This study was conducted to get a complete clinical and mycological picture of invasive aspergillosis (IA) in respiratory medicine ICU of a tertiary care hospital.
From the cohort of 235 patients ...only one had proven IA. Based on AspICU algorithm, 21 had putative IA (8.9%), 12 were colonised (5.1%).
Adjusting the confounding factors, significant risk factors for IA were chronic obstructive pulmonary disease (COPD), temperature of ≥38°C, pneumonia and acute respiratory distress syndrome (ARDS). The best predictor of IA was AspICU algorithm (AUC, 1) followed by serum galactomannan antigen (GM) cut-off (≥1.24) calculated based on AspICU algorithm (AUC, 0.822). For 37% of patients, IA diagnoses was made earlier with serum GM than radiology. There were 70/235 (29.8%) deaths within 30 days of enrolment in the study. Aspergillus culture positivity (34/235, 14.5%) was associated with very high mortality (27/34, 79.4%), (p<0.05). The best predictor of mortality was GM cut-off (≥1.24) calculated based on AspICU algorithm (AUC, 0.835).
This study imparts the focus on relatively underestimated Aspergillus infections prevalent in ICUs. The AspICU algorithm was found to be useful over others for IA diagnosis. The prognostic usefulness of serum GM antigen detection test highlighted overlooking the same may not be rewarding for the outcome of IA suspected ICU subpopulation.
Emerging evidence indicates that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals are at an increased risk for coinfections; therefore, physicians need to be ...cognizant about excluding other treatable respiratory pathogens. Here, we report coinfection with SARS-CoV-2 and other respiratory pathogens in patients admitted to the coronavirus disease (COVID) care facilities of an Indian tertiary care hospital. From June 2020 through January 2021, we tested 191 patients with SARS-CoV-2 for 33 other respiratory pathogens using an fast track diagnostics respiratory pathogen 33 (FTD-33) assay. Additionally, information regarding other relevant respiratory pathogens was collected by reviewing their laboratory data. Overall, 13 pathogens were identified among patients infected with SARS-CoV-2, and 46.6% (89/191) of patients had coinfection with one or more additional pathogens. Bacterial coinfections (41.4% 79/191) were frequent, with Staphylococcus aureus being the most common, followed by Klebsiella pneumoniae. Coinfections with SARS-CoV-2 and Pneumocystis jirovecii or Legionella pneumophila were also identified. The viral coinfection rate was 7.3%, with human adenovirus and human rhinovirus being the most common. Five patients in our cohort had positive cultures for Acinetobacter baumannii and K. pneumoniae, and two patients had active Mycobacterium tuberculosis infection. In total, 47.1% (90/191) of patients with coinfections were identified. The higher proportion of patients with coinfections in our cohort supports the systemic use of antibiotics in patients with severe SARS-CoV-2 pneumonia with rapid de-escalation based on respiratory PCR/culture results. The timely and simultaneous identification of coinfections can contribute to improved health of COVID-19 patients and enhanced antibiotic stewardship during the pandemic. IMPORTANCE Coinfections in COVID-19 patients may worsen disease outcomes and need further investigation. We found that a higher proportion of patients with COVID-19 were coinfected with one or more additional pathogens. A better understanding of the prevalence of coinfection with other respiratory pathogens in COVID-19 patients and the profile of pathogens can contribute to effective patient management and antibiotic stewardship during the current pandemic.
•The basic reproduction number R0 for India was 2.08.•The Rt for India reduced to 1.16 on 22 April, about a month into the nation-wide lockdown.•A gradual lockdown relaxation farther after the first ...peak has passed is beneficial.•Testing and isolation prevent more secondary infections when social restrictions are relaxed.•Ramping up testing has many benefits and is much more economically feasible than extending lockdowns.
India imposed one of the world’s strictest population-wide lockdowns on March 25, 2020 for COVID-19. We estimated epidemiological parameters, evaluated the effect of control measures on the epidemic in India, and explored strategies to exit lockdown.
We obtained patient-level data to estimate the delay from onset to confirmation and the asymptomatic proportion. We estimated the basic and time-varying reproduction number (R0 and Rt) after adjusting for imported cases and delay to confirmation using incidence data from March 4 to April 25, 2020. Using a SEIR-QDPA model, we simulated lockdown relaxation scenarios and increased testing to evaluate lockdown exit strategies.
R0 for India was estimated to be 2·08, and the Rt decreased from 1·67 on March 30 to 1·16 on April 22. We observed that the delay from the date of lockdown relaxation to the start of the second wave increases as lockdown is extended farther after the first wave peak—this delay is longer if lockdown is relaxed gradually.
Aggressive measures such as lockdowns may be inherently enough to suppress an outbreak; however, other measures need to be scaled up as lockdowns are relaxed. Lower levels of social distancing when coupled with a testing ramp-up could achieve similar outbreak control as an aggressive social distancing regime where testing was not increased.
Statins and aspirin have been proposed for treatment of COVID-19 because of their anti-inflammatory and anti-thrombotic properties. Several observational studies have shown favourable results. There ...is a need for a randomised controlled trial. In this single-center, open-label, randomised controlled trial, 900 RT-PCR positive COVID-19 patients requiring hospitalisation, were randomly assigned to receive either atorvastatin 40 mg (Group A, n = 224), aspirin 75 mg (Group B, n = 225), or both (Group C, n = 225) in addition to standard of care for 10 days or until discharge whichever was earlier or only standard of care (Group D, n = 226). The primary outcome variable was clinical deterioration to WHO Ordinal Scale for Clinical Improvement greater than or equai to 6. The secondary outcome was change in serum C-reactive protein, interleukin-6, and troponin I. The primary outcome occurred in 25 (2.8%) patients: 7 (3.2%) in Group A, 3 (1.4%) in Group B, 8 (3.6%) in Group C, and 7 (3.2%) in Group D. There was no difference in primary outcome across the study groups (P = 0.463). Comparison of all patients who received atorvastatin or aspirin with the control group (Group D) also did not show any benefit Atorvastatin: HR 1.0 (95% CI 0.41-2.46) P = 0.99; Aspirin: HR 0.7 (95% CI 0.27-1.81) P = 0.46. The secondary outcomes revealed lower serum interleukin-6 levels among patients in Groups B and C. There was no excess of adverse events. Among patients admitted with mild to moderate COVID-19 infection, additional treatment with aspirin, atorvastatin, or a combination of the two does not prevent clinical deterioration.
Objective
Programmed death‐ligand 1 (PD‐L1) immunohistochemistry (IHC) is essential in patients of advanced non‐small‐cell lung cancer to determine eligibility for immunotherapy. PD‐L1 IHC assays ...have been clinically validated only on formalin‐fixed paraffin‐embedded tissue; however, lung cancer is frequently diagnosed on cytology. PD‐L1 immunocytochemistry (ICC) has shown high concordance of immunoexpression between cytology samples and paired small biopsies. Feasibility of liquid‐based cytology (LBC) smears for PD‐L1 ICC has not been analysed previously.
Methods
PD‐L1 ICC and IHC (clone SP263) were performed on paired LBC smears and small biopsies, respectively, in patients with advanced non‐small‐cell lung cancer. Cases with fewer than 100 viable tumour cells on LBC smear/biopsy were excluded from analysis. PD‐L1 was interpreted positive when 25% or more tumour cells showed membranous and/or cytoplasmic protein expression of any intensity greater than background staining.
Results
A total of 26 patients, harbouring adenocarcinomas (50%) and squamous cell carcinomas (50%), had available bronchial brushings/washings processed as LBC smears and concurrently obtained endobronchial biopsies. PD‐L1 IHC was interpreted positive in 46% (12/26) biopsies. PD‐L1 ICC was interpreted positive in 35% (9/26) LBC smears, all of which were IHC‐positive. No IHC‐negative case was positive on cytology. The overall concordance between LBC smears and small biopsies was 88.4%.
Conclusion
PD‐L1 ICC can be performed on LBC processed smears, with certain challenges in interpretation inherent to LBC smears and their processing methods. Nevertheless, they represent a potential resource for ICC, especially when alternate histology material is not available. Future studies are required to validate the predictive value of PD‐L1 ICC on LBC smears.
Analysis of PD‐L1 expression in liquid based cytology samples and matched biopsies in advanced stage of NSCLC.
CD4(+)CD25(+)Foxp3(+) regulatory T cells (Treg) and programmed death-1 (PD-1) molecules have emerged as pivotal players in immune suppression of chronic diseases. However, their impact on the disease ...severity, therapeutic response and restoration of immune response in human tuberculosis remains unclear. Here, we describe the possible role of Treg cells, their M. tuberculosis driven expansion and contribution of PD-1 pathway to the suppressive function of Treg cells among pulmonary tuberculosis (PTB) patients. Multicolor flow cytometry, cell culture, cells sorting and ELISA were employed to execute the study. Our results showed significant increase in frequency of antigen-reactive Treg cells, which gradually declined during successful therapy and paralleled with decline of M. tuberculosis-specific IL-10 along with elevation of IFN-γ production, and raising the IFN-γ/IL-4 ratio. Interestingly, persistence of Treg cells tightly correlated with MDR tuberculosis. Also, we show that blocking PD-1/PD-L1 pathway abrogates Treg-mediated suppression, suggesting that the PD-1/PD-L1 pathway is required for Treg-mediated suppression of the antigen-specific T cells. Treg cells possibly play a role in dampening the effector immune response and abrogating PD-1 pathway on Treg cells significantly rescued protective T cell response, suggesting its importance in immune restoration among tuberculosis patients.
Lung cancer continues to be a menace to the managing clinician in spite of several advances in the diagnostics and therapeutics of this dreaded disease. Since the recognition of epidermal growth ...factor receptor (EGFR) exon 19 and 21 mutations in the pathogenesis of non-small cell lung cancer (NSCLC) as driver mutation, substantial progress has been made in terms of diagnosis as well as management protocols for nonsquamous NSCLC. The concept of mutation testing in blood or blood products is termed as a liquid biopsy. ...there is a growing utility of rapid plasma genotyping or “liquid biopsies” which employs circulating tumor DNA (ctDNA) in peripheral blood for molecular profiling. Liquid biopsy, in this sense, represents the tumor burden as a whole rather than a part of it. ...digital droplet PCR can determine the absolute quantity of mutant EGFR levels in plasma samples and can also be used to monitor treatment response or disease progression serially.
Coronavirus disease-2019 (COVID-19) may lead to hypoxemia, requiring intensive care in many patients. Awake prone positioning (PP) is reported to improve oxygenation and is a relatively safe ...modality. We performed a systematic review of the literature to evaluate the available evidence and performed meta-analysis of the effect of awake PP in non-intubated patients on improvement in oxygenation and reducing the need for intubation. We searched the PubMed and EMBASE databases to identify studies using awake PP as a therapeutic strategy in the management of COVID-19. Studies were included if they reported respiratory outcomes and included five or more subjects. The quality of individual studies was assessed by the Qualsyst tool. A meta-analysis was performed to estimate the proportion of patients requiring intubation. The degree of improvement in oxygenation parameters (PaO2: FiO2 or PaO2 or SpO2) was also calculated. Sixteen studies (seven prospective trials, three before-after studies, six retrospective series) were selected for review. The pooled proportion of patients who required mechanical ventilation was 0.25 (95% confidence interval (CI) 0.16-0.34). There was a significant improvement in PaO2: FiO2 ratio, PaO2, and SpO2 during awake PP. To conclude, there is limited evidence to support the efficacy of awake PP for the management of hypoxemia in COVID-19. Further RCTs are required to study the impact of awake PP on key parameters like avoidance of mechanical ventilation, length of stay, and mortality.
The effective treatment modalities for severe coronavirus disease 2019 (COVID-19) are needed. As the primary cause of mortality is a hyperinflammatory state, the interleukin-6 antagonist tocilizumab ...has been used in multiple clinical studies. We conducted this systematic review and meta-analysis to estimate the effectiveness of tocilizumab in reduction of mortality due to COVID-19. A systematic search of the Pubmed and Embase databases was performed to extract randomized controlled trials (RCTs) regarding the use of tocilizumab therapy for COVID-19. An overall pooled mortality analysis was performed, and odds ratios were reported. Cochrane risk of bias assessment tool was used to assess the risk of bias. Heterogeneity was assessed using the I2 statistic. Nine RCTs, including 6489 patients, were selected for meta-analysis. Seven trials reported 28-day mortality, and one trial each reported 21-day and 30-day mortality. There were 846 deaths among 3358 participants in the steroid group while 943 deaths among 3131 patients randomized to the control group (random-effects odds ratio 0.87, 95% confidence interval 0.73-1.03, p=0.11). There was some heterogeneity among the trials as the I2 value was 15%, with a p-value of 0.31. There was a reduction in the need for ICU admission in the tocilizumab group. A higher risk of secondary infections was noted in the tocilizumab group (fixed-effects odds ratio 0.72, 95% confidence interval 0.55-0.95, p=0.02). This meta-analysis of RCTs demonstrated that the use of tocilizumab was not associated with a reduction in all-cause mortality in patients with COVID-19 and had higher odds of secondary infections.
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