regression, only delays in dental care relative to RT would influence the evolution of ORN lesions. Despite being the only study conducted in Tunisia on this topic, this research has several limitations that should be acknowledged. First, as a retrospective study, it has missing clinical data. Second, evaluating the efficacy of HBOT ideally requires a control group, which could potentially be addressed with a matched sample from another center. Third, the limited number of cases and the heterogeneity among patients in terms of therapeutic modalities prevent definitive conclusions. Additionally, the variability in radiation doses received by different parts of the jaw, depending on tumor histology and location, may also influence the outcomes. For these reasons, further research is needed to gain a deeper understanding of the therapeutic strategies for ORN tailored to individual patient profiles. Despite these limitations, our study offers valuable insights into the management of ORN within the Tunisian context and provides a foundation for future, more comprehensive investigations. Conclusion In conclusion, our study yields crucial insights into the management of ORN by identifying significant predictors influencing post-therapeutic evolution of head and neck ORN. These findings underscore the multifactorial nature of ORN progression, implicating patient characteristics, tumor attributes, and treatment modalities. Notably, advanced T stage, higher RT doses, and shorter delays between dental care and RT initiation were associated with worsened ORN evolution. Conversely, longer delays between dental care and RT initiation, mandibular horizontal branch localization and increased number of HBOT sessions were associated with improved lesion evolution. Logistic regression identified delay between dental care and RT initiation and number of HBOT sessions as independent factors influencing lesion evolution. These findings highlight the importance of timely intervention and comprehensive treatment strategies in reducing ORN progression and improving patient outcomes. Moreover, our study underscores the potential of HBOT as a valuable adjunctive treatment option in ORN management. However, the long-term effects of HBOT, including potential complications such as barotrauma, oxygen toxicity, and claustrophobia, must be carefully considered in treatment planning. Further research is warranted to validate these findings and develop targeted therapeutic approaches tailored to individual patient profiles. Consent for publication All photographs included in this manuscript have been published with the explicit written consent of the individuals depicted. Written consent to publish these images was obtained from the participants prior to submission of the manuscript. Any identifiable features, such as personal details or medical record numbers, have been removed to ensure privacy and confidentiality. Ethical and consent This study was approved by the Ethics Committee of the Military Hospital of Tunis, under decision number 81/2024/CLPP, dated July 22, 2024. The study was conducted in accordance with the ethical principles outlined in the Declaration of Helsinki ( https://www.wma.net/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/ ). The research was conducted ethically, with all study procedures being performed in accordance with the requirements of the World Medical Association’s Declaration of Helsinki. Written informed consent for publication of their clinical details and/or clinical images was obtained from the patient/parent/guardian/relative of the patient. Author contributions Dr Sameh Mezri: Conceptualization, Methodology Dr Chaima Zitouni: Writing – Original Draft Preparation – Review and editing Dr Khadija Bahrini: Formal Analysis Dr Mounir Haggui: Supervision Dr Wiem Boughzala: Investigation Dr Hedi Gharsallah: Resources Data availability statement The underlying data for this project are available in the Zenodo repository. Zenodo: Factors influencing osteoradionecrosis progression during hyperbaric oxygen therapy: A case study 1. https://doi.org/10.5281/zenodo.13901089 39 This project contains the following data: Case Report Form 2. https://doi.org/10.5281/zenodo.13901073 40 This project contains the following data: Participant Information Sheet Details of license: The data files are published under a Creative Commons Attribution 4.0 International license (CC BY 4.0). Software availability statement The statistical analyses in this study were conducted using SPSS version 22.0 (IBM Corp, Armonk, NY, USA). Since SPSS is proprietary software, a free alternative that can perform similar statistical functions is R ( https://www.r-project.org/ ), an open-source software environment for statistical computing and graphics. References 1. Mody MD, Rocco JW, Yom SS, et al. : Head and neck cancer. Lancet. 2021 Dec; 398 (10318): 2289–2299. Publisher Full Text 2. Lee IJ, Koom WS, Lee CG, et al. : Risk factors and dose-effect relationship for mandibular osteoradionecrosis in oral and oropharyngeal cancer patients. Int. J. Radiat. Oncol. Biol. Phys. 2009; 75 (4): 1084–1091. PubMed Abstract | Publisher Full Text 3. El-Rabbany M, Duchnay M, Raziee HR, et al. : Interventions for preventing osteoradionecrosis of the jaws in adults receiving head and neck radiotherapy.Cochrane Database Syst. Rev.2019; 2019 (11): CD011559. Publisher Full Text 4. Rivero JA, Shamji O, Kolokythas A: Osteoradionecrosis: a review of pathophysiology, prevention and pharmacologic management using pentoxifylline, α-tocopherol, and clodronate. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. 2017; 124 (5): 464–471. PubMed Abstract | Publisher Full Text 5. Ishihara A: Mild hyperbaric oxygen: mechanisms and effects. J. Physiol. Sci. 2019; 69 (4): 573–580. PubMed Abstract | Publisher Full Text | Free Full Text 6. Nabil S, Samman N: Risk factors for osteoradionecrosis after head and neck radiation: a systematic review. Oral Surg. Oral Med. Oral Pathol. Oral Radiol. 2012; 113 : 54–69. PubMed Abstract | Publisher Full Text 7. Mainous EG, Hart GB: Osteoradionecrosis of the mandible. Treatment with hyperbaric oxygen. Arch. Otolaryngol. Chic. Ill 1960. Mar 1975; 101 (3): 173–177. 8. Dieleman FJ, Phan TTT, van den Hoogen FJA , et al. : The efficacy of hyperbaric oxygen therapy related to the clinical stage of osteoradionecrosis of the mandible. Int. J. Oral Maxillofac. Surg. 2017; 46 (4): 428–433. 9. Owosho AA, Tsai CJ, Lee RS, et al. : The prevalence and risk factors associated with osteoradionecrosis of the jaw in oral and oropharyngeal cancer patients treated with intensity-modulated radiation therapy (IMRT): The Memorial Sloan Kettering Cancer Center experience. Oral Oncol. 2017; 64 : 44–51. PubMed Abstract | Publisher Full Text | Free Full Text 10. D’Souza J, Goru J, Goru S, et al. : The influence of hyperbaric oxygen on the outcome of patients treated for osteoradionecrosis: 8 year study. Int. J. Oral Maxillofac. Surg. 2007; 36 (9): 783–787. PubMed Abstract | Publisher Full Text 11. Chen JA, Wang CC, Wong YK, et al. : Osteoradionecrosis of mandible bone in patients with oral cancer—associated factors and treatment outcomes. Head Neck. 2016; 38 (5): 762–768. PubMed Abstract | Publisher Full Text 12. Gupta P, Sahni T, Jadhav GK, et al. : A Retrospective Study of Outcomes in Subjects of Head and Neck Cancer Treated with Hyperbaric Oxygen Therapy for Radiation Induced Osteoradionecrosis of Mandible at a Tertiary Care Centre: An Indian Experience. Indian J. Otolaryngol. Head Neck Surg. 2013; 65 (S1): 140–143. Publisher Full Text 13. Hampson NB, Holm JR, Wreford-Brown CE, et al. : Prospective assessment of outcomes in 411 patients treated with hyperbaric oxygen for chronic radiation tissue injury: Hyperbaric Oxygen for Radiation Injury. Cancer. 2012; 118 (15): 3860–3868. PubMed Abstract | Publisher Full Text 14. Oh HK, Chambers MS, Martin JW, et al. : Osteoradionecrosis of the mandible: treatment outcomes and factors influencing the progress of osteoradionecrosis. J. Oral Maxillofac. Surg. 2009; 67 (7): 1378–1386. PubMed Abstract | Publisher Full Text 15. Dieleman FJ, Phan TTT, van den Hoogen FJA , et al. : The efficacy of hyperbaric oxygen therapy related to the clinical stage of osteoradionecrosis of the mandible. Int. J. Oral Maxillofac. Surg. 2017; 46 (4): 428–433. PubMed Abstract | Publisher Full Text 16. Niezgoda JA, Serena TE, Carter MJ: Outcomes of Radiation Injuries Using Hyperbaric Oxygen Therapy: An Observational Cohort Study. Adv. Skin Wound Care. 2016 Jan; 29 (1): 12–19. Publisher Full Text 17. Tahir ARM, Westhuyzen J, Dass J, et al. : Hyperbaric oxygen therapy for chronic radiation-induced tissue injuries: Australasia’s largest study. Asia Pac. J. Clin. Oncol. 2015; 11 (1): 68–77. PubMed Abstract | Publisher Full Text 18. Weaver LK: Undersea and Hyperbaric Medical Society (UHMS), editors. Hyperbaric oxygen therapy indications. 14th ed.Durham, NC: Undersea and Hyperbaric Medical Society; 2019. 19. Annane D, Depondt J, Aubert P, et al. : Hyperbaric Oxygen Therapy for Radionecrosis of the Jaw: A Randomized, Placebo-Controlled, Double-Blind Trial From the ORN96 Study Group. J. Clin. Oncol. 2004; 22 (24): 4893–4900. PubMed Abstract | Publisher Full Text 20. Mathieu D, Marroni A, Kot J: Tenth European Consensus Conference on Hyperbaric Medicine: recommendations for accepted and non-accepted clinical indications and practice of hyperbaric oxygen treatment. Diving Hyperb. Med. 2017; 47 (1): 24–32. PubMed Abstract | Publisher Full Text 21. Bennett MH, Feldmeier J, Hampson NB, et al. : Hyperbaric oxygen therapy for late radiation tissue injury. Cochrane Database Syst. Rev. 2016; 4 (4): CD005005. PubMed Abstract | Publisher Full Text 22. Marx RE, Ehler WJ, Tayapongsak P, et al. : Relationship of oxygen dose to angiogenesis induction in irradiated tissue. Am. J. Surg. 1990; 160 (5): 519–524. PubMed Abstract | Publisher Full Text 23. Marx RE: A new concept in the treatment of osteoradionecrosis. J. Oral Maxillofac. Surg. 1983; 41 (6): 351–357. PubMed Abstract | Publisher Full Text 24. McLeod NM, Bater MC, Brennan PA: Management of patients at risk of osteoradionecrosis: results of survey of dentists and oral & maxillofacial surgery units in the United Kingdom, and suggestions for best practice. Br. J. Oral Maxillofac. Surg. 2010; 48 (4): 301–304. PubMed Abstract | Publisher Full Text 25. Meyer I: Infectious diseases of the jaws. J. Oral Surg. Am. Dent. Assoc. 1970; 28 (1): 17–26. 26. Forner D, Phillips T, Kovacs AF, et al. : Hyperbaric Oxygen Therapy Combined With Surgical Treatment for Osteoradionecrosis of the Mandible: A Multicenter Randomized Trial. JAMA Otolaryngol. Head Neck Surg. 2021; 147 (7): 602–610. 27. Chrcanovic BR, Reher P, Sousa AA, et al. : Osteoradionecrosis of the jaws--a current overview--Part 2: dental management and therapeutic options for treatment. Oral Maxillofac. Surg. 2010; 14 (2): 81–95. PubMed Abstract | Publisher Full Text 28. Aas JA, Reime L, Pedersen K, et al. : Osteoradionecrosis contains a wide variety of cultivable and non-cultivable bacteria. J. Oral Microbiol. 2010; 2 : 2. Publisher Full Text 29. Cimşit M, Uzun G, Yildiz S: Hyperbaric oxygen therapy as an anti-infective agent. Expert. Rev. Anti Infect. Ther. 2009; 7 (8): 1015–1026. PubMed Abstract | Publisher Full Text 30. Lee J, Taneja V, Vassallo R: Cigarette smoking and inflammation: cellular and molecular mechanisms. J. Dent. Res. 2012; 91 (2): 142–149. PubMed Abstract | Publisher Full Text | Free Full Text 31. Van de Loo AJAE, Mackus M, Kwon O, et al. : The Inflammatory Response to Alcohol Consumption and Its Role in the Pathology of Alcohol Hangover.J. Clin. Med.2020 2; 9 (7): 2081. Publisher Full Text 32. Dharmashankar K, Widlansky ME: Vascular endothelial function and hypertension: insights and directions. Curr. Hypertens. Rep. 2010; 12 (6): 448–455. PubMed Abstract | Publisher Full Text | Free Full Text 33. Zehr LJ, Cooper JS: Mandible osteoradionecrosis [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 [updated 2023 Jul 17]. https://www.statpearls.com 34. Beumer J, Harrison RE, Sanders B, et al. : Osteoradionecrosis: predisposing factors and outcomes of therapy. Head Neck Surg. 1984; 6 (5): 819–827. Publisher Full Text 35. Karim S, Mirza Z, Chaudhary AG, et al. : Assessment of Radiation Induced Therapeutic Effect and Cytotoxicity in Cancer Patients Based on Transcriptomic Profiling.Int. J. Mol. Sci.2016 19; 17 (2): 250. PubMed Abstract | Publisher Full Text | Free Full Text 36. MD Anderson Head and Neck Cancer Symptom Working Group: Dose-volume correlates of mandibular osteoradionecrosis in Oropharynx cancer patients receiving intensity-modulated radiotherapy: Results from a case-matched comparison. Radiother. Oncol. 2017; 124 (2): 232–239. Publisher Full Text 37. Lee J, Hueniken K, Cuddy K, et al. : Dental Extractions Before Radiation Therapy and the Risk of Osteoradionecrosis in Patients With Head and Neck Cancer.JAMA Otolaryngol. Head Neck Surg.2023; 149 (12): 1130–1139. Publisher Full Text 38. De Felice F, Tombolini V, Ruoppolo G, et al. : Osteoradionecrosis (ORN) of the jaws: definition, pathogenesis, clinical manifestations and management strategies. A literature review. Radiol. Med. 2014; 119 (10): 712–721. 39. Zitouni C: Case report form. Zenodo. 2024. Publisher Full Text 40. Zitouni C: Participant Information Sheet. Zenodo. 2024. Publisher Full Text Comments on this article Comments (0) Version 2 VERSION 2 PUBLISHED 14 Oct 2024 ADD YOUR COMMENT Comment Author details Author details 1 University of Tunis El Manar, Rommana, Tunis, 1068, Tunisia 2 ENT department, Military hospital of Tunis, Montfleury, Tunis, 1008, Tunisia 3 Research Unit UR17DN05, Military hospital of Tunis, Montfleury, Tunis, 1008, Tunisia 4 Emergency department, Military hospital of Tunis, Montfleury, Tunis, 1008, Tunisia 5 Department of hyperbaric oxygen therapy, Military Hospital of Tunis, Montfleury, Tunis, 1008, Tunisia Sameh Mezri Roles: Conceptualization Chaima Zitouni Roles: Writing – Original Draft Preparation, Writing – Review & Editing Khadija Bahrini Roles: Formal Analysis Mounir Haggui Roles: Supervision Wiem Boughzala Roles: Investigation Hedi Gharsallah Roles: Resources Competing interests No competing interests were disclosed. Grant information The author(s) declared that no grants were involved in supporting this work. Article Versions (2) version 2 Revised Published: 02 Jan 2025, 13:1225 https://doi.org/10.12688/f1000research.155112.2 version 1 Published: 14 Oct 2024, 13:1225 https://doi.org/10.12688/f1000research.155112.1 Copyright © 2025 Mezri S et al . This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Download Export To Sciwheel Bibtex EndNote ProCite Ref. Manager (RIS) Sente metrics Views Downloads F1000Research - - PubMed Central info_outline Data from PMC are received and updated monthly. - - Citations open_in_new 0 open_in_new 0 open_in_new SEE MORE DETAILS CITE how to cite this article Mezri S, Zitouni C, Bahrini K et al. Factors influencing osteoradionecrosis progression during hyperbaric oxygen therapy: A case study [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2025, 13 :1225 ( https://doi.org/10.12688/f1000research.155112.2 ) NOTE: If applicable, it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS track receive updates on this article Track an article to receive email alerts on any updates to this article. TRACK THIS ARTICLE Share Open Peer Review Current Reviewer Status: ? Key to Reviewer Statuses VIEW HIDE Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Version 2 VERSION 2 PUBLISHED 02 Jan 2025 Revised Views 0 Cite How to cite this report: Shudo A. Reviewer Report For: Factors influencing osteoradionecrosis progression during hyperbaric oxygen therapy: A case study [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2025, 13 :1225 ( https://doi.org/10.5256/f1000research.175997.r355375 ) The direct URL for this report is: https://f1000research.com/articles/13-1225/v2#referee-response-355375 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 03 Jan 2025 Atsushi Shudo , Kishiwada Tokushukai Hospital, Kishiwada, Japan Approved VIEWS 0 https://doi.org/10.5256/f1000research.175997.r355375 Dear Authors, Your manuscript has been well revised. The ... Continue reading READ ALL Dear Authors, Your manuscript has been well revised. The insightful article would be very useful to clinicians. Thank you for your careful revisions. Best regards. Competing Interests: No competing interests were disclosed. Reviewer Expertise: oral and maxillofacial surgery, oral oncology, jaw deformity, dental infection, osteonecrosis of the jaws, osteoradionecrosis I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Shudo A. Reviewer Report For: Factors influencing osteoradionecrosis progression during hyperbaric oxygen therapy: A case study [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2025, 13 :1225 ( https://doi.org/10.5256/f1000research.175997.r355375 ) The direct URL for this report is: https://f1000research.com/articles/13-1225/v2#referee-response-355375 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Respond or Comment COMMENT ON THIS REPORT Version 1 VERSION 1 PUBLISHED 14 Oct 2024 Views 0 Cite How to cite this report: Amaliya A. Reviewer Report For: Factors influencing osteoradionecrosis progression during hyperbaric oxygen therapy: A case study [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2025, 13 :1225 ( https://doi.org/10.5256/f1000research.170239.r332802 ) The direct URL for this report is: https://f1000research.com/articles/13-1225/v1#referee-response-332802 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 08 Nov 2024 Amaliya Amaliya , Universitas Padjadjaran, Bandung, West Java, Indonesia Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.170239.r332802 Dear Authors, The manuscript you submitted is well-written and well-read, but unfortunately, I have some comments that need to be addressed by you to improve the article. 1. First of all, I would like to suggest a minor ... Continue reading READ ALL Dear Authors, The manuscript you submitted is well-written and well-read, but unfortunately, I have some comments that need to be addressed by you to improve the article. 1. First of all, I would like to suggest a minor revision to the title. It would be better if the title also mentioned the type of the study. The authors defined the study as retrospective, but I may suggest it as a case-control study. Either it may be like Factors influencing osteoradionecrosis progression during hyperbaric oxygen therapy: A retrospective study or Factors influencing osteoradionecrosis progression during hyperbaric oxygen therapy: A case-control study. 2. The introduction is too short, the authors only cite 2 articles in there. Please explain the current state of the knowledge, with references. Identify the knowledge gap that you wish to fill with your study. 3. The result section is lacking demographic data/table of the subjects. 4. Did the authors adjust the collected data, for example for differences in age and gender? 5. In the discussion, please explain the mechanism or at least biological plausibility for the factors associated or influencing the ORN progression, for example, hypertension, what is the explanation or biological plausibility. Is the background of the cases’ history and progression described in sufficient detail? Partly Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Partly Is the conclusion balanced and justified on the basis of the findings? Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: Periodontology, Tobacco Harm Reduction, Nutrition and Periodontal Health I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Amaliya A. Reviewer Report For: Factors influencing osteoradionecrosis progression during hyperbaric oxygen therapy: A case study [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2025, 13 :1225 ( https://doi.org/10.5256/f1000research.170239.r332802 ) The direct URL for this report is: https://f1000research.com/articles/13-1225/v1#referee-response-332802 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 02 Jan 2025 Chaima zitouni , ENT department, Military hospital of Tunis, Montfleury, 1008, Tunisia 02 Jan 2025 Author Response Response to Reviewer Report by Amaliya Amaliya, Universitas Padjadjaran, Bandung, West Java, Indonesia We sincerely thank Dr. Amaliya for the thoughtful review and valuable comments, and here are our detailed ... Continue reading Response to Reviewer Report by Amaliya Amaliya, Universitas Padjadjaran, Bandung, West Java, Indonesia We sincerely thank Dr. Amaliya for the thoughtful review and valuable comments, and here are our detailed responses to the comments provided: 1. First of all, I would like to suggest a minor revision to the title. It would be better if the title also mentioned the type of the study. The authors defined the study as retrospective, but I may suggest it as a case-control study. Either it may be like Factors influencing osteoradionecrosis progression during hyperbaric oxygen therapy: A retrospective study or Factors influencing osteoradionecrosis progression during hyperbaric oxygen therapy: A case-control study. Author Response: The initial title of the manuscript was "Factors influencing osteoradionecrosis progression during hyperbaric oxygen therapy: A retrospective study" , but this was rejected by the journal editors. They proposed the revised title, and we followed their recommendation. 2. The introduction is too short, the authors only cite 2 articles in there. Please explain the current state of the knowledge, with references. Identify the knowledge gap that you wish to fill with your study. Author Response: We have expanded the introduction to include a detailed explanation of the current state of knowledge with additional references and have clearly identified the knowledge gap our study aims to address. 3. The result section is lacking demographic data/table of the subjects. Author Response: I have included a table to address the reviewer’s concern and enhance the clarity of the results section. 4. Did the authors adjust the collected data, for example for differences in age and gender? Author Response: We have adjusted the collected data for potential differences in age and gender in our analysis. Regression analysis was applied to account for these factors and ensure that the results are not confounded by demographic variables. 5. In the discussion, please explain the mechanism or at least biological plausibility for the factors associated or influencing the ORN progression, for example, hypertension, what is the explanation or biological plausibility. Author Response: We have addressed the concern regarding the biological plausibility of factors influencing the progression of ORN, including hypertension. Response to Reviewer Report by Amaliya Amaliya, Universitas Padjadjaran, Bandung, West Java, Indonesia We sincerely thank Dr. Amaliya for the thoughtful review and valuable comments, and here are our detailed responses to the comments provided: 1. First of all, I would like to suggest a minor revision to the title. It would be better if the title also mentioned the type of the study. The authors defined the study as retrospective, but I may suggest it as a case-control study. Either it may be like Factors influencing osteoradionecrosis progression during hyperbaric oxygen therapy: A retrospective study or Factors influencing osteoradionecrosis progression during hyperbaric oxygen therapy: A case-control study. Author Response: The initial title of the manuscript was "Factors influencing osteoradionecrosis progression during hyperbaric oxygen therapy: A retrospective study" , but this was rejected by the journal editors. They proposed the revised title, and we followed their recommendation. 2. The introduction is too short, the authors only cite 2 articles in there. Please explain the current state of the knowledge, with references. Identify the knowledge gap that you wish to fill with your study. Author Response: We have expanded the introduction to include a detailed explanation of the current state of knowledge with additional references and have clearly identified the knowledge gap our study aims to address. 3. The result section is lacking demographic data/table of the subjects. Author Response: I have included a table to address the reviewer’s concern and enhance the clarity of the results section. 4. Did the authors adjust the collected data, for example for differences in age and gender? Author Response: We have adjusted the collected data for potential differences in age and gender in our analysis. Regression analysis was applied to account for these factors and ensure that the results are not confounded by demographic variables. 5. In the discussion, please explain the mechanism or at least biological plausibility for the factors associated or influencing the ORN progression, for example, hypertension, what is the explanation or biological plausibility. Author Response: We have addressed the concern regarding the biological plausibility of factors influencing the progression of ORN, including hypertension. Competing Interests: No competing interests were disclosed. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 02 Jan 2025 Chaima zitouni , ENT department, Military hospital of Tunis, Montfleury, 1008, Tunisia 02 Jan 2025 Author Response Response to Reviewer Report by Amaliya Amaliya, Universitas Padjadjaran, Bandung, West Java, Indonesia We sincerely thank Dr. Amaliya for the thoughtful review and valuable comments, and here are our detailed ... Continue reading Response to Reviewer Report by Amaliya Amaliya, Universitas Padjadjaran, Bandung, West Java, Indonesia We sincerely thank Dr. Amaliya for the thoughtful review and valuable comments, and here are our detailed responses to the comments provided: 1. First of all, I would like to suggest a minor revision to the title. It would be better if the title also mentioned the type of the study. The authors defined the study as retrospective, but I may suggest it as a case-control study. Either it may be like Factors influencing osteoradionecrosis progression during hyperbaric oxygen therapy: A retrospective study or Factors influencing osteoradionecrosis progression during hyperbaric oxygen therapy: A case-control study. Author Response: The initial title of the manuscript was "Factors influencing osteoradionecrosis progression during hyperbaric oxygen therapy: A retrospective study" , but this was rejected by the journal editors. They proposed the revised title, and we followed their recommendation. 2. The introduction is too short, the authors only cite 2 articles in there. Please explain the current state of the knowledge, with references. Identify the knowledge gap that you wish to fill with your study. Author Response: We have expanded the introduction to include a detailed explanation of the current state of knowledge with additional references and have clearly identified the knowledge gap our study aims to address. 3. The result section is lacking demographic data/table of the subjects. Author Response: I have included a table to address the reviewer’s concern and enhance the clarity of the results section. 4. Did the authors adjust the collected data, for example for differences in age and gender? Author Response: We have adjusted the collected data for potential differences in age and gender in our analysis. Regression analysis was applied to account for these factors and ensure that the results are not confounded by demographic variables. 5. In the discussion, please explain the mechanism or at least biological plausibility for the factors associated or influencing the ORN progression, for example, hypertension, what is the explanation or biological plausibility. Author Response: We have addressed the concern regarding the biological plausibility of factors influencing the progression of ORN, including hypertension. Response to Reviewer Report by Amaliya Amaliya, Universitas Padjadjaran, Bandung, West Java, Indonesia We sincerely thank Dr. Amaliya for the thoughtful review and valuable comments, and here are our detailed responses to the comments provided: 1. First of all, I would like to suggest a minor revision to the title. It would be better if the title also mentioned the type of the study. The authors defined the study as retrospective, but I may suggest it as a case-control study. Either it may be like Factors influencing osteoradionecrosis progression during hyperbaric oxygen therapy: A retrospective study or Factors influencing osteoradionecrosis progression during hyperbaric oxygen therapy: A case-control study. Author Response: The initial title of the manuscript was "Factors influencing osteoradionecrosis progression during hyperbaric oxygen therapy: A retrospective study" , but this was rejected by the journal editors. They proposed the revised title, and we followed their recommendation. 2. The introduction is too short, the authors only cite 2 articles in there. Please explain the current state of the knowledge, with references. Identify the knowledge gap that you wish to fill with your study. Author Response: We have expanded the introduction to include a detailed explanation of the current state of knowledge with additional references and have clearly identified the knowledge gap our study aims to address. 3. The result section is lacking demographic data/table of the subjects. Author Response: I have included a table to address the reviewer’s concern and enhance the clarity of the results section. 4. Did the authors adjust the collected data, for example for differences in age and gender? Author Response: We have adjusted the collected data for potential differences in age and gender in our analysis. Regression analysis was applied to account for these factors and ensure that the results are not confounded by demographic variables. 5. In the discussion, please explain the mechanism or at least biological plausibility for the factors associated or influencing the ORN progression, for example, hypertension, what is the explanation or biological plausibility. Author Response: We have addressed the concern regarding the biological plausibility of factors influencing the progression of ORN, including hypertension. Competing Interests: No competing interests were disclosed. Close Report a concern COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Yilmaz B. Reviewer Report For: Factors influencing osteoradionecrosis progression during hyperbaric oxygen therapy: A case study [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2025, 13 :1225 ( https://doi.org/10.5256/f1000research.170239.r332798 ) The direct URL for this report is: https://f1000research.com/articles/13-1225/v1#referee-response-332798 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 31 Oct 2024 Busra Yilmaz , Istinye University, Istanbul, Turkey Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.170239.r332798 Comments to Authors This study addresses the effects of hyperbaric oxygen therapy (HBOT) on osteoradionecrosis (ORN) and analyzes the factors influencing the progression of ORN. The study presents significant clinical insights on the subject; however, several critical gaps need ... Continue reading READ ALL Comments to Authors This study addresses the effects of hyperbaric oxygen therapy (HBOT) on osteoradionecrosis (ORN) and analyzes the factors influencing the progression of ORN. The study presents significant clinical insights on the subject; however, several critical gaps need to be addressed and supplemented with additional information: 1. The authors should explain how the clinical and radiological diagnosis of ORN was determined and provide appropriate references. 2. The criteria for tooth extraction indications should be clarified, with sources cited. 3. Details on the pre-treatment dental care performed to minimize the risk of ORN should be provided. Specifically, it should be explained what procedures were carried out as part of dental care, including professional cleaning, fluoride treatments, necessary extractions, restorations, and any patient education to promote oral hygiene during and after radiation therapy. 4. The criteria used for diagnosing radiation-induced trismus must be explained in detail, along with relevant references. 5. A key parameter in ORN is the specific radiation dose received by the affected region. For instance, the Dmean Vx doses at extraction sites are not reported. 6. It would be beneficial to discuss the clinical and laboratory factors that can influence ORN development and treatment from all angles. Recently published reviews may provide useful insights. 7. In Table 1, the tumor histological types and locations are quite heterogeneous, meaning the radiation doses received by different parts of the jaw also vary, which could affect the outcomes. This limitation should be explicitly addressed. Long-term follow-up processes in ORN management could be emphasized. In particular, the effects of patient compliance during long-term treatments, such as HBOT, should be discussed. 8. The long-term effects of HBOT and any potential complications should also be addressed. Is the background of the cases’ history and progression described in sufficient detail? Partly Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Partly Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Partly Is the conclusion balanced and justified on the basis of the findings? Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: osteoradionecrosis, radiation induced trismus, head and neck cancers, chemotherapy, radiotherapy, oral management, oral oncology, side effects I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Yilmaz B. Reviewer Report For: Factors influencing osteoradionecrosis progression during hyperbaric oxygen therapy: A case study [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2025, 13 :1225 ( https://doi.org/10.5256/f1000research.170239.r332798 ) The direct URL for this report is: https://f1000research.com/articles/13-1225/v1#referee-response-332798 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 02 Jan 2025 Chaima zitouni , ENT department, Military hospital of Tunis, Montfleury, 1008, Tunisia 02 Jan 2025 Author Response Response to Reviewer Report by Busra Yilmaz, Istinye University, Istanbul, Turkey We sincerely thank Dr. Yilmaz for the thoughtful review and valuable comments, and here are our detailed responses to ... Continue reading Response to Reviewer Report by Busra Yilmaz, Istinye University, Istanbul, Turkey We sincerely thank Dr. Yilmaz for the thoughtful review and valuable comments, and here are our detailed responses to the comments provided: The authors should explain how the clinical and radiological diagnosis of ORN was determined and provide appropriate references. The diagnosis of ORN in our study was based on both clinical assessment and radiological imaging, as follows: Clinical Diagnosis: The primary clinical symptoms included pain, mastication difficulties, trismus, dental mobility, and bone exposure. These are typical symptoms of ORN and were observed in the majority of patients. Additionally, the presence of cutaneous fistulas was noted in 39% of cases, which is a key indicator of more advanced ORN. Radiological Diagnosis: Radiological examinations, including panoramic radiographs, CT scans, and MRI, were used to assess the severity of ORN. CT scans were the primary imaging modality for evaluating ORN progression. In our study, ORN lesions were classified according to the LENT/SOMA grading system The criteria for tooth extraction indications should be clarified, with sources cited. We have clarified the criteria for tooth extraction indications in the discussion section. Details on the pre-treatment dental care performed to minimize the risk of ORN should be provided. Specifically, it should be explained what procedures were carried out as part of dental care, including professional cleaning, fluoride treatments, necessary extractions, restorations, and any patient education to promote oral hygiene during and after radiation therapy. We provided the necessary details about the pre-treatment dental care performed to minimize the risk of ORN. The criteria used for diagnosing radiation-induced trismus must be explained in detail, along with relevant references. The diagnosis of radiation-induced trismus was not part of the objectives of our study, and therefore, we did not include detailed criteria for its diagnosis. A key parameter in ORN is the specific radiation dose received by the affected region. For instance, the Dmean Vx doses at extraction sites are not reported. We did not measure the specific radiation doses, such as the Dmean Vx doses at the extraction sites, in our study. However, we acknowledge the importance of radiation dose as a key parameter in ORN and have included a discussion of its role and relevance in the progression of ORN in the manuscript. It would be beneficial to discuss the clinical and laboratory factors that can influence ORN development and treatment from all angles. Recently published reviews may provide useful insights. In our study, we have made an effort to enrich the discussion by including relevant clinical factors that could influence the development and treatment of ORN. 7. In Table 1, the tumor histological types and locations are quite heterogeneous, meaning the radiation doses received by different parts of the jaw also vary, which could affect the outcomes. This limitation should be explicitly addressed. Long-term follow-up processes in ORN management could be emphasized. In particular, the effects of patient compliance during long-term treatments, such as HBOT, should be discussed. We have addressed this limitation by acknowledging the variability in radiation doses due to the heterogeneity of tumor histology and locations in the revised discussion. We have included a discussion on the importance of long-term follow-up in ORN management, emphasizing that patient compliance during extended treatments, such as HBOT, plays a crucial role in achieving optimal outcomes. The long-term effects of HBOT and any potential complications should also be addressed. We have added information on the long-term effects of HBOT, including potential complications. Response to Reviewer Report by Busra Yilmaz, Istinye University, Istanbul, Turkey We sincerely thank Dr. Yilmaz for the thoughtful review and valuable comments, and here are our detailed responses to the comments provided: The authors should explain how the clinical and radiological diagnosis of ORN was determined and provide appropriate references. The diagnosis of ORN in our study was based on both clinical assessment and radiological imaging, as follows: Clinical Diagnosis: The primary clinical symptoms included pain, mastication difficulties, trismus, dental mobility, and bone exposure. These are typical symptoms of ORN and were observed in the majority of patients. Additionally, the presence of cutaneous fistulas was noted in 39% of cases, which is a key indicator of more advanced ORN. Radiological Diagnosis: Radiological examinations, including panoramic radiographs, CT scans, and MRI, were used to assess the severity of ORN. CT scans were the primary imaging modality for evaluating ORN progression. In our study, ORN lesions were classified according to the LENT/SOMA grading system The criteria for tooth extraction indications should be clarified, with sources cited. We have clarified the criteria for tooth extraction indications in the discussion section. Details on the pre-treatment dental care performed to minimize the risk of ORN should be provided. Specifically, it should be explained what procedures were carried out as part of dental care, including professional cleaning, fluoride treatments, necessary extractions, restorations, and any patient education to promote oral hygiene during and after radiation therapy. We provided the necessary details about the pre-treatment dental care performed to minimize the risk of ORN. The criteria used for diagnosing radiation-induced trismus must be explained in detail, along with relevant references. The diagnosis of radiation-induced trismus was not part of the objectives of our study, and therefore, we did not include detailed criteria for its diagnosis. A key parameter in ORN is the specific radiation dose received by the affected region. For instance, the Dmean Vx doses at extraction sites are not reported. We did not measure the specific radiation doses, such as the Dmean Vx doses at the extraction sites, in our study. However, we acknowledge the importance of radiation dose as a key parameter in ORN and have included a discussion of its role and relevance in the progression of ORN in the manuscript. It would be beneficial to discuss the clinical and laboratory factors that can influence ORN development and treatment from all angles. Recently published reviews may provide useful insights. In our study, we have made an effort to enrich the discussion by including relevant clinical factors that could influence the development and treatment of ORN. 7. In Table 1, the tumor histological types and locations are quite heterogeneous, meaning the radiation doses received by different parts of the jaw also vary, which could affect the outcomes. This limitation should be explicitly addressed. Long-term follow-up processes in ORN management could be emphasized. In particular, the effects of patient compliance during long-term treatments, such as HBOT, should be discussed. We have addressed this limitation by acknowledging the variability in radiation doses due to the heterogeneity of tumor histology and locations in the revised discussion. We have included a discussion on the importance of long-term follow-up in ORN management, emphasizing that patient compliance during extended treatments, such as HBOT, plays a crucial role in achieving optimal outcomes. The long-term effects of HBOT and any potential complications should also be addressed. We have added information on the long-term effects of HBOT, including potential complications. Competing Interests: No competing interests were disclosed. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 02 Jan 2025 Chaima zitouni , ENT department, Military hospital of Tunis, Montfleury, 1008, Tunisia 02 Jan 2025 Author Response Response to Reviewer Report by Busra Yilmaz, Istinye University, Istanbul, Turkey We sincerely thank Dr. Yilmaz for the thoughtful review and valuable comments, and here are our detailed responses to ... Continue reading Response to Reviewer Report by Busra Yilmaz, Istinye University, Istanbul, Turkey We sincerely thank Dr. Yilmaz for the thoughtful review and valuable comments, and here are our detailed responses to the comments provided: The authors should explain how the clinical and radiological diagnosis of ORN was determined and provide appropriate references. The diagnosis of ORN in our study was based on both clinical assessment and radiological imaging, as follows: Clinical Diagnosis: The primary clinical symptoms included pain, mastication difficulties, trismus, dental mobility, and bone exposure. These are typical symptoms of ORN and were observed in the majority of patients. Additionally, the presence of cutaneous fistulas was noted in 39% of cases, which is a key indicator of more advanced ORN. Radiological Diagnosis: Radiological examinations, including panoramic radiographs, CT scans, and MRI, were used to assess the severity of ORN. CT scans were the primary imaging modality for evaluating ORN progression. In our study, ORN lesions were classified according to the LENT/SOMA grading system The criteria for tooth extraction indications should be clarified, with sources cited. We have clarified the criteria for tooth extraction indications in the discussion section. Details on the pre-treatment dental care performed to minimize the risk of ORN should be provided. Specifically, it should be explained what procedures were carried out as part of dental care, including professional cleaning, fluoride treatments, necessary extractions, restorations, and any patient education to promote oral hygiene during and after radiation therapy. We provided the necessary details about the pre-treatment dental care performed to minimize the risk of ORN. The criteria used for diagnosing radiation-induced trismus must be explained in detail, along with relevant references. The diagnosis of radiation-induced trismus was not part of the objectives of our study, and therefore, we did not include detailed criteria for its diagnosis. A key parameter in ORN is the specific radiation dose received by the affected region. For instance, the Dmean Vx doses at extraction sites are not reported. We did not measure the specific radiation doses, such as the Dmean Vx doses at the extraction sites, in our study. However, we acknowledge the importance of radiation dose as a key parameter in ORN and have included a discussion of its role and relevance in the progression of ORN in the manuscript. It would be beneficial to discuss the clinical and laboratory factors that can influence ORN development and treatment from all angles. Recently published reviews may provide useful insights. In our study, we have made an effort to enrich the discussion by including relevant clinical factors that could influence the development and treatment of ORN. 7. In Table 1, the tumor histological types and locations are quite heterogeneous, meaning the radiation doses received by different parts of the jaw also vary, which could affect the outcomes. This limitation should be explicitly addressed. Long-term follow-up processes in ORN management could be emphasized. In particular, the effects of patient compliance during long-term treatments, such as HBOT, should be discussed. We have addressed this limitation by acknowledging the variability in radiation doses due to the heterogeneity of tumor histology and locations in the revised discussion. We have included a discussion on the importance of long-term follow-up in ORN management, emphasizing that patient compliance during extended treatments, such as HBOT, plays a crucial role in achieving optimal outcomes. The long-term effects of HBOT and any potential complications should also be addressed. We have added information on the long-term effects of HBOT, including potential complications. Response to Reviewer Report by Busra Yilmaz, Istinye University, Istanbul, Turkey We sincerely thank Dr. Yilmaz for the thoughtful review and valuable comments, and here are our detailed responses to the comments provided: The authors should explain how the clinical and radiological diagnosis of ORN was determined and provide appropriate references. The diagnosis of ORN in our study was based on both clinical assessment and radiological imaging, as follows: Clinical Diagnosis: The primary clinical symptoms included pain, mastication difficulties, trismus, dental mobility, and bone exposure. These are typical symptoms of ORN and were observed in the majority of patients. Additionally, the presence of cutaneous fistulas was noted in 39% of cases, which is a key indicator of more advanced ORN. Radiological Diagnosis: Radiological examinations, including panoramic radiographs, CT scans, and MRI, were used to assess the severity of ORN. CT scans were the primary imaging modality for evaluating ORN progression. In our study, ORN lesions were classified according to the LENT/SOMA grading system The criteria for tooth extraction indications should be clarified, with sources cited. We have clarified the criteria for tooth extraction indications in the discussion section. Details on the pre-treatment dental care performed to minimize the risk of ORN should be provided. Specifically, it should be explained what procedures were carried out as part of dental care, including professional cleaning, fluoride treatments, necessary extractions, restorations, and any patient education to promote oral hygiene during and after radiation therapy. We provided the necessary details about the pre-treatment dental care performed to minimize the risk of ORN. The criteria used for diagnosing radiation-induced trismus must be explained in detail, along with relevant references. The diagnosis of radiation-induced trismus was not part of the objectives of our study, and therefore, we did not include detailed criteria for its diagnosis. A key parameter in ORN is the specific radiation dose received by the affected region. For instance, the Dmean Vx doses at extraction sites are not reported. We did not measure the specific radiation doses, such as the Dmean Vx doses at the extraction sites, in our study. However, we acknowledge the importance of radiation dose as a key parameter in ORN and have included a discussion of its role and relevance in the progression of ORN in the manuscript. It would be beneficial to discuss the clinical and laboratory factors that can influence ORN development and treatment from all angles. Recently published reviews may provide useful insights. In our study, we have made an effort to enrich the discussion by including relevant clinical factors that could influence the development and treatment of ORN. 7. In Table 1, the tumor histological types and locations are quite heterogeneous, meaning the radiation doses received by different parts of the jaw also vary, which could affect the outcomes. This limitation should be explicitly addressed. Long-term follow-up processes in ORN management could be emphasized. In particular, the effects of patient compliance during long-term treatments, such as HBOT, should be discussed. We have addressed this limitation by acknowledging the variability in radiation doses due to the heterogeneity of tumor histology and locations in the revised discussion. We have included a discussion on the importance of long-term follow-up in ORN management, emphasizing that patient compliance during extended treatments, such as HBOT, plays a crucial role in achieving optimal outcomes. The long-term effects of HBOT and any potential complications should also be addressed. We have added information on the long-term effects of HBOT, including potential complications. Competing Interests: No competing interests were disclosed. Close Report a concern COMMENT ON THIS REPORT Views 0 Cite How to cite this report: Shudo A. Reviewer Report For: Factors influencing osteoradionecrosis progression during hyperbaric oxygen therapy: A case study [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2025, 13 :1225 ( https://doi.org/10.5256/f1000research.170239.r332796 ) The direct URL for this report is: https://f1000research.com/articles/13-1225/v1#referee-response-332796 NOTE: it is important to ensure the information in square brackets after the title is included in this citation. Close Copy Citation Details Reviewer Report 25 Oct 2024 Atsushi Shudo , Kishiwada Tokushukai Hospital, Kishiwada, Japan Approved with Reservations VIEWS 0 https://doi.org/10.5256/f1000research.170239.r332796 Dear Authors, Thanks for the chance to review the manuscript entitled “Factors influencing osteoradionecrosis progression during hyperbaric oxygen therapy: A case study”. The reviewer is an oral maxillofacial surgeon. I read with great interest your ... Continue reading READ ALL Dear Authors, Thanks for the chance to review the manuscript entitled “Factors influencing osteoradionecrosis progression during hyperbaric oxygen therapy: A case study”. The reviewer is an oral maxillofacial surgeon. I read with great interest your paper. I also use HBOT to treat ORN, and found this paper extremely useful. Please consider the following points. - Since ORN is an infectious osteomyelitis, I suggest a more detailed description regarding antimicrobials should be done. Would it be possible to consider the type of antibiotics and the administration duration? As the authors know, HBOT is believed to enhance the effectiveness of antibiotics. - In relation to the above, could you please mention bacterial testing? The presence or absence of anaerobic bacteria seems important in discussing the effectiveness of HBOT. Best regards. Is the background of the cases’ history and progression described in sufficient detail? Yes Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes Is the conclusion balanced and justified on the basis of the findings? Yes Competing Interests: No competing interests were disclosed. Reviewer Expertise: oral and maxillofacial surgery, oral oncology, jaw deformity, dental infection, osteonecrosis of the jaws, osteoradionecrosis I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. Close READ LESS CITE CITE HOW TO CITE THIS REPORT Shudo A. Reviewer Report For: Factors influencing osteoradionecrosis progression during hyperbaric oxygen therapy: A case study [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2025, 13 :1225 ( https://doi.org/10.5256/f1000research.170239.r332796 ) The direct URL for this report is: https://f1000research.com/articles/13-1225/v1#referee-response-332796 NOTE: it is important to ensure the information in square brackets after the title is included in all citations of this article. COPY CITATION DETAILS Report a concern Author Response 02 Jan 2025 Chaima zitouni , ENT department, Military hospital of Tunis, Montfleury, 1008, Tunisia 02 Jan 2025 Author Response Response to Reviewer Report by Atsushi Shudo, Kishiwada Tokushukai Hospital, Kishiwada, Japan We sincerely thank Dr. Atsushi Shudo for the thoughtful review and valuable comments, and here are our detailed ... Continue reading Response to Reviewer Report by Atsushi Shudo, Kishiwada Tokushukai Hospital, Kishiwada, Japan We sincerely thank Dr. Atsushi Shudo for the thoughtful review and valuable comments, and here are our detailed responses to the comments provided: Since ORN is an infectious osteomyelitis, I suggest a more detailed description regarding antimicrobials should be done. Would it be possible to consider the type of antibiotics and the administration duration? As the authors know, HBOT is believed to enhance the effectiveness of antibiotics. We have addressed this suggestion by providing a more detailed description of the antimicrobials used, including the types of antibiotics and their administration duration, while also discussing the potential role of HBOT in enhancing antibiotic effectiveness. In relation to the above, could you please mention bacterial testing? The presence or absence of anaerobic bacteria seems important in discussing the effectiveness of HBOT. We have included a discussion on bacterial testing, highlighting the importance of anaerobic bacteria in ORN, and emphasized the potential role of HBOT in enhancing the effectiveness of antibiotics against these bacterial profiles. Response to Reviewer Report by Atsushi Shudo, Kishiwada Tokushukai Hospital, Kishiwada, Japan We sincerely thank Dr. Atsushi Shudo for the thoughtful review and valuable comments, and here are our detailed responses to the comments provided: Since ORN is an infectious osteomyelitis, I suggest a more detailed description regarding antimicrobials should be done. Would it be possible to consider the type of antibiotics and the administration duration? As the authors know, HBOT is believed to enhance the effectiveness of antibiotics. We have addressed this suggestion by providing a more detailed description of the antimicrobials used, including the types of antibiotics and their administration duration, while also discussing the potential role of HBOT in enhancing antibiotic effectiveness. In relation to the above, could you please mention bacterial testing? The presence or absence of anaerobic bacteria seems important in discussing the effectiveness of HBOT. We have included a discussion on bacterial testing, highlighting the importance of anaerobic bacteria in ORN, and emphasized the potential role of HBOT in enhancing the effectiveness of antibiotics against these bacterial profiles. Competing Interests: No competing interests were disclosed. Close Report a concern Respond or Comment COMMENTS ON THIS REPORT Author Response 02 Jan 2025 Chaima zitouni , ENT department, Military hospital of Tunis, Montfleury, 1008, Tunisia 02 Jan 2025 Author Response Response to Reviewer Report by Atsushi Shudo, Kishiwada Tokushukai Hospital, Kishiwada, Japan We sincerely thank Dr. Atsushi Shudo for the thoughtful review and valuable comments, and here are our detailed ... Continue reading Response to Reviewer Report by Atsushi Shudo, Kishiwada Tokushukai Hospital, Kishiwada, Japan We sincerely thank Dr. Atsushi Shudo for the thoughtful review and valuable comments, and here are our detailed responses to the comments provided: Since ORN is an infectious osteomyelitis, I suggest a more detailed description regarding antimicrobials should be done. Would it be possible to consider the type of antibiotics and the administration duration? As the authors know, HBOT is believed to enhance the effectiveness of antibiotics. We have addressed this suggestion by providing a more detailed description of the antimicrobials used, including the types of antibiotics and their administration duration, while also discussing the potential role of HBOT in enhancing antibiotic effectiveness. In relation to the above, could you please mention bacterial testing? The presence or absence of anaerobic bacteria seems important in discussing the effectiveness of HBOT. We have included a discussion on bacterial testing, highlighting the importance of anaerobic bacteria in ORN, and emphasized the potential role of HBOT in enhancing the effectiveness of antibiotics against these bacterial profiles. Response to Reviewer Report by Atsushi Shudo, Kishiwada Tokushukai Hospital, Kishiwada, Japan We sincerely thank Dr. Atsushi Shudo for the thoughtful review and valuable comments, and here are our detailed responses to the comments provided: Since ORN is an infectious osteomyelitis, I suggest a more detailed description regarding antimicrobials should be done. Would it be possible to consider the type of antibiotics and the administration duration? As the authors know, HBOT is believed to enhance the effectiveness of antibiotics. We have addressed this suggestion by providing a more detailed description of the antimicrobials used, including the types of antibiotics and their administration duration, while also discussing the potential role of HBOT in enhancing antibiotic effectiveness. In relation to the above, could you please mention bacterial testing? The presence or absence of anaerobic bacteria seems important in discussing the effectiveness of HBOT. We have included a discussion on bacterial testing, highlighting the importance of anaerobic bacteria in ORN, and emphasized the potential role of HBOT in enhancing the effectiveness of antibiotics against these bacterial profiles. Competing Interests: No competing interests were disclosed. Close Report a concern COMMENT ON THIS REPORT Comments on this article Comments (0) Version 2 VERSION 2 PUBLISHED 14 Oct 2024 ADD YOUR COMMENT Comment keyboard_arrow_left keyboard_arrow_right Open Peer Review Reviewer Status info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Reviewer Reports Invited Reviewers 1 2 3 Version 2 (revision) 02 Jan 25 read Version 1 14 Oct 24 read read read Atsushi Shudo , Kishiwada Tokushukai Hospital, Kishiwada, Japan Busra Yilmaz , Istinye University, Istanbul, Turkey Amaliya Amaliya , Universitas Padjadjaran, Bandung, Indonesia Comments on this article All Comments (0) Add a comment Sign up for content alerts Sign Up You are now signed up to receive this alert Browse by related subjects keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2025 Shudo A. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 03 Jan 2025 | for Version 2 Atsushi Shudo , Kishiwada Tokushukai Hospital, Kishiwada, Japan 0 Views copyright © 2025 Shudo A. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (0) Approved info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Dear Authors, Your manuscript has been well revised. The insightful article would be very useful to clinicians. Thank you for your careful revisions. Best regards. Competing Interests No competing interests were disclosed. Reviewer Expertise oral and maxillofacial surgery, oral oncology, jaw deformity, dental infection, osteonecrosis of the jaws, osteoradionecrosis I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard. reply Respond to this report Responses (0) Shudo A. Peer Review Report For: Factors influencing osteoradionecrosis progression during hyperbaric oxygen therapy: A case study [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2025, 13 :1225 ( https://doi.org/10.5256/f1000research.175997.r355375) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/13-1225/v2#referee-response-355375 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2024 Amaliya A. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 08 Nov 2024 | for Version 1 Amaliya Amaliya , Universitas Padjadjaran, Bandung, West Java, Indonesia 0 Views copyright © 2024 Amaliya A. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Dear Authors, The manuscript you submitted is well-written and well-read, but unfortunately, I have some comments that need to be addressed by you to improve the article. 1. First of all, I would like to suggest a minor revision to the title. It would be better if the title also mentioned the type of the study. The authors defined the study as retrospective, but I may suggest it as a case-control study. Either it may be like Factors influencing osteoradionecrosis progression during hyperbaric oxygen therapy: A retrospective study or Factors influencing osteoradionecrosis progression during hyperbaric oxygen therapy: A case-control study. 2. The introduction is too short, the authors only cite 2 articles in there. Please explain the current state of the knowledge, with references. Identify the knowledge gap that you wish to fill with your study. 3. The result section is lacking demographic data/table of the subjects. 4. Did the authors adjust the collected data, for example for differences in age and gender? 5. In the discussion, please explain the mechanism or at least biological plausibility for the factors associated or influencing the ORN progression, for example, hypertension, what is the explanation or biological plausibility. Is the background of the cases’ history and progression described in sufficient detail? Partly Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Partly Is the conclusion balanced and justified on the basis of the findings? Yes Competing Interests No competing interests were disclosed. Reviewer Expertise Periodontology, Tobacco Harm Reduction, Nutrition and Periodontal Health I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 02 Jan 2025 Chaima zitouni, ENT department, Military hospital of Tunis, Montfleury, 1008, Tunisia Response to Reviewer Report by Amaliya Amaliya, Universitas Padjadjaran, Bandung, West Java, Indonesia We sincerely thank Dr. Amaliya for the thoughtful review and valuable comments, and here are our detailed responses to the comments provided: 1. First of all, I would like to suggest a minor revision to the title. It would be better if the title also mentioned the type of the study. The authors defined the study as retrospective, but I may suggest it as a case-control study. Either it may be like Factors influencing osteoradionecrosis progression during hyperbaric oxygen therapy: A retrospective study or Factors influencing osteoradionecrosis progression during hyperbaric oxygen therapy: A case-control study. Author Response: The initial title of the manuscript was "Factors influencing osteoradionecrosis progression during hyperbaric oxygen therapy: A retrospective study" , but this was rejected by the journal editors. They proposed the revised title, and we followed their recommendation. 2. The introduction is too short, the authors only cite 2 articles in there. Please explain the current state of the knowledge, with references. Identify the knowledge gap that you wish to fill with your study. Author Response: We have expanded the introduction to include a detailed explanation of the current state of knowledge with additional references and have clearly identified the knowledge gap our study aims to address. 3. The result section is lacking demographic data/table of the subjects. Author Response: I have included a table to address the reviewer’s concern and enhance the clarity of the results section. 4. Did the authors adjust the collected data, for example for differences in age and gender? Author Response: We have adjusted the collected data for potential differences in age and gender in our analysis. Regression analysis was applied to account for these factors and ensure that the results are not confounded by demographic variables. 5. In the discussion, please explain the mechanism or at least biological plausibility for the factors associated or influencing the ORN progression, for example, hypertension, what is the explanation or biological plausibility. Author Response: We have addressed the concern regarding the biological plausibility of factors influencing the progression of ORN, including hypertension. View more View less Competing Interests No competing interests were disclosed. reply Respond Report a concern Amaliya A. Peer Review Report For: Factors influencing osteoradionecrosis progression during hyperbaric oxygen therapy: A case study [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2025, 13 :1225 ( https://doi.org/10.5256/f1000research.170239.r332802) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/13-1225/v1#referee-response-332802 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2024 Yilmaz B. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 31 Oct 2024 | for Version 1 Busra Yilmaz , Istinye University, Istanbul, Turkey 0 Views copyright © 2024 Yilmaz B. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Comments to Authors This study addresses the effects of hyperbaric oxygen therapy (HBOT) on osteoradionecrosis (ORN) and analyzes the factors influencing the progression of ORN. The study presents significant clinical insights on the subject; however, several critical gaps need to be addressed and supplemented with additional information: 1. The authors should explain how the clinical and radiological diagnosis of ORN was determined and provide appropriate references. 2. The criteria for tooth extraction indications should be clarified, with sources cited. 3. Details on the pre-treatment dental care performed to minimize the risk of ORN should be provided. Specifically, it should be explained what procedures were carried out as part of dental care, including professional cleaning, fluoride treatments, necessary extractions, restorations, and any patient education to promote oral hygiene during and after radiation therapy. 4. The criteria used for diagnosing radiation-induced trismus must be explained in detail, along with relevant references. 5. A key parameter in ORN is the specific radiation dose received by the affected region. For instance, the Dmean Vx doses at extraction sites are not reported. 6. It would be beneficial to discuss the clinical and laboratory factors that can influence ORN development and treatment from all angles. Recently published reviews may provide useful insights. 7. In Table 1, the tumor histological types and locations are quite heterogeneous, meaning the radiation doses received by different parts of the jaw also vary, which could affect the outcomes. This limitation should be explicitly addressed. Long-term follow-up processes in ORN management could be emphasized. In particular, the effects of patient compliance during long-term treatments, such as HBOT, should be discussed. 8. The long-term effects of HBOT and any potential complications should also be addressed. Is the background of the cases’ history and progression described in sufficient detail? Partly Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Partly Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Partly Is the conclusion balanced and justified on the basis of the findings? Yes Competing Interests No competing interests were disclosed. Reviewer Expertise osteoradionecrosis, radiation induced trismus, head and neck cancers, chemotherapy, radiotherapy, oral management, oral oncology, side effects I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 02 Jan 2025 Chaima zitouni, ENT department, Military hospital of Tunis, Montfleury, 1008, Tunisia Response to Reviewer Report by Busra Yilmaz, Istinye University, Istanbul, Turkey We sincerely thank Dr. Yilmaz for the thoughtful review and valuable comments, and here are our detailed responses to the comments provided: The authors should explain how the clinical and radiological diagnosis of ORN was determined and provide appropriate references. The diagnosis of ORN in our study was based on both clinical assessment and radiological imaging, as follows: Clinical Diagnosis: The primary clinical symptoms included pain, mastication difficulties, trismus, dental mobility, and bone exposure. These are typical symptoms of ORN and were observed in the majority of patients. Additionally, the presence of cutaneous fistulas was noted in 39% of cases, which is a key indicator of more advanced ORN. Radiological Diagnosis: Radiological examinations, including panoramic radiographs, CT scans, and MRI, were used to assess the severity of ORN. CT scans were the primary imaging modality for evaluating ORN progression. In our study, ORN lesions were classified according to the LENT/SOMA grading system The criteria for tooth extraction indications should be clarified, with sources cited. We have clarified the criteria for tooth extraction indications in the discussion section. Details on the pre-treatment dental care performed to minimize the risk of ORN should be provided. Specifically, it should be explained what procedures were carried out as part of dental care, including professional cleaning, fluoride treatments, necessary extractions, restorations, and any patient education to promote oral hygiene during and after radiation therapy. We provided the necessary details about the pre-treatment dental care performed to minimize the risk of ORN. The criteria used for diagnosing radiation-induced trismus must be explained in detail, along with relevant references. The diagnosis of radiation-induced trismus was not part of the objectives of our study, and therefore, we did not include detailed criteria for its diagnosis. A key parameter in ORN is the specific radiation dose received by the affected region. For instance, the Dmean Vx doses at extraction sites are not reported. We did not measure the specific radiation doses, such as the Dmean Vx doses at the extraction sites, in our study. However, we acknowledge the importance of radiation dose as a key parameter in ORN and have included a discussion of its role and relevance in the progression of ORN in the manuscript. It would be beneficial to discuss the clinical and laboratory factors that can influence ORN development and treatment from all angles. Recently published reviews may provide useful insights. In our study, we have made an effort to enrich the discussion by including relevant clinical factors that could influence the development and treatment of ORN. 7. In Table 1, the tumor histological types and locations are quite heterogeneous, meaning the radiation doses received by different parts of the jaw also vary, which could affect the outcomes. This limitation should be explicitly addressed. Long-term follow-up processes in ORN management could be emphasized. In particular, the effects of patient compliance during long-term treatments, such as HBOT, should be discussed. We have addressed this limitation by acknowledging the variability in radiation doses due to the heterogeneity of tumor histology and locations in the revised discussion. We have included a discussion on the importance of long-term follow-up in ORN management, emphasizing that patient compliance during extended treatments, such as HBOT, plays a crucial role in achieving optimal outcomes. The long-term effects of HBOT and any potential complications should also be addressed. We have added information on the long-term effects of HBOT, including potential complications. View more View less Competing Interests No competing interests were disclosed. reply Respond Report a concern Yilmaz B. Peer Review Report For: Factors influencing osteoradionecrosis progression during hyperbaric oxygen therapy: A case study [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2025, 13 :1225 ( https://doi.org/10.5256/f1000research.170239.r332798) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/13-1225/v1#referee-response-332798 keyboard_arrow_left Back to all reports Reviewer Report 0 Views copyright © 2024 Shudo A. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 25 Oct 2024 | for Version 1 Atsushi Shudo , Kishiwada Tokushukai Hospital, Kishiwada, Japan 0 Views copyright © 2024 Shudo A. This is an open access peer review report distributed under the terms of the Creative Commons Attribution License , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. format_quote Cite this report speaker_notes Responses (1) Approved With Reservations info_outline Alongside their report, reviewers assign a status to the article: Approved The paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. Not approved Fundamental flaws in the paper seriously undermine the findings and conclusions Dear Authors, Thanks for the chance to review the manuscript entitled “Factors influencing osteoradionecrosis progression during hyperbaric oxygen therapy: A case study”. The reviewer is an oral maxillofacial surgeon. I read with great interest your paper. I also use HBOT to treat ORN, and found this paper extremely useful. Please consider the following points. - Since ORN is an infectious osteomyelitis, I suggest a more detailed description regarding antimicrobials should be done. Would it be possible to consider the type of antibiotics and the administration duration? As the authors know, HBOT is believed to enhance the effectiveness of antibiotics. - In relation to the above, could you please mention bacterial testing? The presence or absence of anaerobic bacteria seems important in discussing the effectiveness of HBOT. Best regards. Is the background of the cases’ history and progression described in sufficient detail? Yes Are enough details provided of any physical examination and diagnostic tests, treatment given and outcomes? Yes Is sufficient discussion included of the importance of the findings and their relevance to future understanding of disease processes, diagnosis or treatment? Yes Is the conclusion balanced and justified on the basis of the findings? Yes Competing Interests No competing interests were disclosed. Reviewer Expertise oral and maxillofacial surgery, oral oncology, jaw deformity, dental infection, osteonecrosis of the jaws, osteoradionecrosis I confirm that I have read this submission and believe that I have an appropriate level of expertise to confirm that it is of an acceptable scientific standard, however I have significant reservations, as outlined above. reply Respond to this report Responses (1) Author Response 02 Jan 2025 Chaima zitouni, ENT department, Military hospital of Tunis, Montfleury, 1008, Tunisia Response to Reviewer Report by Atsushi Shudo, Kishiwada Tokushukai Hospital, Kishiwada, Japan We sincerely thank Dr. Atsushi Shudo for the thoughtful review and valuable comments, and here are our detailed responses to the comments provided: Since ORN is an infectious osteomyelitis, I suggest a more detailed description regarding antimicrobials should be done. Would it be possible to consider the type of antibiotics and the administration duration? As the authors know, HBOT is believed to enhance the effectiveness of antibiotics. We have addressed this suggestion by providing a more detailed description of the antimicrobials used, including the types of antibiotics and their administration duration, while also discussing the potential role of HBOT in enhancing antibiotic effectiveness. In relation to the above, could you please mention bacterial testing? The presence or absence of anaerobic bacteria seems important in discussing the effectiveness of HBOT. We have included a discussion on bacterial testing, highlighting the importance of anaerobic bacteria in ORN, and emphasized the potential role of HBOT in enhancing the effectiveness of antibiotics against these bacterial profiles. View more View less Competing Interests No competing interests were disclosed. reply Respond Report a concern Shudo A. Peer Review Report For: Factors influencing osteoradionecrosis progression during hyperbaric oxygen therapy: A case study [version 2; peer review: 1 approved, 2 approved with reservations] . F1000Research 2025, 13 :1225 ( https://doi.org/10.5256/f1000research.170239.r332796) NOTE: it is important to ensure the information in square brackets after the title is included in this citation. The direct URL for this report is: https://f1000research.com/articles/13-1225/v1#referee-response-332796 Alongside their report, reviewers assign a status to the article: Approved - the paper is scientifically sound in its current form and only minor, if any, improvements are suggested Approved with reservations - A number of small changes, sometimes more significant revisions are required to address specific details and improve the papers academic merit. 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