Effect of pulmonary rehabilitation on functional status dyspnea and quality of life among post COVID-19 patients.

OBJECTIVES: To determine the Effect of pulmonary rehabilitation on functional status dyspnea and quality of life among post-COVID-19 patients. METHODS: The study utilized an experimental study design with a total of 120 participants to examine the effects of pulmonary rehabilitation. The participants were divided into two groups: Group A (experimental group) and Group B (control group). Demographic variables such as age, weight, and height were collected. Health-related quality of life (HRQL), post-COVID-19 functional status, and perceived exertion were assessed before and after the intervention. RESULTS: Group A demonstrated a higher mean age than Group B, indicating a significant age difference between the two groups, with no significant difference observed in weight and height. Following the intervention, Group A exhibited significant improvement in HRQL, post-COVID-19 functional status, and perceived exertion compared to Group B. CONCLUSION: Pulmonary rehabilitation had positive effects on health-related quality of life, post-COVID-19 functional status, and perceived exertion. The experimental group benefited from improved HRQL, suggesting an overall enhancement in their well-being. The study provides preliminary evidence supporting the effectiveness of pulmonary rehabilitation as an intervention for improving outcomes in individuals post-COVID-19.

Pursuing Clinical Predictors and Biomarkers for Progression in ILD: Analysis of the Pulmonary Fibrosis Foundation (PFF) Registry.

INTRODUCTION: Pulmonary fibrosis is a characteristic of various interstitial lung diseases (ILDs) with differing etiologies. Clinical trials in progressive pulmonary fibrosis (PPF) enroll patients based on previously described clinical criteria for past progression, which include a clinical practice guideline for PPF classification and inclusion criteria from the INBUILD trial. In this study, we compared the ability of past FVC (forced vital capacity) progression and baseline biomarker levels to predict future progression in a cohort of patients from the PFF Patient Registry. METHODS: Biomarkers previously associated with pathobiology and/or progression in pulmonary fibrosis were selected to reflect cellular senescence (telomere length), pulmonary epithelium (SP-D, RAGE), myeloid activation (CXCL13, YKL40, CCL18, OPN) and fibroblast activation (POSTN, COMP, PROC3). RESULTS: PFF or INBUILD-like clinical criteria was used to separate patients into past progressor and non-past progressor groups, and neither clinical criterion appeared to enrich for patients with greater future lung function decline. All baseline biomarkers measured were differentially expressed in patient groups compared to healthy controls. Baseline levels of SP-D and POSTN showed the highest correlations with FVC slope over one year, though correlations were low. CONCLUSIONS: Our findings provide further evidence that prior decline in lung function may not predict future disease progression for ILD patients, and elevate the need for molecular definitions of a progressive phenotype. Across ILD subtypes, certain shared pathobiologies may be present based on the molecular profile of certain biomarker groups observed. In particular, SP-D may be a common marker of pulmonary injury and future lung function decline across ILDs.

RNA-driven JAZF1-SUZ12 gene fusion in human endometrial stromal cells.

Oncogenic fusion genes as the result of chromosomal rearrangements are important for understanding genome instability in cancer cells and developing useful cancer therapies. To date, the mechanisms that create such oncogenic fusion genes are poorly understood. Previously we reported an unappreciated RNA-driven mechanism in human prostate cells in which the expression of chimeric RNA induces specified gene fusions in a sequence-dependent manner. One fundamental question yet to be addressed is whether such RNA-driven gene fusion mechanism is generalizable, or rather, a special case restricted to prostate cells. In this report, we demonstrated that the expression of designed chimeric RNAs in human endometrial stromal cells leads to the formation of JAZF1-SUZ12, a cancer fusion gene commonly found in low-grade endometrial stromal sarcomas. The process is specified by the sequence of chimeric RNA involved and inhibited by estrogen or progesterone. Furthermore, it is the antisense rather than sense chimeric RNAs that effectively drive JAZF1-SUZ12 gene fusion. The induced fusion gene is validated both at the RNA and the genomic DNA level. The ability of designed chimeric RNAs to drive and recapitulate the formation of JAZF1-SUZ12 gene fusion in endometrial cells represents another independent case of RNA-driven gene fusion, suggesting that RNA-driven genomic recombination is a permissible mechanism in mammalian cells. The results could have fundamental implications in the role of RNA in genome stability, and provide important insight in early disease mechanisms related to the formation of cancer fusion genes.

Acute Kidney Injury and ECMO: Two Sides of the Same Coin.

How to cite this article: Gupta S, Tomar DS. Acute Kidney Injury and ECMO: Two Sides of the Same Coin. Indian J Crit Care Med 2024;28(1):3-4.

Genome-wide, integrative analysis of circular RNA dysregulation and the corresponding circular RNA-microRNA-mRNA regulatory axes in autism.

Circular RNAs (circRNAs), a class of long noncoding RNAs, are known to be enriched in mammalian neural tissues. Although a wide range of dysregulation of gene expression in autism spectrum disorder (ASD) have been reported, the role of circRNAs in ASD remains largely unknown. Here, we performed genome-wide circRNA expression profiling in postmortem brains from individuals with ASD and controls and identified 60 circRNAs and three coregulated modules that were perturbed in ASD. By integrating circRNA, microRNA, and mRNA dysregulation data derived from the same cortex samples, we identified 8170 ASD-associated circRNA-microRNA-mRNA interactions. Putative targets of the axes were enriched for ASD risk genes and genes encoding inhibitory postsynaptic density (PSD) proteins, but not for genes implicated in monogenetic forms of other brain disorders or genes encoding excitatory PSD proteins. This reflects the previous observation that ASD-derived organoids show overproduction of inhibitory neurons. We further confirmed that some ASD risk genes (NLGN1, STAG1, HSD11B1, VIP, and UBA6) were regulated by an up-regulated circRNA (circARID1A) via sponging a down-regulated microRNA (miR-204-3p) in human neuronal cells. Particularly, alteration of NLGN1 expression is known to affect the dynamic processes of memory consolidation and strengthening. To the best of our knowledge, this is the first systems-level view of circRNA regulatory networks in ASD cortex samples. We provided a rich set of ASD-associated circRNA candidates and the corresponding circRNA-microRNA-mRNA axes, particularly those involving ASD risk genes. Our findings thus support a role for circRNA dysregulation and the corresponding circRNA-microRNA-mRNA axes in ASD pathophysiology.

Delineating Marker-Trait Associations for Fusarium Wilt in Chickpea Using the Axiom® CicerSNP Array.

Fusarium wilt (FW) caused by Fusarium oxysporum f. sp. ciceri is a devastating disease of chickpea (Cicer arietinum). To identify promising resistant genotypes and genomic loci for FW resistance, a core set of 179 genotypes of chickpea was tested for FW reactions at the seedling and reproductive stages under field conditions and controlled conditions in the greenhouse. Our results revealed that at the seedling stage, most of the genotypes were resistant, whereas at the reproductive stage, most of the genotypes were susceptible. Genotyping using a 50K Axiom® CicerSNP Array and trait data of FW together led to the identification of 26 significant (P ≤ E-05) marker-trait associations (MTAs) for FW resistance. Among the 26 MTAs, 12 were identified using trait data recorded in the field (three at the seedling and nine at the reproductive stage), and 14 were identified using trait data recorded under controlled conditions in the greenhouse (six at the seedling and eight at the reproductive stage). The phenotypic variation explained by these MTAs varied from 11.75 to 15.86%, with an average of 13.77%. Five MTAs were classified as major, explaining more than 15% of the phenotypic variation for FW, and two were declared stable, being identified in two environments. One of the promising stable and major MTAs (Affx_123280060) detected in field conditions at the reproductive stage was also detected in greenhouse conditions at the seedling and reproductive stages. The stable and major (>15% PVE) MTAs can be used in chickpea breeding programs.

Distal junctional kyphosis in adult cervical deformity patients: where does it occur?

PURPOSE: To evaluate the impact of the lowest instrumented vertebra (LIV) on Distal Junctional kyphosis (DJK) incidence in adult cervical deformity (ACD) surgery. METHODS: Prospectively collected data from ACD patients undergoing posterior or anterior-posterior reconstruction at 13 US sites was reviewed up to 2-years postoperatively (n = 140). Data was stratified into five groups by level of LIV: C6-C7, T1-T2, T3-Apex, Apex-T10, and T11-L2. DJK was defined as a kyphotic increase > 10° in Cobb angle from LIV to LIV-1. Analysis included DJK-free survival, covariate-controlled cox regression, and DJK incidence at 1-year follow-up. RESULTS: 25/27 cases of DJK developed within 1-year post-op. In patients with a minimum follow-up of 1-year (n = 102), the incidence of DJK by level of LIV was: C6-7 (3/12, 25.00%), T1-T2 (3/29, 10.34%), T3-Apex (7/41, 17.07%), Apex-T10 (8/11, 72.73%), and T11-L2 (4/8, 50.00%) (p < 0.001). DJK incidence was significantly lower in the T1-T2 LIV group (adjusted residual = -2.13), and significantly higher in the Apex-T10 LIV group (adjusted residual = 3.91). In covariate-controlled regression using the T11-L2 LIV group as reference, LIV selected at the T1-T2 level (HR = 0.054, p = 0.008) or T3-Apex level (HR = 0.081, p = 0.010) was associated with significantly lower risk of DJK. However, there was no difference in DJK risk when LIV was selected at the C6-C7 level (HR = 0.239, p = 0.214). CONCLUSION: DJK risk is lower when the LIV is at the upper thoracic segment than the lower cervical segment. DJK incidence is highest with LIV level in the lower thoracic or thoracolumbar junction.

Evaluation of a paraffin-based moisturizer compared to a ceramide-based moisturizer in children with atopic dermatitis: A double-blind, randomized controlled trial.

BACKGROUND: Moisturizers are first-line therapy for treatment of atopic dermatitis (AD). Although there are multiple types of moisturizers available, head-to-head trials between different moisturizers are limited. OBJECTIVE: To evaluate if a paraffin-based moisturizer is as effective as ceramide-based moisturizer in children with AD. MATERIALS AND METHODS: In this double-blind, randomized comparative trial of pediatric patients with mild to moderate AD, subjects applied either a paraffin-based or ceramide-based moisturizer twice daily. Clinical disease activity using SCOring Atopic Dermatitis (SCORAD), quality of life using Children/Infants Dermatology Life Quality Index (CDLQI/IDLQI), and transepidermal water loss (TEWL) were measured at baseline and at follow-up at 1, 3, and 6 months. RESULTS: Fifty-three patients were recruited (27 ceramide group and 26 paraffin group) with a mean age of 8.2 years and mean disease duration of 60 months. The mean change in SCORAD at 3 months in the ceramide-based and paraffin-based moisturizer groups was 22.1 and 21.4, respectively (p = .37). The change in CDLQI/IDLQI, TEWL over forearm and back, amount and days of topical corticosteroid required, median time to remission and disease-free days at 3 months were similar in both groups. As the 95% confidence interval (CI) of mean change in SCORAD at 3 months in both groups (0.78, 95% CI: -7.21 to 7.52) was not within the predefined margin of equivalence (-4 to +4), the conclusion of equivalence could not be proven. CONCLUSION: Both the paraffin-based and ceramide-based moisturizers were comparable in improving the disease activity in children with mild to moderate AD.

Sulfonated polystyrenes: pH and Mg2+-insensitive amphiphilic copolymers for detergent-free membrane protein isolation.

Amphiphilic polymers are increasingly applied in the detergent-free isolation and functional studies of membrane proteins. However, the carboxylate group present in the structure of many popular variants, such as styrene-maleic acid (SMA) copolymers, brings limitations in terms of polymer sensitivity to precipitation at acidic pH or in the presence of divalent metal cations. Herein, we addressed this problem by replacing carboxylate with the more acidic sulfonate groups. To this end, we synthesized a library of amphiphilic poly[styrene-co-(sodium 4-styrene sulfonate)] copolymers (termed SSS), differing in their molecular weight and overall polarity. Using model cell membranes (Jurkat), we identified two copolymer compositions (SSS-L30 and SSS-L36) that solubilized membranes to an extent similar to SMA. Interestingly, the density gradient ultracentrifugation/SDS-PAGE/Western blotting analysis of cell lysates revealed a distribution of studied membrane proteins in the gradient fractions that was different than for SMA-solubilized membranes. Importantly, unlike SMA, the SSS copolymers remained soluble at low pH and in the presence of Mg2+ ions. Additionally, the solubilization of DMPC liposomes by the lead materials was studied by turbidimetry, DLS, SEC, and high-resolution NMR, revealing, for SSS-L36, the formation of stable particles (nanodiscs), facilitated by the direct hydrophobic interaction of the copolymer phenyls with lipid acyl chains.

Remdesivir-Induced Bradycardia.

Remdesivir, a viral RNA-dependent RNA polymerase inhibitor, found extensive use in coronavirus disease 2019-infected patients because it curbs the viral load expansion. Among patients hospitalized as a result of lower respiratory tract infection, remdesivir proved to improve recovery time; however, remdesivir also can induce significant cytotoxic effects on cardiac myocytes. In this narrative review, we discuss the pathophysiological mechanism of remdesivir-induced bradycardia and diagnostic and management strategies for these patients. We conclude that further research is necessary to understand better the mechanism of bradycardia in coronavirus disease 2019 patients with or without cardiovascular disorder treated with remdesivir.

Influenza A (H1N1): Now is it a Thing of the Past?

How to cite this article: Gupta S, Tomar DS. Influenza A (H1N1): Now is it a Thing of the Past? Indian J Crit Care Med 2023;27(7):461-462.

Seroprevalence of anti SARS-CoV-2 IgG antibodies among adults in Jammu district, India: A community-based study.

Background & objectives: Serology testing is essential for immunological surveillance in the population. This serosurvey was conducted to ascertain the cumulative population immunity against SARS-CoV-2 among adults in Jammu district and to understand the association of seropositivity with sociodemographic and clinical correlates. Methods: On September 30 and October 1, 2020, a household survey was done in 20 villages/wards chosen from 10 health blocks in district Jammu, India. Demographic, clinical and exposure information was collected from 2000 adults. Serum samples were screened for IgG antibodies using COVID Kavach MERILISA kit. Tests of association were used to identify risk factors associated with IgG positivity. Crude odds ratio with 95 per cent confidence intervals (CIs) was calculated during univariate analysis followed by logistic regression. Results: Overall adjusted seroprevalence for SARS-CoV-2 was 8.8 per cent (95% CI: 8.78-8.82); it varied from 4.1 per cent in Chauki choura to 16.7 per cent Pallanwalla across 10 blocks in the district. Seropositivity was observed to be comparatively higher in 41-50 and 61-70 yr age groups, among males and in rural areas. Fever, sore throat, cough, dyspnoea, myalgias, anosmia, ageusia, fatigue, seizures, history of exposure, medical consultation, hospitalization and missing work showed significant association with seropositivity on univariate analysis. On logistic regression, only sore throat, myalgia and missing work showed significant adjusted odds of IgG positivity. Extrapolation to adult population suggested that exposure to SARS-CoV-2 was 14.4 times higher than reported cases, translating into Infection fatality rate of 0.08 per cent. Interpretation & conclusions: Since a major part of population was immunologically naive, all efforts to contain COVID-19 need to be vigorously followed while these baseline results provide an important yardstick to monitor the trends of COVID-19 and guide locally appropriate control strategies in the region.

Association between frailty and clinical outcomes in hospitalised patients requiring Code Blue activation.

BACKGROUND: Code Blues allow a rapid, hospital wide response to acutely deteriorating patients. The concept of frailty is being increasingly recognised as an important element in determining outcomes of critically ill patients. We hypothesised that increasing frailty would be associated with worse outcomes following a Code Blue. AIMS: To investigate the association between increasing frailty and outcomes of Code Blues. METHODS: Single-centre retrospective design of patients admitted to Frankston Hospital in Australia between 1 January 2013 and 31 December 2017 who triggered a Code Blue. Frailty evaluation was made based on electronic medical records as were the details and the outcomes of the Code Blue. The primary outcome measure was a composite of hospital mortality or Cerebral Performance Categories scale ≥3. Secondary outcomes included the immediate outcome of the Code Blue and hospital mortality. RESULTS: One hundred and forty-eight of 911 screened patients were included in the final analysis. Seventy-three were deemed 'frail' and the remainder deemed 'fit'. Seventy-eight percent of frail patients reached the primary outcome, compared with 41% of fit patients (P < 0.001). Multivariable analysis demonstrated frailty to be associated with primary outcome (odds ratio = 2.87; 95% confidence interval (CI) 1.28-6.44; P = 0.01). A cardiac aetiology for the Code Blue was also associated with an increased odds of primary outcome (OR = 3.52; 95% CI 1.51-8.05; P = 0.004). CONCLUSIONS: Frailty is independently associated with the composite outcome of hospital mortality or severe disability following a Code Blue. Frailty is an important tool in prognostication for these patients and might aid in discussions regarding treatment limitations.

Patterns of azithromycin use in obstructive airway diseases: a real-world observational study.

BACKGROUND: Low-dose long-term azithromycin is recommended in clinical practice guidelines for obstructive airway diseases (OAD); however, an optimal therapeutic regimen is not yet established. AIM: To understand the patterns of azithromycin use in OAD, characterise the patients who received it and evaluate its safety and efficacy using real-world data. METHODS: We audited 91 patients who had received azithromycin for at least 4 weeks for the management of asthma, chronic obstructive pulmonary disease (COPD) or non-cystic fibrosis bronchiectasis. RESULTS: The mean age was 65 ± 18 years, 60% were female and 48% were ex-smokers. The majority had asthma (75%), either alone (50%) or in combination with COPD (12%) or bronchiectasis (13%). Most (64%) reported cough or sputum at baseline. The most common treatment regimen was azithromycin 250 mg daily (73%) for more than 1 year (57%), with only seven adverse events. There was a significant reduction in the proportions of patients requiring emergency department visits (48% vs 32%; P < 0.001) and hospital admissions (35% vs 31%; P < 0.001) after starting azithromycin. In 88% of cases, physicians favoured the use of azithromycin. CONCLUSION: Physicians are currently using low-dose azithromycin for a long duration of more than 1 year for the management of OAD. The typical case definition is an older non-smoking adult with persistent asthma, often in combination with another OAD and presenting with bothersome cough or sputum. Azithromycin was well tolerated and led to reduced healthcare utilisation. Further research is required to establish an optimal dosage regimen of azithromycin in OAD.

Patients with allergic asthma have lower risk of severe COVID-19 outcomes than patients with nonallergic asthma.

BACKGROUND: Although asthma does not appear to be a risk factor for severe coronavirus disease 2019 (COVID-19), outcomes could vary for patients with different asthma subtypes. The objective of this analysis was to compare COVID-19 outcomes in real-world cohorts in the United States among patients with asthma, with or without evidence of allergy. METHODS: In a retrospective analysis of the COVID-19 Optum electronic health record dataset (February 20, 2020-January 28, 2021), patients diagnosed with COVID-19 with a history of moderate-to-severe asthma were divided into 2 cohorts: those with evidence of allergic asthma and those without (nonallergic asthma). After 1:1 propensity score matching, in which covariates were balanced and potential bias was removed, COVID-19 outcomes were compared between cohorts. RESULTS: From a COVID-19 population of 591,198 patients, 1595 patients with allergic asthma and 8204 patients with nonallergic asthma were identified. After propensity score matching (n = 1578 per cohort), risk of death from any cause after COVID-19 diagnosis was significantly lower for patients with allergic vs nonallergic asthma (hazard ratio, 0.48; 95% CI 0.28-0.83; P = 0.0087), and a smaller proportion of patients with allergic vs nonallergic asthma was hospitalized within - 7 to + 30 days of COVID-19 diagnosis (13.8% [n = 217] vs 18.3% [n = 289]; P = 0.0005). Among hospitalized patients, there were no significant differences between patients with allergic or nonallergic asthma in need for intensive care unit admission, respiratory support, or COVID-19 treatment. CONCLUSIONS: Asthma subtype may influence outcomes after COVID-19; patients with allergic asthma are at lower risk for hospitalization/death than those with nonallergic asthma.

Ensemble multimodal deep learning for early diagnosis and accurate classification of COVID-19.

Over the past few years, the awful COVID-19 pandemic effect has become a lethal sickness. The processing of the gathered samples requires extra time due to the use of medical diagnostic equipment, methodologies, and clinical testing procedures for the early diagnosis of infected individuals. An innovative multimodal paradigm for the early diagnosis and precise categorization of COVID-19 is put up as a solution to this issue. To extract distinguishing features from the prepared chest X-ray picture and cough (audio) database, chest X-ray-based and cough-based model are used here. Other public chest X-ray image datasets, and the Coswara cough (audio) dataset containing 92 COVID-19 positive, and 1079 healthy subjects (people) using the deep Uniform-Net, and Convolutional Neural Network (CNN). The weighted sum-rule fusion method and ensemble deep learning algorithms are utilized to further combine the extracted features. For the early diagnosis of patients, the framework offers an accuracy of 98.67%.

Chest X ray and cough sample based deep learning framework for accurate diagnosis of COVID-19.

All witnessed the terrible effects of the COVID-19 pandemic on the health and work lives of the population across the world. It is hard to diagnose all infected people in real time since the conventional medical diagnosis of COVID-19 patients takes a couple of days for accurate diagnosis results. In this paper, a novel learning framework is proposed for the early diagnosis of COVID-19 patients using hybrid deep fusion learning models. The proposed framework performs early classification of patients based on collected samples of chest X-ray images and Coswara cough (sound) samples of possibly infected people. The captured cough samples are pre-processed using speech signal processing techniques and Mel frequency cepstral coefficient features are extracted using deep convolutional neural networks. Finally, the proposed system fuses extracted features to provide 98.70% and 82.7% based on Chest-X ray images and cough (audio) samples for early diagnosis using the weighted sum-rule fusion method.

Non-hypertension-associated Posterior Reversible Encephalopathy Syndrome in COVID-19.

Background: Coronavirus disease-2019 (COVID-19) infection-related neurological events are not uncommon but presenting as posterior reversible encephalopathy syndrome (PRES) without hypertension is a very rare presentation and requires a high index of suspicion. Case summary: We report a case of a middle-aged female who presented with severe COVID-19 disease with no neurological symptoms. She complained of diminished vision on day 7 of the illness and underwent an MRI brain to rule out an ischemic stroke but the findings were suggestive of PRES. She had no episode of hypertension during the hospital stay. Probably severe COVID-related inflammation was the reason for such a presentation. Conservative management resolved the issue and her symptoms weaned off. Conclusion: Severe COVID disease can lead to PRES-like symptoms and requires neuroimaging to validate it. Conservative management is the best treatment for such patients. How to cite this article: Sharma D, Tomar DS, Gupta S. Non-hypertension-associated Posterior Reversible Encephalopathy Syndrome in COVID-19. Indian J Crit Care Med 2022;26(5):641-642.

Competencies for Point-of-care Ultrasonography in ICU: An ISCCM Expert Panel Practice Recommendation.

How to cite this article: Srinivasan S, Kumar PG, Govil D, Gupta S, Kumar V, Pichamuthu K, et al. Competencies for Point-of-care Ultrasonography in ICU: An ISCCM Expert Panel Practice Recommendation. Indian J Crit Care Med 2022;26(S2):S7-S12.

PDGFRA defines the mesenchymal stem cell Kaposi's sarcoma progenitors by enabling KSHV oncogenesis in an angiogenic environment.

Kaposi's sarcoma (KS) is an AIDS-defining cancer caused by the KS-associated herpesvirus (KSHV). Unanswered questions regarding KS are its cellular ontology and the conditions conducive to viral oncogenesis. We identify PDGFRA(+)/SCA-1(+) bone marrow-derived mesenchymal stem cells (Pα(+)S MSCs) as KS spindle-cell progenitors and found that pro-angiogenic environmental conditions typical of KS are critical for KSHV sarcomagenesis. This is because growth in KS-like conditions generates a de-repressed KSHV epigenome allowing oncogenic KSHV gene expression in infected Pα(+)S MSCs. Furthermore, these growth conditions allow KSHV-infected Pα(+)S MSCs to overcome KSHV-driven oncogene-induced senescence and cell cycle arrest via a PDGFRA-signaling mechanism; thus identifying PDGFRA not only as a phenotypic determinant for KS-progenitors but also as a critical enabler for viral oncogenesis.