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.

Am I Sedated or in Pain? Please Monitor by Brain.

How to cite this article: Gupta A, Tomar DS. Am I Sedated or in Pain? Please Monitor by Brain. Indian J Crit Care Med 2024;28(6):531-532.

ISCCM Position Statement on the Management of Invasive Fungal Infections in the Intensive Care Unit.

Rationale: Invasive fungal infections (IFI) in the intensive care unit (ICU) are an emerging problem owing to the use of broad-spectrum antibiotics, immunosuppressive agents, and frequency of indwelling catheters. Timely diagnosis which is imperative to improve outcomes can be challenging. This position statement is aimed at understanding risk factors, providing a rational diagnostic approach, and guiding clinicians to optimize antifungal therapy. Objectives: To update evidence on epidemiology, risk factors, diagnostic approach, antifungal initiation strategy, therapeutic interventions including site-specific infections and role of therapeutic drug monitoring in IFI in ICU and focus on some practice points relevant to these domains. Methodology: A committee comprising critical care specialists across the country was formed and specific aspects of fungal infections and antifungal treatment were assigned to each member. They extensively reviewed the literature including the electronic databases and the international guidelines and cross-references. The information was shared and discussed over several meetings and position statements were framed to ensure their reliability and relevance in critical practice. The draft document was prepared after obtaining inputs and consensus from all the members and was reviewed by an expert in this field. Results: The existing evidence on the management of IFI was updated and practice points were prepared under each subheading to enable critical care practitioners to streamline diagnosis and treatment strategies for patients in the ICU with additional detail on site-specific infections therapeutic drug monitoring. Conclusion: This position statement attempts to address the management of IFI in immunocompetent and non-neutropenic ICU patients. The practice points should guide in optimization of the management of critically ill patients with suspected or proven fungal infections. How to cite this article: Bhattacharya PK, Chakrabarti A, Sinha S, Pande R, Gupta S, Kumar AAK, et al. ISCCM Position Statement on the Management of Invasive Fungal Infections in the Intensive Care Unit. Indian J Crit Care Med 2024;28(S2):S20-S41.

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.