Prevalence of co-existent COVID-19-associated pulmonary aspergillosis (CAPA) and its impact on early mortality in patients with COVID-19-associated pulmonary mucormycosis (CAPM).

BACKGROUND: Data on mixed mould infection with COVID-19-associated pulmonary aspergillosis (CAPA) and COVID-19-associated pulmonary mucormycosis (CAPM) are sparse. OBJECTIVES: To ascertain the prevalence of co-existent CAPA in CAPM (mixed mould infection) and whether mixed mould infection is associated with early mortality (≤7 days of diagnosis). METHODS: We retrospectively analysed the data collected from 25 centres across India on COVID-19-associated mucormycosis. We included only CAPM and excluded subjects with disseminated or rhino-orbital mucormycosis. We defined co-existent CAPA if a respiratory specimen showed septate hyphae on smear, histopathology or culture grew Aspergillus spp. We also compare the demography, predisposing factors, severity of COVID-19, and management of CAPM patients with and without CAPA. Using a case-control design, we assess whether mixed mould infection (primary exposure) were associated with early mortality in CAPM. RESULTS: We included 105 patients with CAPM. The prevalence of mixed mould infection was 20% (21/105). Patients with mixed mould infection experienced early mortality (9/21 [42.9%] vs. 15/84 [17.9%]; p = 0.02) and poorer survival at 6 weeks (7/21 [33.3] vs. 46/77 [59.7%]; p = 0.03) than CAPM alone. On imaging, consolidation was more commonly encountered with mixed mould infections than CAPM. Co-existent CAPA (odds ratio [95% confidence interval], 19.1 [2.62-139.1]) was independently associated with early mortality in CAPM after adjusting for hypoxemia during COVID-19 and other factors. CONCLUSION: Coinfection of CAPA and CAPM was not uncommon in our CAPM patients and portends a worse prognosis. Prospective studies from different countries are required to know the impact of mixed mould infection.

Dextromethorphan premedication in the alleviation of cough during flexible bronchoscopy in adults: A randomized double-blind placebo-controlled trial.

BACKGROUND AND OBJECTIVE: Cough is invariably encountered during flexible bronchoscopy despite sedation and topical anaesthetics. The ideal cough suppressant during flexible bronchoscopy is not known. We assessed the role of dextromethorphan premedication in relieving the cough during flexible bronchoscopy in adults. METHODS: In this single-centre study, we randomized patients aged ≥18 years to receive dextromethorphan syrup 30 ml (90 mg) or an equal volume of placebo 1 h before the procedure. Patients rated their cough severity and discomfort on a visual analogue scale at the end of the procedure. Bronchoscopists also rated cough severity at the end of the procedure. RESULTS: Out of 112 patients screened, 94 patients (median (interquartile range [IQR]) age 51 (36.25-60.75) years, male: female 2.13:1) were randomized to either the dextromethorphan (n = 47) or placebo (n = 47) groups. The patients-rated median (IQR) cough scores at the end of the procedure were 15 (10-23) mm in dextromethorphan versus 20 (12-45.5) mm in placebo groups (p = 0.03). Patients-rated median cough scores at 1 h (5 mm vs. 6 mm, p = 0.21), discomfort scores (12.5 mm vs. 12.5 mm, p = 0.49), and midazolam and lignocaine usage were similar between the two groups. The bronchoscopist-rated median cough score was non-significantly lower in the intervention compared to the placebo (26 mm vs. 35 mm, p = 0.09) groups. CONCLUSION: Dextromethorphan premedication 1 h before flexible bronchoscopy may have an additive effect on cough suppression under conscious sedation and topical lignocaine. Further trials are needed to reiterate our findings with certainty.

Spectrum of Bacterial Pathogens in Critical COVID-19 Patients Admitted in Intensive Care Units of a Tertiary Care Hospital During the First and Second Wave of the Pandemic.

OBJECTIVE: This study intends to compare the clinical characteristics and the prevalence and spectrum of bacterial pathogens in COVID-19 patients admitted to ICU during the first and second waves at a tertiary care, teaching and referral hospital of eastern India. METHOD: This is a hospital-based retrospective study which analysed demographic details, clinical profile and bacterial culture results of severe and critically ill COVID-19 patients admitted in intensive care units (ICU) during April -Oct 2020 (1st wave) and April -July 2021 (2nd wave). RESULT: The patients admitted during the 2nd wave were comparatively older and had multiple comorbidities compared to the 1st wave. (23.8%) (45/189) and 50% (173/346) of the COVID-19 patients admitted to ICU developed bacterial infection during the 1st and 2nd wave respectively. Overall, there was predominance of multidrug resistant Gram negative bacilli in both the waves. There was increased isolation of intrinsic colistin resistant microorganisms. CONCLUSION: Multidrug resistant Gram negative bacterial infections, remain a dreaded complication in severe and critically ill hospitalised COVID-19 patients requiring ICU care and high usage of colistin spirals the emergence and spread of pathogens intrinsically resistant to colistin.

Tuberculous splenic abscess in the immunocompetent host: a report and review of literature.

Tubercular splenic abscess is rare, particularly in immunocompetent patients. Diagnostic difficulties usually arise in patients with tubercular splenic abscess because of its non-specific presentation. We report an elderly male who presented with cough and fever and had pulmonary infiltrates suspicious of tuberculosis. Bronchoalveolar lavage microbiology including XpertMTB/Rif assay was non-contributory. Contrast enhanced computed tomography scan of abdomen revealed multiple non-enhancing lesions in the spleen. Ultrasound guided splenic aspirate revealed pus that was positive for Mycobacterium tuberculosis in XpertMTB/Rif assay confirming the diagnosis of tuberculosis.

ROS1 positive non-small cell lung cancer with pulmonary embolism in a 22-year woman.

ROS1-rearrangement occurs in 1-2% of non-small cell lung cancer (NSCLC). This mutation is predominantly seen in relatively young, non-smoker, female with adenocarcinoma. Association of pulmonary embolism with ROS1-rearranged NSCLC has been suggested. We report a case of a 22-year-old woman with ROS1-positive NSCLC and pulmonary embolism. This case possibly represents the youngest patient in the literature.

A case of systemic melioidosis: unravelling the etiology of chronic unexplained fever with multiple presentations.

Melioidosis, caused by the environmental saprophyte, Burkholderia pseudomallei, is an important public health problem in Southeast Asia and Northern Australia. It is being increasingly reported from other parts, including India, China, and North and South America expanding the endemic zone of the disease. We report a case of systemic melioidosis in a 58-year-old diabetic, occupationally-unexposed male patient, who presented with chronic fever, sepsis, pneumonia, pleural effusion and subcutaneous abscess, was undiagnosed for long, misidentified as Pseudomonas aeruginosa infection elsewhere, but was saved due to correct identification of the etiologic agent and timely institution of appropriate therapy at our institute. A strong clinical and microbiological suspicion for melioidosis should be considered in the differential diagnosis of acute pyrexia of unknown origin, acute respiratory distress syndrome and acute onset of sepsis, especially in the tropics.

A 37-Year-Old Man With Dyspnea, Bilateral Lung Consolidation, and a Tracheal Mass.

CASE PRESENTATION: A 37-year-old man presented to the ED with symptoms of productive cough, self-reported fever, and shortness of breath for the past 15 days. He was placed on noninvasive mechanical ventilation for respiratory distress. IV piperacillin-tazobactam and inhaled bronchodilators were promptly administered, and he was subsequently transferred to the respiratory ICU for further care. He had no history of bowel and bladder disturbance, altered sensorium, swelling of feet, or abdominal distention. He never used tobacco and denied a history of TB. Medical history was notable for recurrent hospitalizations and administration of multiple courses of antibiotics in the past for similar complaints. He often used inhaled bronchodilators/corticosteroids when clinically stable to relieve symptoms.

VCL::ROS1: A Novel ROS1 Oncogenic Fusion Detected on Next Generation Sequencing.

Advanced Non-Small Cell Lung Carcinoma (NSCLC) patients with ROS1 gene rearrangement have shown significant therapeutic responses to tyrosine kinase inhibitors approved by the US Food and Drug Administration, with approximately 40 fusion partners documented in the existing literature. Our report highlights a novel fusion partner of ROS1 that has demonstrated a conclusive response to the current standard of treatment.

Health system factors related to COVID-19 mortality in Eastern India: Hospital-based cross-sectional study.

Introduction: Mortality from coronavirus disease 2019 (COVID-19) pandemic has left footprints across all ages and socio-economic strata. The deaths because of COVID-19 are usually multi-factorial. The study aimed to assess the health system factors related to COVID-19-related deaths. Materials and Methods: A hospital-based retrospective study was conducted at a tertiary care hospital of eastern India. A total of 272 COVID-19 deaths that occurred between April and November 2020 were investigated. Data were extracted from Medical Record Department, and telephonic interviews were conducted to assess the different delays related to death. Data were analysed using Statistical Package for Social Sciences. Travel time, travel distance, delay in testing, and delay in receiving quality care were presented as median with inter-quartile range. Results: Complete information could be collected from 243 COVID deaths of the 272 deaths (89.3%). The duration of hospital stay was 1-7 days for 42% of the deceased. The median travel time was 120 min, and the median distance travelled was 60 km. The median time to receive first attention of health care workers was 10 minutes. There was hardly any delay in reporting of test results, whereas the median time from symptoms to test and the median time from symptoms to admission were 4 days each. Conclusion: Health system factors related to death of COVID-19 need to be addressed to avoid the avoidable deaths during the pandemic situation. The resilience of the health system can be helpful in reducing death toll in a low-resource country like India.

Predictors of Mortality among Patients Hospitalized with COVID-19 during the First Wave in India: A Multisite Case-Control Study.

Severe acute respiratory syndrome coronavirus 2 disease (COVID-19) has caused more than 6 million deaths globally. Understanding predictors of mortality will help in prioritizing patient care and preventive approaches. This was a multicentric, unmatched, hospital-based case-control study conducted in nine teaching hospitals in India. Cases were microbiologically confirmed COVID-19 patients who died in the hospital during the period of study and controls were microbiologically confirmed COVID-19 patients who were discharged from the same hospital after recovery. Cases were recruited sequentially from March 2020 until December-March 2021. All information regarding cases and controls was extracted retrospectively from the medical records of patients by trained physicians. Univariable and multivariable logistic regression was done to assess the association between various predictor variables and deaths due to COVID-19. A total of 2,431 patients (1,137 cases and 1,294 controls) were included in the study. The mean age of patients was 52.8 years (SD: 16.5 years), and 32.1% were females. Breathlessness was the most common symptom at the time of admission (53.2%). Increasing age (adjusted odds ratio [aOR]: 46-59 years, 3.4 [95% CI: 1.5-7.7]; 60-74 years, 4.1 [95% CI: 1.7-9.5]; and ≥ 75 years, 11.0 [95% CI: 4.0-30.6]); preexisting diabetes mellitus (aOR: 1.9 [95% CI: 1.2-2.9]); malignancy (aOR: 3.1 [95% CI: 1.3-7.8]); pulmonary tuberculosis (aOR: 3.3 [95% CI: 1.2-8.8]); breathlessness at the time of admission (aOR: 2.2 [95% CI: 1.4-3.5]); high quick Sequential Organ Failure Assessment score at the time of admission (aOR: 5.6 [95% CI: 2.7-11.4]); and oxygen saturation < 94% at the time of admission (aOR: 2.5 [95% CI: 1.6-3.9]) were associated with mortality due to COVID-19. These results can be used to prioritize patients who are at increased risk of death and to rationalize therapy to reduce mortality due to COVID-19.

Post COVID sequelae among COVID-19 survivors: insights from the Indian National Clinical Registry for COVID-19.

INTRODUCTION: The effects of COVID-19 infection persist beyond the active phase. Comprehensive description and analysis of the post COVID sequelae in various population groups are critical to minimise the long-term morbidity and mortality associated with COVID-19. This analysis was conducted with an objective to estimate the frequency of post COVID sequelae and subsequently, design a framework for holistic management of post COVID morbidities. METHODS: Follow-up data collected as part of a registry-based observational study in 31 hospitals across India since September 2020-October 2022 were used for analysis. All consenting hospitalised patients with COVID-19 are telephonically followed up for up to 1 year post-discharge, using a prestructured form focused on symptom reporting. RESULTS: Dyspnoea, fatigue and mental health issues were reported among 18.6%, 10.5% and 9.3% of the 8042 participants at first follow-up of 30-60 days post-discharge, respectively, which reduced to 11.9%, 6.6% and 9%, respectively, at 1-year follow-up in 2192 participants. Patients who died within 90 days post-discharge were significantly older (adjusted OR (aOR): 1.02, 95% CI: 1.01, 1.03), with at least one comorbidity (aOR: 1.76, 95% CI: 1.31, 2.35), and a higher proportion had required intensive care unit admission during the initial hospitalisation due to COVID-19 (aOR: 1.49, 95% CI: 1.08, 2.06) and were discharged at WHO ordinal scale 6-7 (aOR: 49.13 95% CI: 25.43, 94.92). Anti-SARS-CoV-2 vaccination (at least one dose) was protective against such post-discharge mortality (aOR: 0.19, 95% CI: 0.01, 0.03). CONCLUSION: Hospitalised patients with COVID-19 experience a variety of long-term sequelae after discharge from hospitals which persists although in reduced proportions until 12 months post-discharge. Developing a holistic management framework with engagement of care outreach workers as well as teleconsultation is a way forward in effective management of post COVID morbidities as well as reducing mortality.

Clinico-Epidemiological Characteristics of Healthcare Workers with SARS-CoV-2 Infection during the First and Second Waves in a Teaching Hospital from Eastern India: A Comparative Analysis.

In this retrospective observational study, we have performed a comparative analysis of the demographic, clinical and epidemiological characteristics of the HCWs affected with SARS-CoV-2 infection during first two waves in India. The overall prevalence of SARS-CoV-2 infection among HCWs was found to be 15.24% (14.20-16.33) and 23.38% (22.14-25.65) during first and second waves respectively. The second wave showed an adjusted odds ratio of 0.04(0.02-0.07) and 2.09(1.49-2.93) for hospitalization and being symptomatic, respectively. We detected significantly higher level of C-reactive protein (CRP) among admitted HCWs during the second wave (5.10 -14.60 mg/dl) as compared to the first wave (2.00 - 2.80 mg/dl). Our study found the relative risk of SARS-CoV-2 reinfection among HCWs during the second wave to be 0.68 [0.57-0.82, p < 0.001)]. Although, the prevalence of SARS CoV-2 infection and risk of being symptomatic was higher during second wave, the risk of hospitalization was less when compared with the first wave.

Robust home brew fragment sizing assay for detection of MET exon 14 skipping mutation in non-small cell lung cancer patients in resource constrained community hospitals.

BACKGROUND: A mutation/deletion involving donor or acceptor sites for exon 14 results in splicing out of exon 14 of the mesenchymal epithelial transition (MET) gene and is known as "MET exon 14 skipping" (ΔMET14). The two recent approvals with substantial objective responses and improved progression-free survival to MET inhibitors namely capmatinib and tepotinib necessitate the identification of this alteration upfront. We herein describe our experience of ΔMET14 detection by an mRNA-based assay using polymerase chain reaction followed by fragment sizing. METHODS: This is a home brew assay which was developed with the concept that the transcripts from true ΔMET14 will be shorter by ~140 bases than their wild type counterparts. The cases which were called MET exon 14 skipping positive on next-generation sequencing (NGS) were subjected to this assay, along with 13 healthy controls in order to establish the validity for true negatives. RESULTS: Thirteen cases of ΔMET14 mutation were detected on NGS using RNA-based sequencing. Considering NGS as a gold standard, the sizing assay using both gel and capillary electrophoresis that showed 100% specificity for both with concordance rates of 84.6% and 88.2% with NGS, respectively, were obtained. CONCLUSIONS: Owing to the cost-effective nature and easy to use procedures, this assay will prove beneficial for small- and medium-sized laboratories where skilled technical personnel and NGS platforms are unavailable.

Comparison of endobronchial ultrasound-guided transbronchial needle aspiration cytology versus cell blocks in adults with undiagnosed mediastinal lymphadenopathy.

INTRODUCTION: Retrospective studies have shown improved diagnostic yield of combined cytology and cell blocks specimens from endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) with variable additional yields in cell blocks. In this prospective study, we assessed the diagnostic performance of cytology and cell blocks in patients undergoing EBUS-TBNA. METHODS: This was a single-center, cross-sectional study conducted between December 2017 and November 2019 including patients aged ≥18 years with mediastinal lymphadenopathy. EBUS-TBNA was performed under conscious sedation using 22G needles. Both cytology smears and cell blocks by the tissue coagulum clot technique were prepared for each patient without rapid on-site evaluation. RESULTS: Data were analyzed for 93 patients (mean age 54.25 ± 13.7 years, 73 males) where both cytology and cell blocks were available. Sample adequacy was 100%. Overall diagnostic yield either by cytology or cell block was 83%. Cytology yield was 79.6%, whereas cell block was diagnostic in 73% of patients (P < 0.001). The overall additional yield of cell blocks was 3.2%. Cell blocks had additional yields of 1.8%, 0%, and 14.3% in malignancy, tuberculosis, and sarcoidosis, respectively. Tumor histology was better identified in 76% of positive cell blocks, and accurate histological subtyping was possible in 32.6% cases. Immunohistochemistry was feasible in 82.5% of all positive cell blocks, and these were judged to be adequate for the mutational analysis. CONCLUSIONS: Compared to cytology, EBUS-TBNA cell blocks did not significantly increase the overall diagnostic yield in unselected patients. However, cell blocks are beneficial in the characterization of tumor morphology and histological subtyping of lung cancer.

Pulmonary anaplastic large-cell lymphoma: A case-based systematic review of world literature.

We describe a case of ALK1 negative (-) pulmonary anaplastic large-cell lymphoma (pALCL) in an adult female with an unfavorable outcome following combination chemotherapy and present a systematic review of 39 such sporadic cases reported over the past 28 years (1990-2018). pALCL occurred in 26 males and 13 females (median age, 43 years [5-81]) and 13/39 (33.33%) were ≤18 years. The lesions were endobronchial in 21 (53.85%) and parenchymal in 18 (46.15%) cases. Twenty-six cases were ALK1-; 13 were ALK1+ (positive); and 27/34 cases had a T cell phenotype (where tested). ALK- cases were characterized by higher age (P = 0.012) at presentation, more B symptoms (P = 0.002), and more parenchymal than endobronchial lesions (P = 0.039). The median survival (N = 29/39) was 60 months; pediatric group had a better survival than adult/elderly group (log-rank, P = 0.026). pALCL is rare and may have a distinct biological behavior.