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We performed a case–control study across 25 hospitals in India for the period of January–June 2021 to evaluate the reasons for an COVID-19–associated mucormycosis (CAM) outbreak. We investigated whether COVID-19 treatment practices (glucocorticoids, zinc, tocilizumab, and others) were associated with CAM. We included 1,733 cases of CAM and 3,911 age-matched COVID-19 controls. We found cumulative glucocorticoid dose (odds ratio [OR] 1.006, 95% CI 1.004–1.007) and zinc supplementation (OR 2.76, 95% CI 2.24–3.40), along with elevated C-reactive protein (OR 1.004, 95% CI 1.002–1.006), host factors (renal transplantation [OR 7.58, 95% CI 3.31–17.40], diabetes mellitus [OR 6.72, 95% CI 5.45–8.28], diabetic ketoacidosis during COVID-19 [OR 4.41, 95% CI 2.03–9.60]), and rural residence (OR 2.88, 95% CI 2.12–3.79), significantly associated with CAM. Mortality rate at 12 weeks was 32.2% (473/1,471). We emphasize the judicious use of COVID-19 therapies and optimal glycemic control to prevent CAM.

Tuberculosis is prevalent throughout the world and is a major public health problem in most developing countries. Standardized and directly observed treatment under NTEP (National Tuberculosis Elimination Programme) is currently recommended for drug-sensitive pulmonary tuberculosis in India. It is generally well tolerated, with few minor side effects. Severe side effects necessitating discontinuation of therapy are rare with standard TB treatment regimens. Drug-resistant tuberculosis (DR-TB) has become more common in recent years, posing a challenge to global efforts to control the disease. Therapy for DR-TB has been associated with many adverse effects. Therefore, close monitoring of patients on DR-TB therapy is necessary to ensure that adverse effects of drugs are recognized early by healthcare personnel and treated accordingly. This will improve drug compliance and, hence, treatment goals. Here we report three cases of tuberculosis who had unusual adverse effects while receiving anti-tuberculous medication, prompting drug discontinuation.

Background: Forced vital capacity (FVC) and six-minute walk distance (6MWD) are robust markers in interstitial lung diseases (ILD) to assess severity and prognosis. It is unknown whether high-resolution computed tomography pattern has any independent effect on the exercise capacity in ILD. We compared six-minute walk test (6MWT) parameters between usual interstitial pneumonia (UIP) and non-UIP ILD after adjusting for FVC. Methods: Data from a tertiary care ILD clinic were retrospectively analysed. Based on HRCT, patients were classified as UIP and non-UIP. 6MWT parameters and FVC were recorded for enrolled patients. 6MWD, distance-saturation product (DSP) and exertional desaturation were compared between UIP and non-UIP, using analysis of covariance (ANCOVA), with per cent predicted FVC as covariate. Patients were grouped as mild (≥70%), moderate (51%–69%) and severe (≤50%) based on FVC severity. Results: Out of 169 patients enrolled, only patients with all three data points: spirometry, 6MWT and HRCT were included in the analysis (n = 139). UIP group comprised 56 (40.3%), while non-UIP group had 83 (59.7%) patients. More females and lesser smokers were present in non-UIP group. Mean predicted FVC% was similar between the two HRCT groups (P = 0.611) and had a statistically significant, though very weak to weak correlation with 6MWT parameters {6MWD (r = 0.138); pred 6MWD% (r = 0.170); desaturation (r = -0.227); DSP index (r = 0.166)}. Analysis of covariance showed no statistically significant difference in the 6MWT parameters between UIP and non-UIP groups for similar FVC levels. Conclusion: For a similar level of lung function, exercise capacity was similar for patients with UIP and non-UIP pattern ILD.

Background and Aim: High-resolution computed tomography (HRCT) of the chest has been the conventionally accepted modality of radiological investigation utilized in the evaluation and management of interstitial lung diseases (ILDs). The aim of this study was to compare the utilization of lung ultrasound (LUS) as a radiological modality versus HRCT scan of the chest, in the diagnosis of cases of ILD in autoimmune connective tissue disease (AICTD) patients at a tertiary care center in Northern India. Methods: In this descriptive study, 42 consecutive diagnosed cases of AICTD with clinical risk of ILD were included, between July 2016 and March 2019, attending the rheumatology outpatient department of CH WC. They were assessed with lung ultrasonography and HRCT chest. Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of LUS were estimated considering HRCT as the reference method. Results: Of these 42 patients, 30 (71.4%) had abnormal LUS findings. HRCT findings suggestive of ILD were seen in 31 (73.8%). Considering HRCT as gold standard, LUS resulted in 01 false-positive and 02 false-negative results. Sensitivity and specificity of LUS with respect to HRCT were 93.55% and 90.91%, respectively. Positive predictive value (PPV) and negative predictive value (NPV) of LUS were calculated at 89.38% and 94.51%, respectively. In 91.6% (11/12) patients with nonspecific interstitial pneumonitis pattern on HRCT, B-lines were found to be numerous and compact (

During and following the COVID-19 pandemic, the world has witnessed a surge in high-flow oxygen therapy (HFOT) use. The ability to provide high oxygenation levels with remarkable comfort levels has been the grounds for the same. Despite the advantages, delay in intubation leading to poor overall outcomes has been noticed in subgroup of patients on HFOT. ROX index has been proposed to be a useful indicator to predict HFOT success. In this study, we have examined the utility of the ROX index prospectively in cases of acute hypoxemic respiratory failure (AHRF) due to infective etiologies. Seventy participants were screened, and 55 were recruited for the study. The majority of participants were males (56.4%), with diabetes mellitus being the most common comorbidity (29.1%). The mean age of the study subjects was 46.27±15.6 years. COVID-19 (70.9%) was the most common etiology for AHRF, followed by scrub typhus (21.8%). Nineteen (34.5%) experienced HFOT failure and 9 (16.4%) subjects died during the study period. Demographic characteristics did not differ between either of the two groups (HFOT success versus failure and survived group versus expired group). ROX index was significantly different between the HFOT success versus failure group at baseline, 2, 4, 6, 12 and 24 h. The best cut-off of ROX index at baseline and 2 h were 4.4 (sensitivity 91.7%, specificity 86.7%) and 4.3 (sensitivity 94.4% and specificity 86.7%), respectively. ROX index was found to be an efficient tool in predicting HFOT failure in cases with AHRF with infective etiology.

Drugs that target human thymidylate synthase (hTS), a dimeric enzyme, are widely used in anticancer therapy. However, treatment with classical substrate-site-directed TS inhibitors induces over-expression of this protein and development of drug resistance. We thus pursued an alternative strategy that led us to the discovery of TS-dimer destabilizers. These compounds bind at the monomer-monomer interface and shift the dimerization equilibrium of both the recombinant and the intracellular protein toward the inactive monomers. A structural, spectroscopic, and kinetic investigation has provided evidence and quantitative information on the effects of the interaction of these small molecules with hTS. Focusing on the best among them, E7, we have shown that it inhibits hTS in cancer cells and accelerates its proteasomal degradation, thus causing a decrease in the enzyme intracellular level. E7 also showed a superior anticancer profile to fluorouracil in a mouse model of human pancreatic and ovarian cancer. Thus, over sixty years after the discovery of the first TS prodrug inhibitor, fluorouracil, E7 breaks the link between TS inhibition and enhanced expression in response, providing a strategy to fight drug-resistant cancers.

BackgroundThe modified International Society for Human and Animal Mycology (ISHAM) allergic bronchopulmonary aspergillosis (ABPA) working group (AWG) criteria lists up to five components for diagnosing ABPA in asthmatics. Whether eliminating specific components of the existing criteria would have the same diagnostic utility as the original remains unknown.ObjectiveTo evaluate the performance of several simplified criteria for diagnosing ABPA.MethodsWe compared the performance of seven new criteria (after excluding or modifying one or more of the components of the ISHAM-AWG criteria) with the modified ISHAM-AWG criteria in asthmatic subjects using latent class analysis (LCA). We also tested the performance of the newer criteria using accuracy measures against a multidisciplinary team (MDT) diagnosis of ABPA. We considered the diagnostic accuracy of the newer criteria to be acceptable if the correct classification and false-negative rates were >95% and 95% for three of the seven and

Scrub typhus is a rickettsial disease caused by gram negative coccobacilli and transmitted through the bite of larval stage of mite. The disease is notable in the Asia-Pacific belt with few sporadic and epidemic cases reported from India as well. The disease is well identified from North Western part of Rajasthan that are the areas with dense vegetation. The clinical scenario ranges from acute febrile illness to multiple organ dysfunction by virtue of haematogenous seedling. This case series highlights the neurological manifestations of scrub typhus that are diverse and life threatening but holding dearth of literature to convoy appropriately timed diagnosis and treatment.

Ecthyma gangrenosum (EG) is a relatively rare skin manifestation that is most commonly described in Pseudomonas aeruginosa bacteremia. It is more frequently seen in immunocompromised individuals. We report a case of 60-year-old renal transplant recipient on triple immunosuppressants and diabetes mellitus type 2 on insulin therapy who developed EG-like lesions due to disseminated mycobacterial tuberculosis (MTB) infection. To the best of our knowledge, this is the first case report of EG-like lesions associated with disseminated kochs.

Central venous catheterization is one of the most prevalent procedures in the Intensive Care Unit. Complications are reported in about 15% of the patients and usually comprise of infection, arterial puncture, malpositioning, pneumothorax, local hematoma, hemothorax, and so on. Chylothorax is a rare complication of this procedure. We present a 42-year-old lady, who developed bilateral massive chylothorax after cannulation of her left internal jugular vein (IJV), due to direct injury to the thoracic duct during the procedure. The patient was successfully managed with bilateral chest tube drainage and omission of oral feeds for four days. Development of bilateral chylothorax as a complication of IJV cannulation is rare, but merits reporting, in view of a large number of central venous cannulations being undertaken. Critical care professionals should be aware of this rare complication of a common procedure to facilitate early identification and institute appropriate therapy.

Thymidylate synthase (TS) is a prominent drug target for different cancer types. However, the prolonged use of its classical inhibitors, substrate analogs that bind at the active site, leads to TS overexpression and drug resistance in the clinic. In the effort to identify anti-TS drugs with new modes of action and able to overcome platinum drug resistance in ovarian cancer, octapeptides with a new allosteric inhibition mechanism were identified as cancer cell growth inhibitors that do not cause TS overexpression. To improve the biological properties, 10 cyclic peptides (cPs) were designed from the lead peptides and synthesized. The cPs were screened for the ability to inhibit recombinant human thymidylate synthase (hTS), and peptide 7 was found to act as an allosteric inhibitor more potent than its parent open-chain peptide [Pro3]LR. In cytotoxicity studies on three human ovarian cancer cell lines, IGROV-1, A2780, and A2780/CP, peptide 5 and two other cPs, including 7, showed IC50 values comparable with those of the reference drug 5-fluorouracil, of the open-chain peptide [d-Gln4]LR, and of another seven prolyl derivatives of the lead peptide LR. These promising results indicate cP 7 as a possible lead compound to be chemically modified with the aim of improving both allosteric TS inhibitory activity and anticancer effectiveness.

Background: It is thought that price increase in tobacco products leads to reduced consumption. Though many studies have substantiated this concept, it has not been well studied in India. Recently, price of tobacco products was increased due to ban on plastic sachets of chewing tobacco and increased tax in Rajasthan. This study was designed to evaluate the effect of price rise on overall consumption of tobacco in Jaipur city, Rajasthan. Materials and Methods: This study was carried out in Jaipur city. Two-staged stratified sampling was used. In the first phase of study, cost and consumption of various tobacco products in the months of February and April were enquired from 25 retail tobacco shops. In the second phase, tobacco consumption was enquired from 20 consecutive consumers purchasing any tobacco product from all the above retail tobacco shops. The data were statistically analyzed using descriptive statistics and paired "t" test. Results: The comparison of prices of tobacco products between February and April revealed that the price of cigarette, bidi, and chewing tobacco has increased by 19%, 21%, and 68%, respectively. Average decrease in sales of cigarettes, bidi, and chewing tobacco at shops included in the study were 14%, 23%, and 38%, respectively. The consumers purchasing tobacco also reported decreased consumption. Chewing tobacco showed the maximum reduction (21%). Consumption of cigarette and bidi has also reduced by 15% and 13%, respectively. Conclusion: It may be concluded that reduction in consumption is associated with increased price of tobacco products. Reduced consumption is comparative to the magnitude of price increase.

Shrinking lung syndrome (SLS) is a infrequently reported manifestation of systemic lupus erythematosus (SLE). Reported prevalence of SLS is about 0.5% in SLE patients. Pathogenesis is not fully understood and different therapeutic modalities have been employed with variable results, as only 77 cases of SLS have been documented in literature. SLS in SLE-Scleroderma overlap has not been reported yet. We report a patient of SLE - scleroderma overlap presenting with dyspnea, intermittent orthopnea and pleuritic chest pain. Evaluation revealed elevated hemidiaphragms and severe restrictive defect. She was eventually diagnosed as a case of SLS. This case report is a reminder to the medical fraternity that SLS although a rare complication must be thought of in the special subset of patients of SLE having respiratory symptoms.