Publications by authors named "Ankur Jindal"

266 Publications

Targeted Gene Sanger Sequencing Should Remain the First-Tier Genetic Test for Children Suspected to Have the Five Common X-Linked Inborn Errors of Immunity.

Front Immunol 2022 8;13:883446. Epub 2022 Jul 8.

Division of Allergy, Immunology and Rheumatology, Department of Pediatrics, National Taiwan University Children's Hospital, Taipei, Taiwan.

To address inborn errors of immunity (IEI) which were underdiagnosed in resource-limited regions, our centre developed and offered free genetic testing for the most common IEI by Sanger sequencing (SS) since 2001. With the establishment of The Asian Primary Immunodeficiency (APID) Network in 2009, the awareness and definitive diagnosis of IEI were further improved with collaboration among centres caring for IEI patients from East and Southeast Asia. We also started to use whole exome sequencing (WES) for undiagnosed cases and further extended our collaboration with centres from South Asia and Africa. With the increased use of Next Generation Sequencing (NGS), we have shifted our diagnostic practice from SS to WES. However, SS was still one of the key diagnostic tools for IEI for the past two decades. Our centre has performed 2,024 IEI SS genetic tests, with in-house protocol designed specifically for 84 genes, in 1,376 patients with 744 identified to have disease-causing mutations (54.1%). The high diagnostic rate after just one round of targeted gene SS for each of the 5 common IEI (X-linked agammaglobulinemia (XLA) 77.4%, Wiskott-Aldrich syndrome (WAS) 69.2%, X-linked chronic granulomatous disease (XCGD) 59.5%, X-linked severe combined immunodeficiency (XSCID) 51.1%, and X-linked hyper-IgM syndrome (HIGM1) 58.1%) demonstrated targeted gene SS should remain the first-tier genetic test for the 5 common X-linked IEI.
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http://dx.doi.org/10.3389/fimmu.2022.883446DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9304939PMC
July 2022

Negative pressure flash pulmonary edema in a child with hereditary angioedema.

Pediatr Allergy Immunol 2022 07;33(7):e13825

Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

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http://dx.doi.org/10.1111/pai.13825DOI Listing
July 2022

Features of Hemophagocytic Lymphohistiocytosis in Infants With Severe Combined Immunodeficiency: Our Experience From Chandigarh, North India.

Front Immunol 2022 23;13:867753. Epub 2022 Jun 23.

Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Background: Hemophagocytic lymphohistiocytosis (HLH) is characterized by uncontrolled and excessive inflammation leading to high mortality. Aetiology of HLH can be primarily due to genetic causes or secondarily due to infections or rheumatological illness. However, rarely T-cell deficiencies like severe combined immunodeficiency (SCID) can develop HLH.

Objective: To describe clinical and laboratory features of SCID cases who developed HLH.

Methods: We collected clinical, laboratory, and molecular details of patients with SCID who developed HLH at our center at Chandigarh, North India.

Results: Of the 94 cases with SCID, 6 were noted to have developed HLH-like manifestations. Male-female ratio was 5:1. Median (inter-quartile range) age of onset of clinical symptoms was 4.25 months (2-5 months). Median (inter-quartile range) delay in diagnosis was 1 month (1-3.5 months). Family history of deaths was seen in 4 cases. Molecular defects in were seen in 5 out of 6 cases. Documented infections include disseminated bacillus calmette-guerin (BCG) infection (n=2), blood stream infections (n=3) with (n=1), (n=1), and (n=1), pneumonia (influenza H1N1 strain, and K. (n=1).

Conclusion: Children with SCID can present with HLH-like manifestations secondary to fulminant infections. A high index of suspicion of SCID is needed in infants who present with HLH who have an associated infection or a suggestive family history. Occurrence of HLH-like manifestations in SCID suggests that T-lymphocytes may not have a significant role in immunopathogenesis of HLH.
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http://dx.doi.org/10.3389/fimmu.2022.867753DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9260510PMC
June 2022

Autoimmune Cytopenias in Common Variable Immunodeficiency Are a Diagnostic and Therapeutic Conundrum: An Update.

Front Immunol 2022 20;13:869466. Epub 2022 Jun 20.

Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency (PID). CVID is a heterogenous condition and clinical manifestations may vary from increased susceptibility to infections to autoimmune manifestations, granulomatous disease, polyclonal lymphoproliferation, and increased risk of malignancy. Autoimmune manifestations may, at times, be the first and only clinical presentation of CVID, resulting in diagnostic dilemma for the treating physician. Autoimmune cytopenias (autoimmune haemolytic anaemia and/or thrombocytopenia) are the most common autoimmune complications seen in patients with CVID. Laboratory investigations such as antinuclear antibodies, direct Coomb's test and anti-platelet antibodies may not be useful in patients with CVID because of lack of specific antibody response. Moreover, presence of autoimmune cytopenias may pose a significant therapeutic challenge as use of immunosuppressive agents can be contentious in these circumstances. It has been suggested that serum immunoglobulins must be checked in all patients presenting with autoimmune cytopenia such as immune thrombocytopenia or autoimmune haemolytic anaemia. It has been observed that patients with CVID and autoimmune cytopenias have a different clinical and immunological profile as compared to patients with CVID who do not have an autoimmune footprint. Monogenic defects have been identified in 10-50% of all patients with CVID depending upon the population studied. Monogenic defects are more likely to be identified in patients with CVID with autoimmune complications. Common genetic defects that may lead to CVID with an autoimmune phenotype include and In this review, we update on recent advances in pathophysiology and management of CVID with autoimmune cytopenias.
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http://dx.doi.org/10.3389/fimmu.2022.869466DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9251126PMC
July 2022

Letter to the editor: IL-1 receptor antagonist plus pentoxifylline and zinc for severe alcoholic hepatitis-More questions than answers!

Hepatology 2022 Jul 1. Epub 2022 Jul 1.

Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.

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http://dx.doi.org/10.1002/hep.32648DOI Listing
July 2022

Utility of targeted next generation sequencing for inborn errors of immunity at a tertiary care centre in North India.

Sci Rep 2022 Jun 21;12(1):10416. Epub 2022 Jun 21.

Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India.

Inborn errors of immunity (IEI) are a heterogeneous group of monogenic disorders that include primary immunodeficiency's and other disorders affecting different aspects of the immune system. Next-Generation Sequencing (NGS) is an essential tool to diagnose IEI. We report our 3-year experience in setting up facilities for NGS for diagnosis of IEI in Chandigarh, North India. We used a targeted, customized gene panel of 44 genes known to result in IEI. Variant analysis was done using Ion Reporter software. The in-house NGS has enabled us to offer genetic diagnoses to patients with IEI at minimal costs. Of 121 patients who were included pathogenic variants were identified in 77 patients. These included patients with Chronic Granulomatous Disease, Severe Combined Immune Deficiency, leukocyte adhesion defect, X-linked agammaglobulinemia, Ataxia Telangiectasia, Hyper-IgE syndrome, Wiskott Aldrich syndrome, Mendelian susceptibility to mycobacterial diseases, Hyper-IgM syndrome, autoimmune lymphoproliferative syndrome, and GATA-2 deficiency. This manuscript discusses the challenges encountered while setting up and running targeted NGS for IEI in our unit. Genetic diagnosis has helped our patients with IEI in genetic counselling, prenatal diagnosis, and accessing appropriate therapeutic options.
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http://dx.doi.org/10.1038/s41598-022-14522-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9213413PMC
June 2022

A Novel CEBPE Variant Causes Severe Infections and Profound Neutropenia.

J Clin Immunol 2022 Jun 20. Epub 2022 Jun 20.

Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Center (APC), Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India.

Purpose: Specific granule deficiency (SGD) is a rare inborn error of immunity resulting from loss-of-function variants in CEBPE gene (encoding for transcription factor C/EBPε). Although this genetic etiology has been known for over two decades, only a few patients with CEBPE variant-proven SGD (type I) have been reported. Herein, we describe two siblings with a novel homozygous CEBPE deletion who were noted to have profound neutropenia on initial evaluation. We aimed to evaluate the immunohematological consequences of this novel variant, including profound neutropenia.

Methods: Light scatter characteristics of granulocytes were examined on various automated hematology analyzers. Phagocyte immunophenotype, reactive oxygen species generation, and Toll-like receptor (TLR) signaling were assessed using flow cytometry. Relative expression of genes encoding various granule proteins was studied using RT-PCR. Western blot analysis and luciferase reporter assay were performed to explore variant C/EBPε expression and function.

Results: Severe infections occurred in both siblings. Analysis of granulocyte light scatter plots revealed automated hematology analyzers can provide anomalously low neutrophil counts due to abnormal neutrophil morphology. Neutrophils displayed absence/marked reduction of CD15/CD16 expression and overexpression (in a subset) of CD14/CD64. Three distinct populations of phagocytes with different oxidase activities were observed. Impaired shedding of CD62-ligand was noted on stimulation with TLR-4, TLR-2/6, and TLR-7/8 agonists. We demonstrated the variant C/EBPε to be functionally deficient.

Conclusion: Homozygous c.655_665del variant in CEBPE causes SGD. Anomalous automated neutrophil counts may be reported in patients with SGD type I. Aberrant TLR signaling might be an additional pathogenetic mechanism underlying immunodeficiency in SGD type I.
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http://dx.doi.org/10.1007/s10875-022-01304-7DOI Listing
June 2022

T Cell Abnormalities in X-Linked Agammaglobulinaemia: an Updated Review.

Clin Rev Allergy Immunol 2022 Jun 16. Epub 2022 Jun 16.

Allergy Immunology Unit, Department of Paediatrics, Advanced Paediatrics Centre, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India.

X-linked agammaglobulinaemia (XLA) is a primary immunodeficiency (PID) resulting from a defect in the B cell development. It has conventionally been thought that T cells play a major role in the development and function of the B cell compartment. However, it has also been shown that B cells and T cells undergo bidirectional interactions and B cells also influence the structure and function of the T cell compartment. Patients with XLA offer a unique opportunity to understand the effect of absent B cells on the T cell compartment. In this review, we provide an update on abnormalities in the T cell compartment in patients with XLA. Studies have shown impaired memory T cells, follicular helper T cells, T regulatory cells and T helper 17 in patients with XLA. In addition, these patients have also been reported to have abnormal delayed cell-mediated immune responses and vaccine-specific T cell-mediated immune responses; defective T helper cell polarization and impaired T cell receptor diversity. At present, the clinical significance of these T cell abnormalities has not been studied in detail. However, these abnormalities may result in an increased risk of viral infections, autoimmunity, autoinflammation and possibly chronic lung disease. Abnormal response to SARS-Cov2 vaccine in patients with XLA and prolonged persistence of SARS-Cov2 virus in the respiratory tract of these patients may be related to abnormalities in the T cell compartment.
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http://dx.doi.org/10.1007/s12016-022-08949-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9201264PMC
June 2022

Direct Oral Anticoagulants in Budd-Chiari Syndrome: Need a Closer Look!

Clin Gastroenterol Hepatol 2022 Jun 11. Epub 2022 Jun 11.

Department of Intervention Radiology, Institute of Liver and Biliary Sciences, New Delhi, India.

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http://dx.doi.org/10.1016/j.cgh.2022.05.034DOI Listing
June 2022

Application of Noninvasive Tools to Decide the Need for Beta-Blockers for Variceal Bleeding Prophylaxis in Compensated Advanced Liver Disease: A Decision Curve Analysis.

J Clin Exp Hepatol 2022 May-Jun;12(3):917-926. Epub 2021 Sep 25.

Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, 110026, India.

Background And Aims: Noninvasive tools (NITs) reliably categorise patients with compensated advanced chronic liver disease (cACLD) into high-risk and low-risk group for harbouring varices needing treatment. Here, we assess the ability of these NITs to predict the need for nonselective beta-blockers at baseline based on risk of variceal bleeding (VB) on follow-up.

Methods: This was a retrospective multicentre analysis of patients with cACLD categorised at baseline into different risk groups by NITs (Baveno-VI, expanded Baveno-VI, platelet-albumin, platelet-model for end-stage liver disease (MELD) and anticipate study platelet criteria) and by endoscopy (high risk vs low risk/no varices). VB event rates on follow-up were estimated in different risk strata. Decision curve analysis (DCA) was used to estimate the benefit of administering nonselective beta-blockers (NSBB) using NITs over endoscopic classification at different threshold probabilities of VB event rates and estimating the number needed to treat (NNT) to identify one additional bleeder over endoscopy.

Results: A total of 1284 patients (mean age: 44.7 ± 13.5 years, 72.4% males) of hepatitis B (29.2%), nonalcoholic fatty liver disease (24.9%), hepatitis C (20.1%), and alcohol (17.5%)-related cACLD were included with 323 (25.2%) having high-risk varices. Ninety-eight (7.6%) patients developed VB over a median follow-up of 20 (9-35) months. The 1-year and 3-year rate of VB with all NITs was 5.7-7.4% and 13.2-16.4% among high-risk and 0-2.3% and 0-5% among low-risk subgroups, respectively ( < 0.001) in both viral and nonviral aetiologies. Among patients classified as low risk on Baveno-VI criteria, none developed VB on follow-up. At thresholds of <3% event rate of VB, Baveno-VI (NNT-176), platelet-albumin (NNT-576) and anticipate platelet (NNT-233) criteria were superior, whereas endoscopic stratification was superior above this event rate on DCA.

Conclusions: The use of both elastography and blood-based NITs at baseline can accurately identify the need for NSBB for VB prophylaxis in patients of cACLD on follow-up.
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http://dx.doi.org/10.1016/j.jceh.2021.09.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9168689PMC
September 2021

Carvedilol reduces the risk of decompensation and mortality in patients with compensated cirrhosis in a competing-risk meta-analysis.

J Hepatol 2022 May 31. Epub 2022 May 31.

Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Spain; Department of BioMedical Research, Visceral Surgery and Medicine, University of Bern, Switzerland.

Background & Aims: Whether non-selective β-blockers can prevent decompensation of cirrhosis warrants clarification. Carvedilol might be particularly effective since its intrinsic vasodilatory activity may ameliorate hepatic vascular resistance, a major mechanism of portal hypertension in early cirrhosis. We assessed whether carvedilol may prevent decompensation and improve survival in patients with compensated cirrhosis and clinically significant portal hypertension (CSPH).

Methods: By systematic review we identified randomized-controlled trials (RCTs) comparing carvedilol vs. control therapy (no-active treatment or endoscopic variceal ligation [EVL]) in patients with cirrhosis and CSPH without previous bleeding. We performed a competing-risk time-to-event meta-analysis using individual patient data (IPD) obtained from principal investigators of RCTs. Only compensated patients were included. Primary outcomes were prevention of decompensation (liver transplantation and death were competing events) and death (liver transplantation was a competing event). Models were adjusted using propensity scores for baseline covariates with the inverse probability of treatment weighting (IPTW) approach.

Results: Among 125 full-text studies evaluated, 4 RCTs were eligible. The 4 provided IPD and were included, comprising 352 patients with compensated cirrhosis, 181 treated with carvedilol and 171 controls (79 received EVL and 92 placebo). Baseline characteristics were similar between groups. Standardized differences were <10% by IPTW. The risk of developing decompensation of cirrhosis was lower with carvedilol than in controls (subdistribution hazard ratio [SHR] 0.506; 95% CI 0.289-0.887; p = 0.017; I = 0.0%, Q-statistic-p = 0.880), mainly due to a reduced risk of ascites (SHR 0.491; 95% CI 0.247-0.974; p = 0.042; I = 0.0%, Q-statistic-p = 0.384). The risk of death was also lower with carvedilol (SHR 0.417; 95% CI 0.194-0.896; p = 0.025; I = 0.0%, Q-statistic-p = 0.989).

Conclusions: Long-term carvedilol therapy reduced decompensation of cirrhosis and significantly improved survival in compensated patients with CSPH. This suggests that screening patients with compensated cirrhosis for CSPH to enable the prompt initiation of carvedilol could improve outcomes.

Prospero Registration Number: CRD42019144786.

Lay Summary: The transition from compensated cirrhosis to decompensated cirrhosis is associated with markedly reduced life expectancy. Therefore, preventing decompensation in patients with compensated cirrhosis would be associated with greatly improved patient outcomes. There has been controversy regarding the use of non-selective β-blockers (portal pressure-lowering medications) in patients with cirrhosis and elevated portal blood pressure (portal hypertension). Herein, using a competing-risk meta-analysis to optimize sample size and properly investigate cirrhosis as a multistate disease and outcomes as time-dependent events, we show that carvedilol (a non-selective β-blocker) is associated with a reduced risk of decompensating events and improved survival in patients with cirrhosis and portal hypertension.
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http://dx.doi.org/10.1016/j.jhep.2022.05.021DOI Listing
May 2022

Epidemiology of liver failure in Asia-Pacific region.

Liver Int 2022 08 10;42(9):2093-2109. Epub 2022 Jun 10.

Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.

The global burden of deaths caused by liver failure is substantial. The Asia-Pacific region is home to more than half of the global population and accounted for 62.6% of global deaths because of liver diseases in 2015. The aetiology of liver failure varies in different countries at different times. Viruses (Hepatitis A, B and E), drugs (herbs and anti-tuberculous drugs), toxins (alcohol use) and autoimmune flares are mainly responsible of majority of liver failure in individuals with normal liver (acute liver failure; ALF); else these may precipitate liver failure in those with chronic liver disease (acute-on-chronic liver failure; ACLF). Concomitant increases in alcohol misuse and metabolic syndrome in recent years are concerning. Ongoing efforts to address liver failure-related morbidity and mortality require accurate contemporary estimates of epidemiology and outcomes. In light of the ever-changing nature of liver disease epidemiology, accurate estimates for the burden of liver failure across the countries are vital for setting clinical, research and policy priorities. In this review, we aimed to describe the current as well as changing epidemiological trends of common liver failure syndromes, ALF and ACLF in the Asia-Pacific region.
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http://dx.doi.org/10.1111/liv.15328DOI Listing
August 2022

Deficiency of Human Adenosine Deaminase Type 2 - A Diagnostic Conundrum for the Hematologist.

Front Immunol 2022 3;13:869570. Epub 2022 May 3.

Pediatric Allergy Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

Deficiency of adenosine deaminase type 2 (DADA2) was first described in 2014 as a monogenic cause of polyartertitis nodosa (PAN), early onset lacunar stroke and livedo reticularis. The clinical phenotype of DADA2 is, however, very broad and may involve several organ systems. Apart from vasculitis, children may present with i) Hematological manifestations (ii) Lymphoproliferation and iii) Immunodeficiencies. Patients with DADA2 can have variable patterns of cytopenias and bone marrow failure syndromes. Patients with DADA2 who have predominant haematological manifestations are associated with ADA2 gene variants that result in minimal or no residual ADA2 activity. Lymphoproliferation in patients with DADA2 may range from benign lymphoid hyperplasia to lymphoreticular malignancies. Patients may present with generalized lymphadenopathy, splenomegaly, autoimmune lymphoproliferative syndrome (ALPS) like phenotype, Hodgkin lymphoma, T-cell large granular lymphocytic infiltration of bone marrow and multicentric Castleman disease. Immunodeficiencies associated with DADA are usually mild. Affected patients have variable hypogammaglobulinemia, decrease in B cells, low natural killer cells, common variable immunodeficiency and rarely T cell immunodeficiency. To conclude, DADA2 has an extremely variable phenotype and needs to be considered as a differential diagnosis in diverse clinical conditions. In this review, we describe the evolving clinical phenotypes of DADA2 with a special focus on haematological and immunological manifestations.
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http://dx.doi.org/10.3389/fimmu.2022.869570DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9110783PMC
May 2022

Intravenous Immunoglobulin for Bilateral Phrenic Nerve Palsy Due to Neonatal Lupus Erythematosus.

Indian J Pediatr 2022 07 17;89(7):734. Epub 2022 May 17.

Department of Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

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http://dx.doi.org/10.1007/s12098-022-04217-wDOI Listing
July 2022

Hepatic Regeneration in Cirrhosis.

J Clin Exp Hepatol 2022 Mar-Apr;12(2):603-616. Epub 2021 Sep 4.

Department of Research, Institute of Liver and Biliary Sciences, New Delhi 110070, India.

End-stage liver disease is characterized by massive hepatocyte death resulting in clinical decompensation and organ failures. Clinical consequences in cirrhosis are the results of the loss of functional hepatocytes and excessive scarring. The only curative therapy in advanced cirrhosis is orthotropic liver transplantation, but the clinical demand outweighs the availability of acceptable donor organs. Moreover, this also necessitates lifelong immunosuppression and carries associated risks. The liver has a huge capability for regeneration. Self-replication of quiescent differentiated hepatocytes and cholangiocytes occurs in patients with acute liver injury. Due to limited hepatocyte self-renewal capacity in advanced cirrhosis, great interest has therefore been shown in characterizing the possible role of hepatic progenitor cells and bone marrow-derived stem cells to therapeutically aid this process. Transplantation of cells from various sources that can be properly differentiated into functional liver cells or use of growth factors for ex-vivo expansion of progenitor cells is needed at utmost priority. Multiple researches over the last two decades have aided researchers in refining proliferation, differentiation, and storage techniques and understand the functionality of these cells for use in clinical practice. However, these cell-based therapies are still experimental and have to be used in trial settings.
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http://dx.doi.org/10.1016/j.jceh.2021.08.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9077225PMC
September 2021

Distal Coronary Artery Abnormalities in Kawasaki disease: experience on CT Coronary Angiography in 176 children.

Rheumatology (Oxford) 2022 Apr 8. Epub 2022 Apr 8.

Paediatric Allergy Immunology Unit, Department of Pediatrics, Advanced Paediatrics Centre, Post Graduate Institute of Medical education and Research, Chandigarh, India -160012.

Objective: Precise evaluation of coronary artery abnormalities (CAAs) in Kawasaki disease (KD) is essential. The aim of this study is to determine role of CT coronary angiography (CTCA) for detection of CAAs in distal segments of coronary arteries in patients with KD.

Methods: CTCA findings of KD patients with distal coronary artery involvement were compared with those on transthoracic echocardiography (TTE) during the period 2013-2021.

Results: Amongst 176 patients with KD who underwent CTCA (128-Slice Dual Source scanner), 23 (13.06%) had distal CAAs (right coronary - 15/23; left anterior descending - 14/23; left circumflex - 4/23 patients). CTCA identified 60 aneurysms - 37 proximal (36 fusiform; 1 saccular) and 23 distal (17 fusiform; 6 saccular); 11 patients with proximal aneurysms had distal contiguous extension; 9 patients showed non-contiguous aneurysms in both proximal and distal segments; 4 patients showed distal segment aneurysms in absence of proximal involvement of same coronary artery; 4 patients had isolated distal CAAs. On TTE, only 40 aneurysms could be identified. Further, distal CAAs could not be identified on TTE. CTCA also identified complications (thrombosis, mural calcification and stenosis) that were missed on TTE.

Conclusions: CAAs can, at times, occur in distal segments in isolation and also in association with, or extension of, proximal CAAs. CTCA demonstrates CAAs in distal segments of coronary arteries, including branches, in a significant number of children with KD - these cannot be detected on TTE. CTCA, therefore, may be considered as a complimentary imaging modality in children with KD who have CAAs on TTE.
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http://dx.doi.org/10.1093/rheumatology/keac217DOI Listing
April 2022

Cutaneous involvement in DOCK8-related immunodeficiency syndrome responding to thalidomide.

Dermatol Ther 2022 Jun 11;35(6):e15491. Epub 2022 Apr 11.

Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

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http://dx.doi.org/10.1111/dth.15491DOI Listing
June 2022

Letter: sPD-1 as a predictor for HBsAg seroconversion-shed light on inactive carriers with chronic hepatsitis B.

Aliment Pharmacol Ther 2022 04;55(8):1056

Department of Hepatology, Institute of Liver and Biliary Sciences, New Delhi, India.

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http://dx.doi.org/10.1111/apt.16833DOI Listing
April 2022

Letter to the editor: Non-invasive diagnosis of porto-sinusoidal vascular disease.

Authors:
Ankur Jindal

Hepatology 2022 Sep 7;76(3):E54. Epub 2022 Apr 7.

Department of Hepatology, Institute of Liver & Biliary Sciences, New Delhi, India.

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http://dx.doi.org/10.1002/hep.32480DOI Listing
September 2022

Letter to the editor: Liver outcomes after bariatric surgery in patients with NASH and advanced fibrosis.

Authors:
Ankur Jindal

Hepatology 2022 Aug 31;76(2):E42. Epub 2022 Mar 31.

Department of Hepatology, Institute of Liver & Biliary Sciences, New Delhi, India.

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http://dx.doi.org/10.1002/hep.32465DOI Listing
August 2022

Association of rectal colonisation by MDROs with new infection in cirrhosis.

J Hepatol 2022 Aug 9;77(2):577-578. Epub 2022 Mar 9.

Department of Hepatology, Institute of Liver & Biliary Sciences, New Delhi, India. Electronic address:

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http://dx.doi.org/10.1016/j.jhep.2022.03.001DOI Listing
August 2022

Unusual clinical manifestations and predominant stopgain ATM gene variants in a single centre cohort of ataxia telangiectasia from North India.

Sci Rep 2022 03 8;12(1):4036. Epub 2022 Mar 8.

Allergy and Immunology Laboratory, Department of Pediatrics, Advanced Pediatric Centre, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India.

Germline ATM gene variations result in phenotypic heterogeneity characterized by a variable degree of disease severity. We retrospectively collected clinical, genetic, and immunological data of 26 cases with A-T. Clinical manifestations included oculocutaneous telangiectasia (100%), ataxia (100%), fever, loose stools or infection (67%), cerebellar atrophy (50%), nystagmus (8%), dysarthria (15.38%), and visual impairment (8%). Genetic analysis confirmed ATM gene variations in 16 unrelated cases. The most common type of variation was stopgain variants (56%). Immunoglobulin profile indicated reduced IgA, IgG, and IgM in 94%, 50%, and 20% cases, respectively. T cell lymphopenia was observed in 80% of cases among those investigated. Unusual presentations included an EBV-associated smooth muscle tumour located in the liver in one case and Hyper IgM syndrome-like presentation in two cases. Increased immunosenescence was observed in T-cell subsets (CD4+CD57+ and CD8+CD57+). T-cell receptor excision circles (TRECs) were reduced in 3/8 (37.50%) cases.
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http://dx.doi.org/10.1038/s41598-022-08019-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8904522PMC
March 2022

Atypical Wiskott-Aldrich syndrome without thrombocytopenia partially responding to omalizumab therapy.

Clin Exp Dermatol 2022 May 6;47(5):1013-1016. Epub 2022 Mar 6.

Department of Dermatology, Venereology and Leprology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Primary immunodeficiencies with eczema can be easily misdiagnosed as atopic eczema, and thus require a high degree of awareness for diagnosis. Wiskott-Aldrich syndrome (WAS) is a rare disease and the fact that WAS without microthrombocytopenia has not been reported to date makes this case more interesting. As the patient's predominant problem was eczema and he had high circulating IgE antibodies in his serum, omalizumab was chosen as an appropriate steroid-sparing treatment option, as it has been shown to be effective in previous studies.
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http://dx.doi.org/10.1111/ced.15119DOI Listing
May 2022

An Autopsy Case of Wiskott-Aldrich Syndrome Revealing "FDC-Only Lymphoid Follicles" in Lymphoid Tissue: A Morphologic Correlate of Defective Immune Synapse.

Pediatr Dev Pathol 2022 May-Jun;25(3):345-350. Epub 2022 Mar 2.

Department of Hematology, RinggoldID:29751Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Wiskott-Aldrich Syndrome (WAS) is an inherited disorder characterized by the classical triad of eczema, micro-thrombocytopenia, and immune deficiency. This disease affects the hematopoietic cells to a variable extent. The spectrum of clinical and laboratory data for WAS has been well described in the literature though there is a paucity of its histopathologic and immunohistochemical correlates. The current case describes the autopsy findings of this rare entity in an 8-year old male child with specific recognition of altered histology noticed in the lymphoreticular tissues. The predominant morphological finding in lymphoid tissue was atretic hyalinized germinal centers labeled as "the follicular dendritic cell (FDC)-only lymphoid follicles." Immunohistochemistry revealed a reduction in germinal-center B-cells, T-follicular helper cells, attenuated mantle zone, FDC proliferation, and paracortical plasmacytosis. This case highlights the crippled immune cell population in WAS, ultimately leading to the morphology of atretic follicles rich in FDCs.
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http://dx.doi.org/10.1177/10935266211058345DOI Listing
June 2022

Letter to the editor: Treatment options for 3-5-cm solitary HCC-Need a closer look!

Hepatology 2022 07 25;76(1):E20-E21. Epub 2022 Feb 25.

Intervention Radiology, Institute of Liver & Biliary Sciences, New Delhi, India.

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http://dx.doi.org/10.1002/hep.32401DOI Listing
July 2022

Association of Physical Activity to Sarcopenia, Liver Fibrosis, and Cardiovascular Disease: Need a Closer Look!

Clin Gastroenterol Hepatol 2022 Feb 3. Epub 2022 Feb 3.

Fortis Healthcare, Noida, India.

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http://dx.doi.org/10.1016/j.cgh.2022.01.036DOI Listing
February 2022

Asian Pacific association for the study of liver (APASL) guidelines: hepatitis B virus in pregnancy.

Hepatol Int 2022 Apr 3;16(2):211-253. Epub 2022 Feb 3.

Department of Laboratory Medicine, Department of Infectious Diseases, Nanjing Drum Tower Hospital, Nanjing University Medical School, Nanjing, China.

Hepatitis B virus (HBV) infection still remains a major public health issue in the Asia-Pacific region. Most of the burden of HBV-related disease results from infections acquired in infancy through perinatal or early childhood exposure to HBV in Asia-Pacific. Hepatitis B during pregnancy presents unique management issues for both the mother and fetus. These APASL guidelines provide a comprehensive review and recommendations based on available evidence in the literature, for the management of females with HBV infection through every stage of pregnancy and postpartum. These also address the concerns, management challenges, and required follow-up of children born to hepatitis B-positive mothers.
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http://dx.doi.org/10.1007/s12072-021-10285-5DOI Listing
April 2022

Clinical Outcomes in Patients with Advanced Chronic Liver Disease and Hepatic Venous Pressure Gradient ≤ 10 mm Hg.

Dig Dis Sci 2022 Feb 3. Epub 2022 Feb 3.

Department of Biostatistics, Institute of Liver and Biliary Sciences, New Delhi, 110070, India.

Background And Aims: Clinically significant portal hypertension (CSPH), defined as hepatic venous pressure gradient (HVPG) ≥ 10 mmHg predicts clinical decompensation (CD) in cirrhosis. A proportion of cirrhosis patients have HVPG 6-10 mmHg. Their natural history is largely unknown.

Design: Consecutive patients with advanced chronic liver disease (aCLD) [histological cirrhosis(n = 196) or liver stiffness measurement (LSM) > 15 kPa(n = 65)] and HVPG 6-10 mmHg were included. Primary objective was to study their natural course and patterns of CD. We also analyzed the predictors of CD at presentation and on follow-up and response to carvedilol.

Results: Of 261 patients with HVPG 6-10 mmHg, 129(49.4%) had CD at first presentation; 78(29.9%) had single and 51(19.5%) had ≥ 2 CD. The most common CDs were ascites(n = 77) and jaundice(n = 65). A baseline HVPG ≥ 8 mmHg was independently associated with greater risk of CD [HR:1.7; p-0.002, AUROC:0.85(95%CI-0.81-0.91)]. New CD developed in 14.4% patients with compensated aCLD (median duration-23.1 months). Despite comparable baseline HVPG, patients developing new CD had higher HVPG on follow-up(15.3 ± 3.7 vs. 8 ± 2.1 mmHg; p < 0.001). Baseline LSM > 26.6 kPa, portosystemic shunt and serum albumin independently predicted new CD. Overall HVPG response to carvedilol(n = 60) was 23.3%, independent of baseline CD and HVPG. Five-year mortality was higher with ≥ 2 CD compared to single or no CD (23.5, 10 and 3%, respectively; p < 0.001).

Conclusion: Nearly one-half of aCLD patients with HVPG 6-10 mmHg had CD, justifying the need to redefine CSPH. Interventions to reduce portal pressure in patients with HVPG ≥ 8 mmHg might improve long-term outcomes.
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http://dx.doi.org/10.1007/s10620-021-07334-2DOI Listing
February 2022

Letter to the editor: Prospective study of stereotactic body radiation therapy for hepatocellular carcinoma on waitlist for liver transplant.

Hepatology 2022 05 27;75(5):1345. Epub 2022 Feb 27.

Department of Interventional Radiology, Institute of Liver and Biliary Sciences, New Delhi, India.

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http://dx.doi.org/10.1002/hep.32354DOI Listing
May 2022

Liver stiffness can predict decompensation and need for beta-blockers in compensated cirrhosis: a step beyond Baveno-VI criteria.

Hepatol Int 2022 Feb 24;16(1):89-98. Epub 2022 Jan 24.

Department of Hepatology and Liver Transplantation, Institute of Liver and Biliary Sciences, New Delhi, 110070, India.

Background And Aims: Liver stiffness measurement (LSM) alone or its combination with platelet counts [Baveno-VI criteria (B6C)] is an important non-invasive tool to predict risk of clinical decompensation in patients with advanced compensated cirrhosis. We compared its utility to decide need for beta-blockers in this regard compared with hepatic venous pressure gradient (HVPG) estimation.

Methods: Patients with compensated cirrhosis with available baseline HVPG and LSM were followed up over a median follow-up of 26 (IQR 7-55) months to determine onset of clinical decompensations. Optimal cut-off for LSM for predicting decompensations was identified and compared with HVPG of 10 mmHg and B6C. Feasibility of initiating beta-blockers based on these strategies was assessed using decision curve analysis (DCA) at different threshold probabilities of rates of clinical decompensation.

Results: 626 patients (mean age: 50.8 ± 12.4 years, 72.4% males) related to alcohol (30.3%), non-alcoholic steatohepatitis (26.4%), hepatitis C (16.6%), hepatitis B (10.2%) were included. Altogether, 132 (21.0%) patients developed clinical decompensation. The time-dependant area under curve over 5 years for HVPG and LSM for predicting clinical decompensation was 0.716-0.742 and 0.709-0.784, respectively. A LSM of 22 kPa (Sensitivity-88.6%/Specificity-51.8%) had a similar negative predictive value but a higher positive predictive value [37.9% (LSM) vs.30.9% (HVPG)vs.30.6% (B6C), p = 0.026 at 3 years] for incident decompensations. On DCA, LSM-based strategy emerged superior for deciding beta-blocker initiation with 150, 47, and 18 additional patients meriting treatment identified over and above B6C and HVPG based strategy at 5%, 10%, 20% annual rates of clinical decompensation, respectively.

Conclusion: Measurement of liver stiffness alone can be a useful alternative to B6C and HVPG in deciding need for beta-blockers to prevent decompensations in compensated cirrhosis.
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http://dx.doi.org/10.1007/s12072-021-10280-wDOI Listing
February 2022
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