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Chronic pulmonary aspergillosis (CPA) complicates conditions including tuberculosis, chronic obstructive pulmonary disease and sarcoidosis, and is associated with high morbidity and mortality. Surgical cure should be considered where feasible; however, many patients are unsuitable for surgery due to extensive disease or poor respiratory function. Azoles are the only oral drug with anti-Aspergillus activity and itraconazole and voriconazole are considered as first-line drugs. A randomized controlled trial demonstrated improvement or stability in three-quarters of patients given 6 months of itraconazole, but a quarter relapsed on stopping therapy. Long-term treatment may therefore be required in some cases. Itraconazole, voriconazole and posaconazole require therapeutic drug monitoring. No published data are yet available for isavuconazole. Adverse drug effects of azoles are common, including peripheral neuropathy, heart failure, elevated liver enzymes, QTc prolongation and sun sensitivity. Many serious drug-drug interactions occur, including major interactions with rifamycins, simvastatin, warfarin, clopidogrel, immunosuppressant drugs like sirolimus. Furthermore, drug resistance occurs, including cross-resistance to all azoles, but the true prevalence is not yet determined. Intravenous therapy is possible with echinocandins or amphotericin B, but long-term use is challenging. Hemoptysis complicates CPA and can be fatal. Tranexamic acid should be given acutely to reduce bleeding. Bronchial artery embolization can stop acute bleeds. In some circumstances, emergency surgery may be necessary to resect the source of the bleed. Current CPA treatments can be beneficial but have many drawbacks. New oral anti-Aspergillus agents are needed, along with optimization of currently available treatments.

Background Surgical resection is considered the most effective therapeutic method for pulmonary aspergilloma (PA), while the necessity of postoperative antifungal therapy remains controversial. Previous studies have several shortcomings such as retrospective design and inadequate follow-up durations. In this study, we aim to address these evidence gaps by evaluating the effects of postoperative antifungal therapy on both Aspergillus infection recurrence and drug-related side effects. Methods We conducted a prospective, randomized, controlled, single-center clinical trial. Eligible patients with PA who underwent surgical resection at our institute were enrolled and randomly assigned to receive either a 3-month course of voriconazole (VRZ) tablet postoperatively or symptomatic treatment alone. Participants were evaluated for Aspergillus infection recurrence and drug-related side effects every 3 months for 2 years. Ultimately, 36 patients in the VRZ group and 14 patients in the control group were included in the analysis, with balanced baseline characteristics between groups. Results After a median follow-up of 27 months, no recurrence of Aspergillus infection was observed in either group. Symptomatic improvements (e.g., hemoptysis and white sputum) were comparable between groups. Although serum IgG level significantly increased by 2.22 g/L after VRZ treatment ( p  < 0.001), other parameters indicating immune activity (CD4 + %, CD8 + %, CD4 + /CD8 + ratio, IgA, IgM and Aspergillus -specific IgG) and pulmonary function showed no significant intergroup differences at the final follow-up. Regarding safety, VRZ intervention was associated with a significant increase in aspartate aminotransferase level (20.9 ± 6.2 U/L to 26.5 ± 7.8 U/L, p  = 0.023). Hypokalemia incidence was numerically higher in the VRZ group (21.4% vs. 0, p  = 0.530), though not statistically significant. Conclusions Our findings demonstrated that postoperative antifungal therapy did not reduce Aspergillus recurrence rate but posed potential safety risks. For immunocompetent patients undergoing complete resection without intraoperative fungal spillage, routine postoperative antifungal agents are not recommended. Trial registration Chinese Clinical Trial Registry Number: ChiCTR1800019990, registration date: December 11th, 2018.

Background In recent years, the incidence of pulmonary aspergilloma has increased. The harm of aspergilloma is life-threatening massive hemoptysis, and the conventional treatment is surgical treatment. However, whether the antifungal treatment after surgery is required and the course of treatment before and after surgery are still unclear. Methods In this study, patients with pulmonary aspergilloma confirmed pathologically after surgery will be selected as subjects to conduct a single-center, randomized, parallel grouping, prospective, 2-year clinical study. Through regular visits, the recurrence of aspergillus infection, quality of life, lung function indicators, safety of antifungal therapy and other indicators were recorded to evaluate the recurrence risk of aspergillus infection and safety of antifungal agents. Cox proportional risk regression model was used to analyze the influencing factors of antifungal therapy on aspergillus infection recurrence after aspergillus bulbectomy. Cox multiple regression model was used for optimal model fitting, and regression coefficient (β), relative risk (RR) and 95% confidence interval of RR were calculated. Discussion The study will explore whether antifungal therapy could improve the quality of life, reduce the recurrence of aspergillus infection, and ultimately improve the prognosis of patients with aspergilloma. The study results will provide high-quality evidence-based medical evidence for the formulation, revision and optimization of international and domestic clinical guidelines and expert consensus on chronic aspergillus lung disease, effectively improve the clinical treatment effect of aspergilloma, and form the latest concept of diagnosis and treatment of aspergilloma. Trial registration : The trial was registered on the Chinese Clinical Trial Registry website ( https://www.chictr.org.cn/showprojen.aspx?proj=33231 ). Registration number: ChiCTR1800019990.

Abstract A 3.5-year-old castrated male domestic medium hair cat was evaluated for dry cough and labored breathing. A cranial mediastinal mass was seen on thoracic radiographs. On computed tomography, the mass displaced the cranial vena cava and dorsally displaced and compressed the intrathoracic trachea. The patient was taken to surgery for attempted mass removal. Intraoperatively, the mass was adhered to the cranial vena cava, aortic arch, left subclavian artery, and had partially engulfed the brachiocephalic trunk. The cat was euthanized and on necropsy the mass was found to invade the lumen of the vena cava and the tracheal lumen. An Aspergillus lentulus fungal granuloma was diagnosed histologically and by fungal culture and PCR. We highlight the difficulty in determining the extent of invasion with invasive aspergillosis and provide evidence that invasive aspergillosis can occur in otherwise healthy, young cats with no concurrent immunosuppressive treatments or comorbidities.

Invasive pulmonary aspergillosis (IPA) has high mortality rate but prognostic factors are not well established. The aim of our study was to evaluate the trend in in-hospital mortality over a period of 11 years and identify factors affecting the clinical outcomes of patients with IPA. We conducted a nationwide inpatient population study using data from the Taiwan National Health Insurance Research Database. A total of 407 IPA patients from 2002 to 2012 were included in the study. Differences in demographics, comorbidities, and treatment were evaluated between in-hospital death group and survival group. Multivariate analysis was also performed to identify risk factors for mortality. Male patients represented 63.14% of the patients (n = 257) and the mean age was 53.15 ± 20.93 years. Hematological cancer (n = 216, 53.07%) and diabetes mellitus (n = 75, 18.43%) were the most common underlying conditions. The overall case fatality rate was 30.22% with female slightly higher then male (32.67% versus 28.79%). The in-hospital case fatality rate increased since 2002 and peaked in 2006. It then declined over time with an in-hospital mortality of 25% in 2012. The in-hospital death group had a higher intubation rate (p<0.0001), a longer ICU stay (p = 0.0062), higher percentages of DM (p = 0.0412) and COPD (p = 0.0178), and a lower percentage of hematological cancer (p = 0.0079) as compared to survivor. The in-hospital death group was more likely to have steroid treatment (p<0.0001), develop acute renal failure (p<0.0001) and other infectious diseases (p = 0.0008) during hospitalization. Multivariate analysis identified female gender, older age (≥ 65 years old), intubation, bone marrow transplantation, acute renal failure, other infectious diseases and steroid use as predictive factors for mortality. The present study shows the trend in mortality among patients with IPA over an 11-year period. Female gender, older age, intubation, bone marrow transplantation, acute renal failure, other infectious diseases and steroid use were identified as risk factors for mortality.

Background Xanthogranulomatous osteomyelitis (XO) is a rare disease characterized radiologically by an osteolytic lesion with cortical expansion or disruption. Differentiating this condition from other osteolytic diseases such as primary or metastatic bone neoplasms is imperative. Several case reports have been published on XO, with previous reports predominantly identifying bacteria such as Pseudomonas or Staphylococcus as causative organisms. However, fungal infection-induced XO has not yet been reported. Case presentation We present the case of a 23-year-old woman with a tumor-like osteolytic lesion in the pubic bone. The patient had experienced pelvic pain and intermittent febrile episodes for 2 months. Plain radiography revealed an osteolytic lesion in the right pubic tubercle. Magnetic resonance imaging suggested a cystic bone tumor or tubercular infection. Surgical intervention included curettage of the lesion and irrigation with normal saline. Histopathological examination of the specimen revealed abundant foamy histiocytes with inflammatory infiltrates consistent with XO. Culture of the osteolytic lesion confirmed an Aspergillus species infection and antifungal treatment was initiated. At 1-year follow-up, no evidence of local recurrence was observed. Conclusions Although rare, XO requires differentiation from similar conditions and is treated with surgical intervention and targeted medical therapy based on the identified organisms. Clinicians should be mindful that XO can also be induced by fungal infections and that combination antifungal treatments may be beneficial in such cases.

Background Fungal spondylitis often occurs in patients with immune dysfunction, and its diagnosis and treatment pose certain challenges. However, even in immunocompromised patients, Aspergillus spondylitis remains rare. This case reports the diagnostic and therapeutic experience of fungal spondylitis in a patient with consolidated cirrhosis and no significant immune impairment. Case presentation A 45-year-old agricultural worker had chest and back pain for 6 months. The patient’s pain was a persistent dull ache that worsened with chronic coughing and postural changes and decreased when he was laying down. Based on the patient’s clinical presentation, biochemical tests and imaging, considered possible spinal tuberculosis. Empirical anti-tuberculosis treatment was not successful. Due to the failure of medication and the formation of an epidural abscess, the decision was made to proceed with surgical treatment. Intraoperative tissue specimens were subjected to high throughput testing for culture, tuberculosis gene X-pert and high-throughput detection of macro-gene infectious agents. It was confirmed that the spinal infection was caused by Aspergillus fumigatus . Tuberculosis medication was ceased and antifungal therapy with voriconazole was started. Three months after surgery, the patient recovered well with no fever or pain. Discussion and conclusion In summary, in addition to patients with low immune function who should be evaluated for fungal spondylitis, patients with infectious diseases of the spine who are immunocompetent but have comorbid cirrhosis should be evaluated when treatment fails. If the diagnosis cannot be made by conventional or unconventional methods, surgical methods should be used in a timely manner for diagnosis and treatment.

We describe 18 nonimmunocompromised patients with chronic pulmonary aspergillosis. Duration of the disease ranged from several months to >12 years. All 18 patients had prior pulmonary disease. Weight loss, chronic cough (often with hemoptysis and shortness of breath), fatigue, and chest pain were the most common symptoms. All 18 patients had cavities, usually multiple and in 1 or both upper lobes of the lung, that expanded over time, with or without intraluminal fungal balls. All had detectable Aspergillus precipitins and inflammatory markers. Elevated levels of total immunoglobulin E were seen in 78% of patients and of Aspergillus-specific immunoglobulin E in 64%. Directed lung biopsies showed chronic inflammation, necrosis, or granulomas without hyphal invasion. Antifungal therapy with itraconazole resulted in 71% of patients improved or stabilized, with relapse common. Interferon-γ treatment was useful in 3 patients. In azole nonresponders, modest responses to intravenous amphotericin B (80%) followed by itraconazole were seen. Surgery removed disease but postoperative pleural aspergillosis was inevitable. Indicators of good long-term medical outcomes were mild symptoms, thin-walled quiescent cavities, residual pleural fibrosis, and normal inflammatory markers.

Background The reported experience of surgical treatment for chronic pulmonary aspergillosis (CPA) mainly focused on simple aspergilloma (SA), few about other types of CPA. The present study aims to evaluate the outcomes of surgical treatment for different types of CPA. Methods We performed a retrospective analysis of 85 patients with CPA who underwent surgery from 2014 to 2020 at Shandong Provincial Chest Hospital. The patients were divided into four types, including SA, chronic cavitary pulmonary aspergillosis (CCPA), chronic fibrosing pulmonary aspergillosis (CFPA), aspergillus nodule (AN). We collected and analyzed the preoperative, perioperative, and postoperative data to evaluate the outcomes of surgical treatment of different types of CPA. Results The four groups had similar age (p = 0.22), symptoms (p = 0.36), lesion location (p = 0.09), VATS rate (p = 0.08), recurrence rate (p = 0.95), and had significant difference in surgical procedures (p < 0.01), time of surgery (p < 0.01), intraoperative blood loss (p < 0.01), postoperative complication (p = 0.01). CFPA (P = 0.01), longer surgical time (P = 0.001), and more intraoperative blood loss (P = 0.004) were risk factors of postoperative complication, more intraoperative blood loss (> 400 ml) was the independent risk factor (OR 13.5, 95% CI 1.6–112.1, P = 0.02). 6 patients relapsed after surgery with a recurrence rate of 7.1%. The mean time to relapse was 14.8 months (2–30 months) after surgery. Relapse occurred in 2 SA patients, 3 CCPA, and 1 CFPA, respectively, while none of the AN patients relapsed. No risk factor for recurrence was found. Conclusions Surgical resection seems safe and effective in the treatment of SA, AN, CCPA with a low complication and recurrence rate, while surgery for CFPA should be limited to selected patients because of its higher complication rate.

In patients with allergic fungal sinusitis, the mainstay of treatment remains surgical removal of allergic mucin and fungal debris. But as a single modality, surgery is associated with high rates of recurrence, so a number of adjunctive medical modalities have been tried, including postoperative corticosteroid therapy. We conducted a study of 63 patients with allergic fungal sinusitis who underwent endoscopic sinus surgery with or without postoperative steroid therapy. A group of 30 patients who had been treated prior to January 2000 had undergone surgery only; their cases were reviewed retrospectively, and they served as historical controls. Another 33 patients who were treated after June 2000 underwent surgery plus oral and nasal steroid therapy. All patients were followed for a minimum of 2 years. Recurrences were seen in 50.0% (15/30) of the no-steroid group and 15.2% (5/33) of the steroid group-a statistically significant difference (p = 0.008). The results of our study strongly support the use of steroids to control allergic fungal sinusitis and prevent its recurrence, and we recommend further study to identify the optimal dosage and duration of therapy.