Publications by authors named "Ankur Gupta"

331 Publications

Rhabdomyolysis: Revisited.

Ulster Med J 2021 May 8;90(2):61-69. Epub 2021 Jul 8.

Department of Medicine, Whakatane Hospital PO BOX 241, Whakatane 3158, New Zealand.

Rhabdomyolysis (RML) is a pathological entity characterized by symptoms of myalgia, weakness and dark urine (which is often not present) resulting in respiratory failure and altered mental status. Laboratory testing for myoglobinuria is pathognomonic but so often not present during the time of testing that serum creatine kinase should always be sent when the diagnosis is suspected. Kidney injury from RML progresses through multiform pathways resulting in acute tubular necrosis. Early treatment (ideally<6 hoursfrom onset) is needed with volume expansion of all non-overloaded patients along with avoidance of nephrotoxins. There is insufficient data to recommend any specific fluid. The mortality rate ranges from 10% to up to 50% with severe AKI, so high index of suspicion and screening should be in care plan of seriously ill patients at risk for RML.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8278949PMC
May 2021

Dissection of External Iliac Artery During Pediatric En bloc Kidney Transplant: Successful Rescue and Reimplant.

Exp Clin Transplant 2021 Jul 16. Epub 2021 Jul 16.

From the Hume-Lee Transplant Center, Virginia Commonwealth University, Richmond, Virginia, USA.

En bloc kidney transplant is a surgical treatment option that increases available donor organs and has excellent graft survival for patients with end-stage renal disease. Herein, we report a case of dissection of the external iliac artery that occurred during en bloc kidney transplant in an adult recipient. The en bloc kidneys were removed, flushed, and then reimplanted after restoring the blood flow to the lower limb. To our knowledge, this is the first case of dissection of the external iliac artery managed successfully during en bloc kidney transplant.
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http://dx.doi.org/10.6002/ect.2021.0150DOI Listing
July 2021

Mucormycosis and COVID-19: An epidemic within a pandemic in India.

Mycoses 2021 Jul 13. Epub 2021 Jul 13.

Division of Neurology, Department of Medicine, National University Hospital and Yong Loo Lin School of Medicine, National University of Singapore, Singapore.

Importance: Coronavirus disease (COVID-19) causes an immunosuppressed state and increases risk of secondary infections like mucormycosis. We evaluated clinical features, predisposing factors, diagnosis and outcomes for mucormycosis among patients with COVID-19 infection.

Methods: This prospective, observational, multi-centre study included 47 consecutive patients with mucormycosis, diagnosed during their course of COVID-19 illness, between January 3 and March 27, 2021. Data regarding demography, underlying medical conditions, COVID-19 illness and treatment were collected. Clinical presentations of mucormycosis, imaging and biochemical characteristics and outcome were recorded.

Results: Of the 2567 COVID-19 patients admitted to 3 tertiary centres, 47 (1.8%) were diagnosed with mucormycosis. Mean age was 55 ± 12.8years, and majority suffered from diabetes mellitus (n = 36, 76.6%). Most were not COVID-19 vaccinated (n = 31, 66.0%) and majority (n = 43, 91.5%) had developed moderate-to-severe pneumonia, while 20 (42.6%) required invasive ventilation. All patients had received corticosteroids and broad-spectrum antibiotics while most (n = 37, 78.7%) received at least one anti-viral medication. Mean time elapsed from COVID-19 diagnosis to mucormycosis was 12.1 ± 4.6days. Eleven (23.4%) subjects succumbed to their disease, mostly (n = 8, 72.7%) within 7 days of diagnosis. Among the patients who died, 10 (90.9%) had pre-existing diabetes mellitus, only 2 (18.2%) had received just one vaccine dose and all developed moderate-to-severe pneumonia, requiring oxygen supplementation and mechanical ventilation.

Conclusions: Mucormycosis can occur among COVID-19 patients, especially with poor glycaemic control, widespread and injudicious use of corticosteroids and broad-spectrum antibiotics, and invasive ventilation. Owing to the high mortality, high index of suspicion is required to ensure timely diagnosis and appropriate treatment in high-risk populations.
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http://dx.doi.org/10.1111/myc.13353DOI Listing
July 2021

Comment - Bold policy changes are needed to meet the need for organ transplantation in India.

Am J Transplant 2021 Jul 8. Epub 2021 Jul 8.

Medanta Institute of Liver Transplantation and Regenerative Medicine.

We read with interest the authors' viewpoints[1] on what ails deceased donor transplantation (DDT) programs in India and their proposed solutions. We present our perspective on how living donor transplantation(LDT) programs service an unmet need in India, and suggest the way forward for DDT.
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http://dx.doi.org/10.1111/ajt.16755DOI Listing
July 2021

Biophysical properties of the isolated spike protein binding helix of human ACE2.

Biophys J 2021 07 30;120(14):2785-2792. Epub 2021 Jun 30.

Department of Chemical Sciences, Tata Institute of Fundamental Research, Colaba, Mumbai, India. Electronic address:

The entry of the severe acute respiratory syndrome coronavirus 2 virus in human cells is mediated by the binding of its surface spike protein to the human angiotensin-converting enzyme 2 (ACE2) receptor. A 23-residue long helical segment (SBP1) at the binding interface of human ACE2 interacts with viral spike protein and therefore has generated considerable interest as a recognition element for virus detection. Unfortunately, emerging reports indicate that the affinity of SBP1 to the receptor-binding domain of the spike protein is much lower than that of the ACE2 receptor itself. Here, we examine the biophysical properties of SBP1 to reveal factors leading to its low affinity for the spike protein. Whereas SBP1 shows good solubility (solubility > 0.8 mM), circular dichroism spectroscopy shows that it is mostly disordered with some antiparallel β-sheet content and no helicity. The helicity is substantial (>20%) only upon adding high concentrations (≥20% v/v) of 2,2,2-trifluoroethanol, a helix promoter. Fluorescence correlation spectroscopy and single-molecule photobleaching studies show that the peptide oligomerizes at concentrations >50 nM. We hypothesized that mutating the hydrophobic residues (F28, F32, and F40) of SBP1, which do not directly interact with the spike protein, to alanine would reduce peptide oligomerization without affecting its spike binding affinity. Whereas the mutant peptide (SBP1) shows substantially reduced oligomerization propensity, it does not show improved helicity. Our study shows that the failure of efforts, so far, to produce a short SBP1 mimic with a high affinity for the spike protein is not only due to the lack of helicity but is also due to the heretofore unrecognized problem of oligomerization.
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http://dx.doi.org/10.1016/j.bpj.2021.06.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8241576PMC
July 2021

Epidemiological and clinical profile, management and outcomes of young patients (≤40 years) with acute coronary syndrome: A single tertiary care center study.

Indian Heart J 2021 May-Jun;73(3):295-300. Epub 2021 Jan 17.

Department of Cardiology, Post Graduate Institute of Medical Education & Research, Chandigarh, 160012, India. Electronic address:

Objective: To study the epidemiological and clinical profile, angiographic patterns, reasons for the delay in presentation, management, and outcomes of the acute coronary syndrome (ACS) in young patients (≤40yrs) presenting to a tertiary care hospital in North India.

Methods: We included a total of 182 patients aged ≤40 years and presenting with ACS to the cardiology critical care unit of our department from January 2018 to July 2019.

Results: The mean age of the study population was 35.5 ± 4.7years. 96.2% were males. Risk factors prevalent were smoking (56%), hypertension (29.7%), family history of premature coronary artery disease (18.2%), and diabetes (15.9%). The median time to first medical contact and revascularization was 300 (10-43200) minutes and 2880 (75-68400) minutes, respectively. ST-elevation ACS (STE-ACS) accounted for 82% and Non-ST-elevation ACS (NSTE-ACS) accounted for 18% of cases. Thrombolysis was done in 51.7% of the cases. Coronary angiography was done in 91.7% and percutaneous coronary intervention (PCI) in 52.2% (95/182) of the total cases. Coronary artery bypass surgery (CABG) was done in 2 patients (1.1%). Among those who underwent coronary angiography, single-vessel disease (SVD) was seen in 53% of the cases. There were no deaths in hospital, and only one patient died during the 30 days follow up.

Conclusions: STE-ACS was the most common presentation of ACS in the young population. Smoking was the most common risk factor. The majority of the patients had single-vessel disease, and there was a significant delay in first medical contact and revascularization.
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http://dx.doi.org/10.1016/j.ihj.2021.01.015DOI Listing
January 2021

Hypertension in the hospitalized patient: An update.

Nefrologia 2021 May 29. Epub 2021 May 29.

Consultant, Department of Medicine, Whakatane Hospital, New Zealand. Electronic address:

In-patient hypertension is a common problem seen in the hospital setting. Current evidence-based guidelines define and address management of hypertension in ambulatory care and hypertensive emergencies in the hospital setting. However, they lack guidance for the management of acute asymptomatic/non-emergent hypertension in the hospitalised patient. The risk-benefit of treating inpatient asymptomatic hypertension is largely unknown. In this narrative review, we discuss current evidence-based perspectives to address this clinical entity.
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http://dx.doi.org/10.1016/j.nefro.2020.12.020DOI Listing
May 2021

Interaction-Deletion: A Composite Energy Method for the Optimization of Molecular Systems Selectively Removing Specific Nonbonded Interactions.

J Phys Chem A 2021 Jun 20;125(21):4668-4682. Epub 2021 May 20.

Department of Chemistry, Indiana University, Bloomington, Indiana 47405, United States.

The complex interactions between different portions of a large molecule can be challenging to analyze through traditional electronic structure calculations. Moreover, standard methods cannot easily quantify the physical consequences of individual pairwise interactions inside a molecule. By creating a set of molecular fragments, we propose a composite energy method to explore changes in a molecule caused by removing selected nonbonded interactions between different molecular portions. Energies and forces are easily obtained with this composite approach, allowing geometry optimizations that lead to chemically meaningful structures that describe how the omitted interactions contribute to changes in the local geometrical minima. We illustrate the application of our new hybrid scheme by computing the influence of intramolecular hydrogen-bonding interactions in two small molecules: 1,6-(tGGTGGg)-hexanediol and a cyclic analogue, -1,4-cyclohexanediol. The resulting structural and energetic changes are interpreted to yield key physical insights and quantify concepts such as "preparation energy" or "reorganization energy". We demonstrate that the composite method can be extended to larger molecular systems by showing its application on a Si(100) surface model containing interactions between dissociated ammonia molecules on adjacent surface dimers. The scheme's efficacy is also tested by applying it to systems having multiple intramolecular interactions, viz., 3-polyglycine and HGPGG. Furthermore, the cooperative nature of intramolecular hydrogen bonds is explored by using interaction-deletion in 2-nitrobenzene-1,3-diol.
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http://dx.doi.org/10.1021/acs.jpca.1c02918DOI Listing
June 2021

Performance of the Aldosterone to Renin Ratio as a Screening Test for Primary Aldosteronism.

J Clin Endocrinol Metab 2021 Jul;106(8):2423-2435

Department of Medicine (Division of Nephrology) and the Ottawa Hospital Research Institute, University of Ottawa, Ottawa, ON,Canada.

Context: The aldosterone to renin ratio (ARR) is the guideline-recommended screening test for primary aldosteronism. However, there are limited data in regard to the diagnostic performance of the ARR.

Objective: To evaluate the sensitivity and specificity of the ARR as a screening test for primary aldosteronism.

Methods: We searched the MEDLINE, Embase, and Cochrane databases until February 2020. Observational studies assessing ARR diagnostic performance as a screening test for primary aldosteronism were selected. To limit verification bias, only studies where dynamic confirmatory testing was implemented as a reference standard regardless of the ARR result were included. Study-level data were extracted and risk of bias and applicability were assessed using the QUADAS-2 tool.

Results: Ten studies, involving a total of 4110 participants, were included. Potential risk of bias related to patient selection was common and present in half of the included studies. The population base, ARR positivity threshold, laboratory assay, and reference standard for confirmatory testing varied substantially between studies. The reported ARR sensitivity and specificity varied widely with sensitivity ranging from 10% to 100% and specificity ranging from 70% to 100%. Notably, 3 of the 10 studies reported an ARR sensitivity of <50%, suggesting a limited ability of the ARR to adequately identify patients with primary aldosteronism.

Conclusions: ARR performance varied widely based on patient population and diagnostic criteria, especially with respect to sensitivity. Therefore, no single ARR threshold for interpretation could be recommended. Limitations in accuracy and reliability of the ARR must be recognized in order to appropriately inform clinical decision-making.
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http://dx.doi.org/10.1210/clinem/dgab348DOI Listing
July 2021

Therapeutic approaches for SARS-CoV-2 infection.

Methods 2021 May 5. Epub 2021 May 5.

Centre for Advanced Research (CFAR), Faculty of Medicine, King George's Medical University (KGMU), Lucknow 226003, India. Electronic address:

Therapeutic approaches to COVID-19 treatment require appropriate inhibitors to target crucial proteins of SARS-CoV-2 replication machinery. It's been approximately 12 months since the pandemic started, yet no known specific drugs are available. However, research progresses with time in terms of high throughput virtual screening (HTVS) and rational design of repurposed, novel synthetic and natural products discovery by understanding the viral life cycle, immuno-pathological and clinical outcomes in patients based on host's nutritional, metabolic, and lifestyle status. Further, complementary and alternative medicine (CAM) approaches have also improved resiliency and immune responses. In this article, we summarize all the therapeutic antiviral strategies for COVID-19 drug discovery including computer aided virtual screening, repurposed drugs, immunomodulators, vaccines, plasma therapy, various adjunct therapies, and phage technology to unravel insightful mechanistic pathways of targeting SARS-CoV-2 and host's intrinsic, innate immunity at multiple checkpoints that aid in the containment of the disease.
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http://dx.doi.org/10.1016/j.ymeth.2021.04.026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096528PMC
May 2021

Antegrade versus retrograde techniques for Chronic Total Occlusions (CTO): a review and comparison of techniques and outcomes.

Expert Rev Cardiovasc Ther 2021 Jun 12;19(6):465-473. Epub 2021 May 12.

Division of Cardiology, Henry Ford Hospital, Detroit, Michigan, US.

: As the field of chronic total occlusion percutaneous coronary intervention has evolved, technical approaches have evolved and been refined.: In this review, we discuss the major techniques utilized in modern CTO PCI including antegrade wiring, antegrade dissection reentry, retrograde wiring, and retrograde dissection reentry. Retrograde techniques have been extensively studied in comparison to antegrade techniques. Retrograde techniques have contributed to increases in CTO PCI success rates and are generally used in higher complexity lesions. Observational data ssuggestincreased sshort-termcomplications in procedures requiring the use of retrograde techniques; however, llong-termCTO PCI durability and patient outcomes have been shown to be similar among procedures using antegrade only versus retrograde techniques.: Retrograde techniques play a vital role in the technical success of CTO PCI, particularly among more complex lesions and in patients with high burdens of comorbidities. Increases in procedural safety with equipment iteration and in the use of adjunctive imaging will play an important role in the selection of appropriate retrograde conduits and the overall success rates of CTO PCI.
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http://dx.doi.org/10.1080/14779072.2021.1924677DOI Listing
June 2021

Radial Artery Pseudoaneurysm Following Percutaneous Coronary Intervention.

J Invasive Cardiol 2021 May;33(5):E406

Department of Cardiology, VMMC and Safdarjung Hospital, New Delhi, India 110029.

Radial artery pseudoaneurysm is a very rare complication. In the presented case, computed tomography 3 months post percutaneous coronary intervention demonstrated contrast extravasation, suggestive of radial artery pseudoaneurysm. This complication was managed with thrombin infusion at the distal radial artery.
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May 2021

An unusual cause of double-lumen tube obstruction in mechanically ventilated patient.

Ann Card Anaesth 2021 Apr-Jun;24(2):275-276

Department of Anaesthesia and Critical Care, Command Hospital (Southern Command), Pune, Maharashtra, India.

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http://dx.doi.org/10.4103/aca.ACA_22_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8253019PMC
April 2021

Real world perspective of coronary chronic total occlusion in third world countries: A tertiary care centre study from northern India.

Indian Heart J 2021 Mar-Apr;73(2):156-160. Epub 2021 Mar 17.

Advanced Cardiac Centre, Post Graduate Institute of Medical Education and Research, PGIMER, Chandigarh, 160012, India. Electronic address:

Objectives: The aim of this study is to determine the prevalence, clinical characteristics, angiographic profile and predictors of outcome for percutaneous coronary interventions (PCI) of coronary chronic total occlusions (CTO) in a tertiary referral centre of north India.

Background: There is no data on the prevalence and very few reports on clinical characteristics, angiographic profile and outcome of PCI in CTO from India.

Methods: Retrospective analysis was done for the data of 12,020 patients undergoing coronary angiography (CAG) between January 2018 to January 2019 at our centre. Detailed baseline clinical, angiographic and revascularization data was collected. Outcome of CTO PCI was also noted. All baseline parameters were analysed for predicting the outcome of CTO PCI.

Results: CTO was identified in 16.3% (1968) patients undergoing CAG and in 24.4% of patients with hemodynamically significant CAD. CTO was predominantly found in LAD (48%) followed by RCA (42.9%) and LCx (25.3%) arterial distribution. Mean JCTO score was 1.93 ± 0.7. PCI as a management strategy was adopted in 456 of 1968 patients (23.1%) and was successful in 340 of 456 (74.6%) of patients. Almost all CTO PCI were attempted by an antegrade approach only. Increasing age, male sex, CTO in LCx arterial distribution and higher J CTO score were associated with poorer outcome in CTO PCI.

Conclusions: CTO's are commonly encountered during CAG procedures. In patients undergoing CTO PCI, a fair success rate can be achieved in a high volume experienced centre.
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http://dx.doi.org/10.1016/j.ihj.2021.03.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065346PMC
March 2021

Relative Predictive Value of Circulating Immune Markers in US Adults Without Cardiovascular Disease: Implications for Risk Reclassification.

Mayo Clin Proc 2021 07 9;96(7):1812-1821. Epub 2021 Apr 9.

Division of Cardiovascular Disease and Comprehensive Cardiovascular Center, University of Alabama at Birmingham, Birmingham, AL; Division of Molecular Imaging and Therapeutics, Department of Radiology, University of Alabama at Birmingham, Birmingham, AL; Section of Cardiology, Birmingham Veteran Affairs Medical Center, Birmingham, AL. Electronic address:

Objective: To investigate the relative predictive value of circulating immune cell markers for cardiovascular mortality in ambulatory adults without cardiovascular disease.

Methods: We analyzed data of participants enrolled in the National Health and Nutrition Examination Survey from January 1, 1999, to December 31, 2010, with the total leukocyte count within a normal range (4000-11,000 cells/μL [to convert to cells ×10/L, multiply by 0.001]) and without cardiovascular disease. The relative predictive value of circulating immune cell markers measured at enrollment-including total leukocyte count, absolute neutrophil count, absolute lymphocyte count, absolute monocyte count, monocyte-lymphocyte ratio (MLR), neutrophil-lymphocyte ratio, and C-reactive protein-for cardiovascular mortality was evaluated. The marker with the best predictive value was added to the 10-year atherosclerotic cardiovascular disease (ASCVD) risk score to estimate net risk reclassification indices for 10-year cardiovascular mortality.

Results: Among 21,599 participants eligible for this analysis, the median age was 47 years (interquartile range, 34-63 years); 10,651 (49.2%) participants were women, and 10,713 (49.5%) were self-reported non-Hispanic white. During a median follow-up of 9.6 years (interquartile range, 6.8-13.1 years), there were 627 cardiovascular deaths. MLR had the best predictive value for cardiovascular mortality. The addition of elevated MLR (≥0.3) to the 10-year ASCVD risk score improved the classification by 2.7%±1.4% (P=.04). Elevated MLR had better predictive value than C-reactive protein and several components of the 10-year ASCVD risk score.

Conclusion: Among ambulatory US adults without preexisting cardiovascular disease, we found that MLR had the best predictive value for cardiovascular mortality among circulating immune markers. The addition of MLR to the 10-year risk score significantly improved the risk classification of participants.
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http://dx.doi.org/10.1016/j.mayocp.2020.11.027DOI Listing
July 2021

Cardiovascular manifestations of COVID-19: An evidence-based narrative review.

Indian J Med Res 2021 Jan & Feb;153(1 & 2):7-16

Department of Cardiology, Advanced Cardiac Centre, Postgraduate Institute of Medical Education & Research, Chandigarh, India.

The recent outbreak of coronavirus disease 2019 (COVID-19) was declared a pandemic by the World Health Organization on March 11, 2020. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, primarily involves the respiratory system with viral pneumonia as a predominant manifestation. In addition, SARS-CoV-2 has various cardiovascular manifestations which increase morbidity and mortality in COVID-19. Patients with underlying cardiovascular diseases and conventional cardiovascular risk factors are predisposed for COVID-19 with worse prognosis. The possible mechanisms of cardiovascular injury are endothelial dysfunction, diffuse microangiopathy with thrombosis and increased angiotensin II levels. Hyperinflammation in the myocardium can result in acute coronary syndrome, myocarditis, heart failure, cardiac arrhythmias and sudden death. The high level of cardiac troponins and natriuretic peptides in the early course of COVID-19 reflects an acute myocardial injury. The complex association between COVID-19 and cardiovascular manifestations requires an in-depth understanding for appropriate management of these patients. Till the time a specific antiviral drug is available for COVID-19, treatment remains symptomatic. This review provides information on the cardiovascular risk factors and cardiovascular manifestations of COVID-19.
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http://dx.doi.org/10.4103/ijmr.IJMR_2450_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8184068PMC
April 2021

System for administering and monitoring hydroxychloroquine prophylaxis for COVID-19 in accordance with a national advisory: preliminary experience of a tertiary care institute in India.

Expert Rev Anti Infect Ther 2021 Apr 15:1-9. Epub 2021 Apr 15.

Department of Pharmacology, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

Background: Hydroxychloroquine (HCQ) was one of the earliest drugs to be recommended for tackling the COVID-19 threat leading to its widespread usage. We provide preliminary findings of the system, established in a tertiary care academic center for the administration of HCQ prophylaxis to healthcare workers (HCW) based on Indian Council of Medical Research (ICMR) advisory.

Methods: A dedicated clinical pharmacology and internal medicine team screened for contraindications, administered informed consent, maintained compliance and monitored for adverse events.

Results: Among the 194 HCWs screened for ruling out contraindications for prophylaxis, 9 were excluded and 185 were initiated on HCQ. A total of 55 adverse events were seen in 38 (20.5%) HCWs out of which 70.9%, 29.1% were mild and moderate & none were severe. Before the completion of therapy, a total of 23 participants discontinued. Change in QTc interval on day 2 was 5 (IQR: -3.75, 11) ms and the end of week 1 was 15 ms (IQR: 2, 18). Out of the 5 HCW who turned positive for COVID-19, 2 were on HCQ.

Conclusion: HCQ prophylaxis was found to be safe and well tolerated in HCW when administered after appropriate screening and with monitoring for adverse events.
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http://dx.doi.org/10.1080/14787210.2021.1909476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054489PMC
April 2021

Adynamic bone disease: Revisited.

Nefrologia (Engl Ed) 2021 Mar 8. Epub 2021 Mar 8.

Department of Medicine, Whakatane Hospital, Whakatane, New Zealand. Electronic address:

The bone and mineral disorders form an integral part of the management of a chronic kidney disease (CKD) patient. Amongst various types of bone pathologies in chronic kidney disease-mineral bone disorder (CKD-MBD), the prevalence of adynamic bone disease (ABD) is increasing. The present review discusses the updated pathophysiology, risk factors, and management of this disorder.
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http://dx.doi.org/10.1016/j.nefro.2020.11.012DOI Listing
March 2021

Complications and challenges of home hemodialysis: A historical review.

Semin Dial 2021 Jul 20;34(4):269-274. Epub 2021 Feb 20.

Division of Nephrology, The Ottawa Hospital, University of Ottawa, Ottawa, Canada.

Home hemodialysis (HHD) has evolved as a preferred and safe kidney replacement modality over the past six decades. Despite advances in technological aspects of HHD, potential complications still pose a challenge to health care givers, patients, and their families. In this narrative review, we describe vascular access and cannulation, anticoagulation, nutritional, residual kidney function, psychosocial, technique failure, and machine/procedural-related complications. Addressing these problems is essential for favorable patient outcomes.
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http://dx.doi.org/10.1111/sdi.12960DOI Listing
July 2021

Genome scale metabolic model driven strategy to delineate host response to Mycobacterium tuberculosis infection.

Mol Omics 2021 04 17;17(2):296-306. Epub 2021 Feb 17.

Complex Analysis Group, Translational Health Science and Technology Institute, NCR Biotech Science Cluster, 3rd Milestone, Faridabad-Gurgaon Expressway, Faridabad-121001, India.

We analyze high throughput proteomics data reflecting the response of the Mφ-like THP1 cell line to Mycobacterium tuberculosis (M. tuberculosis) infection. M. tuberculosis's engagement with the host's metabolic pathways is a known strategy employed by the pathogen to shift the balance in its favour. Our study revisits this strategy through the integration of the temporal proteomics data in the genome-scale metabolic model (GSMM) giving context-specific GSMMs. THP1 cells were infected with H37Ra, H37Rv, BND433 and JAL2287 strains of M. tuberculosis and the host response was studied at 6, 18, 30 and 42 hours after infection. We have developed a modified flux balance analysis (FBA), which does not use an objective function, to find the fluxes of metabolic reactions in different strains and stages of infection and have revealed different functional modules. Hence, we have established a method of rewiring using GSMMs to explore potential strategies to change the flux state of virulent M. tuberculosis infected macrophages as against their avirulent counterparts. Our methodology gives a correlation between different flux states, the extent of which was interpreted as the extent of rewiring. The accuracy of the results from the proposed methodology was validated with gene knockout experimental data. We found that more than one reaction has to be rewired simultaneously to alter virulent to an avirulent response. The identified modules showed influence across the investigated strains and time points suggesting that these reactions could be therapeutically targeted. This novel methodology is now available for use in other systems.
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http://dx.doi.org/10.1039/d0mo00138dDOI Listing
April 2021

A Rare Case of Dengue Hemorrhagic Fever with Myocarditis and Intracranial Hemorrhage.

J Pediatr Neurosci 2020 Jul-Sep;15(3):320-321. Epub 2020 Nov 6.

Department of Anaesthesiology & Critical Care, Armed Forces Medical College, Pune, Maharashtra, India.

We present a rare case of dengue hemorrhagic fever presenting with severe myocardial dysfunction along with intracranial hemorrhage and coagulopathy. It warrants every clinician to be vigilant in diagnosis and management so as to prevent life-threatening morbidity and mortality.
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http://dx.doi.org/10.4103/jpn.JPN_48_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847097PMC
November 2020

Altered Membrane Mechanics Provides a Receptor-Independent Pathway for Serotonin Action.

Chemistry 2021 May 12;27(27):7533-7541. Epub 2021 Mar 12.

Department of Chemical Sciences, Tata Institute of Fundamental Research, Homi Bhabha Road, Colaba, Mumbai, 400005, India.

Serotonin, an important signaling molecule in humans, has an unexpectedly high lipid membrane affinity. The significance of this finding has evoked considerable speculation. Here we show that membrane binding by serotonin can directly modulate membrane properties and cellular function, providing an activity pathway completely independent of serotonin receptors. Atomic force microscopy shows that serotonin makes artificial lipid bilayers softer, and induces nucleation of liquid disordered domains inside the raft-like liquid-ordered domains. Solid-state NMR spectroscopy corroborates this data at the atomic level, revealing a homogeneous decrease in the order parameter of the lipid chains in the presence of serotonin. In the RN46A immortalized serotonergic neuronal cell line, extracellular serotonin enhances transferrin receptor endocytosis, even in the presence of broad-spectrum serotonin receptor and transporter inhibitors. Similarly, it increases the membrane binding and internalization of oligomeric peptides. Our results uncover a mode of serotonin-membrane interaction that can potentiate key cellular processes in a receptor-independent fashion.
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http://dx.doi.org/10.1002/chem.202100328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8252079PMC
May 2021

Point-of-Care Echocardiography and Hemodynamic Monitoring in Cirrhosis and Acute-on-Chronic Liver Failure in the COVID-19 Era.

J Intensive Care Med 2021 May 13;36(5):511-523. Epub 2021 Jan 13.

Department of Nephrology, 29751Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Point-of-Care (POC) transthoracic echocardiography (TTE) is transforming the management of patients with cirrhosis presenting with septic shock, acute kidney injury, hepatorenal syndrome and acute-on-chronic liver failure (ACLF) by correctly assessing the hemodynamic and volume status at the bedside using combined echocardiography and POC ultrasound (POCUS). When POC TTE is performed by the hepatologist or intensivist in the intensive care unit (ICU), and interpreted remotely by a cardiologist, it can rule out cardiovascular conditions that may be contributing to undifferentiated shock, such as diastolic dysfunction, myocardial infarction, myocarditis, regional wall motion abnormalities and pulmonary embolism. The COVID-19 pandemic has led to a delay in seeking medical treatment, reduced invasive interventions and deferment in referrals leading to "collateral damage" in critically ill patients with liver disease. Thus, the use of telemedicine in the ICU (Tele-ICU) has integrated cardiology, intensive care, and hepatology practices across the spectrum of ICU, operating room, and transplant healthcare. Telecardiology tools have improved bedside diagnosis when introduced as part of COVID-19 care by remote supervision and interpretation of POCUS and echocardiographic data. In this review, we present the contemporary approach of using POC echocardiography and offer a practical guide for primary care hepatologists and gastroenterologists for cardiac assessment in critically ill patients with cirrhosis and ACLF. Evidenced based use of Tele-ICU can prevent delay in cardiac diagnosis, optimize safe use of expert resources and ensure timely care in the setting of critically ill cirrhosis, ACLF and liver transplantation in the COVID-19 era.
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http://dx.doi.org/10.1177/0885066620988281DOI Listing
May 2021

Cardiovascular manifestations of COVID-19: An evidence-based narrative review.

Indian J Med Res 2020 Dec 7. Epub 2020 Dec 7.

Department of Cardiology, Advanced Cardiac Centre, Postgraduate Institute of Medical Education & Research, Chandigarh,, India.

The recent outbreak of coronavirus disease 2019 (COVID-19) was declared a pandemic by the World Health Organization on March 11, 2020. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, primarily involves the respiratory system with viral pneumonia as a predominant manifestation. In addition, SARS-CoV-2 has various cardiovascular manifestations which increase morbidity and mortality in COVID-19. Patients with underlying cardiovascular diseases and conventional cardiovascular risk factors are predisposed for COVID-19 with worse prognosis. The possible mechanisms of cardiovascular injury are endothelial dysfunction, diffuse microangiopathy with thrombosis and increased angiotensin II levels. Hyperinflammation in the myocardium can result in acute coronary syndrome, myocarditis, heart failure, cardiac arrhythmias and sudden death. The high level of cardiac troponins and natriuretic peptides in the early course of COVID-19 reflects an acute myocardial injury. The complex association between COVID-19 and cardiovascular manifestations requires an in-depth understanding for appropriate management of these patients. Till the time a specific antiviral drug is available for COVID-19, treatment remains symptomatic. This review provides information on the cardiovascular risk factors and cardiovascular manifestations of COVID-19.
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http://dx.doi.org/10.4103/ijmr.IJMR_2450_20DOI Listing
December 2020

Atypical bilateral acute retinal necrosis in a coronavirus disease 2019 positive immunosuppressed patient.

Eur J Ophthalmol 2020 Nov 22:1120672120974941. Epub 2020 Nov 22.

Imperial College Healthcare NHS Trust, Western Eye Hospital, London, UK.

Purpose: To present the clinical features of a rare case of atypical acute retinal necrosis in a Coronavirus Disease 2019 (COVID-19) positive immunosuppressed patient.

Methods: Retrospective observational case report.

Results: A 75-year-old lady presented with a left eye pan uveitis picture with vitritis and extensive peripheral and mid-peripheral necrotising retinitis. In the right eye, she had a very mild superior peripheral retinitis with minimal anterior or vitreous inflammation. Two months prior to her diagnosis she completed a course of rituximab and chlorambucil chemotherapy for a relapse of diffuse large cell B-cell lymphoma (DLBCL). The patient's nasopharyngeal swabs tested positive for COVID-19 in a reverse transcription polymerase chain reaction (RT-PCR) assay. The vitreous sample PCR tested positive for Varicella Zoster Virus and was negative for SARS-CoV-2.

Conclusion And Significance: To the best of our knowledge this is the first description of a case that has undergone vitreous PCR testing for COVID-19. It is interesting to note the high level of vitreous inflammation which would not be expected in an immunosuppressed state. We present a number of possible links between the SARS-CoV-2 virus and the unusual ocular presentation of bilateral VZV viral retinitis in this patient.While extra ocular VZV outbreaks have been reported with rituximab treated patients, this report should also raise the awareness of VZV related viral retinitis in DLBCL patients on rituximab chemotherapy which is a very rare occurrence.This case may provide some evidence to healthcare policy makers who are making decisions regarding the re-introduction of routine Ophthalmic surgery.
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http://dx.doi.org/10.1177/1120672120974941DOI Listing
November 2020

Ionic Layering and Overcharging in Electrical Double Layers in a Poisson-Boltzmann Model.

Phys Rev Lett 2020 Oct;125(18):188004

Department of Mechanical and Aerospace Engineering, Princeton University, Princeton, New Jersey 08544, USA.

Electrical double layers (EDLs) play a significant role in a broad range of physical phenomena related to colloidal stability, diffuse-charge dynamics, electrokinetics, and energy storage applications. Recently, it has been suggested that for large ion sizes or multivalent electrolytes, ions can arrange in a layered structure inside the EDLs. However, the widely used Poisson-Boltzmann models for EDLs are unable to capture the details of ion concentration oscillations and the effect of electrolyte valence on such oscillations. Here, by treating a pair of ions as hard spheres below the distance of closest approach and as point charges otherwise, we are able to predict ionic layering without any additional parameters or boundary conditions while still being compatible with the Poisson-Boltzmann framework. Depending on the combination of ion valence, size, and concentration, our model reveals a structured EDL with spatially oscillating ion concentrations. We report the dependence of critical ion concentration, i.e., the ion concentration above which the oscillations are observed, on the counter-ion valence and the ion size. More importantly, our model displays quantitative agreement with the results of computationally intensive models of the EDL. Finally, we analyze the nonequilibrium problem of EDL charging and demonstrate that ionic layering increases the total charge storage capacity and the charging timescale.
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http://dx.doi.org/10.1103/PhysRevLett.125.188004DOI Listing
October 2020

Serotonin Alters the Phase Equilibrium of a Ternary Mixture of Phospholipids and Cholesterol.

Front Physiol 2020 23;11:578868. Epub 2020 Oct 23.

Institute for Medical Physics and Biophysics, University of Leipzig, Leipzig, Germany.

Unsaturated and saturated phospholipids tend to laterally segregate, especially in the presence of cholesterol. Small molecules such as neurotransmitters, toxins, drugs etc. possibly modulate this lateral segregation. The small aromatic neurotransmitter serotonin (5-HT) has been found to bind to membranes. We studied the lipid structure and packing of a ternary membrane mixture consisting of palmitoyl-oleoyl-phosphatidylcholine, palmitoyl-sphingomyelin, and cholesterol at a molar ratio of 4/4/2 in the absence and in the presence of 5-HT, using a combination of solid-state H NMR, atomic force microscopy, and atomistic molecular dynamics (MD) simulations. Both NMR and MD report formation of a liquid ordered (L ) and a liquid disordered (L ) phase coexistence with small domains. Lipid exchange between the domains was fast such that single component H NMR spectra are detected over a wide temperature range. A drastic restructuring of the domains was induced when 5-HT is added to the membranes at a 9 mol% concentration relative to the lipids. H NMR spectra of all components of the mixture showed two prominent contributions indicative of molecules of the same kind residing both in the disordered and the ordered phase. Compared to the data in the absence of 5-HT, the lipid chain order in the disordered phase was further decreased in the presence of 5-HT. Likewise, addition of serotonin increased lipid chain order within the ordered phase. These characteristic lipid chain order changes were confirmed by MD simulations. The 5-HT-induced larger difference in lipid chain order results in more pronounced differences in the hydrophobic thickness of the individual membrane domains. The correspondingly enlarged hydrophobic mismatch between ordered and disordered phases is assumed to increase the line tension at the domain boundary, which drives the system into formation of larger size domains. These results not only demonstrate that small membrane binding molecules such as neurotransmitters have a profound impact on essential membrane properties. It also suggests a mechanism by which the interaction of small molecules with membranes can influence the function of membrane proteins and non-cognate receptors. Altered membrane properties may modify lateral sorting of membrane protein, membrane protein conformation, and thus influence their function as suspected for neurotransmitters, local anesthetics, and other small drug molecules.
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http://dx.doi.org/10.3389/fphys.2020.578868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7645218PMC
October 2020

Pituitary Macroadenoma Presenting With Monocular Temporal Hemianopia.

J Neuroophthalmol 2021 Jun;41(2):e267-e268

Ophthalmology Department, North Middlesex Hospital NHS Trust, London, United Kingdom.

Abstract: A 35-year-old primigravida woman presented to the eye emergency department with reduced visual acuity in the right eye. Humphrey visual field testing showed a monocular right eye temporal hemianopia before delivery. An MRI after delivery revealed a largely symmetrical pituitary macroadenoma with chiasmal compression. This is a rare presentation of a pituitary macroadenoma especially when the tumor is largely symmetrical.
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http://dx.doi.org/10.1097/WNO.0000000000001119DOI Listing
June 2021

Prediction of outcome of treatment of acute severe ulcerative colitis using principal component analysis and artificial intelligence.

JGH Open 2020 Oct 18;4(5):889-897. Epub 2020 Apr 18.

Department of Gastroenterology Sanjay Gandhi Postgraduate Institute of Medical Sciences Lucknow India.

Background And Aim: About 15% patients with acute severe ulcerative colitis (UC) fail to respond to medical treatment and may require colectomy. An early prediction of response may help the treating team and the patients and their family to prepare for alternative treatment options.

Methods: Data of 263 patients (mean age 37.0 ± 14.0-years, 176, 77% male) with acute severe UC admitted during a 12-year period were used to study predictors of response using univariate analysis, multivariate linear principal component analysis (PCA), and nonlinear artificial neural network (ANN).

Results: Of 263 patients, 231 (87.8%) responded to the initial medical treatment that included oral prednisolone ( = 14, 5.3%), intravenous (IV) hydrocortisone ( = 238, 90.5%), IV cyclosporine ( = 9, 3.4%), and inflixmab ( = 2, 0.7%), and 28 (10.6%) did not respond and the remaining 4 (1.5%) died, all of whom did were also nonresponders. Nonresponding patients had to stay longer in the hospital and died more often. On univariate analysis, the presence of complications, the need for use of cyclosporin, lower Hb, platelets, albumin, serum potassium, and higher C-reactive protein were predictors of nonresponse. Hb and albumin were strong predictive factors on both PCA and ANN. Though the nonlinear modeling using ANN had a good predictive accuracy for the response, its accuracy for predicting nonresponse was lower.

Conclusion: It is possible to predict the response to medical treatment in patients with UC using linear and nonlinear modeling technique. Serum albumin and Hb are strong predictive factors.
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http://dx.doi.org/10.1002/jgh3.12342DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7578272PMC
October 2020