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Coronavirus disease 2019 (COVID-19) is a febrile respiratory illness that has spread rampantly across the globe and has emerged as one of the biggest pandemics of all time. Besides the direct effects of COVID-19 on mortality, collateral impacts on diagnosis and management of acute febrile illnesses (AFI) is a matter of great concern. The overlap in presentation, shunting of available resources and infection control precautions in patients with suspected COVID-19 result in a significant delay in diagnoses and management of AFI. This review highlights the challenges in the management of acute febrile illness during COVID pandemic and possible solutions for the same. [ABSTRACT FROM AUTHOR]

Mucormycosis is an uncommon aggressive fungal infection usually seen in immunocompromised hosts or patients with burns and trauma. The common presentations include rhino-orbital-cerebral and pulmonary involvement. Osteoarticular involvement is a rare presentation of this disease. We present two cases of osteoarticular mucormycosis of pelvis and long bones of the lower limb, one in a patient with burn injury and other one in a patient with chronic granulomatous disease, hitherto a rarely reported association. Delayed diagnosis in a setting where tuberculosis is a common cause of chronic osteomyelitis, challenges in medical and surgical management of these patients are discussed in this report. [ABSTRACT FROM AUTHOR]

We report a case of advanced human immunodeficiency virus (HIV) infection with multiple opportunistic infections (Pneumocystis carinii pneumonia, cryptosporidiosis, oesophagal candidiasis and cytomegalovirus infection). The patient was presumed to be adherent on antiretroviral therapy (ART) and was initiated on respective treatments for the opportunistic infections but continued to deteriorate. On further reviewing, he was found to be poorly adherent to ART and was advised enhanced adherence counselling after which his condition improved. We report this case to emphasize the importance of adherence to ART medications in the management of patients with HIV. [ABSTRACT FROM AUTHOR]

The clinical practice guidelines on nosocomial pneumonia recommends an empirical regimen that would work in 95% of the patients based on the local antibiogram. The aim of the study was development of an antibiogram for guiding empiric therapy in settings with high prevalence of multi-drug resistant organisms. A retrospective review of electronic health records (e-hospital portal) was done to analyze all respiratory isolates from patients admitted in medical wards and intensive care unit between May 2016 and May 2017. The samples included brocho-alveolar lavage (BAL), mini broncho-alveolar lavage (mini-BAL) and endotracheal aspirate. The sensitivity pattern (combined and individual) of all bacterial isolates were analysed for commonly used antibiotics and their combinations. Out of the 269 isolates, the most common organisms were Pseudomonas aeruginosa (125, 46%), Acinetobacter baumanni (74, 27%) and Klebsiella pneumoniae (50, 19%). Cefoperazone-sulbactam (43%) had the best sensitivity pattern overall. Cefoperazone-sulbactam plus amikacin (56%) was the combination with the best combined sensitivity overall. There is a high prevalence of resistance in the commonly implicated organisms to the available antibiotics. There is an urgent need for implementation of effective anti-microbial stewardship programmes and development of newer antimicrobials. [ABSTRACT FROM AUTHOR]

Introduction: Conidiobolomycosis is a subcutaneous rhinofacialzygomycosis caused by Conidiobolus spp. Its epidemiology in the Indian subcontinent is not well understood. Aim: The aim of this study was epidemiological characterisation of conidiobolomycosis in the Indian subcontinent. Materials and Methods: We conducted a review of literature using the terms "conidiobolomycosis", "conidiobolus", "entomophthoramycosis" and "entomophthoromycosis" in the Pubmed database combined with the following: India and publication language (English). Results: A total of 75 cases of conidiobolomycosis were reported from 12 states of India, between October 1966 and December 2017, who presented with centrofacial swelling (males-62, females-13). The mean age of presentation was 35 years. Majority of the patients were immunocompetent with only one patient being immunosuppressed (acute leukaemia). A total of 21 patients were diagnosed only on the basis of culture, while the rest of them were diagnosed either on histopathology alone (n=33) or a combination of histopathology and culture (n=21). Saturated solution of potassium iodide (SSKI) was the most common drug (alone or in combination) used for treatment. Except one mortality, which was unrelated to the disease, all patients (n=56) responded to therapy. Conclusion: Conidiobolomycosis is reported from most parts of the country, primarily in immunocompetent males and has an excellent response to anti-fungals. [ABSTRACT FROM AUTHOR]

Background & objectives: Limited data are available on malignancies in human immunodeficiency virus (HIV)-infected patients from India. We undertook this study to assess the frequency and spectrum of malignancies in HIV-infected adult patients during the first eight years of highly active antiretroviral therapy (HAART) rollout under the National ART Programme at a tertiary care centre in New Delhi, India. Methods: Retrospective analysis of records of patients registered at the ART clinic between May 2005 and December 2013 was done. Results: The study included 2598 HIV-infected adult patients with 8315 person-years of follow up. Malignancies were diagnosed in 26 patients with a rate of 3.1 (IQR 2.1-4.5) cases per 1000 person-years. The median age for those diagnosed with malignancy was 45 (IQR 36-54) yr, which was significantly (P<0.01) higher compared with those not developing malignancies 35 (IQR 30-40) yr. The median baseline CD4+ T-cell count in patients with malignancy was 135 (IQR 68-269) cells/µl compared to 164 (IQR 86-243) cells/µl in those without malignancies. AIDS-defining cancers (ADCs) were seen in 19 (73%) patients, while non-AIDS-defining cancers (NADCs) were observed in seven (27%) patients. Malignancies diagnosed included non-Hodgkin's lymphoma (16), carcinoma cervix (3), Hodgkin's lymphoma (2), carcinoma lung (2), hepatocellular carcinoma (1), and urinary bladder carcinoma (1). One patient had primary central nervous system lymphoma. There was no case of Kaposi's sarcoma. Interpretation & conclusions: Malignancies in HIV-infected adult patients were infrequent in patients attending the clinic. Majority of the patients presented with advanced immunosuppression and the ADCs, NHL in particular, were the commonest malignancies. [ABSTRACT FROM AUTHOR]

Background & objectives: There is a paucity of data from India on response to treatment of tuberculosis (TB) in patients with human immunodeficiency virus (HIV)-TB co-infection. This study was done to assess the frequency and pattern of TB, outcome of anti-tuberculosis treatment, and the factors related to poor outcome of TB treatment in adult patients with HIV infection. Methods: Retrospective review of case records of HIV-TB co-infected patients attending the antiretroviral therapy (ART) clinic in a tertiary care centre in north India was done. Results: Of the 1754 patients included in the study, 583 (33.2%) were diagnosed with active TB and 466 (79.9%) of them had CD4 count less than 200/µl at diagnosis. Extrapulmonary TB was diagnosed in 372 (63.8%) patients [76 (20.4%) had disseminated TB], and pulmonary TB in 211 (36.2%) patients. "Favourable outcome" (cure and completed treatment) was observed in 332 (77%) patients. Unfavourable outcome included default (8.1%), treatment failure (1.6%), and death (13.2%). At 1-year post-treatment follow up, 12 (3.6%) patients had disease relapse. CD4 count of less than 200/ µl at diagnosis [OR-2.32, CI (1.06-5.09)], and retreatment cases [OR-2.91, CI (1.22-6.89)] were independent predictors of unfavourable outcome. Interpretation & conclusions: There is an urgent need to strengthen the information, education, communication activities and expand the ART services to meet the requirement of early testing and treatment initiation in patients co-infected with HIV-TB. The findings highlight the need for performing drug susceptibility testing (DST) for patients starting retreatment regimen to improve treatment outcome. [ABSTRACT FROM AUTHOR]

Most studies have described worse outcomes with coronavirus disease 2019 (COVID-19) in patients with human immunodeficiency virus (HIV). This has been attributed to COVID-19 associated lymphopenia (resulting in lower CD4 count), higher prevalence of comorbidities (established risk factors for severity in COVID-19) and pre-existing lung damage. The problem has been further aggravated by the lack in the access to routine care in HIV patients due to diversion of resources. In this article, we discuss the impact of COVID-19 on patients with HIV infection. [ABSTRACT FROM AUTHOR]

Initial contrast-enhanced computed tomographic abdomen had shown SMV thrombosis and subtle non-specific lesions in the left lobe of the liver [Figure 3], so magnetic resonance imaging was planned which showed multiple hypointense lesions in the liver [Figure 4]. Investigations revealed conjugated hyperbilirubinaemia with transaminitis and hepatosplenomegaly with Grade 3 oesophageal varices and superior mesenteric vein (SMV) thrombosis. Screening for porphyria was negative in urine as protoporphyrin is not excreted in urine, however, plasma porphyrin screen showed peak at 634 nm, suggestive of EPP. [Extracted from the article]

Background & objectives: Growing body of literature on sarcoidosis in India has led to an increased awareness of the disease. With the advent of better imaging tools hitherto under-recognized manifestations of sarcoidosis are likely to be better recognized. We sought to study the rare clinical and radiological manifestations (<5%) in patients with sarcoidosis. Methods: Retrospective review of records of 164 patients with histopathologically proven sarcoidosis seen over six years in a tertiary care centre in north India, was done. Results: Fifty four rare manifestations were observed in 164 patients. Acute presentation in the form of Lofgren syndrome was seen in eight (4.9%) and Heerfordt's syndrome in two (1.2%) patients. Muscuioskeletai manifestations included chronic sarcoid arthritis in three (1.8%), deforming arthritis and bone erosion in one (0.6%) each. Rare initial presentation with dilated cardiomyopathy in one (0.6%), complete heart block in two (1.2%), bilateral sequential facial nerve palsy in two (1.2%), and pyrexia of unknown origin was seen in one (0.6%) patient. Other rare manifestations included chronic respiratory failure in one (0.6%), dysphagia in one (0.6%), sicca syndrome in five (3%), massive splenomegaly in one (0.6%), portal hypertension in two (1.2%), hypersplenism, gastric sarcoidosis, ninth and tenth cranial nerve palsies, moderate pericardial effusion and nephrocalcinosis in one (0.6%) each, and pulmonary artery hypertension in two (1.2%) patients. Rare radiologicai manifestations included moderate pleural effusion in two (1.2%), pleural thickening in five (3%), calcification of intrathoracic lymph nodes in four (2.4%), alveolar (nodular) sarcoidosis in three (1.8%), and myocardial uptake of 18F-fluorodeoxyglucose (F-18 FDG) in two (1.2%) patients. Fourteen patients had airways obstruction and behaved typically like seasonal bronchial asthma with excellent response to corticosteroids. Interpretation & conclusions: Increased awareness of rare manifestations will facilitate better management of these patients. With increasing use of modern diagnostic tools, manifestations hitherto considered rare, are likely to be recognized more frequently in the future. [ABSTRACT FROM AUTHOR]

Antiretroviral therapy (ART) initiation in HIV-infected patients leads to recovery of CD4+T cell numbers and restoration of protective immune responses against a wide variety of pathogens, resulting in reduction in the frequency of opportunistic infections and prolonged survival. However, in a subset of patients, dysregulated immune response after initiation of ART leads to the phenomenon of immune reconstitution inflammatory syndrome (IRIS). The hallmark of the syndrome is paradoxical worsening of an existing infection or disease process or appearance of a new infection/disease process soon after initiation of therapy. The overall incidence of IRIS is unknown, but is dependent on the population studied and the burden of underlying opportunistic infections. The immunopathogenesis of the syndrome is unclear and appears to be result of unbalanced reconstitution of effector and regulatory T-cells, leading to exuberant inflammatory response in patients receiving ART. Biomarkers, including interferon-γ (INF-γ), tumour necrosis factor-α (TNF-α), C-reactive protein (CRP) and interleukin (IL)-2, 6 and 7, are subject of intense investigation at present. The commonest forms of IRIS are associated with mycobacterial infections, fungi and herpes viruses. Majority of patients with IRIS have a self-limiting disease course. ART is usually continued and treatment for the associated condition optimized. The overall mortality associated with IRIS is low; however, patients with central nervous system involvement with raised intracranial pressures in cryptococcal and tubercular meningitis, and respiratory failure due to acute respiratory distress syndrome (ARDS) have poor prognosis and require aggressive management including corticosteroids. Paradigm shifts in management of HIV with earlier initiation of ART is expected to decrease the burden of IRIS in developed countries; however, with enhanced rollout of ART in recent years and the enormous burden of opportunistic infections in developing countries like India, IRIS is likely to remain an area of major concern. [ABSTRACT FROM AUTHOR]

Background Cardiac involvement in dengue fever is underdiagnosed due to low index of suspicion and overlapping clinical manifestations of capillary leak associated with dengue. The frequency of subclinical dengue myocarditis and its relative contribution to the hemodynamic instability in severe dengue needs to be explored. We studied the prevalence of myocarditis and clinical outcomes among admitted patients with dengue. Methods A prospective observational study was carried out in admitted patients with age between 18 and 65 years having confirmed dengue (NS1/IgM ELISA). Patients with electrolyte abnormalities or on medications affecting heat rhythm/ rate, pre-existing heart disease were excluded. The baseline demographic, clinical and laboratory parameters were collected. A baseline ECG was done and repeated every second day. Trop-I and NT-proBNP were done at baseline and repeated only if elevated at baseline or there were ECG changes. The cardiac enzymes were measured using enzyme-linked fluorescent assay (VIDAS, bioMérieux, France). Patients with elevated enzymes underwent 2-dimensional echocardiography. Diagnosis of myocarditis was as per ESC 2013 criteria. Fluid management was as per WHO guidelines (2009). Results A total of 183 patients were recruited with median age of 29 years (IQR 21, 37) and 31% were females. Dengue with warning signs was present in 80 (44%) and severe dengue in 45 (25%) patients. Cardiac enzymes were elevated in 27 (15%) patients (cTnI in 25, NT-proBNP in 22). Among these 27 patients, 11 [6% (2.6–9.4, 95% CI)] had echo evidence and diagnosed as having myocarditis according to ESC 2013 criteria (Figure 1). Clinical features of fluid overload were more common in myocarditis group [8 (73%) vs 4 (2%), P = Overall, 5 (2.7%) patients expired, all of them had myocarditis (5/11 = 45%). These patients had severe dengue, 2 patients developed hospital-acquired pneumonia and 1 had malaria co-infection. Among patients with raised enzymes and normal echo (n = 16), 3 patients developed clinical signs of fluid overload compared with only 1 out of 156 patients without raised enzymes (P < 0.01). Conclusion Myocarditis in admitted patients with dengue is not uncommon [6% (2.6–9.4, 95% CI)] and may lead to a complicated disease course. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background: Oxygen delivery devices with positive end-expiratory pressure (PEEP) valves have been described, but high inspiratory flows may lead to poor tolerance in tachypneic patients. Positive expiratory pressure oxygen therapy (PEP-OT) using an occlusive face mask, oxygen reservoir, and PEEP valve has not been evaluated in clinical settings. Materials and methods: In a single-arm intervention trial, patients aged 19-55 years admitted with acute respiratory illness with oxygen support were enrolled. PEP-OT trial was given with PEEP of 5 and 7 cm of water over 45 minutes. Feasibility was assessed as uninterrupted completion of the PEP-OT trial. The effects of PEP-OT on cardiopulmonary physiology and adverse effects of therapy were recorded. Results: Fifteen patients (6 males) were enrolled. Fourteen patients had pneumonia and one patient had pulmonary edema. Twelve patients (80%) completed the PEP-OT trial. There was significant improvement in respiratory rate (RR) and heart rate (HR) at the end of the 45-minute PEP-OT trial (p-values 0.048 and 0.003, respectively). There was a trend toward improved SpO2 and perceived dyspnea. None of the patients developed desaturation, shock, or air leaks. Positive expiratory pressure oxygen therapy is a feasible oxygen therapy in patients with acute hypoxia. Conclusion: Positive expiratory pressure oxygen therapy seems to be safe and has a positive impact on respiratory mechanics in parenchymal respiratory pathology. [ABSTRACT FROM AUTHOR]

Kikuchi-Fujimoto disease is a rare, benign, and self-limiting condition that mostly affects young females. Cervical lymphadenopathy with fever is the most common presentation of the disease. It may have unusual presentations that can lead to diagnostic dilemma and delay in diagnosis. We report a case of a 25-year-old female who presented with relapsing fever and cervical lymphadenopathy. Because of atypical presentation, there was a delay in diagnosis and increase in morbidity. High index of suspicion with collaboration between clinicians and pathologists is essential for early and accurate diagnosis of the disease. [ABSTRACT FROM AUTHOR]

Iron is an important micronutrient involved in cell biology through vital reactions. We examined the correlations between iron metabolism parameters and the course of invasive fungal sinusitis. Patients with invasive fungal sinusitis were enrolled. Serum iron and ferritin levels, total iron-binding capacity, and transferrin saturation were measured at the initiation of treatment. Patients were followed for 6 months, and the clinical course was categorised as improvement or worsening/death. A total of 35 patients were enrolled. The average ferritin levels in mucormycosis patients was 944.9 ng/ml, versus 110.7 ng/ml for aspergillosis patients. Iron levels were significantly lower in mucormycosis than in aspergillosis (29.14 µg/dl vs. 68.55 µg/dl). Total iron-binding capacity was significantly different between the two groups (16.76 µg/dl vs. 330.36 µg/dl). After 6 months, improvement, worsening, and death were noted for 18, 8, and 9 patients, respectively. Higher iron levels and lower ferritin levels were linked with improvement. Total iron-binding capacity was significantly higher in improved patients (2314 vs. 151). Iron metabolism parameters play significant roles in the preemptive judgment of the course of fungal sinusitis. Based on these findings, studies on drugs affecting iron metabolism should be conducted. [ABSTRACT FROM AUTHOR]

A 29 yr old male† with culture-proven disseminated aspergillosis having cutaneous, orbital involvement and epilepsy was diagnosed with chronic granulomatous disease based on dihydrorhodamine flow cytometry. The patient declined intravenous therapy beyond three weeks and, due to paucity of alternative efficacious oral antifungal agents in disseminated aspergillosis, was continued on voriconazole and remained asymptomatic on follow up for six months.{Figure 1}{Figure 2} Conflicts of Interest: None. Cardiac magnetic resonance imaging (cMRI) revealed an intra-myocardial mass encasing the affected coronary vessels [Figure 1]; MRI of the brain showed ring-enhancing lesions in the bilateral cerebral hemispheres [Figure 2]. [Extracted from the article]

Introduction: The objective of the study was to evaluate the clinical profile and outcome of patients with secondary hemophagocytic lymphohistiocytosis (HLH) in critically ill patients. Materials and methods: A prospective observational study was conducted where critically ill adult patients presenting with fever and bicytopenia were evaluated according to the HLH-2004 diagnostic criteria for the presence of secondary HLH. The underlying trigger, clinical profile, treatment, and outcome of patients with HLH were analyzed. Results: Of the 76 critically ill patients with fever and bicytopenia, 33 (43%) patients were diagnosed with HLH. The following triggers for HLH were identified: bacterial infections (23%), fungal infections (10%), viral infections (10%), parasitic infections (10%), autoimmune diseases (13%), and malignancy (8%). A total of 78% of the HLH cases received steroids, but the use of steroids was not associated with improvement in mortality. Conclusion: There is a high prevalence of HLH in patients presenting with fever and bicytopenia in critically ill adult patients. Infections were identified as the most common trigger of HLH. [ABSTRACT FROM AUTHOR]

Background Diagnostic importance of asymptomatic cryptococcal antigenemia is being increasingly recognized in the last few years. Recently, WHO (World Health Organization) has recommended routine screening of CrAg (cryptococcal antigen) among PLHA with CD4 ≤100/mm3, albeit this procedure is not yet adopted by many developing countries including India. Methods We conducted a prospective observational study in a large tertiary care center of North India, upon ethical clearance. Latex agglutination test was performed to assess serum CrAg levels, followed by the lumbar puncture for detection of CrAg levels in the CSF. We analyzed the prevalence and treatment outcomes of cryptococcal antigenemia among PLHA with CD4 ≤ 100 cells/mm3. Detailed clinical examination was conducted, with follow-up of upto 3 months. Multivariate analysis was performed for the estimation of risk factors. Results The mean age (years) and BMI (kg/m2) of all the participants were 41.4 ± 11.2 and 22.1 ± 2.6, respectively. Notably, the mean CD4 count (cu.mm) at the time of recruitment was 62.3 ± 20.5. Noteworthy, 62 (60.8%) of the patients were ART naïve. We found 9.8% (n = 10) of the patients were positive for serum CrAg, and only 2.9% (n = 3) had clinical features of meningitis and 6.8% (n = 7) were asymptomatic (subclinical) CrAg positive. Strikingly, 3.9% (n = 4) of the asymptomatic cryptococcal antigenemia patients were also positive for CrAg in CSF, with 1.9% (n = 2) were only serum CrAg positive, and 1 patient was lost to follow-up (Graph 1). Multivariate analysis revealed that patients with long duration of HIV (P = 0.04), headache symptoms (P = 0.004) and possessing features of meningismus (P value=0.08) are more likely to be CrAg positive. Conversely, patients on fluconazole were protective against cryptococcal antigenemia (P = 0.1) as shown in Table 1. Overall mortality observed was 11.3% among advanced HIV patients. Moreover, mortality in CrAg-positive patients was 33.3% in comparison to CrAg-negative patients who had 9% (P = 0.06) in 3-months follow-up. Conclusion Cryptococcal antigenemia is common (9.8%) among patients with CD4 count ≤100/mm3 in India. Screening for CrAg should be made routine for PLHA with CD4 count ≤100/mm3 and if required preemptive treatment to be given in this regard. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Background: BBV152 is a whole-virion inactivated SARS-CoV-2 vaccine that has been deployed in India. The results of the phase 3 trial have shown clinical efficacy of BBV152. We aimed to evaluate the effectiveness of BBV152 against symptomatic RT-PCR-confirmed SARS-CoV-2 infection.Methods: We conducted a test-negative, case-control study among employees of the All India Institute of Medical Sciences (a tertiary care hospital in New Delhi, India), who had symptoms suggestive of COVID-19 and had an RT-PCR test for SARS-CoV-2 during the peak of the second wave of the COVID-19 pandemic in India between April 15 and May 15, 2021. Cases (test-positives) and controls (test-negatives) were matched (1:1) on the basis of age and gender. The odds of vaccination with BBV152 were compared between cases and controls and adjusted for level of occupational exposure (to COVID-19), previous SARS-CoV-2 infection, and calendar time, using conditional logistic regression. The primary outcome was effectiveness of two doses of BBV152 (with the second dose received at least 14 days before testing) in reducing the odds of symptomatic RT-PCR-confirmed SARS-CoV-2 infection, expressed as (1 - odds ratio) × 100%.Findings: Between April 15 and May 15, 2021, 3732 individuals had an RT-PCR test. Of these, 2714 symptomatic employees had data on vaccination status, and 1068 matched case-control pairs were available for analysis. The adjusted effectiveness of BBV152 against symptomatic COVID-19 after two doses administered at least 14 days before testing was 50% (95% CI 33-62; p<0·0001). The adjusted effectiveness of two doses administered at least 28 days before testing was 46% (95% CI 22-62) and administered at least 42 days before testing was 57% (21-76). After excluding participants with previous SARS-CoV-2 infections, the adjusted effectiveness of two doses administered at least 14 days before testing was 47% (95% CI 29-61).Interpretation: This study shows the effectiveness of two doses of BBV152 against symptomatic COVID-19 in the context of a huge surge in cases, presumably dominated by the potentially immune-evasive delta (B.1.617.2) variant of SARS-CoV-2. Our findings support the ongoing roll-out of this vaccine to help control the spread of SARS-CoV-2, while continuing the emphasis on adherence to non-pharmacological measures.Funding: None.Translation: For the Hindi translation of the abstract see Supplementary Materials section. [ABSTRACT FROM AUTHOR]

Background: Hydroxychloroquine (HCQ) had generated considerable interest for coronavirus disease 2019 (COVID-19) prophylaxis. We conducted a prospective observational study at a tertiary care hospital in India, with dedicated COVID-19 care facilities. Objectives: Primary objective was incidence of adverse effects, secondary objective being efficacy in preventing COVID-19. Methods: Healthcare workers were recruited and grouped based on voluntary HCQ prophylaxis as per national guidelines. Side effects in HCQ group were graded in accordance with national cancer institute-common terminology criteria for adverse events (NCI-CTCAE) version 5.0. At 3–7-week follow-up, groups were compared for COVID-19 exposure, symptoms development and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RT-PCR results. Results: Among 358 participants recruited, 216 (60.3%) were males and mean age was 31.2 ± 6.6 years. Chemoprophylaxis was initiated by 258 (72%) participants. After loading dose, 7 (2.7%) reported grade 2 and 1 (0.4%) grade 3 adverse effects. Discontinuation of HCQ due to side effects was reported in 11 (4.3%) participants. Electrocardiogram was done by 50 (19.4%) participants on HCQ; no abnormalities were noted. A total of 106 (41%) among those taking and 63 (63%) among those not taking HCQ were tested for SARS-CoV-2 due to influenza-like illness or significant exposure. Among all participants, 25 (6.9%, 95% confidence interval [CI] 4.3–9.6) developed COVID-19 during the study period. In the group taking HCQ, 10 (3.9%) tested positive compared to 15 (15%) in the group not taking HCQ (P < 0.001). Odds ratio with HCQ intake was 0.34 (95% CI 0.13–0.83, P = 0.01) and the number needed to treat was 12. Conclusion: HCQ is safe at the recommended dose for pre-exposure prophylaxis of COVID-19. [ABSTRACT FROM AUTHOR]

Objectives: IgG4-related disease (IgG4-RD) is a chronic inflammatory disorder with prominent fibrosis. This retrospective analysis was undertaken to study the clinical, laboratory, and radiological characteristics of patients with extra-pancreatic IgG4-RD and their response to treatment at a tertiary care centre located in northern India. Material and methods: Patient data from our centre between January 2017 and January 2021 were reviewed. Probable/definite IgG4-RD cases were included in the analysis. Results: A total of 14 cases were identified with a median age of 39 years (range 19-56 years). There were 10 males and 4 females. All patients presented with slowly progressive soft tissue swellings with pain/discomfort related to local mass effect. The median delay in diagnosis was 9.5 months (range 2-72 months). Cross-sectional imaging showed soft tissue masses in all cases. All contrast-enhanced studies (n = 7) showed enhancement on computed tomography and magnetic resonance imaging scan. F-18 fluorodeoxyglucose-avidity was observed in 8 of 9 (88.9%) cases. Biopsies performed in 12 of these were classified as definite in 8 and possible IgG4-RD in 4 cases. Patients were treated with a median dose of 1 mg/kg/day (range 0.5-1 mg/kg/day) prednisolone. Steroids were successfully tapered in all 12 cases with 41.6% (5 of 12) being off corticosteroids at a median follow-up of 10 months (range 0-18 months). Two patients were lost to follow-up. Conclusions: IgG4-related disease is a chronic illness with a wide spectrum of manifestations, in which the diagnosis is often delayed, but it shows an excellent response to treatment. Efforts must be made to increase awareness among physicians about this disease to institute appropriate treatment as early as possible. [ABSTRACT FROM AUTHOR]

Use of systemic corticosteroids is well-established in COVID-19 patients with hypoxia; however, there is scant data on its role in patients with mild disease and prolonged symptoms as a measure to prevent disease progression. The aim of this study is to evaluate the role of systemic corticosteroids in preventing hypoxia (SpO2 = 93% on room-air) among mild COVID-19 patients. An observational study was conducted among symptomatic COVID-19 patients taking oral corticosteroids and attending institute teleconsultation facility between 10th-30th June 2021. Patients who were already on corticosteroids for other indication or required oxygen supplementation before or within 24-hours of initiation of corticosteroids were excluded. A total of 140 consecutive symptomatic COVID-19 patients were included. Higher baseline C-reactive protein (OR: 1.03, 95% CI: 1.02-1.06, p < 0.001) and early systemic corticosteroid (within 7 days) initiation (OR: 6.5, 95% CI: 2.1-20.1, p = 0.001) were independent risk factors for developing hypoxia (SpO2 = 93%). Progression to hypoxia was significantly higher in patients who received corticosteroids before day 7 of illness (36.7%, 95% CI, 23.4-51.7%) compared to = 7 of illness (14.3%, 95% CI, 7.8-23.2%) for persistent fever. Systemic corticosteroids within 7 days from symptom-onset were harmful and increased the risk of progression to hypoxia, whereas it may decrease the risk of progression when administered on or beyond 7 days in patients with mild COVID-19 and persistent symptoms. A well-designed randomised controlled trial is required to validate the findings. [ABSTRACT FROM AUTHOR]

Post COVID-19 sequelae are a constellation of symptoms often reported after recovering from COVID-19. There is a need to better understand the clinical spectrum and long-term course of this clinical entity. The aim of this study is to describe the clinical features and risk factors of post COVID-19 sequelae in the North Indian population. This prospective observational study was conducted at a tertiary healthcare centre in Northern India between October 2020 and February 2021. Patients aged >18 years with laboratory-confirmed COVID-19 were recruited after at least two weeks of diagnosis, and details were captured. A total of 1234 patients were recruited and followed up for a median duration of 91 days (IQR: 45-181 days). Among them, 495 (40.1%) had persistent symptoms post-discharge or recovery. In 223 (18.1%) patients, the symptoms resolved within four weeks; 150 (12.1%) patients had symptoms till 12 weeks, and 122 (9.9%) patients had symptoms beyond 12 weeks of diagnosis/symptom-onset of COVID-19. Most common symptoms included myalgia (10.9%), fatigue (5.5%), shortness of breath (6.1%), cough (2.1%), insomnia (1.4%), mood disturbances (0.48%) and anxiety (0.6%). Patients who were hospitalized were more likely to report fatigue as a feature of long COVID. Hypothyroidism (OR: 4.13, 95% CI: 2.2-7.6, p-value < 0.001) and hypoxia (SpO2 = 93%) (OR: 1.7, 95% CI: 1.1-2.4, p-value 0.012) were identified as risk factors for long COVID sequelae. In conclusion, long COVID symptoms were common (22%), and 9.9% had the post COVID-19 syndrome. Myalgias, fatigue and dyspnoea were common symptoms. Patients with hypothyroidism and hypoxia during acute illness were at higher risk of long COVID. [ABSTRACT FROM AUTHOR]

As of February 29, 2020, more than 85,000 cases of coronavirus disease 2019 (COVID-19) have been reported from China and 53 other countries with 2,924 deaths. On January 30, 2020, the first laboratory-confirmed case of COVID was reported from Kerala, India. In view of the earlier evidence about effectiveness of repurposed lopinavir/ritonavir against severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronavirus (CoV), as well as preliminary docking studies conducted by the ICMR-National Institute of Virology, Pune, the Central Drugs Standard Control Organization approved the restricted public health use of lopinavir/ritonavir combination amongst symptomatic COVID-19 patients detected in the country. Hospitalized adult patients with laboratory-confirmed SARS-CoV-2 infection with any one of the following criteria will be eligible to receive lopinavir/ritonavir for 14 days after obtaining written informed consent: (i) respiratory distress with respiratory rate ≥22/min or SpO2of <94 per cent; (ii) lung parenchymal infiltrates on chest X-ray; (iii) hypotension defined as systolic blood pressure <90 mmHg or need for vasopressor/inotropic medication; (iv) new-onset organ dysfunction; and (v) high-risk groups - age >60 yr, diabetes mellitus, renal failure, chronic lung disease and immunocompromised persons. Patients will be monitored to document clinical (hospital length of stay and mortality at 14, 28 and 90 days), laboratory (presence of viral RNA in serial throat swab samples) and safety (adverse events and serious adverse events) outcomes. Treatment outcomes amongst initial cases would be useful in providing guidance about the clinical management of patients with COVID-19. If found useful in managing initial SARS-CoV-2-infected patients, further evaluation using a randomized control trial design is warranted to guide future therapeutic use of this combination. [ABSTRACT FROM AUTHOR]

Background: Early diagnosis and treatment of drug-resistant tuberculosis (TB) is crucial to halt the spread of drug resistance in the community. Aim: The aim of the study was to compare rapid diagnostic tests (GeneXpert and line probe assay, LPA) with conventional liquid culture for the diagnosis of drug-resistant TB and to assess the risk factors for it. Method: This cross-sectional study recruited 229 multidrug-resistant TB suspects who were sputum smear positive. They were evaluated by the rapid diagnostic tests and sensitivity, specificity, positive predictive value and negative predictive value were calculated for drug resistance detection as compared to liquid culture drug susceptibility testing. The risk factors for the development of drug resistance were also assessed and the P value of < 0.05 was considered significant. Results: In the final comparison, 193 samples were included. The sensitivity and specificity of GeneXpert for detection of drug resistance (rifampicin) was 100% (95% confidence interval, CI: 88.8–100%) and 99.4% (95% CI: 96.6–99.9%), respectively. Whereas sensitivity and specificity of LPA was 94.3% (95% CI: 80.8–99.3%) and 100% (95% CI: 97.7–100%), respectively. Only three discordant samples were observed. Defaulting to antitubercular therapy, contact with resistant TB, and disseminated disease were found to be significant risk factors for the development of drug-resistant TB with high statistical significance (P value < 0.05). Conclusion: Both rapid diagnostic tests have very high sensitivity and specificity for detection of drug resistance in sputum smear positive with the advantage of short turn-around time. Defaulting to antitubercular therapy, contact with resistant TB, and disseminated disease are significant risk factors for drug resistance. [ABSTRACT FROM AUTHOR]

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus-associated pneumonia and acute respiratory distress syndrome (ARDS) were often associated with hyperinflammation and elevation of several serum inflammatory markers but usually less than what is observed in non-coronavirus disease (COVID) ARDS. Elevated inflammatory markers such as C-reactive protein, interleukin (IL)-6, etc., are associated with severe infection. This study identified subphenotypes of COVID-19 ARDS patients by latent profile analysis in a cohort of Indian patients. Methods Data of n = 233 adult Indian patients with laboratory-confirmed SARS-CoV-2 infection admitted to a tertiary care teaching hospital were analyzed in this retrospective study. Only patients with acute respiratory failure (defined by partial pressure of oxygen/fraction of inspired oxygen ratio < 200 mm Hg) and chest X-ray showing bilateral infiltrates were included. Results The patients' mean (standard deviation) age was 53.3 (14.9) years, and 62% were male. A two subphenotypic model was formulated based on the lowest Bayesian information criterion. Neutrophil-to-lymphocyte ratio and serum IL-6 were latent variables in that model (entropy 0.91). The second phenotype (hyperinflammatory) had lower platelet count (p = 0.02), higher serum creatinine (p = 0.004), higher C-reactive protein (p = 0.001), higher ferritin (p < 0.001), and serum lactate dehydrogenase (p = 0.009). Age-adjusted hospital mortality (p = 0.007), duration of hospital stay (p < 0.001), and duration of intensive care unit stay (p < 0.001) were significantly higher in the second subphenotype. Conclusion Two distinct but overlapping subphenotypes were identified in SARS-CoV-2-associated respiratory failure. Hyperinflammatory subphenotype was associated with significantly poor short-term outcomes. [ABSTRACT FROM AUTHOR]

The association between the stiffening of barosensitive regions of central arteries and the derangements in baroreflex functions remains unexplored in COVID‐19 survivors. Fifty‐seven survivors of mild COVID‐19 (defined as presence of upper respiratory tract symptoms and/or fever without shortness of breath or hypoxia; SpO2 > 93%), with an age range of 22–66 years (27 females) participated at 3–6 months of recovering from the acute phase of RT‐PCR positive COVID‐19. Healthy volunteers whose baroreflex sensitivity (BRS) and arterial stiffness data were acquired prior to the onset of the pandemic constituted the control group. BRS was found to be significantly lower in the COVID survivor group for the systolic blood pressure‐based sequences (BRSSBP) [9.78 (7.16–17.74) ms/mmHg vs 16.5 (11.25–23.78) ms/mmHg; p = 0.0253]. The COVID survivor group showed significantly higher carotid β stiffness index [7.16 (5.75–8.18) vs 5.64 (4.34–6.96); (p = 0.0004)], and pulse wave velocity β (PWVβ) [5.67 (4.96–6.32) m/s vs 5.12 (4.37–5.41) m/s; p = 0.0002]. BRS quantified by both the sequence and spectral methods showed an inverse correlation with PWVβ in the male survivors. Impairment of BRS in the male survivors of mild COVID‐19 at 3–6 months of clinical recovery shows association with carotid artery stiffness. [ABSTRACT FROM AUTHOR]

CD8 T cells are important tools for protection against intracellularly replicating pathogens such as viruses. Previous studies showed that a discrete population of HLADR and CD38-expressing CD8 T cells expands massively during the acute febrile phase of human dengue virus infection--but very few of these cells secrete IFNγ upon in vitro stimulation with dengue peptides. To gain a better understanding of what other cytokines/chemokines do these massively expanding HLADR+CD38+ CD8 T cells express, we performed RNA seq of sorted HLADR+CD38+ CD8 T cell subsets after peptide stimulation. A majority of these peptide-stimulated HLADR+CD38+ CD8 T cells were CD69- IFNγ-, nearly a third were CD69+ IFNγ-, whereas very few (<10%) were CD69+ IFNγ+. The CD69- IFNγ- subset was enriched for the expression of key genes implicated in the negative regulation of T cell receptor (TCR) signaling and T-cell exhaustion, attraction of B cells and other lymphocytes, and cytokines related to Tc17/T-reg lineages or those that are implicated in immunosuppression/immunomodulatory and anti-inflammatory activities and angiogenesis. The CD69+ IFNγ- subset showed enriched transcription of key genes implicated in cytotoxic effector functions as well as costimulatory and signaling adaptors implicated in fine balancing of T cell receptor signaling. The CD69+ IFNγ+ subset largely shared the transcriptional profile with the CD69+ IFNγsubset--but with relatively more pronounced expression along with additional genes such as chemokines XCL1/XCL2. Our findings showing distinct functional subsets among these massively expanding CD8 T cells in dengue CD8 T cells warrant further studies to carefully examine the precise role of these T cell subsets in protection against dengue. [ABSTRACT FROM AUTHOR]

Oligoarticular arthritis (inflammation of upto 4 joints) has a wide range of infectious and non-infectious etiologies. The aim of our study was to identify the features which could help in the differentiation of infectious from non-infectious arthritis. The study was prospective and observational, and included 100 patients with oligoarticular inflammatory arthritis. The final diagnosis was made using standard diagnostic criteria and the patients were categorized into infectious and non-infectious groups. Among the 100 patients who were recruited, the following final diagnosis were made: peripheral spondyloarthritis (n = 37), axial spondyloarthritis (n = 11), tuberculosis (n = 19), brucellosis (n = 6), septic arthritis (n = 6), gouty arthritis (n = 5), early rheumatoid arthritis (n = 5), non-tubercular mycobacteria (n = 2), SLE (n = 2), post-chikungunya arthritis (n = 2), acute lymphocytic leukaemia (n = 1), pachydermoperiostosis (n = 1), sarcoidosis (n = 1) and juvenile idiopathoic arthritis (n = 1). The patients were categorized into two groups: infectious (33) and non-infectious (60). The presence of monoarthritis, clinically-significant weight loss, hepatomegaly, splenomegaly and erosive arthritis were significantly more common in the infectious group as compared to the non-infectious group. [ABSTRACT FROM AUTHOR]

Acute febrile illness (AFI) is one of the commonest indications for hospitalization and can present with varying severity including single or multiple organ dysfunction syndrome (MODS). During monsoon season, there is a spurt of AFI often caused by vector borne diseases leading to substantial morbidity and mortality. Our aim was to determine distribution of etiological causes, differential organ involvement and predictors of mortality in critically ill patients with AFI. It was a hospital based observational study which included patients with AFI with dysfunction of at least one organ system. The study was conducted over 4 months during monsoon season. Admitted patients were included who had been subjected to a standard battery of tests and managed with standard hospital based management protocol. 145 patients were included and etiology of fever was ascertained in 81.4% of patients with the most common single infection being chikungunya (20.7%) followed by dengue (20%) fever. Thrombocytopenia and deranged liver biochemistry each were seen in nearly 75% of the patients. Renal (50.3%) and nervous system (46.2%) dysfunction were the predominant organ failures. 49 patients died (33.8%) which correlated with predicted mortality by APACHE (acute physiological assessment and chronic health evaluation) II score. Independent predictors for mortality were older age (> 55 years) (p = 0.01), acidemia (p = 0.01), altered sensorium (p = 0.02) and coagulopathy (p = 0.048). Sub-group analysis revealed that amongst patients with MODS, hypotension could help differentiate between bacterial and non-bacterial causes (p = 0.01). Critically ill patients with AFI suffer from significant morbidity and mortality. Features like the presence of hypotension in MODS may differentiate between a bacterial cause vis-àvis viral or protozoal etiology. [ABSTRACT FROM AUTHOR]

The authors reflect on the treatment and association of the prevalence of obstructive sleep apnea (OSA) with metabolic syndrome. The authors relate the study of S. R. Coughlin and colleagues which indicates that the risk for cardiovascular disease is increased by the co-occurrence of the OSA and metabolic syndrome. They add that he results of the study on the effects of continuous positive airway pressure (CPAP) therapy on metabolic syndrome have shown favorable effects on blood pressure.

Invasive fungal infections (IFI) are commonly seen in immunosuppressed individuals but their epidemiology in critically ill patients has not been well described. The aim of this study was to determine the frequency, risk factors and outcome of invasive fungal infections in a medical intensive care unit. A prospective observational study was carried out between August 2016 and March 2018 in the medical intensive care unit. Patients above the age of 14 years with endotracheal intubation and/or central venous catheter for at-least three days and sepsis (not responding to 48 hours of intravenous antibiotic therapy) were included in the study. Suitable samples were collected and were subjected to fungal diagnostics. Invasive fungal disease was defined according to standard guidelines. Of the 100 recruited patients, a total of 11 patients had invasive aspergillosis, three patients had invasive candidiasis and one patient had both invasive aspergillosis and mucormycosis. IFI was more commonly seen in patients with auto-immune diseases (p = 0.002, odds ratio-10.13 (95% CI: 2.3-44)). A mortality of 73% was observed in patients with IFI. In conclusion, IFI, especially aspergillosis is grossly underreported in critical settings. Early suspicion, thorough investigation and timely diagnosis may alleviate patients of significant mortality and morbidity. [ABSTRACT FROM AUTHOR]

Introduction: Critically ill severe malaria constitutes one of the major hospital admissions in Indian setting. Clinical studies identifying the factors associated with acute kidney injury (AKI) in malaria are lacking. This study aimed to identify these factors. Methods: This prospective observational study was conducted in a tertiary care center of North India. All adult patients with severe malaria were studied during 2012–2014. Results: The study included 79 patients and AKI was observed in 36 patients. Of these 79 patients, 52.7% were Plasmodium falciparum positive and 47.2% were Plasmodium vivax positive. In AKI patients, thrombocytopenia and jaundice were the most common other complications seen. Among P. vivax malarial patients, 17 (36%) patients had AKI. Features associated with AKI among patients admitted with P. vivax malaria were as follows: tachycardia (adjusted relative risk [RR]: 3.9; 95% confidence interval [CI]: 1.1–13.7), direct hyperbilirubinemia (adjusted RR: 4.7; 95% CI: 1.4–15.2), anemia (adjusted RR: 6; 95% CI: 1.7–22.4), and sepsis (adjusted RR: 3.3; 95% CI: 1.1–13.7). The presence of tachycardia, acidosis, cerebral malaria, acute respiratory distress syndrome/acute lung injury, hypotensive shock, and poor Glasgow Coma Scale were associated with higher mortality in patients with AKI. Patients who required mechanical ventilation and/or vasopressor support had higher mortality. Conclusion: P. vivax is an important cause of severe malaria with AKI in our setting. Various other clinical features are associated with AKI and related mortality. [ABSTRACT FROM AUTHOR]

Background: Hyperglycemia is a common comorbidity in hospitalized patients and may add to adverse outcomes. Various associations have issued guidelines for optimal management of hyperglycemia in ill patients. This study aims to assess the adherence to current guidelines in inpatient setting and the impact of educational interventions on the improvement in adherence to guidelines as well as its effect on the level of blood sugar control and patient outcomes. Materials and Methods: It was a quasi-experimental pretest and posttest study and was done in three phases, viz., observation of current practices, intervention in the form of educational interventions, and its effect on change in practices and patient outcomes. Results: There was statistically significant 22% increase in the use of recommended insulin regimens (P = 0.028). The proportion of blood sugars within recommended range in the first 48 h, mean daily blood sugars, and the incidence of severe hyperglycemia improved in phase 3 vs phase 1 and was statistically significant. On comparing the subgroups, viz., those who followed and those who did not follow the guidelines, the results of the proportion of blood sugar in recommended range and proportions of blood sugar of more than 250 were found to be statistically significant. Conclusion: Dedicated educational interventions help in improving healthcare practices. According to current guidelines, rapid improvement in hyperglycemia and better glycemic control occur with adherence to protocol-based management of hyperglycemia. [ABSTRACT FROM AUTHOR]

Context: Sputum smear-negative and sputum-scarce pulmonary tuberculosis (PTB) is a diagnostic challenge. Xpert® Mycobacterium tuberculosis/rifampin (MTB/RIF) provides a rapid diagnosis on high-quality biological specimen obtained by bronchoscopy. Aims: The aim of this study is to evaluate Xpert® MTB/RIF on bronchoalveolar lavage (BAL) fluid in sputum smear-negative and sputum-scarce PTB patients. Settings: Tertiary care hospital in India. Design: This was prospective observational study. Materials and Methods: Between January 2015 and November 2016, we prospectively recruited sputum-smear negative and sputum-scarce patients under evaluation for PTB and performed BAL. Sensitivity, specificity, positive, and negative predictive values were calculated for the diagnosis of PTB on BAL fluid for acid-fast bacilli smear and Xpert® MTB/RIF using liquid culture as the reference standard and compared to the final diagnosis based on composite reference standard. Sensitivity, specificity, and predictive values were calculated with 95% class intervals. McNemar's test was used for comparison of sensitivities. Results: Of the 60 patients included, 52 (88.3%) had a final diagnosis of PTB and 16 (26.7%) were culture confirmed. Xpert® MTB/RIF had a sensitivity and specificity of 81% (54%-96%) and 73% (56%-85%) in culture confirmed cases; 46% (32%-60%) and 100% (63%-100%) for the final diagnosis; 32% (17%-51%) and 100% (54%-100%) in culture negative cases, respectively. Culture had a sensitivity of 32% (20%-47%) for the final diagnosis. Conclusions: In sputum smear-negative and sputum-scarce patients with clinico-radiological features of PTB Xpert® MTB/RIF has good sensitivity for diagnosis on BAL fluid. It is useful even when cultures are negative. [ABSTRACT FROM AUTHOR]

Introduction: Lack of restorative sleep and altered sleep-wake cycle is a frequent problem among patients admitted to the Intensive Care Unit (ICU). This study was conducted to estimate the prevalence of poor sleep and patient's perspective of factors governing poor sleep in the ICU. Materials and Methods: A cross-sectional study was performed in medical ICU of a tertiary care hospital. A total of 32 patients admitted to the ICU for at least 24 h were recruited. A 72-h actigraphy was done followed by a subjective assessment of sleep quality by the Richards-Campbell Sleep Questionnaire (RCSQ). Patient's perspective of sleep quality and quantity and possible risk factors for poor sleep were recorded. Results: Poor sleep (defined as RCSQ <50, sensitivity 88% and specificity 87%) was found in 15 out of the 32 patients (47%). The prevalence of poor sleep was higher among patients on mechanical ventilation (n = 15) (66.7% vs. 33.3%, P < 0.05). Patients with poor sleep had higher age (median age [in years] 42.8 vs. 31.4, P = 0.008), acute physiology, and chronic health evaluation II score (mean 14 ± 5.15 vs. 9.3 ± 5.64, P = 0.02), SAPS 3 score (62.7 ± 8.9 vs. 45.6 ± 10.5, P ≤ 0.0001), and worse actigraphy parameters. Only 55.63% of total sleep time was in the night (2200-0600). All patients had discomfort from indwelling catheters and suctioning of endotracheal tubes. All patients suggested that there be a minimum interruption in the sleep for interventions or medications. Conclusion: There is a high prevalence of poor sleep among patients admitted to the ICU. There is a dire need to minimize untimely interventions and design nonpharmacological techniques to allow patients to sleep comfortably. [ABSTRACT FROM AUTHOR]

Fungal rhino-orbital sinusitis due to mucormycetes is a rapidly progressive condition with high mortality, rarely seen in immunocompetent individuals. A 26-year-old immunocompetent male presented with rhino-orbital mucormycosis after a history of dental manipulation. The patient was successfully managed with a combination of surgery, amphotericin B, and posaconazole. Here, we highlight the delay in diagnosis and challenges faced in the management. [ABSTRACT FROM AUTHOR]

The article discusses the case of a 17-year-old boy with actionomycosis, an unusual cause of fibrosing mediastinitis (FM) and superior vena cava syndrome. Soft tissue density in the anterior and middle mediastinum was shown in contrast-enhanced computed tomography (CECT) while hypointense mass in T2-weighed axial image was revealed by magnetic resonance imaging (MRI). FM has been associated with histoplasmosis and tuberculosis.

Angiotensin-converting enzyme 2 (ACE2) is a key host protein by which severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) enters and multiplies within cells. The level of ACE2 expression in the lung is hypothesised to correlate with an increased risk of severe infection and complications in COrona VIrus Disease 2019 (COVID-19). To test this hypothesis, we compared the protein expression status of ACE2 by immunohistochemistry (IHC) in post-mortem lung samples of patients who died of severe COVID-19 and lung samples obtained from non-COVID-19 patients for other indications. IHC for CD61 and CD163 was performed for the assessment of platelet-rich microthrombi and macrophages, respectively. IHC for SARS-CoV-2 viral antigen was also performed. In a total of 55, 44 COVID-19 post-mortem lung samples were tested for ACE2, 36 for CD163, and 26 for CD61, compared to 15 non-covid 19 control lung sections. Quantification of immunostaining, random sampling, and correlation analysis were used to substantiate the morphologic findings. Our results show that ACE2 protein expression was significantly higher in COVID-19 post-mortem lung tissues than in controls, regardless of sample size. Histomorphology in COVID-19 lungs showed diffuse alveolar damage (DAD), acute bronchopneumonia, and acute lung injury with SARS-CoV-2 viral protein detected in a subset of cases. ACE2 expression levels were positively correlated with increased expression levels of CD61 and CD163. In conclusion, our results show significantly higher ACE2 protein expression in severe COVID-19 disease, correlating with increased macrophage infiltration and microthrombi, suggesting a pathobiological role in disease severity. [ABSTRACT FROM AUTHOR]

Objective: The objective was to study the sensitivity, specificity, and diagnostic accuracy of various computed tomography (CT) chest findings in diagnosing recurrence among pulmonary tuberculosis (PTB) suspects. Materials and Methods: A prospective observational study was conducted in a tertiary care hospital in New Delhi. A total of 130 suspects with a past history of treatment for PTB, who presented with any of the symptoms suggestive of recurrence were included. Sputum-positive, HIV-positive patients, pregnant females, and patients aged <18 years were excluded. Patients underwent CT chest followed by bronchoalveolar lavage (BAL). Results: A total of 62 patients were there in the final analysis. The median age of the patients with recurrent PTB was 27.5 years. Cough was the universal symptom in all these patients (>90%). Hemoptysis was the predominant symptom among patients with chronic pulmonary aspergillosis (66.6%). Necrotic mediastinal lymph nodes had good diagnostic accuracy of 88.71% with area under the curve of 0.806, P < 0.001 in diagnosing recurrent TB. BAL GeneXpert and mycobacteria growth indicator tube had good sensitivity (83.33% and 84.62%, respectively), specificity (100% for both), and excellent diagnostic accuracy (95.16% and 96.36%, respectively) for diagnosing recurrence in sputum negative and sputum scarce patient, (P < 0.001) when compared with composite reference standard. For culture-positive cases, BAL GeneXpert MTB/RIF had 100% sensitivity and 97.73% specificity in diagnosing recurrent PTB patients. Conclusion: The presence of mediastinal necrotic lymph node is the most accurate CT finding that can differentiate recurrent TB from post-TB sequelae. No other single chest CT scan finding had reliable diagnostic accuracy in comparison to microbiological tools in diagnosing recurrence among sputum negative or scarce previously treated PTB suspects. [ABSTRACT FROM AUTHOR]

The World Health Organization (WHO) has declared coronavirus disease 2019 (COVID-19) as pandemic in March 2020. Currently there is no specific effective treatment for COVID-19. The major cause of death in COVID-19 is severe pneumonia leading to respiratory failure. Radiation in low doses (<100 cGy) has been known for its anti-inflammatory effect and therefore, low dose radiation therapy (LDRT) to lungs can potentially mitigate the severity of pneumonia and reduce mortality. We conducted a pilot trial to study the feasibility and clinical efficacy of LDRT to lungs in the management of patients with COVID-19. From June to Aug 2020, we enrolled 10 patients with COVID-19 having moderate to severe risk disease [National Early Warning Score (NEWS) of ≥5]. Patients were treated as per the standard COVID-19 management guidelines along with LDRT to both lungs with a dose of 70cGy in single fraction. Response assessment was done based on the clinical parameters using the NEWS. All patients completed the prescribed treatment. Nine patients had complete clinical recovery mostly within a period ranging from 3 to 7 days. One patient, who was a known hypertensive, showed clinical deterioration and died 24 days after LDRT. No patients showed the signs of acute radiation toxicity. The results of our pilot study suggest that LDRT is feasible in COVID-19 patients having moderate to severe disease. Its clinical efficacy may be tested by conducting randomized controlled trials. LDRT has shown promising results in COVID-19 pneumonia and should be researched further through randomized controlled trials. [ABSTRACT FROM AUTHOR]

Background: Pulmonary aspergilloma (PA) is a common complication seen in patients with pulmonary tuberculosis sequelae. Antifungal therapy, including oral azoles, is commonly used though only surgical resection offers curative benefit. Local administration of amphotericin B, like intracavitary instillation, has been effective in aspergilloma patients though nebulised amphotericin B (nAB) has never been formally assessed. Objective: The aim of this prospective, non‐inferior, open‐label, randomised control trial is to evaluate the efficacy and safety of nebulised amphotericin B compared to oral itraconazole therapy in the treatment of PA. Patients/Methods: Diagnosed cases of PA (n=33) were randomised into the control group receiving oral itraconazole (n=18) and intervention group receiving nebulised amphotericin B (n = 15). Response to treatment was assessed both clinically and radiologically at the end 6 months. Results and Conclusion: The number of patients showing overall improvement at the end of 6 months in the control arm(oral itraconazole) vs intervention arm(nebulised amphotericin B) was 65% (95% CI 38.3–85.8) and 67%(95% CI 38.4%–88.2%), respectively, in the intention‐to‐treat and 79% (95% CI 49.2%–95.3%), and 65% (95% CI 38.4%–88.2%), respectively, in the per‐protocol analysis. While there was no statistically significant difference between the intervention and control arm in both the analyses, non‐inferiority was shown in the per‐protocol but not in the intention‐to‐treat analysis. No major adverse events were noted in either group; however, a significant proportion of patients receiving nAB reported minor cough (40%), which, however, did not lead to discontinuation of therapy in any patients. Nebulised amphotericin B can be an effective therapeutic option for pulmonary aspergilloma patients. [ABSTRACT FROM AUTHOR]

Dengue is a life-threatening mosquito borne viral disease. We are still in the era of supportive treatment where morbidity and mortality are a major concern. Dengue infection in presence of other co-infections makes this scenario rather worse. Timely recognition and raising alarm to be intensive is the need of the hour for primary care physicians practicing in the community and indoors. This review provides a comprehensive knowledge about the recent trends of coinfection in dengue as well as their management consideration which will be particularly helpful for physicians practicing in rural and remote areas of India. [ABSTRACT FROM AUTHOR]

Central airway abnormalities are the most overlooked part of the respiratory system during high‑resolution computed tomography thorax specifically when these are subtle and read by less experienced eyes. In this article, we have tried to emphasize the importance to include central airways in reporting checklist. Systematically, analysis of airways can give important clues and narrow down the differentials and clinch the diagnosis in some cases like in our index one. [ABSTRACT FROM AUTHOR]

Background & objectives: In the present scenario, the most common sample for diagnosis of COVID-19 by reverse transcription polymerase chain reaction (RT-PCR) is nasal and throat swab (NTS). Other sampling options such as gargle lavage have found limited application in clinical use mostly because of unavailability of an appropriate gargling liquid. This study was conducted to assess the stability of SARS-CoV-2 RNA in normal saline at 4°C that can serve as a gargling liquid as well as a transport medium. The study also looked at the agreement between NTS and gargle lavage/saliva for the detection of SARS-CoV-2. Methods: In 29 consecutive real-time RT-PCR (rRT-PCR) positive COVID-19 patients, paired NTS, gargle and saliva samples were taken. Samples were processed by rRT-PCR for the detection of SARS-CoV-2 RNA. To assess the SARS-CoV-2 RNA stability in normal saline, gargle lavage specimens were divided into two aliquots; one subset of the specimen was run within 4-6 h along with the routine samples (NTS and saliva) and the other subset was stored at 4°C and processed after 24-30 h. Agreement between cycle threshold (Ct) values from both the runs was compared using Bland–Altman (BA) analysis. Results: The positivity rates of rRT-PCR in NTS, saliva and gargle lavage samples were 82.7 (24/29), 79.3 (23/29) and 86.2 per cent (25/29), respectively. BA plot showed a good agreement between the Ct values of fresh and stored gargle samples, stipulating that there were no significant differences in the approximate viral load levels between the fresh and stored gargle lavage samples (bias: E gene −0.64, N gene −0.51, ORF gene −0.19). Interpretation & conclusions: Our study results show stability of SARS-CoV-2 RNA in the gargle samples collected using normal saline up to 24-30 h. Gargle lavage and saliva specimen collection are cost-effective and acceptable methods of sampling for the detection of SARS-CoV-2 RNA by rRT-PCR. These simplified, inexpensive and acceptable methods of specimen collection would reduce the cost and workload on healthcare workers for sample collection. [ABSTRACT FROM AUTHOR]

Myelopathy in central nervous system tuberculosis is notorious for poor outcomes, determined by the severity of inflammation and cord level involved. Acute-onset quadriplegia or paraplegia in these cases represents a neuro-emergency. We report a young female with disseminated tuberculosis who presented with acute onset flaccid quadriparesis with loss of bladder and bowel function. Imaging helped identify the extensive involvement of the neuraxis. We propose that, in addition to anti-tubercular therapy, high-dose corticosteroids such as pulse methylprednisolone may result in a meaningful improvement and show greater rapidity of response in cases of severe central nervous system inflammation such as arachnoiditis or myelopathy. [ABSTRACT FROM AUTHOR]

Lymph node tuberculosis is one of the most common forms of extrapulmonary tuberculosis worldwide. The study aimed to evaluate the role of positron emission tomography-computed tomography (PETCT) in determining post-treatment response in lymph node tuberculosis. A PET-CT was done in all treatment naïve tubercular lymphadenitis adults at baseline and after six months of therapy. The post-treatment clinical response was compared with the metabolic response on PET-CT. Of the 25 patients with tubercular lymphadenitis, 9/25 patients showed a complete metabolic response (CMR) at six months, while 16 patients had a partial metabolic response (PMR). All patients with CMR had a good clinical response. However, discordance between clinical and PET findings was noticed in those with PMR. The role of PET-CT in evaluating post-treatment response in patients with tubercular lymphadenitis needs further evaluation with a larger sample size. [ABSTRACT FROM AUTHOR]