Sphenoid Sinus Osteitis After Endoscopic Transsphenoidal Surgery: A Bone-Centered Postoperative Entity

Sphenoid Sinus Osteitis After Endoscopic Transsphenoidal Surgery: A Bone-Centered Postoperative Entity | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Sphenoid Sinus Osteitis After Endoscopic Transsphenoidal Surgery: A Bone-Centered Postoperative Entity Burak Çabuk, Atılay Yaylacı, Fatih Shatri, Sertaç Ayyıldız, Eren Yılmaz, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8636545/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 27 Apr, 2026 Read the published version in Acta Neurochirurgica → Version 1 posted 9 You are reading this latest preprint version Abstract Purpose Despite advances in endoscopic skull base surgery, postoperative sinonasal inflammation remains poorly characterized. In particular, sphenoid sinus osteitis has received little attention, as complications after endoscopic transsphenoidal surgery (ETS) have largely been assessed in terms of mucosal pathology. This study aims to determine the incidence of sphenoid sinus osteitis after ETS, describe its clinical and radiological features, and identify associated surgical and demographic risk factors. Methods We retrospectively reviewed patients undergoing primary ETS for sellar or parasellar tumors between September 2021 and September 2024. Osteitis was assessed on high-resolution CT using the Lee and Kennedy classification. Clinical symptoms, particularly cacosmia, and surgical approach and reconstruction techniques were analyzed as potential risk factors. Results Among 1,443 patients, sphenoid sinus osteitis was identified in 12 cases (0.83%). All cases occurred in patients who underwent sellar reconstruction, with no osteitis observed in those without reconstruction (p < 0.001). Regarding reconstruction techniques, the nasoseptal flap showed a borderline statistical significance (p = 0,045). Radiologically, osteitis was Grade 1 in 50%, Grade 2 in 25%, and Grade 3 in 25% of cases. Cacosmia was the presenting symptom in 75% of affected patients (p < 0.001). Surgical revision was required in 11 patients (91.7%), while medical treatment alone was sufficient in one case. Conclusion Sphenoid sinus osteitis represents a rare but clinically relevant bone-centered complication following ETS, distinct from conventional rhinonasal morbidity. Its exclusive association with sellar reconstruction highlights the potential role of reconstruction-related bone contact and localized inflammatory responses in its pathogenesis. Recognizing sphenoid sinus osteitis as a distinct postoperative entity may improve diagnostic accuracy and guide more targeted management of postoperative rhinonasal symptoms. Osteitis Endoscopic Skull base Sfenoid sinus Sinusitis Pituitary Figures Figure 1 INTRODUCTION Endoscopic transsphenoidal surgery has become the standard surgical approach for the treatment of pituitary adenomas and other sellar and parasellar pathologies.[ 5 , 17 , 34 ] Advances in endoscopic techniques and skull base reconstruction have significantly improved surgical outcomes; however, postoperative sinonasal and skull base–related complications continue to affect patient comfort, quality of life, and long-term surgical success. [ 1 ] In the existing literature, postoperative complications following endoscopic transsphenoidal surgery have predominantly been evaluated under the headings of sinonasal infections, mucosal inflammation, crusting, and sinusitis, with reported rates reaching up to 3–4%. [ 1 , 22 , 30 ] While these studies provide valuable information regarding mucosal morbidity, the potential long-term effects of these inflammatory processes on the underlying sphenoid sinus bone have received little attention. Nevertheless, it is well established that chronic inflammatory conditions may involve not only the mucosa but also the adjacent bone tissue. [ 2 , 11 , 33 ] Osteitis represents an inflammatory reaction of bone and has been described using terms such as hyperostosis, bony involvement, and neo-osteogenesis. [ 2 , 19 , 20 , 32 ]In the context of chronic rhinosinusitis, persistent mucosal inflammation has been shown to induce structural changes in the adjacent bone, including sclerosis and thickening, as demonstrated by both radiological and histopathological studies. [ 2 , 28 ] In neurosurgical practice, osteitis is commonly discussed in relation to cranioplasty and craniotomy flap infections, where the use of synthetic materials and compromised bone vascularity play a critical role. [ 14 , 25 , 35 ] During endoscopic transsphenoidal and extended endonasal skull base procedures, various reconstruction techniques—including collagen-based dural substitutes, autologous fascia lata grafts, and vascularized nasoseptal flaps—are routinely employed to prevent cerebrospinal fluid leakage. [ 13 , 17 , 24 , 30 , 34 ] Although these techniques are essential for surgical success, their direct contact with the sphenoid sinus bony walls may trigger inflammatory bone responses. Despite this potential mechanism, sphenoid sinus osteitis following endoscopic transsphenoidal surgery has not been systematically investigated as a distinct, bone-centered complication, as existing studies have largely focused on mucosal pathology. [ 1 , 16 , 22 , 30 ] Therefore, the aim of this study is to determine the incidence of sphenoid sinus osteitis in a large cohort of patients undergoing endoscopic transsphenoidal surgery, to characterize its clinical and radiological features, and to analyze potential demographic and surgical risk factors associated with its development. MATERIALS AND METHODS Study Design and Patient Selection This study was designed as a retrospective cohort study and conducted in accordance with the ethical standards of the institutional research committee and with the principles of the Declaration of Helsinki. Ethical approval was obtained from the Kocaeli University Faculty of Medicine Clinical Research Ethics Committee (GOKAEK-2025/22/36). Prior to surgery, written surgical informed consent was obtained from all patients, which included permission for the use of anonymized hospital records for scientific research purposes. Due to the retrospective nature of the study and the use of anonymized data, the requirement for additional study-specific informed consent was waived by the ethics committee. Medical records of patients who underwent endoscopic transsphenoidal surgery for sellar or parasellar tumors between September 2021 and September 2024 were retrospectively reviewed. During the study period, a total of 1,908 patients underwent endoscopic transsphenoidal surgery. Inclusion criteria consisted of patients who had undergone primary endoscopic transsphenoidal surgery for a sellar or parasellar tumor. Patients were excluded if they had a history of previous transsphenoidal or paranasal sinus surgery, preoperative imaging evidence of sphenoid sinus pathology (such as sinusitis or mucocele), or insufficient postoperative follow-up data. Definition of Postoperative Osteitis The primary endpoint of the study was the presence of postoperative sphenoid sinus osteitis. The diagnosis of osteitis was established based on a combination of radiological findings and clinical symptoms, as detailed below. Radiological Evaluation All patients had preoperative sellar magnetic resonance imaging (MRI) and paranasal sinus computed tomography (CT) scans available for evaluation. According to the institutional postoperative follow-up protocol, cranial MRI was routinely performed at 1, 3, and 6 months postoperatively, at 1 year, and annually thereafter. Patients who demonstrated suspicious sphenoid sinus mucosal thickening or contrast enhancement on follow-up MRI, as well as those with clinical suspicion of osteitis, underwent high-resolution paranasal sinus CT to allow detailed assessment of bony structures. Postoperative CT scans of patients with suspected osteitis were evaluated according to the radiological osteitis classification proposed by Lee and Kennedy (2006). [ 19 ] In this system, osteitis is graded for each sinus (excluding the frontal sinus) based on the degree of bony thickening and sclerosis as follows: Grade 1 (mild): bone thickness up to 3 mm, Grade 2 (moderate): bone thickness of 4–5 mm, Grade 3 (severe): bone thickness greater than 5 mm. High-resolution CT images were independently evaluated by two observers. In cases of disagreement, a consensus was reached to determine the final grade. When necessary, MRI findings were correlated with CT images to improve diagnostic accuracy. Clinical Evaluation All patients were systematically evaluated during postoperative follow-up visits for symptoms potentially associated with osteitis. Particular emphasis was placed on cacosmia (persistent foul odor perception), a symptom known to significantly impair postoperative quality of life following endoscopic transsphenoidal surgery. At each follow-up visit, patients were actively questioned regarding the presence, onset, and severity of cacosmia, as well as its impact on daily activities. Additional symptoms, including persistent nasal obstruction, purulent postnasal discharge, and atypical headache, were also recorded. Patients presenting with these symptoms underwent further evaluation with paranasal sinus CT. Clinical findings were correlated with radiological results to support the diagnosis of postoperative osteitis. Surgical Approach Demographic data (age and sex), comorbidities, and were recorded for all patients. Surgical variables considered potential risk factors for osteitis development were also documented. Based on the anatomical extent of surgical dissection, surgical approaches were categorized into two groups. Middle turbinate resection was not performed in any patient. Standard endoscopic endonasal approach, defined as procedures in which the surgical corridor remained within the boundaries of the sella turcica and was used for conventional pituitary lesions. Extended endoscopic endonasal approach, defined as procedures in which the surgical corridor extended beyond the sella turcica to adjacent regions such as the planum sphenoidale, olfactory groove, clivus, or cavernous sinus. These approaches required wider bone and mucosal resection. Sellar Reconstruction Sellar reconstruction techniques were classified according to the size of the defect and the risk of cerebrospinal fluid (CSF) leakage. Simple Closure applied in cases with low-risk or suspected low-flow CSF leakage, consisting of placement of a collagen-based dural substitute followed by fibrin sealant application. Multilayer Autologous Grafting used in cases with evident intraoperative CSF leakage, involving multilayer reconstruction with non-vascularized autologous tissues such as fascia lata and/or abdominal fat. Vascularized Flap Reconstruction, Preferred for large skull base defects following extended approaches and in cases of high-flow CSF leakage, using a vascularized nasoseptal flap (NSF). Statistical Analysis Statistical analysis was performed using the IBM SPSS Statistics for Windows, Version 26.0 (IBM Corp., Armonk, NY, USA). Descriptive statistics were expressed as mean ± standard deviation (SD) for continuous variables and as frequencies (n) and percentages (%) for categorical variables. The normality of the distribution for continuous variables was evaluated. Comparisons of continuous variables (e.g., age) between the osteitis and non-osteitis groups were performed using the Student's t-test . Categorical variables (e.g., sex, surgical approach, reconstruction type) were compared using the Pearson Chi-square test . When the expected frequency in any cell of the contingency table was less than 5, Fisher's exact test was used. A p-value of less than 0.05 was considered statistically significant. RESULTS Between September 2021 and September 2024, a total of 1,443 patients who underwent endoscopic transsphenoidal surgery and met the study inclusion criteria were retrospectively analyzed. Of these patients, 54.9% were female (n = 792) and 45.1% were male (n = 651). The mean age of the entire cohort was 44.6 years (range: 18–80). When comparing the osteitis and non-osteitis groups, there were no statistically significant differences regarding mean age (41.92 ± 9.10 years vs. 44.65 ± 13.11 years, p = 0.471) or sex distribution (p = 0.244). Regarding surgical approaches, the majority of patients underwent a standard transsphenoidal approach (n = 1,341, 93.0%), while an extended approach was performed in a smaller proportion of cases (n = 102, 7.0%). Postoperative sphenoid sinus osteitis was identified in 12 patients, corresponding to an overall incidence of 0.83%. The incidence of osteitis was 0.75% (10/1,341) in the standard approach group and 1.96% (2/102) in the extended approach group; however, this difference was not statistically significant (p = 0.206). When reconstruction techniques were evaluated, osteitis was observed exclusively in patients who underwent sellar reconstruction. No cases of osteitis were detected among the 747 patients who did not receive reconstruction (0.0%). Among the specific reconstruction subgroups, osteitis occurred in 5 of 255 patients (1.96%) reconstructed with a nasoseptal flap, 3 of 133 patients (2.26%) receiving fascia lata grafts, and 4 of 308 patients (1.3%) treated with Duragen/Tisseel. Statistical analysis revealed that the use of a nasoseptal flap was associated with a statistically significant difference (p = 0.045), whereas the fascia lata (p = 0.091) and Duragen/Tisseel (p = 0.297) subgroups did not reach statistical significance. Clinically, cacosmia was present in 9 of the 12 patients with osteitis (75.0%), which was significantly higher than the 1.5% incidence (21/1,410) observed in the non-osteitis group (p < 0.001). Among patients reporting cacosmia, culture results did not show a statistically significant difference between negative and positive growth subgroups (p = 0.572). Radiological evaluation of the 12 osteitis cases according to the Lee and Kennedy classification revealed Grade 1 osteitis in 6 patients (50%), Grade 2 in 3 patients (25%), and Grade 3 in 3 patients (25%). In Grade 2 and higher cases, computed tomography demonstrated cortical irregularity and sclerotic thickening of the sphenoid sinus floor, with associated mucosal contrast enhancement in some patients. In Grade 3 cases, diffuse mucosal thickening accompanying extensive bony involvement was observed. CT findings were dominated by cortical thickening and sclerosis of the sphenoid sinus walls. (Fig. 1 ) No bone marrow edema was detected on magnetic resonance imaging. Positron emission tomography/computed tomography (PET/CT) was not routinely performed in the study population and was reserved for selected cases with diagnostic uncertainty or for systemic evaluation. PET/CT was used in 2 patients to support the diagnosis and in 1 patient for metastatic screening. In these cases, increased fluorodeoxyglucose (FDG) uptake in the sphenoid region was consistent with the clinical and radiological findings of osteitis. Regarding treatment strategies for the osteitis group, 11 patients (91.7%) underwent surgical revision (second operation), while one patient (8.3%) was managed with medical therapy alone. Microbiological cultures were obtained in all 12 patients, with positive growth identified in 4 cases (33.3%). The most frequently isolated microorganism was Staphylococcus aureus (n = 3). Other isolated organisms included Klebsiella pneumoniae (n = 1), Candida albicans (n = 1), Serratia marcescens (n = 1), and Pseudomonas aeruginosa (n = 1). Despite negative culture results in the remaining cases, clinical and radiological findings of osteitis were present. DISCUSSION The results of the study suggest that sphenoid sinus osteitis represents a rare but distinct postoperative entity following endoscopic transsphenoidal surgery. The exclusive occurrence of osteitis in patients who underwent sellar reconstruction, its association with specific reconstruction techniques, and its frequent clinical presentation with cacosmia indicate that postoperative osteitis is more than a nonspecific sinonasal complication. These observations warrant a focused discussion on the potential pathophysiological mechanisms, the role of surgical technique and reconstruction materials, and the clinical implications of sphenoid sinus osteitis in the postoperative period. Endoscopic transsphenoidal surgery (ETS) has become the standard approach for the treatment of pituitary and adjacent sellar–parasellar lesions. [ 5 , 17 , 34 ] Despite its minimally invasive nature, postoperative sinonasal and skull base–related complications may significantly affect patient comfort, quality of life, and long-term surgical outcomes. [ 1 , 22 ] In the existing literature, infectious complications following ETS have predominantly been discussed under the umbrella of sinusitis, mucosal inflammation, or nasal cavity–related disorders, whereas inflammatory involvement of the sphenoid sinus bony walls—namely osteitis—has rarely been addressed as a distinct pathological entity. [ 2 , 22 ] To our knowledge, the present study represents the first large patient series systematically investigating the incidence, clinical manifestations, and surgery-related risk factors of sphenoid sinus osteitis following endoscopic transsphenoidal surgery. The development of osteitis is a multifactorial process, with periosteal injury secondary to surgical trauma, local bone ischemia, and inflammatory responses to reconstruction materials constituting the main contributing factors. [ 2 , 11 , 20 ] In the chronic rhinosinusitis literature, osteitis has been defined as an inflammatory process involving the bony framework, characterized by sclerosis, cortical thickening, and neo-osteogenesis. [ 19 , 20 , 28 ] The radiological osteitis criteria proposed by Lee and Kennedy provide an imaging-based representation of this inflammatory process. [ 29 ] In endoscopic skull base surgery, collagen-based dural substitutes, autologous fascia lata grafts, and vascularized nasoseptal flaps are widely used for sellar reconstruction to reduce the risk of cerebrospinal fluid (CSF) leakage; however, direct contact of these materials with the underlying bone surface may trigger a chronic, low-grade inflammatory response. [ 4 , 13 , 24 , 30 , 34 ] In particular, extensive contact of a vascularized nasoseptal flap with the sphenoid sinus floor may induce a bone remodeling process characterized by regional hyperemia, increased osteoblastic activity, and neo-osteogenesis. [ 13 , 31 ] The exclusive occurrence of osteitis in patients who underwent sellar reconstruction in our cohort strongly supports the pivotal role of surgical reconstruction in the pathogenesis of postoperative sphenoid sinus osteitis. In neurosurgical practice, the terms “osteitis” and “osteomyelitis” are commonly used to describe infections of free bone flaps following craniotomy or complications related to cranioplasty. [ 12 , 14 , 35 ] In such settings, devascularized bone flaps, the presence of foreign materials, and high-grade infection typically predominate, and the condition is generally considered within the spectrum of osteomyelitis. [ 14 , 35 ] In contrast, osteitis involving the sphenoid sinus floor following endoscopic transsphenoidal surgery represents a pathophysiologically distinct entity. The compact structure of the sphenoid bone, its limited bone marrow content, and the preservation of surrounding vascular connections—unlike intracranial free bone flaps—appear to favor a localized osteitis pattern rather than overt osteomyelitis. [ 17 , 25 ] This distinction is clinically relevant both for accurate terminology and for appropriate management strategies. Postoperative sinonasal complications reported after ETS primarily include sinusitis, nasal crusting, mucosal edema, and infection, while cacosmia has often been regarded as a secondary or nonspecific symptom. [ 1 , 10 ]However, the presence of cacosmia in 75% of patients diagnosed with osteitis in our series suggests that inflammatory involvement of the sphenoid sinus bone may play a significant role in the development of this symptom. Chronic inflammation associated with osteitis may impair local mucosal healing, promote secretion stasis, and facilitate low-grade infection, thereby contributing to the perception of foul odor. [ 3 , 15 , 21 ]These findings indicate that, in patients presenting with persistent or late-onset cacosmia after endoscopic transsphenoidal surgery, radiological evaluation should extend beyond mucosal pathology to include assessment of the underlying bony structures. From a management perspective, surgical drainage or revision was required in the vast majority of patients diagnosed with osteitis (91.7%). This observation suggests that osteitis may respond poorly to medical treatment alone—including antibiotics, nasal irrigation, and topical steroids—and that surgical intervention may be more effective in controlling the inflammatory process. [ 6 , 21 ] Although positron emission tomography/computed tomography (PET/CT) was not routinely used in this study, increased FDG uptake supporting the diagnosis of osteitis was observed in a limited number of patients with diagnostic uncertainty. Previous reports have indicated that PET/CT may serve as a useful adjunct in differentiating chronic osteitis from osteomyelitis. [ 18 , 23 ] Microbiological evaluation revealed a culture positivity rate of 33.3%, with Staphylococcus aureus being the most frequently isolated organism. The presence of pronounced radiological osteitis findings in culture-negative cases raises the possibility of sterile inflammation or biofilm-associated low-grade infection independent of overt microbial growth. [ 9 , 18 ] The role of biofilm formation in the pathogenesis of chronic rhinosinusitis and osteitis has been previously demonstrated, and similar mechanisms may contribute to sphenoid sinus osteitis. [ 7 , 26 ] Furthermore, osteitic processes originating from the sphenoid region have, albeit rarely, been reported to progress to serious intracranial complications. [ 26 ] Although the nasoseptal flap reached statistical significance (), this borderline finding should be interpreted with caution due to the limited number of cases, which precludes a definitive assertion of superiority over other reconstruction techniques. Nevertheless, osteitis occurred exclusively in patients who underwent sellar reconstruction, all of which involved the use of fibrin sealant, suggesting—consistent with existing experimental evidence—that contact between fibrin sealant and exposed bone may contribute to localized inflammatory or osteitic processes.[ 8 , 27 ] Experimental studies suggest that fibrin sealants, while generally considered biocompatible, may be associated with localized inflammatory changes when applied to sinonasal tissues. In particular, prolonged contact between fibrin-based materials and exposed bone could potentially contribute to low-grade inflammatory responses, submucosal fibrosis, or reactive bone remodeling, supporting the possibility of a bone-centered process rather than a purely mucosal reaction. [ 8 , 27 ] Taken together, the findings of the present study and the existing literature on endoscopic skull base surgery suggest that no single surgical maneuver can completely prevent the development of osteitis during endoscopic transsphenoidal surgery. Nevertheless, attention to certain technique-related factors may potentially reduce the risk. [ 5 , 22 , 34 ] Avoiding unnecessary extensive bone exposure of the sphenoid sinus floor, preserving periosteal integrity whenever possible, and positioning the vascularized nasoseptal flap to cover only the required area without excessive bone contact appear to be particularly important. [ 2 , 20 ] In addition, tailoring the sellar reconstruction strategy according to defect size and CSF leakage risk may help avoid unnecessary use of reconstruction materials. [ 4 , 16 , 24 , 30 ] Although these measures may not entirely prevent osteitis, they may contribute to reducing the risk of chronic low-grade inflammation within the sphenoid sinus floor. [ 2 , 11 , 17 ]Prospective studies are required to validate these recommendations. The main limitations of this study include its retrospective design and the relatively small number of osteitis cases. Histopathological confirmation was not available, and advanced imaging modalities were used only in selected patients. Nevertheless, the large patient cohort and systematic radiological evaluation constitute notable strengths of the study. Future research should focus on prospective designs, histopathological and microbiological correlation, long-term assessment of sinonasal functional outcomes (such as NOSE scores and objective olfactometry), and comparative analyses of the biological effects of different reconstruction materials on bone tissue, which may further elucidate sphenoid sinus osteitis following endoscopic transsphenoidal surgery. CONCLUSION Sphenoid sinus osteitis following endoscopic transsphenoidal surgery is an uncommon but clinically relevant complication. In this study, osteitis occurred exclusively in patients who underwent sellar reconstruction, suggesting a potential association between reconstruction techniques and the development of this pathology. Direct contact between reconstruction materials and the sphenoid sinus floor, together with a localized inflammatory response, may represent a key underlying mechanism. Cacosmia emerged as the most frequent and clinically distinctive symptom in affected patients. These findings indicate that persistent or delayed-onset olfactory disturbances after endoscopic transsphenoidal surgery should prompt evaluation of the underlying bony structures in addition to routine assessment of sinonasal mucosa. Overall, this study identifies sphenoid sinus osteitis as a distinct, bone-involving postoperative entity rather than a conventional rhinonasal complication and highlights the need for heightened awareness in clinical practice. By systematically characterizing this complication in a large surgical cohort, the present work addresses an important gap in the literature and provides a framework for future studies aimed at refining preventive strategies and optimizing postoperative management. Recognizing sphenoid sinus osteitis as a distinct postoperative entity may improve diagnostic accuracy and guide more targeted management of postoperative rhinonasal symptoms. Declarations Ethics Approval and Consent to Participate This study was conducted in accordance with the Declaration of Helsinki. Ethical approval was obtained from the Kocaeli University Faculty of Medicine Clinical Research Ethics Committee (GOKAEK-2025/22/36). Due to the retrospective design of the study, the requirement for written informed consent was waived by the ethics committee. Human Ethics and Consent to Participate Declarations Human Ethics and Consent to Participate declarations: Ethical approval was obtained from the Kocaeli University Faculty of Medicine Clinical Research Ethics Committee, and the study was conducted in accordance with the Declaration of Helsinki. Informed consent was waived due to the retrospective nature of the study. Funding This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors. Conflict of Interest The authors declare that they have no competing interests. Author Contribution Concept and study design: B.Ç., A.Y.Data collection: F.S., S.A., E.Y., A. E. M.Ç.Radiological evaluation and grading: M.Ç., A.E.Data analysis and interpretation: B.Ç., A.E., M.Ç.Manuscript drafting: B.Ç., A.E.Critical revision of the manuscript: İ.A., S.C.Supervision: İ.A., S.C. References De Almeida JR, Snyderman CH, Gardner PA, Carrau RL, Vescan AD (2011) Nasal morbidity following endoscopic skull base surgery: A prospective cohort study. Head Neck 33(4):547–551 Bhandarkar ND, Sautter NB, Kennedy DW, Smith TL (2013) Osteitis in chronic rhinosinusitis: A review of the literature. Int Forum Allergy Rhinol 3(5):355–363 Bhenswala PN, Schlosser RJ, Nguyen SA, Munawar S, Rowan NR (2019) Sinonasal quality-of-life outcomes after endoscopic endonasal skull base surgery. Int Forum Allergy Rhinol 9(10):1105–1118 Biello AR, Lim JH (2021) Late Infectious Complication Following Skull Base Reconstruction With Bone Cement: Two Case Reports. 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Turk Otolarengoloji Arsivi/Turkish Archives Otolaryngol 54(2):63–68 Snidvongs K, Earls P, Dalgorf D, Sacks R, Pratt E, Harvey RJ (2014) Osteitis is a misnomer: A histopathology study in primary chronic rhinosinusitis. Int Forum Allergy Rhinol 4(5):390–396 Snidvongs K, Mclachlan R, Sacks R, Earls P, Harvey RJ (2013) Correlation of the Kennedy Osteitis Score to clinico-histologic features of chronic rhinosinusitis. Int Forum Allergy Rhinol 3(5):369–375 Soudry E, Turner JH, Nayak JV, Hwang PH (2014) Endoscopic reconstruction of surgically created skull base defects: A systematic review. Otolaryngol - Head Neck Surg (United States) 150(5):730–738 Sumislawski P, Piotrowska M, Regelsberger J, Flitsch J, Rotermund R (2024) Sphenoid Sinus Mucosal Flap after Transsphenoidal Surgery—A. Syst Rev Med (Lithuania). 10.3390/medicina60020282 Tovi F, Benharroch D, Gatot A, Hertzanu Y (1992) Osteoblastic osteitis of the maxillary sinus. Laryngoscope 102(4):426–430 Tsuda T, Takeda K, Terada R, Tanaka S, Waki S, Akama T, Nishimura H (2024) Osteitis in Diseases With Unilateral Opacification of Paranasal Sinuses. Ear Nose Throat J 103(10):633–639 Wang EW, Zanation AM, Gardner PA et al (2019) ICAR: endoscopic skull-base surgery. Int Forum Allergy Rhinol 9(S3):S145–S365 Zanaty M, Chalouhi N, Starke RM et al (2015) Complications following cranioplasty: Incidence and predictors in 348 cases. J Neurosurg 123(1):182–188 Tables Table 1. Demographic Characteristics and Surgical Distribution Variable Value Total patients 1,443 Female, n (%) 792 (54.9) Male, n (%) 651 (45.1) Age, mean (min–max) 44.6 years (18–80) Standard approach, n (%) 1,341 (92.9) Extended approach, n (%) 102 (7.1) Total osteitis, n (%) 12 (0.83) Table 2. Incidence of Osteitis and Surgical/Reconstruction Factors Variable Category No Osteitis (n=1431) Osteitis (n=12) P-value Age (Years) Mean ± SD 44.65 ± 13.11 41.92 ± 9.10 0.471 Sex Male 648 (45.3%) 3 (25.0%) 0.244* Female 783 (54.7%) 9 (75.0%) Surgical Approach Standard 1331 (93.0%) 10 (83.3%) 0.206* Extended 100 (7.0%) 2 (16.7%) Reconstruction Type No Reconstruction 747 (52.2%) 0 (0.0%) - Nasoseptal Flap 250 (17.5%) 5 (41.7%) 0.297 Fascia lata 130 (9.1%) 3 (25.0%) 0.091 Duragen/Tisseel 304 (21.2%) 4 (33.3%) 0.045 Cacosmia No 1410 (98.5%) 3 (25.0%) <0.001* Yes 21 (1.5%) 9 (75.0%) Culture Result in Cacosmia Patients (Subset n=33) Negative 13 (61.9%) 8 (66.7%) 0.572* Positive 8 (38.1%) 4 (33.3%) Treatment (Osteitis Group Only) Surgery - 11 (91.7%) - Medical - 1 (8.3%) *Fisher's Exact Test was used. SD: Standard Deviation Table 3. Clinical and Radiological Characteristics of Osteitis-Positive Patients Age Sex Approach Reconstruction Lee grade Cacosmia Culture result PET/CT Treatment 40 F Standard Nasoseptal flap 1 No Candida albicans No Surgery 25 F Extended Nasoseptal flap 1 Yes P. aeruginosa and S. aureus No Surgery 41 F Standard Nasoseptal flap 1 Yes S. marcescens, S. aureus Right nasal FDG uptake Surgery 60 F Extended Nasoseptal flap 1 Yes Unknown Right nasal FDG uptake Surgery 47 M Standard Duragen/Tisseel 1 Yes Unknown No Surgery 37 M Standard Duragen/Tisseel 3 Yes S. aureus, K. pneumoniae No Surgery 43 M Standard Fascia lata 3 Yes Unknown No Surgery 40 F Standard Fascia lata 2 Yes Unknown No Surgery 39 F Standard Fascia lata 2 No Unknown No Medical 33 F Standard Duragen/Tisseel 2 No Unknown No Surgery 54 F Standard Nasoseptal flap 1 Yes No growth Right nasal FDG uptake Surgery 44 F Standard Duragen/Tisseel 3 Yes Unknown No Surgery Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 27 Apr, 2026 Read the published version in Acta Neurochirurgica → Version 1 posted Editorial decision: Revision requested 16 Mar, 2026 Reviews received at journal 16 Mar, 2026 Reviewers agreed at journal 01 Mar, 2026 Reviews received at journal 01 Mar, 2026 Reviewers agreed at journal 12 Feb, 2026 Reviewers invited by journal 28 Jan, 2026 Editor assigned by journal 27 Jan, 2026 Submission checks completed at journal 27 Jan, 2026 First submitted to journal 19 Jan, 2026 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8636545","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":581958437,"identity":"29f91651-5744-47ad-b105-98991f7304a8","order_by":0,"name":"Burak Çabuk","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA1klEQVRIiWNgGAWjYFACHgbGxgYQzXyAgbGBNC1sCSRr4TEgTgt/+9ljkjN3HM7n7znzTeLnDhs5BvbDRzfg0yJxJi9NcuOZw5YzzvZuk+w9k2bMwJOWdgOfFgOGHDPJh22HDRjO826T4G07nNggwWOGXwv/G4gW+fM8zyT/EqVFAmjLRqAWg7M9bNJE2SJx412y5cwz6QaGZ44ZW8u2pRmzEfILf3/uwZu9O6wN5M4kP7z5ts1Gjp/98DG8WpABiwSIZCNWOQgwfyBF9SgYBaNgFIwcAAAwM010fYKnHgAAAABJRU5ErkJggg==","orcid":"","institution":"Kocaeli University","correspondingAuthor":true,"prefix":"","firstName":"Burak","middleName":"","lastName":"Çabuk","suffix":""},{"id":581958438,"identity":"370d3177-53ad-4267-a894-df9f88c8e244","order_by":1,"name":"Atılay Yaylacı","email":"","orcid":"","institution":"Kocaeli University","correspondingAuthor":false,"prefix":"","firstName":"Atılay","middleName":"","lastName":"Yaylacı","suffix":""},{"id":581958439,"identity":"26af44ff-f7f6-4819-a814-aee9ba581387","order_by":2,"name":"Fatih Shatri","email":"","orcid":"","institution":"Kocaeli University","correspondingAuthor":false,"prefix":"","firstName":"Fatih","middleName":"","lastName":"Shatri","suffix":""},{"id":581958440,"identity":"246e1896-a83e-469a-bf89-f7cce6580c4b","order_by":3,"name":"Sertaç Ayyıldız","email":"","orcid":"","institution":"Kocaeli University","correspondingAuthor":false,"prefix":"","firstName":"Sertaç","middleName":"","lastName":"Ayyıldız","suffix":""},{"id":581958442,"identity":"b1b00185-7c20-48c9-ba23-0b5f668cde0c","order_by":4,"name":"Eren Yılmaz","email":"","orcid":"","institution":"Istinye University","correspondingAuthor":false,"prefix":"","firstName":"Eren","middleName":"","lastName":"Yılmaz","suffix":""},{"id":581958444,"identity":"8074369a-3171-4584-9610-b7c2900a5036","order_by":5,"name":"Anıl Ergen","email":"","orcid":"","institution":"Kocaeli University","correspondingAuthor":false,"prefix":"","firstName":"Anıl","middleName":"","lastName":"Ergen","suffix":""},{"id":581958445,"identity":"52b20878-b41a-4ccf-801a-18360558f509","order_by":6,"name":"Melih Çaklılı","email":"","orcid":"","institution":"Kocaeli University","correspondingAuthor":false,"prefix":"","firstName":"Melih","middleName":"","lastName":"Çaklılı","suffix":""},{"id":581958447,"identity":"cbd33d27-c85e-49dc-8379-a2ed3a0f1410","order_by":7,"name":"İhsan Anık","email":"","orcid":"","institution":"Kocaeli University","correspondingAuthor":false,"prefix":"","firstName":"İhsan","middleName":"","lastName":"Anık","suffix":""},{"id":581958449,"identity":"07c3492e-f570-4ffc-a57c-b4bfc33cf980","order_by":8,"name":"Savaş Ceylan","email":"","orcid":"","institution":"Bahcesehir University School of Medicine","correspondingAuthor":false,"prefix":"","firstName":"Savaş","middleName":"","lastName":"Ceylan","suffix":""}],"badges":[],"createdAt":"2026-01-19 08:35:44","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-8636545/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8636545/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1007/s00701-026-06880-w","type":"published","date":"2026-04-27T15:57:17+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":101517838,"identity":"dee6955e-ad00-42a9-ab37-3e1a844ccccc","added_by":"auto","created_at":"2026-01-30 16:25:37","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":299011,"visible":true,"origin":"","legend":"\u003cp\u003ePreoperative (A) and postoperative (B) computed tomography (CT) images in axial, coronal, and sagittal planes of Patient 12, showing marked bony thickening and sclerosis consistent with Lee–Kennedy Grade 3 sphenoid sinus osteitis. Red arrow: Bony thickening\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8636545/v1/7052ee00b0746abf29d27aaa.png"},{"id":108437594,"identity":"bd8d81d6-6a1c-430d-a12d-3d11b8178351","added_by":"auto","created_at":"2026-05-04 15:59:51","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":656119,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8636545/v1/09a524d5-777f-4bd9-92bd-b51833bad923.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Sphenoid Sinus Osteitis After Endoscopic Transsphenoidal Surgery: A Bone-Centered Postoperative Entity","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eEndoscopic transsphenoidal surgery has become the standard surgical approach for the treatment of pituitary adenomas and other sellar and parasellar pathologies.[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e] Advances in endoscopic techniques and skull base reconstruction have significantly improved surgical outcomes; however, postoperative sinonasal and skull base\u0026ndash;related complications continue to affect patient comfort, quality of life, and long-term surgical success. [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eIn the existing literature, postoperative complications following endoscopic transsphenoidal surgery have predominantly been evaluated under the headings of sinonasal infections, mucosal inflammation, crusting, and sinusitis, with reported rates reaching up to 3\u0026ndash;4%. [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e] While these studies provide valuable information regarding mucosal morbidity, the potential long-term effects of these inflammatory processes on the underlying sphenoid sinus bone have received little attention. Nevertheless, it is well established that chronic inflammatory conditions may involve not only the mucosa but also the adjacent bone tissue. [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eOsteitis represents an inflammatory reaction of bone and has been described using terms such as hyperostosis, bony involvement, and neo-osteogenesis. [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]In the context of chronic rhinosinusitis, persistent mucosal inflammation has been shown to induce structural changes in the adjacent bone, including sclerosis and thickening, as demonstrated by both radiological and histopathological studies. [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] In neurosurgical practice, osteitis is commonly discussed in relation to cranioplasty and craniotomy flap infections, where the use of synthetic materials and compromised bone vascularity play a critical role. [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eDuring endoscopic transsphenoidal and extended endonasal skull base procedures, various reconstruction techniques\u0026mdash;including collagen-based dural substitutes, autologous fascia lata grafts, and vascularized nasoseptal flaps\u0026mdash;are routinely employed to prevent cerebrospinal fluid leakage. [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e] Although these techniques are essential for surgical success, their direct contact with the sphenoid sinus bony walls may trigger inflammatory bone responses. Despite this potential mechanism, sphenoid sinus osteitis following endoscopic transsphenoidal surgery has not been systematically investigated as a distinct, bone-centered complication, as existing studies have largely focused on mucosal pathology. [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eTherefore, the aim of this study is to determine the incidence of sphenoid sinus osteitis in a large cohort of patients undergoing endoscopic transsphenoidal surgery, to characterize its clinical and radiological features, and to analyze potential demographic and surgical risk factors associated with its development.\u003c/p\u003e"},{"header":"MATERIALS AND METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy Design and Patient Selection\u003c/h2\u003e \u003cp\u003e This study was designed as a retrospective cohort study and conducted in accordance with the ethical standards of the institutional research committee and with the principles of the Declaration of Helsinki. Ethical approval was obtained from the Kocaeli University Faculty of Medicine Clinical Research Ethics Committee (GOKAEK-2025/22/36). Prior to surgery, written surgical informed consent was obtained from all patients, which included permission for the use of anonymized hospital records for scientific research purposes. Due to the retrospective nature of the study and the use of anonymized data, the requirement for additional study-specific informed consent was waived by the ethics committee. Medical records of patients who underwent endoscopic transsphenoidal surgery for sellar or parasellar tumors between September 2021 and September 2024 were retrospectively reviewed.\u003c/p\u003e \u003cp\u003eDuring the study period, a total of 1,908 patients underwent endoscopic transsphenoidal surgery. Inclusion criteria consisted of patients who had undergone primary endoscopic transsphenoidal surgery for a sellar or parasellar tumor. Patients were excluded if they had a history of previous transsphenoidal or paranasal sinus surgery, preoperative imaging evidence of sphenoid sinus pathology (such as sinusitis or mucocele), or insufficient postoperative follow-up data.\u003c/p\u003e \u003c/div\u003e\n\u003ch3\u003eDefinition of Postoperative Osteitis\u003c/h3\u003e\n\u003cp\u003eThe primary endpoint of the study was the presence of postoperative sphenoid sinus osteitis. The diagnosis of osteitis was established based on a combination of radiological findings and clinical symptoms, as detailed below.\u003c/p\u003e\n\u003ch3\u003eRadiological Evaluation\u003c/h3\u003e\n\u003cp\u003eAll patients had preoperative sellar magnetic resonance imaging (MRI) and paranasal sinus computed tomography (CT) scans available for evaluation. According to the institutional postoperative follow-up protocol, cranial MRI was routinely performed at 1, 3, and 6 months postoperatively, at 1 year, and annually thereafter.\u003c/p\u003e \u003cp\u003ePatients who demonstrated suspicious sphenoid sinus mucosal thickening or contrast enhancement on follow-up MRI, as well as those with clinical suspicion of osteitis, underwent high-resolution paranasal sinus CT to allow detailed assessment of bony structures. Postoperative CT scans of patients with suspected osteitis were evaluated according to the radiological osteitis classification proposed by Lee and Kennedy (2006). [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eIn this system, osteitis is graded for each sinus (excluding the frontal sinus) based on the degree of bony thickening and sclerosis as follows: Grade 1 (mild): bone thickness up to 3 mm, Grade 2 (moderate): bone thickness of 4\u0026ndash;5 mm, Grade 3 (severe): bone thickness greater than 5 mm.\u003c/p\u003e \u003cp\u003eHigh-resolution CT images were independently evaluated by two observers. In cases of disagreement, a consensus was reached to determine the final grade. When necessary, MRI findings were correlated with CT images to improve diagnostic accuracy.\u003c/p\u003e\n\u003ch3\u003eClinical Evaluation\u003c/h3\u003e\n\u003cp\u003eAll patients were systematically evaluated during postoperative follow-up visits for symptoms potentially associated with osteitis. Particular emphasis was placed on cacosmia (persistent foul odor perception), a symptom known to significantly impair postoperative quality of life following endoscopic transsphenoidal surgery. At each follow-up visit, patients were actively questioned regarding the presence, onset, and severity of cacosmia, as well as its impact on daily activities.\u003c/p\u003e \u003cp\u003eAdditional symptoms, including persistent nasal obstruction, purulent postnasal discharge, and atypical headache, were also recorded. Patients presenting with these symptoms underwent further evaluation with paranasal sinus CT. Clinical findings were correlated with radiological results to support the diagnosis of postoperative osteitis.\u003c/p\u003e\n\u003ch3\u003eSurgical Approach\u003c/h3\u003e\n\u003cp\u003eDemographic data (age and sex), comorbidities, and were recorded for all patients. Surgical variables considered potential risk factors for osteitis development were also documented. Based on the anatomical extent of surgical dissection, surgical approaches were categorized into two groups. Middle turbinate resection was not performed in any patient.\u003c/p\u003e \u003cp\u003eStandard endoscopic endonasal approach, defined as procedures in which the surgical corridor remained within the boundaries of the sella turcica and was used for conventional pituitary lesions. Extended endoscopic endonasal approach, defined as procedures in which the surgical corridor extended beyond the sella turcica to adjacent regions such as the planum sphenoidale, olfactory groove, clivus, or cavernous sinus. These approaches required wider bone and mucosal resection.\u003c/p\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eSellar Reconstruction\u003c/h2\u003e \u003cp\u003eSellar reconstruction techniques were classified according to the size of the defect and the risk of cerebrospinal fluid (CSF) leakage. Simple Closure applied in cases with low-risk or suspected low-flow CSF leakage, consisting of placement of a collagen-based dural substitute followed by fibrin sealant application. Multilayer Autologous Grafting used in cases with evident intraoperative CSF leakage, involving multilayer reconstruction with non-vascularized autologous tissues such as fascia lata and/or abdominal fat. Vascularized Flap Reconstruction, Preferred for large skull base defects following extended approaches and in cases of high-flow CSF leakage, using a vascularized nasoseptal flap (NSF).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003eStatistical Analysis\u003c/h2\u003e \u003cp\u003eStatistical analysis was performed using the IBM SPSS Statistics for Windows, Version 26.0 (IBM Corp., Armonk, NY, USA). Descriptive statistics were expressed as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation (SD) for continuous variables and as frequencies (n) and percentages (%) for categorical variables.\u003c/p\u003e \u003cp\u003eThe normality of the distribution for continuous variables was evaluated. Comparisons of continuous variables (e.g., age) between the osteitis and non-osteitis groups were performed using the \u003cb\u003eStudent's t-test\u003c/b\u003e. Categorical variables (e.g., sex, surgical approach, reconstruction type) were compared using the \u003cb\u003ePearson Chi-square test\u003c/b\u003e. When the expected frequency in any cell of the contingency table was less than 5, \u003cb\u003eFisher's exact test\u003c/b\u003e was used. A p-value of less than 0.05 was considered statistically significant.\u003c/p\u003e \u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eBetween September 2021 and September 2024, a total of 1,443 patients who underwent endoscopic transsphenoidal surgery and met the study inclusion criteria were retrospectively analyzed. Of these patients, 54.9% were female (n\u0026thinsp;=\u0026thinsp;792) and 45.1% were male (n\u0026thinsp;=\u0026thinsp;651). The mean age of the entire cohort was 44.6 years (range: 18\u0026ndash;80). When comparing the osteitis and non-osteitis groups, there were no statistically significant differences regarding mean age (41.92\u0026thinsp;\u0026plusmn;\u0026thinsp;9.10 years vs. 44.65\u0026thinsp;\u0026plusmn;\u0026thinsp;13.11 years, p\u0026thinsp;=\u0026thinsp;0.471) or sex distribution (p\u0026thinsp;=\u0026thinsp;0.244).\u003c/p\u003e \u003cp\u003eRegarding surgical approaches, the majority of patients underwent a standard transsphenoidal approach (n\u0026thinsp;=\u0026thinsp;1,341, 93.0%), while an extended approach was performed in a smaller proportion of cases (n\u0026thinsp;=\u0026thinsp;102, 7.0%). Postoperative sphenoid sinus osteitis was identified in 12 patients, corresponding to an overall incidence of 0.83%. The incidence of osteitis was 0.75% (10/1,341) in the standard approach group and 1.96% (2/102) in the extended approach group; however, this difference was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.206).\u003c/p\u003e \u003cp\u003eWhen reconstruction techniques were evaluated, osteitis was observed exclusively in patients who underwent sellar reconstruction. No cases of osteitis were detected among the 747 patients who did not receive reconstruction (0.0%). Among the specific reconstruction subgroups, osteitis occurred in 5 of 255 patients (1.96%) reconstructed with a nasoseptal flap, 3 of 133 patients (2.26%) receiving fascia lata grafts, and 4 of 308 patients (1.3%) treated with Duragen/Tisseel. Statistical analysis revealed that the use of a nasoseptal flap was associated with a statistically significant difference (p\u0026thinsp;=\u0026thinsp;0.045), whereas the fascia lata (p\u0026thinsp;=\u0026thinsp;0.091) and Duragen/Tisseel (p\u0026thinsp;=\u0026thinsp;0.297) subgroups did not reach statistical significance.\u003c/p\u003e \u003cp\u003eClinically, cacosmia was present in 9 of the 12 patients with osteitis (75.0%), which was significantly higher than the 1.5% incidence (21/1,410) observed in the non-osteitis group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Among patients reporting cacosmia, culture results did not show a statistically significant difference between negative and positive growth subgroups (p\u0026thinsp;=\u0026thinsp;0.572).\u003c/p\u003e \u003cp\u003eRadiological evaluation of the 12 osteitis cases according to the Lee and Kennedy classification revealed Grade 1 osteitis in 6 patients (50%), Grade 2 in 3 patients (25%), and Grade 3 in 3 patients (25%). In Grade 2 and higher cases, computed tomography demonstrated cortical irregularity and sclerotic thickening of the sphenoid sinus floor, with associated mucosal contrast enhancement in some patients. In Grade 3 cases, diffuse mucosal thickening accompanying extensive bony involvement was observed. CT findings were dominated by cortical thickening and sclerosis of the sphenoid sinus walls. (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) No bone marrow edema was detected on magnetic resonance imaging.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003ePositron emission tomography/computed tomography (PET/CT) was not routinely performed in the study population and was reserved for selected cases with diagnostic uncertainty or for systemic evaluation. PET/CT was used in 2 patients to support the diagnosis and in 1 patient for metastatic screening. In these cases, increased fluorodeoxyglucose (FDG) uptake in the sphenoid region was consistent with the clinical and radiological findings of osteitis.\u003c/p\u003e \u003cp\u003eRegarding treatment strategies for the osteitis group, 11 patients (91.7%) underwent surgical revision (second operation), while one patient (8.3%) was managed with medical therapy alone. Microbiological cultures were obtained in all 12 patients, with positive growth identified in 4 cases (33.3%). The most frequently isolated microorganism was \u003cem\u003eStaphylococcus aureus\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;3). Other isolated organisms included \u003cem\u003eKlebsiella pneumoniae\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;1), \u003cem\u003eCandida albicans\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;1), \u003cem\u003eSerratia marcescens\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;1), and \u003cem\u003ePseudomonas aeruginosa\u003c/em\u003e (n\u0026thinsp;=\u0026thinsp;1). Despite negative culture results in the remaining cases, clinical and radiological findings of osteitis were present.\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThe results of the study suggest that sphenoid sinus osteitis represents a rare but distinct postoperative entity following endoscopic transsphenoidal surgery. The exclusive occurrence of osteitis in patients who underwent sellar reconstruction, its association with specific reconstruction techniques, and its frequent clinical presentation with cacosmia indicate that postoperative osteitis is more than a nonspecific sinonasal complication. These observations warrant a focused discussion on the potential pathophysiological mechanisms, the role of surgical technique and reconstruction materials, and the clinical implications of sphenoid sinus osteitis in the postoperative period.\u003c/p\u003e \u003cp\u003eEndoscopic transsphenoidal surgery (ETS) has become the standard approach for the treatment of pituitary and adjacent sellar\u0026ndash;parasellar lesions. [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e] Despite its minimally invasive nature, postoperative sinonasal and skull base\u0026ndash;related complications may significantly affect patient comfort, quality of life, and long-term surgical outcomes. [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] In the existing literature, infectious complications following ETS have predominantly been discussed under the umbrella of sinusitis, mucosal inflammation, or nasal cavity\u0026ndash;related disorders, whereas inflammatory involvement of the sphenoid sinus bony walls\u0026mdash;namely osteitis\u0026mdash;has rarely been addressed as a distinct pathological entity. [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] To our knowledge, the present study represents the first large patient series systematically investigating the incidence, clinical manifestations, and surgery-related risk factors of sphenoid sinus osteitis following endoscopic transsphenoidal surgery.\u003c/p\u003e \u003cp\u003eThe development of osteitis is a multifactorial process, with periosteal injury secondary to surgical trauma, local bone ischemia, and inflammatory responses to reconstruction materials constituting the main contributing factors. [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] In the chronic rhinosinusitis literature, osteitis has been defined as an inflammatory process involving the bony framework, characterized by sclerosis, cortical thickening, and neo-osteogenesis. [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] The radiological osteitis criteria proposed by Lee and Kennedy provide an imaging-based representation of this inflammatory process. [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eIn endoscopic skull base surgery, collagen-based dural substitutes, autologous fascia lata grafts, and vascularized nasoseptal flaps are widely used for sellar reconstruction to reduce the risk of cerebrospinal fluid (CSF) leakage; however, direct contact of these materials with the underlying bone surface may trigger a chronic, low-grade inflammatory response. [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e] In particular, extensive contact of a vascularized nasoseptal flap with the sphenoid sinus floor may induce a bone remodeling process characterized by regional hyperemia, increased osteoblastic activity, and neo-osteogenesis. [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e] The exclusive occurrence of osteitis in patients who underwent sellar reconstruction in our cohort strongly supports the pivotal role of surgical reconstruction in the pathogenesis of postoperative sphenoid sinus osteitis.\u003c/p\u003e \u003cp\u003eIn neurosurgical practice, the terms \u0026ldquo;osteitis\u0026rdquo; and \u0026ldquo;osteomyelitis\u0026rdquo; are commonly used to describe infections of free bone flaps following craniotomy or complications related to cranioplasty. [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e] In such settings, devascularized bone flaps, the presence of foreign materials, and high-grade infection typically predominate, and the condition is generally considered within the spectrum of osteomyelitis. [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e] In contrast, osteitis involving the sphenoid sinus floor following endoscopic transsphenoidal surgery represents a pathophysiologically distinct entity. The compact structure of the sphenoid bone, its limited bone marrow content, and the preservation of surrounding vascular connections\u0026mdash;unlike intracranial free bone flaps\u0026mdash;appear to favor a localized osteitis pattern rather than overt osteomyelitis. [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] This distinction is clinically relevant both for accurate terminology and for appropriate management strategies.\u003c/p\u003e \u003cp\u003ePostoperative sinonasal complications reported after ETS primarily include sinusitis, nasal crusting, mucosal edema, and infection, while cacosmia has often been regarded as a secondary or nonspecific symptom. [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]However, the presence of cacosmia in 75% of patients diagnosed with osteitis in our series suggests that inflammatory involvement of the sphenoid sinus bone may play a significant role in the development of this symptom. Chronic inflammation associated with osteitis may impair local mucosal healing, promote secretion stasis, and facilitate low-grade infection, thereby contributing to the perception of foul odor. [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]These findings indicate that, in patients presenting with persistent or late-onset cacosmia after endoscopic transsphenoidal surgery, radiological evaluation should extend beyond mucosal pathology to include assessment of the underlying bony structures.\u003c/p\u003e \u003cp\u003eFrom a management perspective, surgical drainage or revision was required in the vast majority of patients diagnosed with osteitis (91.7%). This observation suggests that osteitis may respond poorly to medical treatment alone\u0026mdash;including antibiotics, nasal irrigation, and topical steroids\u0026mdash;and that surgical intervention may be more effective in controlling the inflammatory process. [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e] Although positron emission tomography/computed tomography (PET/CT) was not routinely used in this study, increased FDG uptake supporting the diagnosis of osteitis was observed in a limited number of patients with diagnostic uncertainty. Previous reports have indicated that PET/CT may serve as a useful adjunct in differentiating chronic osteitis from osteomyelitis. [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eMicrobiological evaluation revealed a culture positivity rate of 33.3%, with Staphylococcus aureus being the most frequently isolated organism. The presence of pronounced radiological osteitis findings in culture-negative cases raises the possibility of sterile inflammation or biofilm-associated low-grade infection independent of overt microbial growth. [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] The role of biofilm formation in the pathogenesis of chronic rhinosinusitis and osteitis has been previously demonstrated, and similar mechanisms may contribute to sphenoid sinus osteitis. [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] Furthermore, osteitic processes originating from the sphenoid region have, albeit rarely, been reported to progress to serious intracranial complications. [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eAlthough the nasoseptal flap reached statistical significance (), this borderline finding should be interpreted with caution due to the limited number of cases, which precludes a definitive assertion of superiority over other reconstruction techniques. Nevertheless, osteitis occurred exclusively in patients who underwent sellar reconstruction, all of which involved the use of fibrin sealant, suggesting\u0026mdash;consistent with existing experimental evidence\u0026mdash;that contact between fibrin sealant and exposed bone may contribute to localized inflammatory or osteitic processes.[\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eExperimental studies suggest that fibrin sealants, while generally considered biocompatible, may be associated with localized inflammatory changes when applied to sinonasal tissues. In particular, prolonged contact between fibrin-based materials and exposed bone could potentially contribute to low-grade inflammatory responses, submucosal fibrosis, or reactive bone remodeling, supporting the possibility of a bone-centered process rather than a purely mucosal reaction. [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]\u003c/p\u003e \u003cp\u003eTaken together, the findings of the present study and the existing literature on endoscopic skull base surgery suggest that no single surgical maneuver can completely prevent the development of osteitis during endoscopic transsphenoidal surgery. Nevertheless, attention to certain technique-related factors may potentially reduce the risk. [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e] Avoiding unnecessary extensive bone exposure of the sphenoid sinus floor, preserving periosteal integrity whenever possible, and positioning the vascularized nasoseptal flap to cover only the required area without excessive bone contact appear to be particularly important. [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] In addition, tailoring the sellar reconstruction strategy according to defect size and CSF leakage risk may help avoid unnecessary use of reconstruction materials. [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e] Although these measures may not entirely prevent osteitis, they may contribute to reducing the risk of chronic low-grade inflammation within the sphenoid sinus floor. [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]Prospective studies are required to validate these recommendations.\u003c/p\u003e \u003cp\u003eThe main limitations of this study include its retrospective design and the relatively small number of osteitis cases. Histopathological confirmation was not available, and advanced imaging modalities were used only in selected patients. Nevertheless, the large patient cohort and systematic radiological evaluation constitute notable strengths of the study. Future research should focus on prospective designs, histopathological and microbiological correlation, long-term assessment of sinonasal functional outcomes (such as NOSE scores and objective olfactometry), and comparative analyses of the biological effects of different reconstruction materials on bone tissue, which may further elucidate sphenoid sinus osteitis following endoscopic transsphenoidal surgery.\u003c/p\u003e"},{"header":"CONCLUSION","content":"\u003cp\u003eSphenoid sinus osteitis following endoscopic transsphenoidal surgery is an uncommon but clinically relevant complication. In this study, osteitis occurred exclusively in patients who underwent sellar reconstruction, suggesting a potential association between reconstruction techniques and the development of this pathology. Direct contact between reconstruction materials and the sphenoid sinus floor, together with a localized inflammatory response, may represent a key underlying mechanism.\u003c/p\u003e \u003cp\u003eCacosmia emerged as the most frequent and clinically distinctive symptom in affected patients. These findings indicate that persistent or delayed-onset olfactory disturbances after endoscopic transsphenoidal surgery should prompt evaluation of the underlying bony structures in addition to routine assessment of sinonasal mucosa.\u003c/p\u003e \u003cp\u003eOverall, this study identifies sphenoid sinus osteitis as a distinct, bone-involving postoperative entity rather than a conventional rhinonasal complication and highlights the need for heightened awareness in clinical practice. By systematically characterizing this complication in a large surgical cohort, the present work addresses an important gap in the literature and provides a framework for future studies aimed at refining preventive strategies and optimizing postoperative management. Recognizing sphenoid sinus osteitis as a distinct postoperative entity may improve diagnostic accuracy and guide more targeted management of postoperative rhinonasal symptoms.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics Approval and Consent to Participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was conducted in accordance with the Declaration of Helsinki. Ethical approval was obtained from the Kocaeli University Faculty of Medicine Clinical Research Ethics Committee (GOKAEK-2025/22/36). Due to the retrospective design of the study, the requirement for written informed consent was waived by the ethics committee.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eHuman Ethics and Consent to Participate Declarations\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eHuman Ethics and Consent to Participate declarations: Ethical approval was obtained from the Kocaeli University Faculty of Medicine Clinical Research Ethics Committee, and the study was conducted in accordance with the Declaration of Helsinki. Informed consent was waived due to the retrospective nature of the study.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eThis research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003ch3\u003e\u003cstrong\u003eConflict of Interest\u003c/strong\u003e\u003c/h3\u003e\n\u003cp\u003eThe authors declare that they have no competing interests.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eConcept and study design: B.\u0026Ccedil;., A.Y.Data collection: F.S., S.A., E.Y., A. E. M.\u0026Ccedil;.Radiological evaluation and grading: M.\u0026Ccedil;., A.E.Data analysis and interpretation: B.\u0026Ccedil;., A.E., M.\u0026Ccedil;.Manuscript drafting: B.\u0026Ccedil;., A.E.Critical revision of the manuscript: İ.A., S.C.Supervision: İ.A., S.C.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eDe Almeida JR, Snyderman CH, Gardner PA, Carrau RL, Vescan AD (2011) Nasal morbidity following endoscopic skull base surgery: A prospective cohort study. Head Neck 33(4):547\u0026ndash;551\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBhandarkar ND, Sautter NB, Kennedy DW, Smith TL (2013) Osteitis in chronic rhinosinusitis: A review of the literature. Int Forum Allergy Rhinol 3(5):355\u0026ndash;363\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBhenswala PN, Schlosser RJ, Nguyen SA, Munawar S, Rowan NR (2019) Sinonasal quality-of-life outcomes after endoscopic endonasal skull base surgery. 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Am J Rhinol 20(3):278\u0026ndash;282\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLeung N, Mawby TAR, Turner H, Qureishi A (2016) Osteitis and chronic rhinosinusitis: a review of the current literature. Eur Arch Otorhinolaryngol 273(10):2917\u0026ndash;2923\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLitvack JR, Fong K, Mace J, James KE, Smith TL (2008) Predictors of olfactory dysfunction in patients with chronic rhinosinusitis. Laryngoscope 118(12):2225\u0026ndash;2230\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNaunheim MR, Sedaghat AR, Lin DT, Bleier BS, Holbrook EH, Curry WT, Gray ST (2015) Immediate and Delayed Complications Following Endoscopic Skull Base Surgery. J Neurol Surg B Skull Base 76(5):390\u0026ndash;396\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePalestro CJ (2015) Radionuclide imaging of osteomyelitis. Semin Nucl Med. W.B. 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Laryngoscope 115(4):578\u0026ndash;582\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSarikaya S, Biskin S, Damar M, Ugur MB, Sakalli E, Bektas S (2016) Histopathological Effects of Fibrin Glue and Cyanoacrylate on the Maxillary Sinus. Turk Otolarengoloji Arsivi/Turkish Archives Otolaryngol 54(2):63\u0026ndash;68\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSnidvongs K, Earls P, Dalgorf D, Sacks R, Pratt E, Harvey RJ (2014) Osteitis is a misnomer: A histopathology study in primary chronic rhinosinusitis. Int Forum Allergy Rhinol 4(5):390\u0026ndash;396\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSnidvongs K, Mclachlan R, Sacks R, Earls P, Harvey RJ (2013) Correlation of the Kennedy Osteitis Score to clinico-histologic features of chronic rhinosinusitis. 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Laryngoscope 102(4):426\u0026ndash;430\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTsuda T, Takeda K, Terada R, Tanaka S, Waki S, Akama T, Nishimura H (2024) Osteitis in Diseases With Unilateral Opacification of Paranasal Sinuses. Ear Nose Throat J 103(10):633\u0026ndash;639\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang EW, Zanation AM, Gardner PA et al (2019) ICAR: endoscopic skull-base surgery. Int Forum Allergy Rhinol 9(S3):S145\u0026ndash;S365\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZanaty M, Chalouhi N, Starke RM et al (2015) Complications following cranioplasty: Incidence and predictors in 348 cases. J Neurosurg 123(1):182\u0026ndash;188\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"},{"header":"Tables","content":"\u003cp\u003e\u003cstrong\u003eTable 1. Demographic Characteristics and Surgical Distribution\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eVariable\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eValue\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003eTotal patients\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003e1,443\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003eFemale, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003e792 (54.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003eMale, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003e651 (45.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003eAge, mean (min\u0026ndash;max)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003e44.6 years (18\u0026ndash;80)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003eStandard approach, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003e1,341 (92.9)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003eExtended approach, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003e102 (7.1)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003eTotal osteitis, n (%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 288px;\"\u003e\n \u003cp\u003e12 (0.83)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cstrong\u003eTable 2. Incidence of Osteitis and Surgical/Reconstruction Factors\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" class=\"fr-table-selection-hover\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eVariable\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003eCategory\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003eNo Osteitis (n=1431)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003eOsteitis (n=12)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003eP-value\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eAge (Years)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003eMean \u0026plusmn; SD\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e44.65 \u0026plusmn; 13.11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e41.92 \u0026plusmn; 9.10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e0.471\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eSex\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003eMale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e648 (45.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e3 (25.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e0.244*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003eFemale\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e783 (54.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e9 (75.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eSurgical Approach\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003eStandard\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e1331 (93.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e10 (83.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e0.206*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003eExtended\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e100 (7.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e2 (16.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eReconstruction Type\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003eNo Reconstruction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e747 (52.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e0 (0.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003eNasoseptal Flap\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e250 (17.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e5 (41.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e0.297\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003eFascia lata\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e130 (9.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e3 (25.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e0.091\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003eDuragen/Tisseel\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e304 (21.2%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e4 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e0.045\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eCacosmia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e1410 (98.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e3 (25.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e\u0026lt;0.001*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e21 (1.5%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e9 (75.0%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eCulture Result in Cacosmia Patients\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e(Subset n=33)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003eNegative\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e13 (61.9%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e8 (66.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e0.572*\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003ePositive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e8 (38.1%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e4 (33.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003eTreatment\u003c/p\u003e\n \u003cp\u003e\u003cem\u003e(Osteitis Group Only)\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003eSurgery\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e11 (91.7%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 121px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 131px;\"\u003e\n \u003cp\u003eMedical\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 118px;\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e1 (8.3%)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 117px;\"\u003e\n \u003cp\u003e\u0026nbsp;\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cem\u003e*Fisher\u0026apos;s Exact Test was used.\u003c/em\u003e \u003cem\u003eSD: Standard Deviation\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eTable 3. Clinical and Radiological Characteristics of Osteitis-Positive Patients\u003c/strong\u003e\u003c/p\u003e\n\u003ctable border=\"1\" cellspacing=\"0\" cellpadding=\"0\" width=\"623\"\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 35px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eAge\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eSex\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eApproach\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eReconstruction\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eLee grade\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCacosmia\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eCulture result\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003e\u003cstrong\u003ePET/CT\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003e\u003cstrong\u003eTreatment\u003c/strong\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 35px;\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003eStandard\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eNasoseptal flap\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003eCandida albicans\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003eSurgery\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 35px;\"\u003e\n \u003cp\u003e25\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003eExtended\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eNasoseptal flap\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003eP. aeruginosa and S. aureus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003eSurgery\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 35px;\"\u003e\n \u003cp\u003e41\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003eStandard\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eNasoseptal flap\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003eS. marcescens, S. aureus\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003eRight nasal FDG uptake\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003eSurgery\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 35px;\"\u003e\n \u003cp\u003e60\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003eExtended\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eNasoseptal flap\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003eRight nasal FDG uptake\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003eSurgery\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 35px;\"\u003e\n \u003cp\u003e47\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003eStandard\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eDuragen/Tisseel\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003eSurgery\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 35px;\"\u003e\n \u003cp\u003e37\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003eStandard\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eDuragen/Tisseel\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003eS. aureus, K. pneumoniae\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003eSurgery\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 35px;\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003eM\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003eStandard\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eFascia lata\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003eSurgery\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 35px;\"\u003e\n \u003cp\u003e40\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003eStandard\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eFascia lata\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003eSurgery\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 35px;\"\u003e\n \u003cp\u003e39\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003eStandard\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eFascia lata\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003eMedical\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 35px;\"\u003e\n \u003cp\u003e33\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003eStandard\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eDuragen/Tisseel\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003eSurgery\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 35px;\"\u003e\n \u003cp\u003e54\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003eStandard\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eNasoseptal flap\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003eNo growth\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003eRight nasal FDG uptake\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003eSurgery\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd valign=\"top\" style=\"width: 35px;\"\u003e\n \u003cp\u003e44\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 34px;\"\u003e\n \u003cp\u003eF\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 75px;\"\u003e\n \u003cp\u003eStandard\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 119px;\"\u003e\n \u003cp\u003eDuragen/Tisseel\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 46px;\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 67px;\"\u003e\n \u003cp\u003eYes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 96px;\"\u003e\n \u003cp\u003eUnknown\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 59px;\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd valign=\"top\" style=\"width: 92px;\"\u003e\n \u003cp\u003eSurgery\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"acta-neurochirurgica","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"anch","sideBox":"Learn more about [Acta Neurochirurgica](http://link.springer.com/journal/701)","snPcode":"701","submissionUrl":"https://submission.springernature.com/new-submission/701/3","title":"Acta Neurochirurgica","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Osteitis, Endoscopic, Skull base, Sfenoid sinus, Sinusitis, Pituitary","lastPublishedDoi":"10.21203/rs.3.rs-8636545/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8636545/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e \u003cp\u003eDespite advances in endoscopic skull base surgery, postoperative sinonasal inflammation remains poorly characterized. In particular, sphenoid sinus osteitis has received little attention, as complications after endoscopic transsphenoidal surgery (ETS) have largely been assessed in terms of mucosal pathology. This study aims to determine the incidence of sphenoid sinus osteitis after ETS, describe its clinical and radiological features, and identify associated surgical and demographic risk factors.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003e We retrospectively reviewed patients undergoing primary ETS for sellar or parasellar tumors between September 2021 and September 2024. Osteitis was assessed on high-resolution CT using the Lee and Kennedy classification. Clinical symptoms, particularly cacosmia, and surgical approach and reconstruction techniques were analyzed as potential risk factors.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAmong 1,443 patients, sphenoid sinus osteitis was identified in 12 cases (0.83%). All cases occurred in patients who underwent sellar reconstruction, with no osteitis observed in those without reconstruction (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Regarding reconstruction techniques, the nasoseptal flap showed a borderline statistical significance (p\u0026thinsp;=\u0026thinsp;0,045). Radiologically, osteitis was Grade 1 in 50%, Grade 2 in 25%, and Grade 3 in 25% of cases. Cacosmia was the presenting symptom in 75% of affected patients (p\u0026thinsp;\u0026lt;\u0026thinsp;0.001). Surgical revision was required in 11 patients (91.7%), while medical treatment alone was sufficient in one case.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eSphenoid sinus osteitis represents a rare but clinically relevant bone-centered complication following ETS, distinct from conventional rhinonasal morbidity. Its exclusive association with sellar reconstruction highlights the potential role of reconstruction-related bone contact and localized inflammatory responses in its pathogenesis. Recognizing sphenoid sinus osteitis as a distinct postoperative entity may improve diagnostic accuracy and guide more targeted management of postoperative rhinonasal symptoms.\u003c/p\u003e","manuscriptTitle":"Sphenoid Sinus Osteitis After Endoscopic Transsphenoidal Surgery: A Bone-Centered Postoperative Entity","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-01-30 16:23:20","doi":"10.21203/rs.3.rs-8636545/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2026-03-16T17:12:43+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-16T14:41:35+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"325276044507425030661111108091166492107","date":"2026-03-01T23:35:41+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-03-01T15:19:36+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"210216457313115564009056648402831181779","date":"2026-02-12T09:09:55+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2026-01-28T10:17:55+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2026-01-27T09:32:10+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2026-01-27T09:24:17+00:00","index":"","fulltext":""},{"type":"submitted","content":"Acta Neurochirurgica","date":"2026-01-19T08:09:40+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"acta-neurochirurgica","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"anch","sideBox":"Learn more about [Acta Neurochirurgica](http://link.springer.com/journal/701)","snPcode":"701","submissionUrl":"https://submission.springernature.com/new-submission/701/3","title":"Acta Neurochirurgica","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"em","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"5cb8608b-2088-4c96-b614-4a75eb6831e3","owner":[],"postedDate":"January 30th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-05-04T15:59:26+00:00","versionOfRecord":{"articleIdentity":"rs-8636545","link":"https://doi.org/10.1007/s00701-026-06880-w","journal":{"identity":"acta-neurochirurgica","isVorOnly":false,"title":"Acta Neurochirurgica"},"publishedOn":"2026-04-27 15:57:17","publishedOnDateReadable":"April 27th, 2026"},"versionCreatedAt":"2026-01-30 16:23:20","video":"","vorDoi":"10.1007/s00701-026-06880-w","vorDoiUrl":"https://doi.org/10.1007/s00701-026-06880-w","workflowStages":[]},"version":"v1","identity":"rs-8636545","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8636545","identity":"rs-8636545","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}