Combined medical-interventional approaches for the management of complex fungal balls: a case series as a viable alternative in non-surgical patients.

Intracavitary pulmonary aspergilloma is a persistent and life-threatening infection that carries a mortality rate of up to 15%. It occurs when Aspergillus species gain entry to an existing lung cavity. In the absence of definitive treatment, patients may succumb to severe complications such as massive hemoptysis, cachexia, or secondary infections. Aspergillomas often show limited response to antifungal medications, mainly due to insufficient drug concentrations within the cavities. Surgery is frequently the preferred treatment option, but it poses significant risks, and many individuals are ineligible due to underlying health issues. We present the most extensive non-surgical fungal ball cohort to date, managed using an innovative multimodal strategy that combines antifungal therapy before and after bronchoscopic debulking. This was a cross-sectional observational study. For those who cannot undergo surgery, our medical center has pioneered a multimodal approach to aspergilloma resection. This approach combines bronchoscopic endoscopy with antifungal therapy and has been applied successfully to more than 18 patients that are presented in this series. The median age of the cohort was 58 years (range: 32-73), with an equal sex distribution. The mean percent predicted FEV1 was 65.3%. The mean follow-up duration was 3.6 years (range: 0.5-10 years). The cohort receiving antifungals systematically prior to debridement showed a reduction of the pre-existing cavity (40.38 mm versus 34.02 mm, p = 0.021). Across the 18 patients during the follow-up period, 94% remained recurrence-free (defined by symptoms and radiology). Our study fills a critical knowledge gap regarding the significance of initiating antifungal treatment before bronchoscopic debulking and presents a viable approach in these cases for which there is a current unmet therapeutic need.

The use of both medical and interventional methods to treat difficult fungal masses: A collection of cases showing efficacy for patients who can't undergo surgeryIntracavitary pulmonary aspergilloma is a serious and potentially deadly infection with a death rate of up to 15%. It happens when certain types of fungi invade existing lung cavities. Without proper treatment, patients may experience severe complications like heavy bleeding from the lungs, weight loss, or other infections. Traditional antifungal medications often don't work well because they can't reach high enough concentrations in the cavities. Surgery is usually the best option, but it's risky and not possible for many due to other health problems. Our study introduces a new way to treat aspergilloma without surgery. We've treated a significant number of patients using a combination of antifungal drugs and a procedure called bronchoscopic debulking. This involves removing the fungal growth using a thin tube inserted through the airways. Our research involved observing 18 patients treated this way. They were mostly middle-aged, with equal numbers of men and women. Their lung function was moderately impaired, and we followed them for an average of 3.6 years. We found that giving antifungal drugs before the debulking procedure helped reduce the size of the cavities. After treatment, almost all patients remained free of symptoms and signs of recurrence. This study highlights the importance of starting antifungal therapy before bronchoscopic debulking and offers a promising option for patients who can't have surgery.

Effect of chemotherapy, immunotherapy, and targeted therapies on removal of indwelling pleural catheters in non-small cell lung cancer patients with malignant pleural effusions.

BACKGROUND: Indwelling pleural catheters (IPCs) are a mainstay therapy for malignant pleural effusions (MPEs). Many patients treated with IPCs achieve pleurodesis. We aimed to identify the effect of systemic therapies for non-small cell lung cancer (NSCLC) on IPC removal in patients with associated MPEs. METHODS: We completed a retrospective cohort study of adult IPC recipients with metastatic NSCLC at the pleural effusion clinic at the Royal Alexandra Hospital from 2009 to 2020. We used logistic regression to assess the rates of IPC removal and Cox regression to assess the time to IPC removal. RESULTS: 232 patients met inclusion criteria with 248 IPCs reviewed. The overall pleurodesis rate was 42.7% with a median time to pleurodesis of 68 (IQR 38-140) days. In univariate analysis, chemotherapy (OR 1.86, CI 0.99-3.49) and epidermal growth factor receptor (EGFR) targeted therapy (OR 3.81, CI 1.86-7.79) were associated with higher rates of pleurodesis. In multivariate analysis, increased rates of pleurodesis were associated with an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of ≤2 (OR 4.82, CI 2.24-10.37) and EGFR targeted therapy (OR 3.87, CI 1.80-8.32). Earlier IPC removal was associated with EGFR targeted therapy in both univariate (HR 1.84, CI 1.20-2.83) and multivariate analysis (HR 1.86, CI 1.19-2.92). CONCLUSIONS: Treatment with EGFR targeted therapy is associated with increased rates and earlier removal of IPC in patients with NSCLC in our cohort. Further large cohort studies are required to determine if this relationship persists.

Impact of the COVID-19 pandemic on the HIV care continuum: a mixed methods systematic review protocol.

OBJECTIVE: The objective of this systematic review is to synthesize evidence on the impact of the COVID-19 pandemic on the HIV care continuum for persons living with or at risk of living with HIV. INTRODUCTION: The COVID-19 pandemic affected the self-management and care of people living with HIV. Self-regulation to acquire recurring treatment for HIV is essential for managing symptoms as well as viral suppression. Therefore, this review will systematically appraise and synthesize primary literature on the impact of the COVID-19 pandemic on all phases of the HCC for people living with, or at risk of acquiring, HIV. INCLUSION CRITERIA: This systematic review will include quantitative, qualitative, and mixed methods studies. The search will be limited to studies reporting findings from March 2020. Selected studies must focus on one or more steps of the HIV care continuum, which are diagnosis of HIV infection, linkage to care, retention in care, adherence to antiretroviral therapy, and viral suppression. There are no age, gender, or geographic location restrictions for this review. Studies that examined the impact on other diseases as well as HIV will be included only if the data for HIV can be extracted separately. METHODS: The JBI methodology for convergent integrated mixed methods systematic reviews will guide this review. The following databases will be searched: MEDLINE (Ovid), CINAHL (EBSCOhost), CAB Direct, and Embase. Articles will be screened by 2 independent reviewers. In the case of a disagreement between reviewers, a third independent reviewer will resolve the conflict. Articles will be appraised for methodological quality and their data extracted using an original extraction tool created for the study's purpose. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42021285677.

Combination Tissue Plasminogen Activator and DNase for Loculated Malignant Pleural Effusions: A Single-center Retrospective Review.

BACKGROUND: Indwelling pleural catheters (IPCs) are frequently used for the management of malignant pleural effusions (MPEs), but drainage can be impaired by pleural loculations. We aimed to evaluate the safety and effectiveness of intrapleural tissue plasminogen activator (tPA) versus combination tPA-deoxyribonuclease (DNase) in the treatment of loculated MPE. METHODS: We performed a retrospective review of patients with confirmed or presumed MPEs requiring IPC insertion. We compared the efficacy of intrapleural tPA, tPA-DNase, and procedural intervention on pleural fluid drainage. Secondary endpoints included the need for future pleural procedures (eg, thoracentesis, IPC reinsertion, chest tube insertion, or surgical intervention), IPC removal due to spontaneous pleurodesis, and IPC-related complications. RESULTS: Among 437 patients with MPEs, loculations developed in 81 (19%) patients. Twenty-four (30%) received intrapleural tPA, 46 (57%) received intrapleural tPA-DNase, 4 (5%) underwent a procedural intervention, and 7 (9%) received ongoing medical management. tPA improved pleural drainage in 83% of patients, and tPA-DNase improved pleural drainage in 80% of patients. tPA alone may be associated with increased rates of spontaneous pleurodesis compared with tPA-DNase. There was no difference in complications when comparing tPA, combination tPA-DNase, procedural intervention, and no therapy. CONCLUSION: Both intrapleural tPA and combination tPA-DNase appear to be safe and effective in improving pleural fluid drainage in selected patients with loculated MPE, although further studies are needed.

Association between antibiotics and rehospitalization in patients with acute exacerbations of chronic obstructive pulmonary disease discharged from the emergency department.

BACKGROUND: Patients with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are frequently discharged from the emergency department (ED) and treated with antibiotics. The role of antibiotics in the outpatient management of AECOPD is controversial and has never been studied in the ED setting. METHODS: We conducted a secondary analysis of prospectively collected data from the validation study of the Ottawa COPD Risk Scale. We included adult patients with AECOPD who were discharged from six tertiary care EDs in Canada over a two-year period and assessed rates of rehospitalization within 14 days of ED discharge. To examine the association between antibiotic treatment and rehospitalization, we performed multivariable logistic regression and propensity score-matched analyses. RESULTS: A total of 774 patients were included in the analysis. The mean age was 69.4 years, 388 patients (50.1%) were female, and 451 patients (58.3%) were discharged with antibiotics. Twenty-nine (6.4%) and 36 (11.1%) patients returned to hospital with admission in the antibiotic and no antibiotic groups, respectively (unadjusted OR 0.55; 95% CI 0.33-0.92); adjustment for prespecified baseline characteristics using logistic regression yielded OR 0.65; 95% CI 0.38-1.08. In the propensity score-matched analysis comprising of 197 matched pairs, 15 (7.6%) and 19 patients (9.6%) in the antibiotic and no antibiotic groups returned with admission, respectively (OR 0.69; 95% CI 0.29-1.62). CONCLUSION: For patients with AECOPD discharged from the ED, we did not find an association between outpatient treatment with antibiotics and lower rates of rehospitalization after accounting for differences in baseline patient characteristics. However, the small sample size and low observed rate of the primary outcome created substantial risk of Type II error. Until further evidence is available, clinicians should continue prescribing antibiotics for patients with AECOPD based on clinical judgement and current practice guidelines.

RéSUMé: CONTEXTE: Les patients présentant des exacerbations aiguës de maladie pulmonaire obstructive chronique (EAMPOC) sont fréquemment renvoyés du service des urgences (SU) et traités avec des antibiotiques. Le rôle des antibiotiques dans la prise en charge ambulatoire de l'EAMPOC est controversé et n'a jamais été étudié dans le cadre des urgences. MéTHODES: Nous avons effectué une analyse secondaire des données recueillies prospectivement dans le cadre de l'étude de validation de l'échelle de risque de MPOC d'Ottawa. Nous avons inclus des patients adultes atteints d'EAMPOC qui sont sortis de six urgences de soins tertiaires au Canada sur une période de deux ans et avons évalué les taux de réhospitalisation dans les 14 jours suivant la sortie des urgences. Pour examiner l'association entre le traitement antibiotique et la réhospitalisation, nous avons effectué une régression logistique multivariable et des analyses par appariement de score de propension. RéSULTATS: Un total de 774 patients a été inclus dans l'analyse. L'âge moyen était de 69,4 ans, 388 patients (50,1 %) étaient des femmes et 451 patients (58,3 %) sont sortis avec des antibiotiques. Vingt-neuf (6,4 %) et 36 (11,1 %) patients sont retournés à l'hôpital avec admission dans les groupes avec et sans antibiotique, respectivement (OR non ajusté 0,55 ; IC à 95 % 0,33 à 0,92) ; l'ajustement pour les caractéristiques de base préspécifiées à l'aide de la régression logistique a donné un OR de 0,65 ; IC à 95 % 0,38 à 1,08. Dans l'analyse appariée par score de propension comprenant 197 paires appariées, 15 (7,6 %) et 19 (9,6 %) patients des groupes avec et sans antibiotique sont revenus avec une admission, respectivement (OR 0,69 ; IC 95 % 0,29 à 1,62). CONCLUSION: Pour les patients atteints d'AECOPD sortis des urgences, nous n'avons pas trouvé d'association entre le traitement ambulatoire par antibiotiques et des taux plus faibles de réhospitalisation après avoir pris en compte les différences dans les caractéristiques de base des patients. Toutefois, la petite taille de l'échantillon et le faible taux observé du résultat principal ont créé un risque important d'erreur de type II. Jusqu'à ce que d'autres preuves soient disponibles, les cliniciens doivent continuer à prescrire des antibiotiques aux patients atteints d'AECOPD en se basant sur le jugement clinique et les directives de pratique actuelles.

Organizing pneumonia associated with T-cell lymphoma.

A 61-year-old male with a history of coeliac disease was diagnosed with organizing pneumonia (OP) on transbronchial and transthoracic lung biopsies. He then developed refractory coeliac disease type II and haemophagocytic lymphohistiocytosis. Nine months after his initial diagnosis of OP and after multiple biopsies of the lung, duodenum, and bone marrow, he was diagnosed with enteropathy-associated T-cell lymphoma (EATL). Although OP in patients with lymphoma is most commonly attributed to chemotherapeutic agents or bone marrow transplant, it may be seen in the absence of prior anticancer treatment. The mechanism linking OP and lymphoma is unclear but OP could represent a syndrome of T-cell dysfunction or develop as a direct reaction to malignant infiltration of the lung. In patients with atypical presentations, exclusion of an alternate diagnosis must be pursued using surgical lung biopsy, wherever possible. This is the first reported case of OP associated with EATL.

Demographic and clinical predictors of progression and mortality in connective tissue disease-associated interstitial lung disease: a retrospective cohort study.

BACKGROUND: Connective tissue disease-associated interstitial lung disease (CTD-ILD) is associated with reduced quality of life and poor prognosis. Prior studies have not identified a consistent combination of variables that accurately predict prognosis in CTD-ILD. The objective of this study was to identify baseline demographic and clinical characteristics that are associated with progression and mortality in CTD-ILD. METHODS: Patients were retrospectively identified from an adult CTD-ILD clinic. The predictive significance of baseline variables on serial forced vital capacity (FVC), diffusion capacity (DLCO), and six-minute walk distance (6MWD) was assessed using linear mixed effects models, and Cox regression analysis was performed to assess impact on mortality. RESULTS: 359 patients were included in the study. Median follow-up time was 4.0 (IQR 1.5-7.6) years. On both unadjusted and multivariable analysis, male sex and South Asian ethnicity were associated with decline in FVC. Male sex, positive smoking history, and diagnosis of systemic sclerosis (SSc) vs. other CTD were associated with decline in DLCO. Male sex and usual interstitial pneumonia (UIP) pattern predicted decline in 6MWD. There were 85 (23.7%) deaths. Male sex, older age, First Nations ethnicity, and a diagnosis of systemic sclerosis vs. rheumatoid arthritis were predictors of mortality on unadjusted and multivariable analysis. CONCLUSION: Male sex, older age, smoking, South Asian or First Nations ethnicity, and UIP pattern predicted decline in lung function and/or mortality in CTD-ILD. Further longitudinal studies may add to current clinical prediction models for prognostication in CTD-ILD.

Systematic review of content and quality of idiopathic pulmonary fibrosis review articles.

Narrative reviews are frequently accessed; however, the content and quality of review articles on idiopathic pulmonary fibrosis (IPF) have not been assessed. A systematic review assessed content and quality of narrative review articles that addressed the diagnosis or management of IPF and were published from 2001 to 2015. Article recommendations were assessed relative to contemporary IPF guidelines. Quality was assessed using the DISCERN instrument. Articles were predominantly written by physicians and published in respiratory journals. Conflicts of interest and sources of funding were reported in 52% and 24% of reviews, respectively. European authors were more likely to recommend bronchoscopy (adjusted p=0.02) and were more likely to recommend pirfenidone or nintedanib prior to publication of definitive clinical trials (adjusted p=0.04). A total of 39% of management-focused articles suggested therapies that were never recommended in guidelines. Predictors of higher article quality were citation of the contemporary IPF guideline (p=0.01) and more recent publication (p=0.001). Quality of reviews increased over time; however, review articles frequently made discordant recommendations compared to IPF guidelines. These findings indicate the need for authors, peer reviewers, editors and readers to critically appraise the content and quality of narrative reviews on IPF, and the need for frequent guideline updates to reflect new evidence.

The Role of Gut Microbiome in the Pathogenesis of Prostate Cancer: A Prospective, Pilot Study.

OBJECTIVE: To elucidate potential biomarkers or mechanistic principles involved with the gut microbiota and its impact on prostate cancer pathogenesis. MATERIALS AND METHODS: We performed a prospective case-control pilot study evaluating the gut microbiome of 20 men with either benign prostatic conditions (n = 8) or intermediate or high risk clinically localized prostate cancer (Gleason ≥4 + 3 cN0M0) (n = 12) undergoing care at tertiary referral center from September 1, 2015 to March 1, 2016. Key exclusion criteria included recent antibiotic use, significant gastrointestinal disorders, hormonal or systemic therapy for prostate cancer. Computational genomics analysis was performed on collected stool samples using MetaPhlAn2 and HUMAnN2 platforms. Linear discriminant analysis effect size method was used to support high-dimensional class comparisons to find biologically relevant features. Kruskal-Wallis sum-rank test was used to detect features with significant differential abundance with respect to class, with biological consistency investigated using a set of pairwise tests among subclasses using the Wilcoxon rank-sum test, both to an α ≤0.05. RESULTS: Higher relative abundance of Bacteriodes massiliensis was seen in prostate cancer cases compared to controls. Faecalibacterium prausnitzii and Eubacterium rectalie had higher relative abundance among controls. Biologically significant differences were also found in relative gene, pathway, and enzyme abundance. CONCLUSION: Biologically significant differences exist in the gut microbial composition of men with prostate cancer compared to benign controls. These differences may play a role in the pathobiology of prostate cancer, and warrant further exploration.

Ectopic ACTH syndrome complicated by multiple opportunistic infections treated with percutaneous ablation of the adrenal glands.

Ectopic adrenocorticotropic hormone (ACTH)-related Cushing's syndrome can lead to multiple complications including severe immunosuppression. If the ACTH-secreting tumour cannot be found, definitive treatment is surgical adrenalectomy, typically followed by glucocorticoid replacement. Here, we present a case of fulminant respiratory failure secondary to coinfection with Pneumocystis jirovecii and cytomegalovirus in a patient with ectopic ACTH-dependent Cushing's syndrome with occult primary. Due to significant deconditioning, she was unable to undergo definitive adrenalectomy and instead underwent percutaneous microwave ablation of the adrenal glands.

Reproductive Health Issues for Adults with a Common Genomic Disorder: 22q11.2 Deletion Syndrome.

22q11.2 deletion syndrome (22q11.2DS) is the most common microdeletion syndrome in humans. Survival to reproductive age and beyond is now the norm. Several manifestations of this syndrome, such as congenital cardiac disease and neuropsychiatric disorders, may increase risk for adverse pregnancy outcomes in the general population. However, there are limited data on reproductive health in 22q11.2DS. We performed a retrospective chart review for 158 adults with 22q11.2DS (75 male, 83 female; mean age 34.3 years) and extracted key variables relevant to pregnancy and reproductive health. We present four illustrative cases as brief vignettes. There were 25 adults (21 > age 35 years; 21 female) with a history of one or more pregnancies. Outcomes for women with 22q11.2DS, compared with expectations for the general population, showed a significantly elevated prevalence of small for gestational age liveborn offspring (p < 0.001), associated mainly with infants with 22q11.2DS. Stillbirths also showed elevated prevalence (p < 0.05). Not all observed adverse events appeared to be attributable to transmission of the 22q11.2 deletion. Recurring issues relevant to reproductive health in 22q11.2DS included the potential impact of maternal morbidities, inadequate social support, unsafe sexual practices, and delayed diagnosis of 22q11.2DS and/or lack of genetic counseling. These preliminary results emphasize the importance of early diagnosis and long term follow-up that could help facilitate genetic counseling for men and women with 22q11.2DS. We propose initial recommendations for pre-conception management, educational strategies, prenatal planning, and preparation for possible high-risk pregnancy and/or delivery.