Arvinder S. Soin

Bio: Arvinder S. Soin is an academic researcher from Medanta. The author has contributed to research in topics: Liver transplantation & Transplantation. The author has an hindex of 25, co-authored 137 publications receiving 1840 citations. Previous affiliations of Arvinder S. Soin include Apollo Hospitals & University of Cambridge.

Pre-existing liver disease is associated with poor outcome in patients with SARS CoV2 infection; The APCOLIS Study (APASL COVID-19 Liver Injury Spectrum Study).

Abstract: COVID-19 is a dominant pulmonary disease, with multisystem involvement, depending upon comorbidities. Its profile in patients with pre-existing chronic liver disease (CLD) is largely unknown. We studied the liver injury patterns of SARS-Cov-2 in CLD patients, with or without cirrhosis. Data was collected from 13 Asian countries on patients with CLD, known or newly diagnosed, with confirmed COVID-19. Altogether, 228 patients [185 CLD without cirrhosis and 43 with cirrhosis] were enrolled, with comorbidities in nearly 80%. Metabolism associated fatty liver disease (113, 61%) and viral etiology (26, 60%) were common. In CLD without cirrhosis, diabetes [57.7% vs 39.7%, OR = 2.1 (1.1–3.7), p = 0.01] and in cirrhotics, obesity, [64.3% vs. 17.2%, OR = 8.1 (1.9–38.8), p = 0.002] predisposed more to liver injury than those without these. Forty three percent of CLD without cirrhosis presented as acute liver injury and 20% cirrhotics presented with either acute-on-chronic liver failure [5 (11.6%)] or acute decompensation [4 (9%)]. Liver related complications increased (p < 0.05) with stage of liver disease; a Child-Turcotte Pugh score of 9 or more at presentation predicted high mortality [AUROC 0.94, HR = 19.2 (95 CI 2.3–163.3), p < 0.001, sensitivity 85.7% and specificity 94.4%). In decompensated cirrhotics, the liver injury was progressive in 57% patients, with 43% mortality. Rising bilirubin and AST/ALT ratio predicted mortality among cirrhosis patients. SARS-Cov-2 infection causes significant liver injury in CLD patients, decompensating one fifth of cirrhosis, and worsening the clinical status of the already decompensated. The CLD patients with diabetes and obesity are more vulnerable and should be closely monitored.

Ultrasound Image Segmentation: A Deeply Supervised Network With Attention to Boundaries

Abstract: Objective: Segmentation of anatomical structures in ultrasound images requires vast radiological knowledge and experience. Moreover, the manual segmentation often results in subjective variations, therefore, an automatic segmentation is desirable. We aim to develop a fully convolutional neural network (FCNN) with attentional deep supervision for the automatic and accurate segmentation of the ultrasound images. Method: FCNN/CNNs are used to infer high-level context using low-level image features. In this paper, a sub-problem specific deep supervision of the FCNN is performed. The attention of fine resolution layers is steered to learn object boundary definitions using auxiliary losses, whereas coarse resolution layers are trained to discriminate object regions from the background. Furthermore, a customized scheme for downweighting the auxiliary losses and a trainable fusion layer are introduced. This produces an accurate segmentation and helps in dealing with the broken boundaries, usually found in the ultrasound images. Results: The proposed network is first tested for blood vessel segmentation in liver images. It results in $F1$ score, mean intersection over union, and dice index of 0.83, 0.83, and 0.79, respectively. The best values observed among the existing approaches are produced by U-net as 0.74, 0.81, and 0.75, respectively. The proposed network also results in dice index value of 0.91 in the lumen segmentation experiments on MICCAI 2011 IVUS challenge dataset, which is near to the provided reference value of 0.93. Furthermore, the improvements similar to vessel segmentation experiments are also observed in the experiment performed to segment lesions. Conclusion: Deep supervision of the network based on the input-output characteristics of the layers results in improvement in overall segmentation accuracy. Significance: Sub-problem specific deep supervision for ultrasound image segmentation is the main contribution of this paper. Currently the network is trained and tested for fixed size inputs. It requires image resizing and limits the performance in small size images.

Pre-Existing Liver Disease Is Associated with Poor Outcome in Patients with SARS CoV-2 Infection; The APCOLIS Study (APASL COVID-19 Liver Injury Spectrum Study)

Abstract: Background and Aims: COVID-19 is a dominant pulmonary disease, with multisystem involvement, depending upon co morbidities Its profile in patients with pre-existing chronic liver disease (CLD) is largely unknown We studied the liver injury patterns of SARS-Cov-2 in CLD patients, with or without cirrhosis Methods: Data was collected from 13 Asian countries on patients with CLD, known or newly diagnosed, with confirmed COVID-19 Result: Altogether, 228 patients [ 185 CLD without cirrhosis and 43 with cirrhosis] were enrolled, with comorbidities in nearly 80% Metabolism associated fatty liver disease (113, 61%) and viral etiology (26, 60%) were common In CLD without cirrhosis, diabetes [577% vs 397%, OR=21(11-37), p=001] and in cirrhotics, obesity, [643% vs 172%, OR=81(19-388), p=0002) predisposed more to liver injury than those without these Forty three percent of CLD without cirrhosis presented as acute liver injury and 20% cirrhotics presented with either acute-on-chronic liver failure [5(116%)] or acute decompensation [4(9%)] Liver related complications increased (p<005) with stage of liver disease; a Child-Turcotte Pugh score of 9 or more at presentation predicted poor outcome [AUROC-094, HR=192(95CI 23-1633), p<0001, sensitivity 857% and specificity 944%) In decompensated cirrhotics, the liver injury was progressive in 57% patients, with 43% mortality Rising bilirubin and AST/ALT ratio predicted mortality among cirrhosis Conclusions: SARS-Cov-2 infection causes significant liver injury in CLD patients, decompensating one fifth of cirrhosis, and worsening the clinical status of the already decompensated The CLD patients with diabetes and obesity are more vulnerable and should be closely monitored Trial Registration: [NCT04345640] Funding Statement: None Declaration of Interests: The authors declare no conflicts of interest Ethics Approval Statement: Institutional ethics committee approval was obtained

An association between cytomegalovirus infection and chronic rejection after liver transplantation.

Abstract: Background. Previous studies suggest a link between cytomegalovirus (CMV) infection and chronic rejection. Since these studies, more sophisticated diagnostic methods with high sensitivity and specificity for CMV have been developed and effective therapy/prophylaxis for CMV is now available. We sought CMV prospectively by polymerase chain reaction of serum and urine and by conventional methods in a group of 33 patients undergoing 57 transplants during 1993 or 1994, selected from a larger series. There were 13 grafts lost to chronic rejection. The remaining 44 grafts that did not develop chronic rejection served as controls and comprised 15 successful primary grafts, 15 second transplants, 8 third transplants, and 6 primary grafts that were lost for reasons other than chronic rejection. Results. The combination donor CMV antibody negative with recipient antibody positive and the duration of CMV infection >30 days were associated with an increased relative risk of chronic rejection. In contrast, the presence of CMV infection alone, symptomatic CMV infection, the detection of CMV by PCR of serum or urine, and the peak/cumulative viral load were not predictive. CMV infection occurred earlier in those undergoing a second transplant for chronic rejection than for those undergoing a second transplant for other reasons. In addition, a human leukocyte antigen B mismatch was associated with prolonged CMV infection. Conclusion. These data are consistent with the hypothesis that prolonged subclinical cytomegalovirus infection is associated with an increased risk of chronic rejection.

Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury

Abstract: Acute kidney injury (AKI) is a complex disorder for which currently there is no accepted definition. Having a uniform standard for diagnosing and classifying AKI would enhance our ability to manage these patients. Future clinical and translational research in AKI will require collaborative networks of investigators drawn from various disciplines, dissemination of information via multidisciplinary joint conferences and publications, and improved translation of knowledge from pre-clinical research. We describe an initiative to develop uniform standards for defining and classifying AKI and to establish a forum for multidisciplinary interaction to improve care for patients with or at risk for AKI. Members representing key societies in critical care and nephrology along with additional experts in adult and pediatric AKI participated in a two day conference in Amsterdam, The Netherlands, in September 2005 and were assigned to one of three workgroups. Each group's discussions formed the basis for draft recommendations that were later refined and improved during discussion with the larger group. Dissenting opinions were also noted. The final draft recommendations were circulated to all participants and subsequently agreed upon as the consensus recommendations for this report. Participating societies endorsed the recommendations and agreed to help disseminate the results. The term AKI is proposed to represent the entire spectrum of acute renal failure. Diagnostic criteria for AKI are proposed based on acute alterations in serum creatinine or urine output. A staging system for AKI which reflects quantitative changes in serum creatinine and urine output has been developed. We describe the formation of a multidisciplinary collaborative network focused on AKI. We have proposed uniform standards for diagnosing and classifying AKI which will need to be validated in future studies. The Acute Kidney Injury Network offers a mechanism for proceeding with efforts to improve patient outcomes.

Guidelines on the Use of Therapeutic Apheresis in Clinical Practice—Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Sixth Special Issue

Abstract: The American Society for Apheresis (ASFA) Journal of Clinical Apheresis (JCA) Special Issue Writing Committee is charged with reviewing, updating, and categorizing indications for the evidence-based use of therapeutic apheresis in human disease. Since the 2007 JCA Special Issue (Fourth Edition), the Committee has incorporated systematic review and evidence-based approaches in the grading and categorization of apheresis indications. This Seventh Edition of the JCA Special Issue continues to maintain this methodology and rigor to make recommendations on the use of apheresis in a wide variety of diseases/conditions. The JCA Seventh Edition, like its predecessor, has consistently applied the category and grading system definitions in the fact sheets. The general layout and concept of a fact sheet that was used since the fourth edition has largely been maintained in this edition. Each fact sheet succinctly summarizes the evidence for the use of therapeutic apheresis in a specific disease entity. The Seventh Edition discusses 87 fact sheets (14 new fact sheets since the Sixth Edition) for therapeutic apheresis diseases and medical conditions, with 179 indications, which are separately graded and categorized within the listed fact sheets. Several diseases that are Category IV which have been described in detail in previous editions and do not have significant new evidence since the last publication are summarized in a separate table. The Seventh Edition of the JCA Special Issue serves as a key resource that guides the utilization of therapeutic apheresis in the treatment of human disease. J. Clin. Apheresis 31:149-162, 2016. © 2016 Wiley Periodicals, Inc.

Calcineurin Inhibitor Nephrotoxicity

Abstract: The use of the calcineurin inhibitors cyclosporine and tacrolimus led to major advances in the field of transplantation, with excellent short-term outcome. However, the chronic nephrotoxicity of these drugs is the Achilles' heel of current immunosuppressive regimens. In this review, the authors summarize the clinical features and histologic appearance of both acute and chronic calcineurin inhibitor nephrotoxicity in renal and nonrenal transplantation, together with the pitfalls in its diagnosis. The authors also review the available literature on the physiologic and molecular mechanisms underlying acute and chronic calcineurin inhibitor nephrotoxicity, and demonstrate that its development is related to both reversible alterations and irreversible damage to all compartments of the kidneys, including glomeruli, arterioles, and tubulo-interstitium. The main question--whether nephrotoxicity is secondary to the actions of cyclosporine and tacrolimus on the calcineurin-NFAT pathway--remains largely unanswered. The authors critically review the current evidence relating systemic blood levels of cyclosporine and tacrolimus to calcineurin inhibitor nephrotoxicity, and summarize the data suggesting that local exposure to cyclosporine or tacrolimus could be more important than systemic exposure. Finally, other local susceptibility factors for calcineurin inhibitor nephrotoxicity are reviewed, including variability in P-glycoprotein and CYP3A4/5 expression or activity, older kidney age, salt depletion, the use of nonsteroidal anti-inflammatory drugs, and genetic polymorphisms in genes like TGF-beta and ACE. Better insight into the mechanisms underlying calcineurin inhibitor nephrotoxicity might pave the way toward more targeted therapy or prevention of calcineurin inhibitor nephrotoxicity.

Ledipasvir and Sofosbuvir Plus Ribavirin for Treatment of HCV Infection in Patients With Advanced Liver Disease

Abstract: Background & Aims There are no effective and safe treatments for chronic hepatitis C virus (HCV) infection of patients who have advanced liver disease. Methods In this phase 2, open-label study, we assessed treatment with the NS5A inhibitor ledipasvir, the nucleotide polymerase inhibitor sofosbuvir, and ribavirin in patients infected with HCV genotypes 1 or 4. Cohort A enrolled patients with cirrhosis and moderate or severe hepatic impairment who had not undergone liver transplantation. Cohort B enrolled patients who had undergone liver transplantation: those without cirrhosis; those with cirrhosis and mild, moderate, or severe hepatic impairment; and those with fibrosing cholestatic hepatitis. Patients were assigned randomly (1:1) to receive 12 or 24 weeks of a fixed-dose combination tablet containing ledipasvir and sofosbuvir, once daily, plus ribavirin. The primary end point was sustained virologic response at 12 weeks after the end of treatment (SVR12). Results We enrolled 337 patients, 332 (99%) with HCV genotype 1 infection and 5 (1%) with HCV genotype 4 infection. In cohort A (nontransplant), SVR12 was achieved by 86%–89% of patients. In cohort B (transplant recipients), SVR12 was achieved by 96%–98% of patients without cirrhosis or with compensated cirrhosis, by 85%−88% of patients with moderate hepatic impairment, by 60%–75% of patients with severe hepatic impairment, and by all 6 patients with fibrosing cholestatic hepatitis. Response rates in the 12- and 24-week groups were similar. Thirteen patients (4%) discontinued the ledipasvir and sofosbuvir combination prematurely because of adverse events; 10 patients died, mainly from complications related to hepatic decompensation. Conclusion The combination of ledipasvir, sofosbuvir, and ribavirin for 12 weeks produced high rates of SVR12 in patients with advanced liver disease, including those with decompensated cirrhosis before and after liver transplantation. ClinTrials.gov: NCT01938430.