Ruptured Pulmonary Aspergilloma complicating into pyopneumothorax and bronchopleural fistula: A case report and review of literature

Ruptured Pulmonary Aspergilloma complicating into pyopneumothorax and bronchopleural fistula: A case report and review of literature | 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 Case Report Ruptured Pulmonary Aspergilloma complicating into pyopneumothorax and bronchopleural fistula: A case report and review of literature Pyrus Bhellum, Shekhar Angirekula, Adeeb Shan, Mahendra Dhaka, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8012598/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 07 Feb, 2026 Read the published version in SN Comprehensive Clinical Medicine → Version 1 posted 10 You are reading this latest preprint version Abstract Introduction: Pyopneumothorax secondary to ruptured pulmonary aspergilloma is a rare but life-threatening complication of invasive pulmonary aspergillosis (IPA), particularly in patients without classical immunosuppression. In tuberculosis-endemic regions, post-tubercular cavities often serve as a nidus for Aspergillus colonization. However, due to overlapping clinical and radiological features with bacterial pneumonia or tuberculosis reactivation, IPA frequently remains underdiagnosed or is recognized late in its course. Case Presentation: A 62-year-old female with poorly controlled diabetes mellitus presented with acute respiratory distress and diabetic ketoacidosis. Chest imaging revealed a right-sided cavitary lesion with hydropneumothorax and underlying lung collapse. Intercostal drainage yielded purulent material, confirming pyopneumothorax. Despite initiation of broad-spectrum antibiotics and liposomal amphotericin B, the patient developed progressive hypoxemia and multiorgan dysfunction. Pleural fluid microscopy and elevated serum galactomannan established the diagnosis of Aspergillus fumigatus infection. Surgical intervention was deferred due to hemodynamic instability, and the patient unfortunately succumbed to her illness. Conclusions This case highlights a fulminant presentation of IPA complicated by pyopneumothorax in a non-classically immunosuppressed host. Review of similar reported cases demonstrates that aspergillus-associated pneumothorax and pyopneumothorax can occur across diverse immune states, often with poor outcomes related to delayed diagnosis. Early clinical suspicion, rapid fungal diagnostics, and timely initiation of antifungal therapy are critical to improving survival in patients with pre-existing pulmonary cavities presenting with acute respiratory compromise. Invasive pulmonary aspergillosis Pyopneumothorax Galactomannan assay Case report Diabetes mellitus Figures Figure 1 Introduction Aspergillus is a ubiquitous fungus which has the potential to cause a wide range of clinical syndromes, ranging from colonisation of the respiratory tract to invasive fulminant disease, which is described as Invasive Pulmonary Aspergillosis (IPA). Usually, host immunity prevents Aspergillosis from causing the disease. Host factors include a history of prolonged neutropenia (more than 3 weeks), hematological malignancies, prolonged corticosteroid therapy, solid organ cancer, Acquired immunodeficiency syndrome (AIDS), and structural lung disease 1 . Underlying structure lung disease damages the immune milieu of the lung, leading to increased risk of infections, which include tuberculosis, aspergillosis, mucormycosis, and others. Pulmonary aspergillosis may present in various forms, ranging from chronic cavitary disease and aspergilloma to necrotizing and angioinvasive disease 2 . Rarely, cavitary rupture due to fungal invasion can lead to complications such as hydropneumothorax, bronchopleural fistula, or massive hemoptysis, which are clinical events associated with high morbidity and mortality. Such presentations often mimic more common conditions like pulmonary tuberculosis or bacterial empyema, making early diagnosis and intervention particularly challenging in resource-limited settings. Only a limited number of case reports have documented rupture of pulmonary cavities leading to hydropneumothorax or aspergillus-related empyema 3 , 4 . Serological assays such as serum galactomannan and imaging modalities like high-resolution computed tomography (HRCT) play a critical role in the diagnostic workup. However, definitive diagnosis often requires microbiological or histopathological confirmation. Bronchopleural fistula is a tract between bronchi and the pleural space, which occurs as a complication following thoracic surgeries such as lobectomy, thoracotomy, and some pulmonary infections 5 . Management involves antifungal therapy with agents like voriconazole or amphotericin B, and in selected cases, surgical resection or drainage procedures. We present a case of a 62-year-old diabetic female who developed Diabetic Ketoacidosis (DKA) and acute respiratory failure due to invasive pulmonary aspergillosis, complicated by pyopneumothorax following cavitary rupture. Case report A 62-year-old female, a known case of type 2 diabetes mellitus on oral hypoglycemic therapy, presented to the Emergency Department of our tertiary care center in Western India with acute onset shortness of breath for one day. Her history revealed a one-month duration of productive cough, associated with significant weight loss, generalized fatigue, and right-sided chest discomfort. She had been evaluated at an outside facility where a chest radiograph had demonstrated a right middle lobe cavitary lesion. Sputum examination for acid-fast bacilli using the Ziehl-Neelsen stain was negative. Empiric oral antibiotics (amoxicillin-clavulanate 625 mg TID for 7 days) had been prescribed, with no significant improvement in symptoms. On presentation, the patient was febrile and visibly dyspneic. Her vital parameters were: heart rate 119 beats/min, respiratory rate 45 breaths/min, blood pressure 106/78 mmHg, and oxygen saturation 75% on room air. Arterial blood gas analysis showed hypoxemia, and laboratory evaluation revealed markedly elevated blood glucose (462 mg/dL) and serum ketones (7.8 mmol/L), confirming diabetic ketoacidosis (DKA). She was managed according to standard DKA protocols with intravenous fluids, electrolyte correction, and insulin infusion. On physical examination, she appeared dehydrated with dry mucous membranes, poor skin turgor, and was using accessory muscles for respiration. She was drowsy but responsive to verbal stimuli (GCS: 13/15). Auscultation revealed cavernous breath sounds over the right upper chest and coarse inspiratory crepitations over the left lower lung zones. Repeat chest X-ray showed right-sided consolidation and possible cavitary extension. She was shifted to the intensive care unit for further management in view of respiratory failure. Initial laboratory investigations showed neutrophilic leukocytosis, thrombocytopenia, mildly deranged liver enzymes, elevated inflammatory markers (CRP and procalcitonin), prolonged prothrombin time, and high serum ferritin (Table 1 ). In view of worsening hypoxia, endotracheal intubation and mechanical ventilation were initiated. Empirical intravenous antibiotics (Meropenem 1 g TID and Teicoplanin 400 mg daily) were started. Table 1 Laboratory parameters of patient at presentation Parameter Patient Value Reference Range Complete Blood Count Hemoglobin 10.4 g/dL 12–16 g/dL Total Leukocyte Count 18,200 /mm³ 4,000–11,000 /mm³ Platelet Count 95,000 /mm³ 150,000–450,000 /mm³ Renal Function Tests Blood Urea 84 mg/dL 10–50 mg/dL Serum Creatinine 2.2 mg/dL 0.6–1.3 mg/dL Liver Function Tests AST (SGOT) 78 IU/L 5–40 IU/L ALT (SGPT) 102 IU/L 7–56 IU/L ALP 140 IU/L 40–129 IU/L Total Bilirubin 1.1 mg/dL 0.3–1.2 mg/dL Albumin 2.7 g/dL 3.4–5.4 g/dL Globulin 3.9 g/dL 2–3.5 g/dL Inflammatory Markers C-Reactive Protein (CRP) 156 mg/L < 6 mg/L Procalcitonin 11.2 ng/mL < 0.5 ng/mL Serum Ferritin 1,420 ng/mL 13–150 ng/mL (female) Metabolic Profile / DKA Panel Random Blood Glucose 462 mg/dL 70–140 mg/dL (postprandial) Serum Ketones 7.8 mmol/L < 0.6 mmol/L Arterial pH 7.14 7.35–7.45 Serum Bicarbonate 10 mmol/L 22–28 mmol/L Anion Gap 21 8–16 Serum Lactate 4.8 mmol/L 0.5–2.2 mmol/L Infective Workup Serum Galactomannan (ODI – Optical Density Index) 3.5 ODI < 0.5 ODI Sputum AFB (Ziehl-Neelsen stain) Negative Negative Serum Galactomannan (ODI) 3.5 < 0.5 Pleural Fluid Microscopy (Fungal) Acute-angle branching, septate hyphae with characteristic conidial heads Not seen A contrast-enhanced CT scan of the thorax revealed a large, thick-walled fibrocavitatory lesion measuring 6.4 x 4.3 x 5.5 cm in the right upper and middle lobes, with communication to a segmental bronchus and rupture into the pleural space (Fig. 1 -A, 1 -B). This had resulted in a large right-sided hydropneumothorax with near-complete collapse of the right lung. An intercostal chest drain (ICD) was inserted, which drained purulent material with an air-fluid level visible radiographically. Despite drainage and ventilation, there was minimal clinical improvement. Microbiological evaluation of pleural fluid revealed fungal elements. Direct microscopy using lactophenol cotton blue staining showed acute-angle branching, septate fungal hyphae with conidial heads characteristic of Aspergillus fumigatus (Fig. 1 -C). Serum galactomannan assay was strongly positive (optical density index: 3.5; reference < 0.5), confirming invasive pulmonary aspergillosis (IPA) with rupture of cavity into pleural space leading to pyopneumothorax. She subsequently developed hypotension requiring escalating vasopressor support with norepinephrine and vasopressin, indicating progression to septic shock. A surgical consultation was obtained; however, given her hemodynamic instability and the family’s unwillingness to consent for high-risk intervention, surgery was deferred. In view of the rapidly progressive cavitary disease and the presence of fungal elements on microscopy, liposomal amphotericin B was initiated empirically at 5 mg/kg/day IV to cover both Aspergillus and possible mucormycosis. Following microbiological confirmation of Aspergillus fumigatus (positive galactomannan and characteristic septate hyphae), voriconazole was added to optimize targeted antifungal therapy. Despite broad-spectrum antibiotics, dual antifungal therapy, mechanical ventilation, and escalating vasopressor support, the patient’s condition continued to worsen. She developed acute kidney injury with anuria requiring hemodialysis and ultimately succumbed to refractory obstructive and septic shock within 72 hours of ICU admission. A table summarising the chronological progression from initial symptoms to final outcome, including key diagnostic findings, therapeutic interventions, and clinical deterioration is given (Table 2 ). Table 2 Timeline of clinical events, interventions, and outcomes in the present case. Time Point Event Intervention Outcome 1 month prior Cough, weight loss, cavity on CXR Oral antibiotics No improvement Day 0 – ED Severe dyspnea, hypoxia, DKA DKA protocol; IV Meropenem + Teicoplanin Partial metabolic correction Day 0 – ICU Respiratory failure Intubation, ventilation Stabilized oxygenation Day 1 CT: ruptured cavitary lesion → hydropneumothorax ICD insertion, Liposomal Amphotericin B added Poor lung re-expansion Day 1 Pleural fluid + GM positive IPA diagnosed; Voriconazole added. Fungal etiology confirmed Day 1–2 Shock worsening Norepinephrine ↑; Vasopressin added; Refractory septic shock Day 2 Anuria, AKI Hemodialysis Persistent MOF Day 3 Refractory septic + obstructive shock Full ICU support Death Discussion Aspergillosis refers to a spectrum of diseases caused by Aspergillus species, ranging from allergic bronchopulmonary aspergillosis (ABPA) to chronic pulmonary aspergillosis and invasive pulmonary aspergillosis (IPA). The clinical manifestation depends on the host’s immune status and underlying lung pathology. Invasive forms, although more common in immunocompromised patients, can occasionally occur in immunocompetent individuals, especially those with structural lung abnormalities, and may progress rapidly with fatal outcomes if not promptly diagnosed and treated. Among immunocompetent individuals, Aspergillus colonization has been reported in 10–15% of cases with pre-existing cavitary lung diseases 6 . One of the rare but potentially fatal complications is pneumothorax or pyopneumothorax due to rupture of a cavitary lesion, often occurring in patients with pre-existing structural lung disease. The diagnosis of IPA requires a combination of host factors and clinical and mycological criteria. It is challenging to obtain evidence to confirm pulmonary aspergillosis in the absence of host factors. Zhang et al. retrospectively examined records of 102 immunocompetent patients for whom surgical specimens for chronic lung granulomas were taken, presumed to be Pulmonary Tuberculosis, and found that 26 of them were eventually diagnosed as IPA on Grocott methenamine silver staining 7 . This implies that a significant proportion of patients are misdiagnosed as Pulmonary tuberculosis, especially in Indian setting and alternative diagnoses such as Aspergillosis and mucormycosis are usually neglected. Early recognition of the same is therefore needed for prompt medical and, if necessary, surgical management. A review of 15 published cases (Supplementary Table 1) revealed that such complications can occur across a wide spectrum of patients, including those with hematologic malignancies, post-tuberculosis fibrosis, COPD, steroid use, and even previously healthy individuals. Common presenting features include sudden onset dyspnea, pleuritic chest pain, fever, and in some cases, hemoptysis. Imaging often shows cavitary lung lesions, air-fluid levels, and associated pleural involvement such as pneumothorax, hydropneumothorax, or subcutaneous emphysema. Diagnostic confirmation is generally achieved through radiological findings combined with microbiological evidence-either from sputum, BAL, pleural fluid, or histopathology. Voriconazole remains the mainstay of medical therapy, though amphotericin B and itraconazole have also been used effectively. In several cases, surgical interventions such as lobectomy, pneumonectomy, or intercostal drainage were required, especially in cases of persistent air leak or extensive disease. However, as in our case and others, hemodynamic instability or high surgical risk precluded operative management 3 , 8 , 9 . Outcomes were generally favorable when diagnosis and intervention were timely. However, mortality was reported in patients with delayed presentation, ICU-associated complications, or profound immunosuppression. Our case is unique in that the patient was non-immunocompromised apart from underlying diabetes and presented with DKA, which may have precipitated the fungal proliferation and subsequent cavitary rupture. Early diagnosis of IPA in such presentations remains challenging due to overlapping clinical features with tuberculosis or bacterial pneumonias, particularly in endemic regions. Conclusions Pulmonary aspergillosis can present with rare but life-threatening complications such as cavitary rupture and hydropneumothorax, even in non-immunocompromised individuals. Our case of a diabetic female presenting with DKA and respiratory failure highlights the rapid progression and poor prognosis associated with such presentations. Despite prompt antifungal therapy and intercostal drainage, the patient succumbed due to hemodynamic instability and multi-organ dysfunction. A review of 15 similar cases showed better outcomes with early diagnosis and surgical intervention. Clinicians must maintain a high index of suspicion for invasive aspergillosis in patients with cavitary lung lesions and acute deterioration, especially in high-risk groups. Declarations Funding: Nil. No financial support was received for this study. Conflicts of Interest/Competing Interests: The authors declare that there are no conflicts of interest or competing interests related to this publication. Ethics Approval: Ethical approval was not required for this single case report as per the institutional ethics committee policy. Consent to Participate: Informed consent for participation in clinical management and data collection was obtained from the patient’s next of kin. Written Consent for Publication: Written informed consent for publication of this case and accompanying images was obtained from the patient’s legally authorized representative. A copy of the consent form is available for review by the journal’s editorial office upon request. Availability of Data and Material: All data supporting the findings of this case report, including anonymized clinical details, imaging studies, and microbiological results, are available from the corresponding author upon reasonable request. No publicly available datasets were generated or analyzed during the current study. Code Availability: Not applicable. Authors’ Contributions: Pyrus Bhellum (PB) and Shekhar Angirekula (SA) contributed to patient management, data acquisition, and manuscript drafting. Adeeb Shan (AS) and Mahendra Dhaka (MD) assisted in diagnostic interpretation, literature review, and manuscript revision. Amit Kumar Rohila (AKR) supervised patient care, critically reviewed the manuscript for intellectual content, and approved the final version. All authors have read and approved the final manuscript and agree to be accountable for the integrity and accuracy of the work. References Tunnicliffe G, Schomberg L, Walsh S, et al.: Airway and parenchymal manifestations of pulmonary aspergillosis. Respir Med. 2013, 107(8):1113-1123. 10.1016/j.rmed.2013.03.016 Kanj A, Abdallah N, Soubani AO: The spectrum of pulmonary aspergillosis. Respir Med. 2018, 1:121-31. 10.1016/j.rmed.2018.06.029 Dixit D, Kuete NT, Bene P, et al.: Invasive Pulmonary Aspergillosis with Hydropneumothorax in a Patient Taking High-Dose Glucocorticoids. Am J Case Rep. 2020, 21:e928499-1-e928499-5. 10.12659/AJCR.928499 Takatsuka H, Yamazaki S, Watanabe A, et al.: Successful treatment of Aspergillus empyema using combined intrathoracic and intravenous administration of voriconazole: A case report. J Infect Chemother. 2020, 26:847-50. 10.1016/j.jiac.2020.03.013 Salik I, Vashisht R, Sharma S, et al.: Bronchopleural Fistula. In. StatPearls [Internet, Treasure Island (FL): StatPearls Publishing; 202520253. D Davies: Aspergilloma and residual tuberculous cavities--the results of a resurvey. . Tubercle. 1970, 51(3):227-45. 10.1016/0041-3879(70)90015-2 Zhang R, Wang S, Lu H, et al.: Misdiagnosis of invasive pulmonary aspergillosis: a clinical analysis of 26 immunocompetent patients. Int J Clin Exp Med. 2014, 15:5075-82. Kant S, Saheer S, Singh A, et al.: Pyopneumothorax secondary to Aspergillus infection: A case report. Oman Med J. 2012, 27:494-6. 10.5001/omj.2012.118 Shrestha GS, Sharma S, Keyal N, et al.: Pneumothorax following rupture of lung cavity due to aspergillosis in a critically ill patient. Bangladesh Crit Care J. 2020, 8:131-3. 10.3329/bccj.v8i2.50037 Serrano-Gonzalez A, Merino-Arribas JM, Ruiz-Lopez MJ, et al.: Invasive pulmonary aspergillosis with pneumopericardium and pneumothorax. Pediatr Radiol. 22:601-602. 10.1007/BF02015364 Zhang W, Hu Y, Chen L, et al.: Pleural aspergillosis complicated by recurrent pneumothorax: a case report. J Med Case Reports. 2010, 17:180. 10.1186/1752-1947-4-180 Vukicevic TA, Dudvarski-Ilic A, Zugic V, et al.: Subacute invasive pulmonary aspergillosis as a rare cause of pneumothorax in immunocompetent patient: brief report. Infection. 45:377-380. 10.1007/s15010-017-0994-3 Ngo Nonga B, Nde P, Zingue S, et al.: Spontaneous tension pneumothorax revealing a pulmonary aspergilloma: A case report. Case Rep Surg. 2018, Feb 15:10.1155/2018/8648732 Bekasiak A, Shnawa A, Tedrow J: Pulmonary aspergilloma with subcutaneous fistula resulting in massive hemoptysis and subcutaneous emphysema. Respir Med Case Rep. 2019, 27:100853. 10.1016/j.rmcr.2019.100853 Chinnasamy S, Sundararajan L, Radhakrishnan C, et al.: Pleuropulmonary aspergillosis presenting as hydropneumothorax in second trimester pregnancy. Indian J Respir Care. 2019, 8:57-9. 10.4103/ijrc.ijrc_27_18 Shah K, Kumar A, Kumar N, et al.: Pulmonary aspergillosis silently presenting as pneumothorax in children with leukemia: A report of three cases. Indian J Med Paediatr Oncol. 2022, 43:439-42. 10.1055/s-0042-1755545 Ibrahim S, Adegbite A, Barrios S: Pulmonary aspergillosis presenting with empyema and bronchopleural fistula. Chest. 2023, 164:1262-3. 10.1016/j.chest.2023.07.895 Rai K, Agarwal R, George R, et al.: Aspergilloma complicated by massive hemothorax: A rare surgical challenge. Cardiothorac Surg. 2024, 166:306. 10.1016/j.chest.2024.06.3835 Additional Declarations No competing interests reported. Supplementary Files CAREchecklistEnglish20131.pdf Table.docx Cite Share Download PDF Status: Published Journal Publication published 07 Feb, 2026 Read the published version in SN Comprehensive Clinical Medicine → Version 1 posted Editorial decision: Revision requested 15 Dec, 2025 Reviews received at journal 11 Dec, 2025 Reviews received at journal 02 Dec, 2025 Reviewers agreed at journal 30 Nov, 2025 Reviewers agreed at journal 30 Nov, 2025 Reviewers agreed at journal 26 Nov, 2025 Reviewers invited by journal 25 Nov, 2025 Editor assigned by journal 24 Nov, 2025 Submission checks completed at journal 24 Nov, 2025 First submitted to journal 02 Nov, 2025 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. 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consolidation and extensive bilateral parenchymal involvement; \u003cstrong\u003e(C)\u003c/strong\u003e Lactophenol cotton blue mount showing acute-angle branching, septate hyphae with characteristic conidial heads, consistent with \u003cem\u003eAspergillus fumigatus\u003c/em\u003e.\u003c/p\u003e","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8012598/v1/eb867975a0d37d55fa65c867.jpeg"},{"id":102234054,"identity":"7bcd275b-ec03-4d75-9b64-26706b0837c8","added_by":"auto","created_at":"2026-02-09 16:05:25","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":925476,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8012598/v1/647ac9df-3e21-4c7c-b78d-76a1b390da7b.pdf"},{"id":97257489,"identity":"85e9e207-c587-4709-be12-555cfc0fff9c","added_by":"auto","created_at":"2025-12-02 13:40:27","extension":"pdf","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":814857,"visible":true,"origin":"","legend":"","description":"","filename":"CAREchecklistEnglish20131.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8012598/v1/48f6b2ff3afa9f8b78bbe1ea.pdf"},{"id":97257482,"identity":"3d94bcc5-e852-4cfb-95b0-757dd59a42f9","added_by":"auto","created_at":"2025-12-02 13:40:27","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":19292,"visible":true,"origin":"","legend":"","description":"","filename":"Table.docx","url":"https://assets-eu.researchsquare.com/files/rs-8012598/v1/cced8a765a5cfb208b3f45e4.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Ruptured Pulmonary Aspergilloma complicating into pyopneumothorax and bronchopleural fistula: A case report and review of literature","fulltext":[{"header":"Introduction","content":"\u003cp\u003e\u003cem\u003eAspergillus\u003c/em\u003e is a ubiquitous fungus which has the potential to cause a wide range of clinical syndromes, ranging from colonisation of the respiratory tract to invasive fulminant disease, which is described as Invasive Pulmonary Aspergillosis (IPA). Usually, host immunity prevents Aspergillosis from causing the disease. Host factors include a history of prolonged neutropenia (more than 3 weeks), hematological malignancies, prolonged corticosteroid therapy, solid organ cancer, Acquired immunodeficiency syndrome (AIDS), and structural lung disease\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. Underlying structure lung disease damages the immune milieu of the lung, leading to increased risk of infections, which include tuberculosis, aspergillosis, mucormycosis, and others.\u003c/p\u003e\u003cp\u003ePulmonary aspergillosis may present in various forms, ranging from chronic cavitary disease and aspergilloma to necrotizing and angioinvasive disease\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e. Rarely, cavitary rupture due to fungal invasion can lead to complications such as hydropneumothorax, bronchopleural fistula, or massive hemoptysis, which are clinical events associated with high morbidity and mortality. Such presentations often mimic more common conditions like pulmonary tuberculosis or bacterial empyema, making early diagnosis and intervention particularly challenging in resource-limited settings.\u003c/p\u003e\u003cp\u003eOnly a limited number of case reports have documented rupture of pulmonary cavities leading to hydropneumothorax or aspergillus-related empyema\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. Serological assays such as serum galactomannan and imaging modalities like high-resolution computed tomography (HRCT) play a critical role in the diagnostic workup. However, definitive diagnosis often requires microbiological or histopathological confirmation.\u003c/p\u003e\u003cp\u003eBronchopleural fistula is a tract between bronchi and the pleural space, which occurs as a complication following thoracic surgeries such as lobectomy, thoracotomy, and some pulmonary infections\u003csup\u003e\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u003c/sup\u003e. Management involves antifungal therapy with agents like voriconazole or amphotericin B, and in selected cases, surgical resection or drainage procedures.\u003c/p\u003e\u003cp\u003eWe present a case of a 62-year-old diabetic female who developed Diabetic Ketoacidosis (DKA) and acute respiratory failure due to invasive pulmonary aspergillosis, complicated by pyopneumothorax following cavitary rupture.\u003c/p\u003e"},{"header":"Case report","content":"\u003cp\u003eA 62-year-old female, a known case of type 2 diabetes mellitus on oral hypoglycemic therapy, presented to the Emergency Department of our tertiary care center in Western India with acute onset shortness of breath for one day. Her history revealed a one-month duration of productive cough, associated with significant weight loss, generalized fatigue, and right-sided chest discomfort. She had been evaluated at an outside facility where a chest radiograph had demonstrated a right middle lobe cavitary lesion. Sputum examination for acid-fast bacilli using the Ziehl-Neelsen stain was negative. Empiric oral antibiotics (amoxicillin-clavulanate 625 mg TID for 7 days) had been prescribed, with no significant improvement in symptoms.\u003c/p\u003e\u003cp\u003eOn presentation, the patient was febrile and visibly dyspneic. Her vital parameters were: heart rate 119 beats/min, respiratory rate 45 breaths/min, blood pressure 106/78 mmHg, and oxygen saturation 75% on room air. Arterial blood gas analysis showed hypoxemia, and laboratory evaluation revealed markedly elevated blood glucose (462 mg/dL) and serum ketones (7.8 mmol/L), confirming diabetic ketoacidosis (DKA). She was managed according to standard DKA protocols with intravenous fluids, electrolyte correction, and insulin infusion.\u003c/p\u003e\u003cp\u003eOn physical examination, she appeared dehydrated with dry mucous membranes, poor skin turgor, and was using accessory muscles for respiration. She was drowsy but responsive to verbal stimuli (GCS: 13/15). Auscultation revealed cavernous breath sounds over the right upper chest and coarse inspiratory crepitations over the left lower lung zones. Repeat chest X-ray showed right-sided consolidation and possible cavitary extension. She was shifted to the intensive care unit for further management in view of respiratory failure.\u003c/p\u003e\u003cp\u003eInitial laboratory investigations showed neutrophilic leukocytosis, thrombocytopenia, mildly deranged liver enzymes, elevated inflammatory markers (CRP and procalcitonin), prolonged prothrombin time, and high serum ferritin (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). In view of worsening hypoxia, endotracheal intubation and mechanical ventilation were initiated. Empirical intravenous antibiotics (Meropenem 1 g TID and Teicoplanin 400 mg daily) were started.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eLaboratory parameters of patient at presentation\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eParameter\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePatient Value\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eReference Range\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eComplete Blood Count\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eHemoglobin\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10.4 g/dL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12\u0026ndash;16 g/dL\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTotal Leukocyte Count\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18,200 /mm\u0026sup3;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4,000\u0026ndash;11,000 /mm\u0026sup3;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePlatelet Count\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e95,000 /mm\u0026sup3;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e150,000\u0026ndash;450,000 /mm\u0026sup3;\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRenal Function Tests\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBlood Urea\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e84 mg/dL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10\u0026ndash;50 mg/dL\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSerum Creatinine\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.2 mg/dL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.6\u0026ndash;1.3 mg/dL\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLiver Function Tests\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAST (SGOT)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e78 IU/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e5\u0026ndash;40 IU/L\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eALT (SGPT)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e102 IU/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7\u0026ndash;56 IU/L\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eALP\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e140 IU/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e40\u0026ndash;129 IU/L\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eTotal Bilirubin\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.1 mg/dL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.3\u0026ndash;1.2 mg/dL\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAlbumin\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.7 g/dL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e3.4\u0026ndash;5.4 g/dL\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eGlobulin\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.9 g/dL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2\u0026ndash;3.5 g/dL\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eInflammatory Markers\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eC-Reactive Protein (CRP)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e156 mg/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;6 mg/L\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eProcalcitonin\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11.2 ng/mL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.5 ng/mL\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSerum Ferritin\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1,420 ng/mL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e13\u0026ndash;150 ng/mL (female)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eMetabolic Profile / DKA Panel\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRandom Blood Glucose\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e462 mg/dL\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e70\u0026ndash;140 mg/dL (postprandial)\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSerum Ketones\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7.8 mmol/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.6 mmol/L\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eArterial pH\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7.14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e7.35\u0026ndash;7.45\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSerum Bicarbonate\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10 mmol/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e22\u0026ndash;28 mmol/L\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAnion Gap\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e8\u0026ndash;16\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSerum Lactate\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4.8 mmol/L\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.5\u0026ndash;2.2 mmol/L\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eInfective Workup\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSerum Galactomannan\u003c/b\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003e(ODI \u0026ndash; Optical Density Index)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.5 ODI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.5 ODI\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSputum AFB (Ziehl-Neelsen stain)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eNegative\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNegative\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSerum Galactomannan (ODI)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e3.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003ePleural Fluid Microscopy (Fungal)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAcute-angle branching, septate hyphae with characteristic conidial heads\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNot seen\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eA contrast-enhanced CT scan of the thorax revealed a large, thick-walled fibrocavitatory lesion measuring 6.4 x 4.3 x 5.5 cm in the right upper and middle lobes, with communication to a segmental bronchus and rupture into the pleural space (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e-A, \u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e-B). This had resulted in a large right-sided hydropneumothorax with near-complete collapse of the right lung. An intercostal chest drain (ICD) was inserted, which drained purulent material with an air-fluid level visible radiographically. Despite drainage and ventilation, there was minimal clinical improvement.\u003c/p\u003e\u003cp\u003eMicrobiological evaluation of pleural fluid revealed fungal elements. Direct microscopy using lactophenol cotton blue staining showed acute-angle branching, septate fungal hyphae with conidial heads characteristic of Aspergillus fumigatus (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e-C). Serum galactomannan assay was strongly positive (optical density index: 3.5; reference\u0026thinsp;\u0026lt;\u0026thinsp;0.5), confirming invasive pulmonary aspergillosis (IPA) with rupture of cavity into pleural space leading to pyopneumothorax.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eShe subsequently developed hypotension requiring escalating vasopressor support with norepinephrine and vasopressin, indicating progression to septic shock. A surgical consultation was obtained; however, given her hemodynamic instability and the family\u0026rsquo;s unwillingness to consent for high-risk intervention, surgery was deferred. In view of the rapidly progressive cavitary disease and the presence of fungal elements on microscopy, liposomal amphotericin B was initiated empirically at 5 mg/kg/day IV to cover both Aspergillus and possible mucormycosis. Following microbiological confirmation of \u003cem\u003eAspergillus fumigatus\u003c/em\u003e (positive galactomannan and characteristic septate hyphae), voriconazole was added to optimize targeted antifungal therapy. Despite broad-spectrum antibiotics, dual antifungal therapy, mechanical ventilation, and escalating vasopressor support, the patient\u0026rsquo;s condition continued to worsen. She developed acute kidney injury with anuria requiring hemodialysis and ultimately succumbed to refractory obstructive and septic shock within 72 hours of ICU admission.\u003c/p\u003e\u003cp\u003eA table summarising the chronological progression from initial symptoms to final outcome, including key diagnostic findings, therapeutic interventions, and clinical deterioration is given (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eTimeline of clinical events, interventions, and outcomes in the present case.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"4\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTime Point\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eEvent\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eIntervention\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eOutcome\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003e1 month prior\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCough, weight loss, cavity on CXR\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eOral antibiotics\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eNo improvement\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDay 0 \u0026ndash; ED\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSevere dyspnea, hypoxia, DKA\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eDKA protocol; IV Meropenem\u0026thinsp;+\u0026thinsp;Teicoplanin\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ePartial metabolic correction\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDay 0 \u0026ndash; ICU\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRespiratory failure\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eIntubation, ventilation\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eStabilized oxygenation\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDay 1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eCT: ruptured cavitary lesion \u0026rarr; hydropneumothorax\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eICD insertion, Liposomal Amphotericin B added\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ePoor lung re-expansion\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDay 1\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003ePleural fluid\u0026thinsp;+\u0026thinsp;GM positive\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eIPA diagnosed; Voriconazole added.\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eFungal etiology confirmed\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDay 1\u0026ndash;2\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eShock worsening\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eNorepinephrine \u0026uarr;; Vasopressin added;\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eRefractory septic shock\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDay 2\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eAnuria, AKI\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eHemodialysis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003ePersistent MOF\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eDay 3\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eRefractory septic\u0026thinsp;+\u0026thinsp;obstructive shock\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003eFull ICU support\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e\u003cb\u003eDeath\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eAspergillosis refers to a spectrum of diseases caused by \u003cem\u003eAspergillus\u003c/em\u003e species, ranging from allergic bronchopulmonary aspergillosis (ABPA) to chronic pulmonary aspergillosis and invasive pulmonary aspergillosis (IPA). The clinical manifestation depends on the host\u0026rsquo;s immune status and underlying lung pathology. Invasive forms, although more common in immunocompromised patients, can occasionally occur in immunocompetent individuals, especially those with structural lung abnormalities, and may progress rapidly with fatal outcomes if not promptly diagnosed and treated. Among immunocompetent individuals, \u003cem\u003eAspergillus\u003c/em\u003e colonization has been reported in 10\u0026ndash;15% of cases with pre-existing cavitary lung diseases\u003csup\u003e\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eOne of the rare but potentially fatal complications is pneumothorax or pyopneumothorax due to rupture of a cavitary lesion, often occurring in patients with pre-existing structural lung disease.\u003c/p\u003e\u003cp\u003eThe diagnosis of IPA requires a combination of host factors and clinical and mycological criteria. It is challenging to obtain evidence to confirm pulmonary aspergillosis in the absence of host factors. Zhang et al. retrospectively examined records of 102 immunocompetent patients for whom surgical specimens for chronic lung granulomas were taken, presumed to be Pulmonary Tuberculosis, and found that 26 of them were eventually diagnosed as IPA on Grocott methenamine silver staining\u003csup\u003e\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e\u003c/sup\u003e. This implies that a significant proportion of patients are misdiagnosed as Pulmonary tuberculosis, especially in Indian setting and alternative diagnoses such as Aspergillosis and mucormycosis are usually neglected. Early recognition of the same is therefore needed for prompt medical and, if necessary, surgical management.\u003c/p\u003e\u003cp\u003eA review of 15 published cases (Supplementary Table\u0026nbsp;1) revealed that such complications can occur across a wide spectrum of patients, including those with hematologic malignancies, post-tuberculosis fibrosis, COPD, steroid use, and even previously healthy individuals. Common presenting features include sudden onset dyspnea, pleuritic chest pain, fever, and in some cases, hemoptysis. Imaging often shows cavitary lung lesions, air-fluid levels, and associated pleural involvement such as pneumothorax, hydropneumothorax, or subcutaneous emphysema. Diagnostic confirmation is generally achieved through radiological findings combined with microbiological evidence-either from sputum, BAL, pleural fluid, or histopathology.\u003c/p\u003e\u003cp\u003eVoriconazole remains the mainstay of medical therapy, though amphotericin B and itraconazole have also been used effectively. In several cases, surgical interventions such as lobectomy, pneumonectomy, or intercostal drainage were required, especially in cases of persistent air leak or extensive disease. However, as in our case and others, hemodynamic instability or high surgical risk precluded operative management\u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eOutcomes were generally favorable when diagnosis and intervention were timely. However, mortality was reported in patients with delayed presentation, ICU-associated complications, or profound immunosuppression.\u003c/p\u003e\u003cp\u003eOur case is unique in that the patient was non-immunocompromised apart from underlying diabetes and presented with DKA, which may have precipitated the fungal proliferation and subsequent cavitary rupture. Early diagnosis of IPA in such presentations remains challenging due to overlapping clinical features with tuberculosis or bacterial pneumonias, particularly in endemic regions.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003ePulmonary aspergillosis can present with rare but life-threatening complications such as cavitary rupture and hydropneumothorax, even in non-immunocompromised individuals. Our case of a diabetic female presenting with DKA and respiratory failure highlights the rapid progression and poor prognosis associated with such presentations. Despite prompt antifungal therapy and intercostal drainage, the patient succumbed due to hemodynamic instability and multi-organ dysfunction. A review of 15 similar cases showed better outcomes with early diagnosis and surgical intervention. Clinicians must maintain a high index of suspicion for invasive aspergillosis in patients with cavitary lung lesions and acute deterioration, especially in high-risk groups.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eNil. No financial support was received for this study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of Interest/Competing Interests:\u0026nbsp;\u003c/strong\u003eThe authors declare that there are no conflicts of interest or competing interests related to this publication.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics Approval:\u0026nbsp;\u003c/strong\u003eEthical approval was not required for this single case report as per the institutional ethics committee policy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent to Participate:\u0026nbsp;\u003c/strong\u003eInformed consent for participation in clinical management and data collection was obtained from the patient\u0026rsquo;s next of kin.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eWritten Consent for Publication:\u0026nbsp;\u003c/strong\u003eWritten informed consent for publication of this case and accompanying images was obtained from the patient\u0026rsquo;s legally authorized representative. A copy of the consent form is available for review by the journal\u0026rsquo;s editorial office upon request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of Data and Material:\u0026nbsp;\u003c/strong\u003eAll data supporting the findings of this case report, including anonymized clinical details, imaging studies, and microbiological results, are available from the corresponding author upon reasonable request. No publicly available datasets were generated or analyzed during the current study.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCode Availability:\u0026nbsp;\u003c/strong\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026rsquo; Contributions:\u0026nbsp;\u003c/strong\u003ePyrus Bhellum (PB) and Shekhar Angirekula (SA) contributed to patient management, data acquisition, and manuscript drafting. Adeeb Shan (AS) and Mahendra Dhaka (MD) assisted in diagnostic interpretation, literature review, and manuscript revision. Amit Kumar Rohila (AKR) supervised patient care, critically reviewed the manuscript for intellectual content, and approved the final version. All authors have read and approved the final manuscript and agree to be accountable for the integrity and accuracy of the work.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eTunnicliffe G, Schomberg L, Walsh S, et al.: Airway and parenchymal manifestations of pulmonary aspergillosis. Respir Med. 2013, 107(8):1113-1123. 10.1016/j.rmed.2013.03.016\u003c/li\u003e\n\u003cli\u003eKanj A, Abdallah N, Soubani AO: The spectrum of pulmonary aspergillosis. Respir Med. 2018, 1:121-31. 10.1016/j.rmed.2018.06.029\u003c/li\u003e\n\u003cli\u003eDixit D, Kuete NT, Bene P, et al.: Invasive Pulmonary Aspergillosis with Hydropneumothorax in a Patient Taking High-Dose Glucocorticoids. Am J Case Rep. 2020, 21:e928499-1-e928499-5. 10.12659/AJCR.928499\u003c/li\u003e\n\u003cli\u003eTakatsuka H, Yamazaki S, Watanabe A, et al.: Successful treatment of Aspergillus empyema using combined intrathoracic and intravenous administration of voriconazole: A case report. J Infect Chemother. 2020, 26:847-50. 10.1016/j.jiac.2020.03.013\u003c/li\u003e\n\u003cli\u003eSalik I, Vashisht R, Sharma S, et al.: Bronchopleural Fistula. In. StatPearls [Internet, Treasure Island (FL): StatPearls Publishing; 202520253.\u003c/li\u003e\n\u003cli\u003eD Davies: Aspergilloma and residual tuberculous cavities--the results of a resurvey. . Tubercle. 1970, 51(3):227-45. 10.1016/0041-3879(70)90015-2\u003c/li\u003e\n\u003cli\u003eZhang R, Wang S, Lu H, et al.: Misdiagnosis of invasive pulmonary aspergillosis: a clinical analysis of 26 immunocompetent patients. Int J Clin Exp Med. 2014, 15:5075-82.\u003c/li\u003e\n\u003cli\u003eKant S, Saheer S, Singh A, et al.: Pyopneumothorax secondary to Aspergillus infection: A case report. Oman Med J. 2012, 27:494-6. 10.5001/omj.2012.118\u003c/li\u003e\n\u003cli\u003eShrestha GS, Sharma S, Keyal N, et al.: Pneumothorax following rupture of lung cavity due to aspergillosis in a critically ill patient. Bangladesh Crit Care J. 2020, 8:131-3. 10.3329/bccj.v8i2.50037\u003c/li\u003e\n\u003cli\u003eSerrano-Gonzalez A, Merino-Arribas JM, Ruiz-Lopez MJ, et al.: Invasive pulmonary aspergillosis with pneumopericardium and pneumothorax. Pediatr Radiol. 22:601-602. 10.1007/BF02015364\u003c/li\u003e\n\u003cli\u003eZhang W, Hu Y, Chen L, et al.: Pleural aspergillosis complicated by recurrent pneumothorax: a case report. J Med Case Reports. 2010, 17:180. 10.1186/1752-1947-4-180\u003c/li\u003e\n\u003cli\u003eVukicevic TA, Dudvarski-Ilic A, Zugic V, et al.: Subacute invasive pulmonary aspergillosis as a rare cause of pneumothorax in immunocompetent patient: brief report. Infection. 45:377-380. 10.1007/s15010-017-0994-3\u003c/li\u003e\n\u003cli\u003eNgo Nonga B, Nde P, Zingue S, et al.: Spontaneous tension pneumothorax revealing a pulmonary aspergilloma: A case report. Case Rep Surg. 2018, Feb 15:10.1155/2018/8648732\u003c/li\u003e\n\u003cli\u003eBekasiak A, Shnawa A, Tedrow J: Pulmonary aspergilloma with subcutaneous fistula resulting in massive hemoptysis and subcutaneous emphysema. Respir Med Case Rep. 2019, 27:100853. 10.1016/j.rmcr.2019.100853\u003c/li\u003e\n\u003cli\u003eChinnasamy S, Sundararajan L, Radhakrishnan C, et al.: Pleuropulmonary aspergillosis presenting as hydropneumothorax in second trimester pregnancy. Indian J Respir Care. 2019, 8:57-9. 10.4103/ijrc.ijrc_27_18\u003c/li\u003e\n\u003cli\u003eShah K, Kumar A, Kumar N, et al.: Pulmonary aspergillosis silently presenting as pneumothorax in children with leukemia: A report of three cases. Indian J Med Paediatr Oncol. 2022, 43:439-42. 10.1055/s-0042-1755545\u003c/li\u003e\n\u003cli\u003eIbrahim S, Adegbite A, Barrios S: Pulmonary aspergillosis presenting with empyema and bronchopleural fistula. Chest. 2023, 164:1262-3. 10.1016/j.chest.2023.07.895\u003c/li\u003e\n\u003cli\u003eRai K, Agarwal R, George R, et al.: Aspergilloma complicated by massive hemothorax: A rare surgical challenge. Cardiothorac Surg. 2024, 166:306. 10.1016/j.chest.2024.06.3835\u003c/li\u003e\n\u003c/ol\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":"sn-comprehensive-clinical-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sncm","sideBox":"Learn more about [SN Comprehensive Clinical Medicine](https://www.springer.com/journal/42399)","snPcode":"42399","submissionUrl":"https://submission.nature.com/new-submission/42399/3","title":"SN Comprehensive Clinical Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Invasive pulmonary aspergillosis, Pyopneumothorax, Galactomannan assay, Case report, Diabetes mellitus","lastPublishedDoi":"10.21203/rs.3.rs-8012598/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8012598/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eIntroduction:\u003c/h2\u003e\u003cp\u003ePyopneumothorax secondary to ruptured pulmonary aspergilloma is a rare but life-threatening complication of invasive pulmonary aspergillosis (IPA), particularly in patients without classical immunosuppression. In tuberculosis-endemic regions, post-tubercular cavities often serve as a nidus for \u003cem\u003eAspergillus\u003c/em\u003e colonization. However, due to overlapping clinical and radiological features with bacterial pneumonia or tuberculosis reactivation, IPA frequently remains underdiagnosed or is recognized late in its course.\u003c/p\u003e\u003ch2\u003eCase Presentation:\u003c/h2\u003e\u003cp\u003eA 62-year-old female with poorly controlled diabetes mellitus presented with acute respiratory distress and diabetic ketoacidosis. Chest imaging revealed a right-sided cavitary lesion with hydropneumothorax and underlying lung collapse. Intercostal drainage yielded purulent material, confirming pyopneumothorax. Despite initiation of broad-spectrum antibiotics and liposomal amphotericin B, the patient developed progressive hypoxemia and multiorgan dysfunction. Pleural fluid microscopy and elevated serum galactomannan established the diagnosis of \u003cem\u003eAspergillus fumigatus\u003c/em\u003e infection. Surgical intervention was deferred due to hemodynamic instability, and the patient unfortunately succumbed to her illness.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e\u003cp\u003eThis case highlights a fulminant presentation of IPA complicated by pyopneumothorax in a non-classically immunosuppressed host. Review of similar reported cases demonstrates that aspergillus-associated pneumothorax and pyopneumothorax can occur across diverse immune states, often with poor outcomes related to delayed diagnosis. Early clinical suspicion, rapid fungal diagnostics, and timely initiation of antifungal therapy are critical to improving survival in patients with pre-existing pulmonary cavities presenting with acute respiratory compromise.\u003c/p\u003e","manuscriptTitle":"Ruptured Pulmonary Aspergilloma complicating into pyopneumothorax and bronchopleural fistula: A case report and review of literature","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-02 13:40:22","doi":"10.21203/rs.3.rs-8012598/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-12-15T16:54:02+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-11T14:41:29+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-12-02T12:23:01+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"124797385696516313800369631968303640805","date":"2025-11-30T16:51:51+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"219069592425974852353326225616898099582","date":"2025-11-30T16:28:38+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"302638828677043180832041139325442904590","date":"2025-11-26T08:04:19+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-11-25T11:01:41+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-11-24T09:24:27+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-11-24T09:06:08+00:00","index":"","fulltext":""},{"type":"submitted","content":"SN Comprehensive Clinical Medicine","date":"2025-11-02T17:57:25+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"sn-comprehensive-clinical-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sncm","sideBox":"Learn more about [SN Comprehensive Clinical Medicine](https://www.springer.com/journal/42399)","snPcode":"42399","submissionUrl":"https://submission.nature.com/new-submission/42399/3","title":"SN Comprehensive Clinical Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"831f7590-1817-4cd9-bf01-e88d4a389af6","owner":[],"postedDate":"December 2nd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-02-09T16:01:45+00:00","versionOfRecord":{"articleIdentity":"rs-8012598","link":"https://doi.org/10.1007/s42399-026-02259-1","journal":{"identity":"sn-comprehensive-clinical-medicine","isVorOnly":false,"title":"SN Comprehensive Clinical Medicine"},"publishedOn":"2026-02-07 15:58:18","publishedOnDateReadable":"February 7th, 2026"},"versionCreatedAt":"2025-12-02 13:40:22","video":"","vorDoi":"10.1007/s42399-026-02259-1","vorDoiUrl":"https://doi.org/10.1007/s42399-026-02259-1","workflowStages":[]},"version":"v1","identity":"rs-8012598","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8012598","identity":"rs-8012598","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}