Papers by Karanvir Kaushal
Journal of Hazardous Materials

Vaccines
COVID-19 has caused devastating effects worldwide ever since its origin in December 2019. IL-6 is... more COVID-19 has caused devastating effects worldwide ever since its origin in December 2019. IL-6 is one of the chief markers used in the management of COVID-19. We conducted a longitudinal study to investigate the role of IL-6 in diagnosis, treatment, and prognosis of COVID-19-related cytokine storm. Patients with COVID-19 who were admitted at AIIMS Rishikesh from March to December 2020 were included in the study. Patients with no baseline IL-6 value at admission and for whom clinical data were not available were excluded. Clinical and laboratory data of these patients were collected from the e-hospital portal and entered in an excel sheet. Correlation was seen with other inflammatory markers and outcomes were assessed using MS Excel 2010 and SPSS software. A total of 131 patients were included in the study. Of these, 74.8% were males, with mean age 55.03 ± 13.57 years, and mean duration from symptom onset being 6.69 ± 6.3 days. A total of 82.4% had WHO severe category COVID-19, with ...

European Journal of Medical Research
Pseudomonas aeruginosa is an adaptable bacterial pathogen that infects a variety of organs, inclu... more Pseudomonas aeruginosa is an adaptable bacterial pathogen that infects a variety of organs, including the respiratory tract, vascular system, urinary tract, and central nervous system, causing significant morbidity and mortality. As the primary goal of this study, we wanted to determine how pigment color production differed between clinical strains of P. aeruginosa, and whether or not that variation was associated with multidrug resistance or the ability to form biofilms. We screened in total 30.1% of yellow, 39.8% green and 30.1% of no pigment-producing P. aeruginosa strains from a total of 143 various clinical isolates. Yellow pigment-producing strains presented significant resistance to antibiotics groups, including β-lactam (91.5%), aminoglycosides (70.5%), and carbapenems (51.9%) compared to green and non-pigmented strains. Notably, 16.3% of yellow pigment-producing strains were resistant to colistin which is used as a last-resort treatment for multidrug-resistant bacteria, whe...

Cells
Cirrhosis is a severe form of liver fibrosis that results in the irreversible replacement of live... more Cirrhosis is a severe form of liver fibrosis that results in the irreversible replacement of liver tissue with scar tissue in the liver. Environmental toxicity, infections, metabolic causes, or other genetic factors including autoimmune hepatitis can lead to chronic liver injury and can result in inflammation and fibrosis. This activates myofibroblasts to secrete ECM proteins, resulting in the formation of fibrous scars on the liver. Fibrosis regression is possible through the removal of pathophysiological causes as well as the elimination of activated myofibroblasts, resulting in the reabsorption of the scar tissue. To date, a wide range of antifibrotic therapies has been tried and tested, with varying degrees of success. These therapies include the use of growth factors, cytokines, miRNAs, monoclonal antibodies, stem-cell-based approaches, and other approaches that target the ECM. The positive results of preclinical and clinical studies raise the prospect of a viable alternative t...

Pharmaceuticals, 2022
The rise in multiple-drug-resistant (MDR) phenotypes in Gram-negative pathogens is a major public... more The rise in multiple-drug-resistant (MDR) phenotypes in Gram-negative pathogens is a major public health crisis. Pseudomonas aeruginosa is one of the leading causes of nosocomial infections in clinics. Treatment options for P. aeruginosa have become increasingly difficult due tdo its remarkable capacity to resist multiple antibiotics. The presence of intrinsic resistance factors and the ability to quickly adapt to antibiotic monotherapy warrant us to look for alternative strategies like combinatorial antibiotic therapy. Here, we report the frequency of P. aeruginosa multidrug-resistant and extensively drug-resistance (XDR) phenotypes in a super-specialty tertiary care hospital in north India. Approximately 60 percent of all isolated P. aeruginosa strains displayed the MDR phenotype. We found highest antibiotic resistance frequency in the emergency department (EMR), as 20 percent of isolates were resistant to 15 antipseudomonal antibiotics. Presence of plasmids with quinolone-resista...

Journal of Critical Care, 2022
Ferritin is a known inflammatory biomarker in COVID-19. However, many factors and co-morbidities ... more Ferritin is a known inflammatory biomarker in COVID-19. However, many factors and co-morbidities can confound the level of serum ferritin. This current metaanalysis evaluates serum ferritin level in different severity levels in COVID-19. Studies evaluating serum ferritin level in different clinical contexts (COVID-19 vs. control, mild to moderate vs. severe to critical, non-survivor vs. survivor, organ involvement, ICU and mechanical ventilation requirement) were included (total 9 literature databases searched). Metaanalysis and metaregression was carried out using metaphor “R” package. Compared to control (COVID-19 negative), higher ferritin levels were found among the COVID-19 patients [SMD −0.889 (95% C.I. −1.201, −0.577), I2 = 85%]. Severe to critical COVID-19 patients showed higher ferritin levels compared to mild to moderate COVID-19 patients [SMD 0.882 (0.738, 1.026), I2 = 85%]. In meta-regression, high heterogeneity was observed could be attributed to difference in “mean age”, and “percentage of population with concomitant co-morbidities”. Non-survivors had higher serum ferritin level compared to survivors [SMD 0.992 (0.672, 1.172), I2 = 92.33%]. In meta-regression, high heterogeneity observed could be attributed to difference in “mean age” and “percentage of male sex”. Patients requiring ICU [SMD 0.674 (0.515 to 0.833), I2 = 80%] and mechanical ventilation [SMD 0.430 (0.258, 0.602), I2 = 32%] had higher serum ferritin levels compared to those who didn't. To conclude, serum ferritin level may serve as an important biomarker which can aid in COVID-19 management. However, presence of other co-morbid conditions/confounders warrants cautious interpretation.
1Department of Microbiology, All India Institute of Medical Sciences, Rishikesh-249203, India; 2D... more 1Department of Microbiology, All India Institute of Medical Sciences, Rishikesh-249203, India; 2Department of Pharmacology, All India Institute of Medical Sciences, Rishikesh-249203, India; 3Department of Biochemistry, All India Institute of Medical Sciences, Rishikesh-249203, India; 4Department of Medical Oncology, All India Institute of Medical Sciences, Rishikesh-249203; 5Department of Cancer Biology, Central Drug Research Institute, Lucknow-226031.

Journal of Biomolecular Structure and Dynamics, 2020
To elucidate the role of artificial intelligence (AI) in therapeutics for coronavirus disease 201... more To elucidate the role of artificial intelligence (AI) in therapeutics for coronavirus disease 2019 (COVID-19). Five databases were searched (December 2019-May 2020). We included both published and preprint original articles in English that applied AI, machine learning or deep learning in drug repurposing, novel drug discovery, vaccine and antibody development for COVID-19. Out of 31 studies included, 16 studies applied AI for drug repurposing, whereas 10 studies utilized AI for novel drug discovery. Only four studies used AI technology for vaccine development, whereas one study generated stable antibodies against SARS-CoV-2. Approx. 50% of studies exclusively targeted 3CLpro of SARS-CoV-2, and only two studies targeted ACE/TMPSS2 for inhibiting host viral interactions. Around 16% of the identified drugs are in different phases of clinical evaluation against COVID-19. AI has emerged as a promising solution of COVID-19 therapeutics. During this current pandemic, many of the researchers have used AI-based strategies to process large databases in a more customized manner leading to the faster identification of several potential targets, novel/repurposing of drugs and vaccine candidates. A number of these drugs are either approved or are in a late-stage clinical trial and are potentially effective against SARS-CoV2 indicating validity of the methodology. However, as the use of AI-based screening program is currently in budding stage, sole reliance on such algorithms is not advisable at this current point of time and an evidence based approach is warranted to confirm their usefulness against this life-threatening disease.

Biology, 2020
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic threat with... more Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic threat with more than 11.8 million confirmed cases and more than 0.5 million deaths as of 3 July 2020. Given the lack of definitive pharmaceutical interventions against SARS-CoV-2, multiple therapeutic strategies and personal protective applications are being used to reduce the risk of high mortality and community spread of this infection. Currently, more than a hundred vaccines and/or alternative therapeutic regimens are in clinical trials, and some of them have shown promising results in improving the immune cell environment and controlling the infection. In this review, we discussed high-performance multi-directory strategies describing the uncontrolled deregulation of the host immune landscape associated with coronavirus disease (COVID-19) and treatment strategies using an anti-neoplastic regimen. We also followed selected current treatment plans and the most important on-going clinical trials ...

Indian Journal of Pharmacology, 2020
PURPOSE: Although the use of steroids in the management of COVID-19 has been addressed by a few s... more PURPOSE: Although the use of steroids in the management of COVID-19 has been addressed by a few systematic review and meta-analysis, however, they also used data from “SARS-CoV” and “MERS-CoV.” Again, most of these studies addressed only one severity category of patients or addressed only one efficacy endpoint (mortality). In this context, we conducted this meta-analysis to evaluate the efficacy and safety of steroid therapy among all severity categories of patients with COVID-19 (mild to moderate and severe to critical category) in terms of “mortality,” “requirement of mechanical ventilation,” “requirement of ICU” and clinical cure parameters. METHODS: 11 databases were screened. Only randomized controlled trials (RCTs) or high quality (on the basis of risk of bias analysis) comparative-observational studies were included in the analysis. RevMan5.3 was used for the meta-analysis. RESULTS: A total of 15 studies (3 RCT and 12 comparative-observational studies) were included. In the mechanically-ventilated COVID-19 population, treatment with dexamethasone showed significant protection against mortality (single study). Among severe and critically ill combined population, steroid administration was significantly associated with lowered mortality (risk ratio [RR] 0.83 [0.76–0.910]), lowered requirement of mechanical ventilation (RR 0.59 [0.51–0.69]), decreased requirement of intensive care unit (ICU) (RR 0.62 [0.45–0.86]), lowered length of ICU stay (single-study) and decreased duration of mechanical ventilation (two-studies). In mild to moderate population, steroid treatment was associated with a higher “duration of hospital stay,” while no difference was seen in other domains. In patients at risk of progression to “acute respiratory distress syndrome,” steroid administration was associated with “reduced requirement of mechanical ventilation” (single-study). CONCLUSION: This study guides the use of steroid across patients with different severity categories of COVID-19. Among mechanically ventilated patients, steroid therapy may be beneficial in terms of reduced mortality. Among “severe and critical” patients; steroid therapy was associated with lowered mortality, decreased requirement of mechanical ventilation, and ICU. However, no benefit was observed in “mild to moderate” population. To conclude, among properly selected patient populations (based-upon clinical severity and biomarker status), steroid administration may prove beneficial in patients with COVID-19.

Scientific Reports, 2019
Renal cell carcinoma (RCC) is the leading cause among cancer-related deaths due to urological can... more Renal cell carcinoma (RCC) is the leading cause among cancer-related deaths due to urological cancers, which results in response to combination of genetic and epigenetic factors. Histone methylations have been implicated in renal tumorigenesis but their clinical significance and underlying pathology are unexplored. Here, we elucidated the histone 3 lysine 4 (H3K4) methylation patterns in clear cell RCC and its underlying pathology. Lower cellular levels of H3K4 mono-methylation, -dimethylation and –tri-methylation were fraternized with higher TNM staging and Fuhrman grading as well as tumor metastasis. Further, the expression profile of 20 H3K4 modifiers revealed the significant over-expression of histone demethylases compared to methyltransferases, indicating their role in the reduction of H3K4 methylation levels. In view of above facts, the role of LSD2 and KDM5A demethylases in RCC pathogenesis were explored using respective siRNAs. The RCC cells exhibited reduced cell viability ...

Journal of gastroenterology and hepatology, Jan 23, 2018
There is lack of data on functional and morphological recovery after an attack of acute pancreati... more There is lack of data on functional and morphological recovery after an attack of acute pancreatitis (AP) or acute recurrent pancreatitis (ARP) in children. This study aims to evaluate the functional impairment and morphological changes in the pancreas after recovery. All consecutive patients presenting with AP (n = 61) or ARP (n = 35), as per standard diagnostic criteria, were enrolled. After 2 months of pancreatitis, fecal elastase-1 (FE-1) (μg/g) and 2-h oral glucose tolerance test to calculate oral disposition index (DI ) (mmol/L) (β-cell function) were performed. Morphological changes were assessed by endoscopic ultrasound and transabdominal ultrasound. Patients with chronic pancreatitis (CP) (n = 27) and healthy children (HC) (n = 26) were included as controls for functional parameters. At a median follow up of 12 (4-44) and 11 (2-108) months, 66.7% and 75.9% (P = 0.57) of AP and ARP demonstrated exocrine insufficiency (FE-1 < 200), respectively. Mean (SD) FE-1 was 183.64 ±...
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Papers by Karanvir Kaushal