Publications by authors named "Kirti Gupta"

247 Publications

IgG4-related Pachymeningitis as a Cause of Spinal Epidural Compression: Can Intraoperative Frozen Sections Predict the Underlying Pathology?

Neurol India 2022 May-Jun;70(3):1223-1225

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

At times, spinal lesions are part of systemic manifestations of autoimmune disease. Awareness regarding their clinicopathological spectrum, particularly the lesions which usually respond to steroids/immunotherapy, is essential to avoid unwanted surgical morbidity. We discuss a case of a young-man presenting with thoracic spinal epidural compressive lesion which was indeed a manifestation of IgG4-related hypertrophic pachymeningitis. The mass was firmly adherent to the dura and extended into left neural foramen/paravertebral space which precluded complete excision. Frozen sections suggested fibro-inflammatory stroma with large areas of fibrosis and lymphoplasmacytic infiltrate. After subtotal excision, the patient improved with medical therapy at 1-year follow-up. Although uncommon, the case highlights the need to consider spinal presentation of this rare entity, especially in the context of autoimmune disorders or even in isolation. In this regard, intraoperative frozen section can hint the underlying inflammatory/autoimmune pathology, guide further course of surgery as well as limit unwarranted operative morbidity.
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http://dx.doi.org/10.4103/0028-3886.349589DOI 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

Congenital Rubella Syndrome as a possible cause for persistent thrombocytopenia in early infancy: The Forgotten Culprit.

Autops Case Rep 2022 6;12:e2021386. Epub 2022 Jun 6.

Post Graduate Institute of Medical Education & Research (PGIMER), Department of Pediatrics, Chandigarh, India.

We present a case of a late preterm intrauterine growth-restricted neonate with isolated and persistent severe thrombocytopenia. At birth, the neonate did not have a complete clinical spectrum of congenital rubella syndrome (CRS) but later developed peculiar findings that helped clinch the diagnosis. The neonate also had interstitial pneumonia and died secondary to superimposed acute viral infection leading to acute respiratory distress syndrome. The serology was positive for IgM antibodies against the rubella virus. The constellation of clinical manifestations of congenital rubella in the presence of positive IgM antibody against rubella and consistent histopathology confirmed the diagnosis of CRS.
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http://dx.doi.org/10.4322/acr.2021.386DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9212083PMC
June 2022

Pathological role of the calcium-sensing receptor in sepsis-induced hypotensive shock: Therapeutic possibilities and unanswered questions.

Drug Dev Res 2022 Jun 11. Epub 2022 Jun 11.

Department of Pharmacology, Maharishi Markandeshwar University, Mullana, Ambala, Haryana, India.

Sepsis is a life-threatening disease involving multiorgan dysfunction, prompted by an unregulated host response to infection. Shock is a complication of sepsis in which the circulatory and cellular metabolism anomalies are significant enough to raise the risk of death. Calcium dyshomeostasis occurs during sepsis condition due to imbalance between calcium uptake and excessive release induced by inflammatory cytokines. This calcium imbalance can cause activation of calcium-sensing receptors (CaSRs) located on the surface of T cells and thereby promote release of reactive oxygen species (ROS). The elevated ROS and inflammatory cytokines during sepsis condition have been reported to directly damage the endothelial cells, disrupt the barrier functions that might result in leakage of fluids, and inflammatory cells in tissues Moreover, several evidence have revealed that the calcium mediated activation of CaSR could produce systemic vasodilatory response by stimulating the nitric oxide production and opening of calcium-activated potassium channels, while infusion of its antagonist elevated the blood pressure. These evidence indicate that activation of CaSR during sepsis conditions results in release of ROS and inflammatory cytokines, which could produce an endothelial barrier damage, cardiomyocyte apoptosis. These pathological events could produce loss of fluid in tissues and cardiac dysfunction. Further the direct vasodilatory effects of CaSR activation might add to the shock-like condition. Thus, we hereby propose that inhibition of CaSR could suppress the release of ROS, inflammatory mediators, and thereby prevent the endothelial damage, cardiac dysfunction, and maintain systemic vascular tone.
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http://dx.doi.org/10.1002/ddr.21959DOI Listing
June 2022

Dextrose Gel for Neonates at Risk With Asymptomatic Hypoglycemia: A Randomized Clinical Trial.

Pediatrics 2022 06;149(6)

Background And Objectives: Hypoglycemia occurs in 5% to 15% of neonates in the first few days. A significant proportion requires admission for intravenous fluids. Dextrose gel may reduce admissions and mother-infant separation. We aimed to study the utility of dextrose gel in reducing the need for intravenous fluids.

Methods: This stratified randomized control trial included at-risk infants with asymptomatic hypoglycemia. Study populations were stratified into 3 categories: small for gestational age (SGA) and intrauterine growth-restriction (IUGR), infants of diabetic mothers (IDM) and large for gestational age (LGA), and late preterm (LPT) neonates. Intervention group received dextrose gel followed by breastfeeding, and the control group (CG) received only breastfeeding.

Results: Among 629 at-risk infants, 291 (46%) developed asymptomatic hypoglycemia; 147 (50.4%) in the dextrose gel group (DGG) and 144 (49.6%) in CG. There were 97, 98, and 96 infants in SGA/IUGR, IDM/LGA, and LPT categories, respectively. Treatment failure in the DGG was 17 (11.5%) compared to 58 (40.2%) in CG, with a risk ratio of 0.28 (95% confidence interval [CI]: 0.17-0.46; P < .001). Treatment failure was significantly less in DGG in all 3 categories: SGA/IUGR, IDM/LGA, and LPT with a risk ratio of 0.29 (95% CI:0.13-0.67), 0.31 (95% CI:0.14-0.66) and 0.24 (95% CI:0.09-0.66), respectively.

Conclusions: Dextrose gel reduces the need for intravenous fluids in at-risk neonates with asymptomatic hypoglycemia in the first 48 hours of life.
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http://dx.doi.org/10.1542/peds.2021-050733DOI Listing
June 2022

Fibrous hamartoma of infancy with sarcomatous transformation: an unusual morphology.

Autops Case Rep 2022 28;12:e2021380. Epub 2022 Apr 28.

Post Graduate Institute of Medical Education & Research, Department of Pediatrics, Chandigarh, India.

Background: Fibrous hamartoma of infancy (FHI) is a rare soft tissue lesion arising as a subcutaneous mass involving the axilla, trunk, and upper arm in infants and children <2yrs. Sarcomatous transformation in FHI is described in anecdotal cases in the literature.

Case Report: We describe one such example arising as a mass in the lower back in a 3-month-old infant. On histology, the tumor contained classic triphasic morphology; however, brisk mitotic activity noted at multiple foci was diagnostically challenging to categorize. The tumor was evaluated for fusion to exclude other common differentials.

Conclusion: While FHI may be frequently encountered in infants, rare sarcomatous transformation are known to occur and merits special attention as it can be misdiagnosed. Also, a close follow-up is warranted as the lesion is known to recur locally.
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http://dx.doi.org/10.4322/acr.2021.380DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9083879PMC
April 2022

Miscellaneous newly recognized types of CNS tumors in the WHO CNS5 classification (other than gliomas, glioneuronal and embryonal tumors).

Indian J Pathol Microbiol 2022 May;65(Supplement):S94-S98

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

In this review, we describe salient features of a few of the newer entities recognized in the fifth edition of World Health Organization (WHO) classification of central nervous system (CNS) tumors. While most of these have been offshoots of the deoxyribonucleic acid (DNA) methylation profiling of CNS tumors with distinct profiling such as desmoplastic myxoid tumor (DMT) of the pineal region, SMARCB1-mutant, these also demonstrate subtle, distinct morphological features, which should be carefully searched for to diagnose them.
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http://dx.doi.org/10.4103/ijpm.ijpm_1038_21DOI Listing
May 2022

Molecular subgrouping of ependymoma across three anatomic sites and their prognostic implications.

Brain Tumor Pathol 2022 Jul 29;39(3):151-161. Epub 2022 Mar 29.

Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

The 2021 WHO classification stratifies ependymoma (EPN) into nine molecular subgroups according to the anatomic locations which outperforms histological grading. We aimed at molecularly reclassifying 200 EPN using immunohistochemistry (IHC) and sequencing for ZFTA fusions in supratentorial (ST) EPN. Further, we assessed the utility of L1CAM, cyclinD1, and p65 markers in identifying ZFTA fusion. Demographic profiles, histologic features, molecular subgroups and clinical outcome were retrospectively analyzed. IHC for L1CAM, cyclinD1, p65, H3K27me3, and H3K27M and sequencing for ZFTA fusion were performed. ZFTA fusions were identified in 44.8% ST EPN. p65 displayed the highest specificity (93.8%), while L1CAM had the highest sensitivity (92.3%) in detecting ZFTA fusions. The negative predictive value approached 96.6% and sensitivity improved to 96.2% with combinatorial IHC (L1CAM, cyclinD1, p65). H3K27me3 loss (PF-A) was noted in 65% PF EPN. Our results provide evidence that a combination of two of three (L1CAM, p65, and cyclinD1) can be used as surrogate markers for predicting fusion. ZFTA fusion, and its surrogate markers in ST, and H3K27me3 and younger age (< 5 years) in PF showed significant correlation with PFS and OS on univariate and Kaplan-Meier analysis. On multivariate analysis, H3K27me3 loss and younger age group are associated with poor clinical outcome.
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http://dx.doi.org/10.1007/s10014-022-00429-2DOI Listing
July 2022

Coordinated activities of Myosin Vb isoforms and mTOR signaling regulate epithelial cell morphology during development.

Development 2022 03 17;149(6). Epub 2022 Mar 17.

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

The maintenance of epithelial architecture necessitates tight regulation of cell size and shape. However, mechanisms underlying epithelial cell size regulation remain poorly understood. We show that the interaction of Myosin Vb with Rab11 prevents the accumulation of apically derived endosomes to maintain cell-size, whereas that with Rab10 regulates vesicular transport from the trans-Golgi. These interactions are required for the fine-tuning of the epithelial cell morphology during zebrafish development. Furthermore, the compensatory cell growth upon cell-proliferation inhibition involves a preferential expansion of the apical domain, leading to flatter epithelial cells, an efficient strategy to cover the surface with fewer cells. This apical domain growth requires post-trans-Golgi transport mediated by the Rab10-interacting Myosin Vb isoform, downstream of the mTOR-Fatty Acid Synthase (FASN) axis. Changes in trans-Golgi morphology indicate that the Golgi synchronizes mTOR-FASN-regulated biosynthetic input and Myosin Vb-Rab10 dependent output. Our study unravels the mechanism of polarized growth in epithelial cells and delineates functions of Myosin Vb isoforms in cell size regulation during development.
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http://dx.doi.org/10.1242/dev.199363DOI Listing
March 2022

Paediatric Pituitary Adenomas: Clinical Presentation, Biochemical Profile and Long-Term Prognosis.

Neurol India 2022 Jan-Feb;70(1):304-311

Department of Endocrinology, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

Context: Paediatric pituitary adenomas (PPAs) are uncommon, with evidence confined to small cohorts.

Aim: We aimed to elucidate the baseline profile and outcomes of PPAs in a large, contemporary, monocentric cohort.

Settings, Design: Pituitary clinic at PGIMER over 8 years (2010-2018).

Subjects And Methods: PPAs in patients (≤20 years at diagnosis) were included. A retrospective review of their baseline clinico-biochemical and radiological profiles and outcomes post pituitary surgery/medical management was performed.

Results: There were a total of 74 patients, of which 42 were female. The median age was 15 (IQR 13-18) years. Corticotropinomas (32.4%) and somatotropinomas (25.7%) were common, with 1 case of TSHoma and pituitary blastoma. The most common presentation was headache (57%) overall and menstrual irregularities (64.2%) in girls. Most (78%) had macroadenomas. Prolactinomas showed an excellent response to primary medical therapy (83.3%). Transsphenoidal surgery was performed in 81% of patients. Diabetes insipidus (30%) and hyponatremia (26.7%) emerged as common postoperative complications. Adjuvant medical management was required in 25%, and radiotherapy in 18%. Remission rates in Cushing's and acromegaly were 62.5% and 57.8%, respectively, with long-term hormone deficits noted in one-third of patients.

Conclusion: PPAs have unique features and management challenges, including effects on growth and puberty. Functional tumours and macroadenomas are common. Remission can be achieved in more than half of the patients, with endocrine deficits persisting in about a third of cases, needing long-term surveillance.
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http://dx.doi.org/10.4103/0028-3886.338667DOI Listing
March 2022

Cerebral phaeohyphomycosis: The 'Dark Side' of fungal infections.

Clin Neurol Neurosurg 2022 03 11;214:107173. Epub 2022 Feb 11.

Department of Neurosurgery, PGIMER, Chandigarh, India. Electronic address:

Purpose: Cerebral phaeohyphomycosis is a rare and fatal fungal infection of the central nervous system (CNS) caused by dematiaceous fungi. The aim of this study was to analyse the clinico- radiological presentation, pathology and outcome of cerebral phaeohyphomycosis and discuss the relevant literature.

Patients And Methods: Data of 7 patients diagnosed with cerebral phaeohyphomycosis and managed at our institute between 2014 and 2020 was collected and reviewed retrospectively. The diagnosis was established after surgery on KOH mount, Sabouraud dextrose agar, frozen section or histopathology. The clinical, radiological and pathological characteristics along with outcomes were analysed.

Results: Three patients with underlying comorbidities [chronic renal failure-2 and haematological malignancy -1] presented with brain abscess. The remaining 4 had no comorbidities. Two of them mimicked cystic glioma and one patient presented as intraventricular tumour. Another patient on anti- tubercular treatment for suspected pulmonary tuberculosis presented with encephalitis. Histopathology in all patients showed diffuse micro abscesses with coarse and reactive gliosis in the adjacent brain parenchyma and chronic lymphomononuclear inflammation without angioinvasion or vasculitis. Four showed granuloma formation. Antifungals were started after diagnosis. Six out of seven patients died and one was lost to follow up.

Conclusion: Cerebral phaeohyphomycosis presents as abscesses in immunocompromised patients and mimics tumours in immunocompetent patients. KOH mount and frozen section examination is simple yet effective tool for establishing early diagnosis. Overall, the prognosis is dismal. Administering antifungals early in the course of management along with aggressive surgical excision may improve outcomes.
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http://dx.doi.org/10.1016/j.clineuro.2022.107173DOI Listing
March 2022

Focal cortical dysplasia (FCD) type IIb: A pathologists' delight.

Indian J Pathol Microbiol 2022 Jan-Mar;65(1):228-229

Department of Radiology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

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http://dx.doi.org/10.4103/IJPM.IJPM_638_20DOI Listing
February 2022

"Benign" Choroid Plexus Papilloma with "Atypical" Transformation and Spinal Drop Lesions.

Neurol India 2021 Nov-Dec;69(6):1890-1892

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

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http://dx.doi.org/10.4103/0028-3886.333457DOI Listing
January 2022

Pituicytoma in a Young Male and Review of Literature.

Neurol India 2021 Nov-Dec;69(6):1870-1872

Department of Neurosurgery, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

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http://dx.doi.org/10.4103/0028-3886.333522DOI Listing
January 2022

Early Initiation of Temozolomide Therapy May Improve Response in Aggressive Pituitary Adenomas.

Front Endocrinol (Lausanne) 2021 17;12:774686. Epub 2021 Dec 17.

Department of Neurosurgery, PGIMER, Chandigarh, India.

Introduction: Aggressive pituitary adenomas (APAs) are, by definition, resistant to optimal multimodality therapy. The challenge lies in their early recognition and timely management. Temozolomide is increasingly being used in patients with APAs, but evidence supporting a favorable response with early initiation is lacking.

Methods: This was a single-center study of all patients with APAs who received at least 3 cycles of temozolomide (150-200 mg/m). Their baseline clinico-biochemical and radiological profiles were recorded. Immunohistochemical evaluation for cell-cycle markers O-methylguanine-DNA methyltransferase (MGMT), MutS homolog 2 (MSH2), MutS homolog 6 (MSH6), MutL homolog 1 (MLH1), and postmeiotic segregation increased 2 (PMS2) was performed, and -scores (product of the number of positive cells and staining intensity) were calculated. Response was assessed in terms of radiological response using the RECIST criteria. Patients with controlled disease (≥30% reduction in tumor volume) were classified as responders.

Results: The study comprised 35 patients (48.6% acromegaly, 37.1% prolactinomas, and 14.3% non-functioning pituitary adenomas). The median number of temozolomide (TMZ) cycles was 9 (IQR 6-14). Responders constituted 68.6% of the cohort and were more likely to have functional tumors, a lower percentage of MGMT-positive staining cells, and lower MGMT -scores. There was a significantly longer lag period in the initiation of TMZ therapy in non-responders as compared with responders (median 36 . 15 months,  = 0.01). ROC-derived cutoffs of 31 months for the duration between diagnosis and TMZ initiation, low-to-intermediate MGMT positivity (40% tumor cells), and MGMT -score of 80 all had a sensitivity exceeding 80% and a specificity exceeding 70% to predict response.

Conclusion: Early initiation of TMZ therapy, functional tumors, and low MGMT -score predict a favorable response to TMZ in APAs.
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http://dx.doi.org/10.3389/fendo.2021.774686DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8718901PMC
February 2022

Benign Renal Tumors in Pediatric Age Group: Retrospective Analysis.

J Indian Assoc Pediatr Surg 2021 Nov-Dec;26(6):380-392. Epub 2021 Nov 12.

Department of Pediatric Hemato Oncology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Background: Benign renal tumors are extremely rare and were studied here. This series also includes a renal teratoma in a horseshoe kidney, probably only the second in the pediatric literature.

Materials And Methods: Retrospective review of children with benign renal tumors operated between 2006 and 2018 at one center.

Results: Twelve patients (M:F ratio 10:2), age range 3 weeks (31-week gestation) to 13 years presented with large palpable renal swelling ( = 12) and hematuria ( = 3). Computed tomography (CT) scan showed features typical of the tumor. Final histopathology (age group [mean]) showed: multilocular cystic nephroma (MLCN) - = 5 (41.7%), (11-16 months [13.6]); congenital mesoblastic nephroma (CMN) - = 4 (33.3%) (classic 1, cellular 3) (0.75-5 months [2.125]); mature cystic teratoma - = 1 (8.3%): (48 months, in a horseshoe kidney), and angiomyolipoma (AML) - = 2 (16.7%) (144 months [sporadic] and 156 months [tuberous sclerosis]) One patient with cystic teratoma with no calcification on CT scan received pre-operative chemotherapy as fine-needle aspiration cytology (FNAC) reported malignant small blue cell tumor. Nephroureterectomy with Gerota's fascia could be done easily in all without intraoperative complications. Delay in presentation in MLCN and CMN led to increased symptoms and CT scan changes. All patients did well in 1.5-12 years (median 3 years) follow-up including cellular mesoblastic nephroma.

Conclusions: Benign renal tumors often occur in specific age groups but may overlap that of Wilms tumor. Proper interpretation of clinical presentation, CT scan, and FNAC findings help in avoiding preoperative chemotherapy. Upfront nephroureterectomy is curative. Histopathological findings decide further treatment. Children with AML and tuberous sclerosis need lifelong follow-up.
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http://dx.doi.org/10.4103/jiaps.JIAPS_214_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8637978PMC
November 2021

Diagnosing metastatic pheochromocytoma: Trick lies in attention to details!

BMJ Case Rep 2021 Nov 29;14(11). Epub 2021 Nov 29.

Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Functional metastatic pheochromocytoma (PCC) is a very rare tumour and cytoreductive adrenalectomy with oligo metastatectomy is recommended in cases of low tumour burden. We report a rare case of metastatic PCC with an incidentally detected suspicious nodule seen on the anterior surface of the right lobe of the liver. The adrenal and the lesion were excised and sent for histopathology which was reported as a metastasis from PCC. This lesion was not visualised preoperatively on DOTA-PET-CT, highlighting the importance of keeping a low threshold for suspicion of metastasis in abnormal lesions and taking a biopsy during surgery. Inspection of the liver and rest of the abdomen for any abnormality should be done even when operating for any apparently benign lesions.
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http://dx.doi.org/10.1136/bcr-2021-245231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8634215PMC
November 2021

Trimetazidine an emerging paradigm in renal therapeutics: Preclinical and clinical insights.

Eur J Pharmacol 2021 Dec 10;913:174624. Epub 2021 Nov 10.

Chitkara College of Pharmacy, Chitkara University, Punjab, India. Electronic address:

Trimetazidine (TMZ) is a well-known anti-ischemic agent used for the treatment of angina pectoris. In the past decades, the efficacy of this drug has been tested in a wide range of kidney injuries, including drug-induced nephrotoxicity (DIN), radio-contrast agent-induced nephropathy, and surgically induced renal ischemic injury. TMZhas renoprotective effects by attenuating oxidative stress, inflammatory cytokine release, maintaining oxygen and energy balance. Moreover, TMZ administration prevented kidney graft rejection in the porcine model by suppressing the infiltration of mononuclear cells, preserving mitochondrial functions, and maintaining Ca+ homeostasis. In DIN and diabetic kidney diseases,TMZ treatment prevents renal injury by inactivating immune cells, attenuating renal fibrosis, inflammation, apoptosis, and histological abnormalities. Interestingly, the clinical therapeutic efficacy of TMZ has also been documented in pre-existing kidney disease patients undergoing contrast exposure for diagnostic intervention. However, the mechanistic insights into the TMZ mediated renoprotective effects in other forms of renal injuries, including type-2 diabetes, drug-induced nephrotoxicity, and hypertension-induced chronic kidney diseases, remain uninvestigated and incomplete. Moreover, the clinical utility of TMZ as a renoprotective agent in radio-contrast-induced nephrotoxicity needs to be tested in a large patient population. Nevertheless, the available pieces of evidence suggest that TMZ is a promising and emerging renal therapy for the treatment and management of kidney diseases of variable etiologies. This review discusses the various pre-clinical and clinical findings and provides mechanistic insights into the TMZ mediated beneficial effects in various kidney diseases.
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http://dx.doi.org/10.1016/j.ejphar.2021.174624DOI Listing
December 2021

Diagnostic Conundrum in a Posterior Fossa Lesion.

Neurol India 2021 Sep-Oct;69(5):1275-1276

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

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http://dx.doi.org/10.4103/0028-3886.329570DOI Listing
November 2021

Role of Cyclin D1 and BCOR Immunohistochemistry in Differentiating Clear Cell Sarcoma of Kidney From its Mimics.

J Pediatr Hematol Oncol 2021 Nov;43(8):294-300

Pediatrics (Paediatric Hemato-Oncology Division), Postgraduate Institute of Medical Education & Research, Chandigarh, India.

Background And Aim: Clear cell sarcoma of kidney (CCSK) is the second most common pediatric renal malignancy, constituting ∼3% of renal tumors. Due to its morphologic diversity, the diagnosis of CCSK is often challenging. Recent studies have identified internal tandem duplication of BCL6 corepressor (BCOR) gene in CCSKs which coupled with cyclin D1 immunoreactivity, is helpful in differentiating it from its mimics, particularly blastema-rich Wilms tumor (WT), malignant rhabdoid tumor (MRT), and congenital mesoblastic nephroma (CMN). We aimed to evaluate the utility of cyclin D1 and BCOR immunohistochemistry in differentiating CCSK from its morphologic mimics.

Materials And Methods: Our cohort comprised of 38 pediatric renal tumors which included CCSK (n=18), WT (n=10), MRT (n=5), and CMN (n=5) cases. A detailed clinicopathologic analysis was performed, and tissue microarray were constructed for CCSK and WT, while MRT and CMN tumors were individually stained.

Results: The age ranged from 2 months to 16 years with male:female ratio of 3:1. Strong, diffuse nuclear immunoreactivity for cyclin D1 and BCOR was noted in 61% (n=11/18) and 83% (n=15/18) of CCSK, respectively, while it was significantly less in WT (n=3/10 for cyclin D1) (n=2/10 for BCOR). None of the MRT and CMN examples demonstrated any immunoreactivity. Interestingly, only the blastemal component of WTs showed distinct, rare nuclear immunoreactivity for cyclin D1 or BCOR and the combination of these was never positive in a given case.

Conclusion: Our results provide evidence that concurrent immunopositivity with cyclin D1 and BCOR is helpful in distinguishing CCSK from its morphologic mimics.
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http://dx.doi.org/10.1097/MPH.0000000000002262DOI Listing
November 2021

Utility of Immunohistochemistry and Immunofluorescence in Determining the Pathogenic Variants of Chronic Granulomatous Disease.

J Clin Immunol 2022 01 14;42(1):85-93. Epub 2021 Oct 14.

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

Background: Chronic granulomatous disease (CGD) is a primary immunodeficiency disorder of phagocytes due to defects in any of the five subunits of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex. An initial diagnosis of CGD is made by flow cytometry-based dihydrorhodamine assay or nitro blue tetrazolium test, which is further confirmed by molecular assays. Expression of five subunits of NADPH oxidase components by either flow cytometric or western blot analysis provides clues toward the potential gene targets which are subsequently confirmed by various genetic assays. Immunohistochemistry (IHC) and immunofluorescence (IF) have never been earlier used to determine the expression of different subunits of NADPH oxidase system. We evaluated the utility of IHC and IF in determining the underlying pathogenic variants of CGD.

Materials And Methods: Twelve genetically confirmed cases of CGD, comprising of biopsy specimens (n = 6), tissue blocks from autopsy cases (n = 3), and cellblocks of cell pellet prepared from peripheral blood (n = 4) were included. IHC for p67phox and p47phox subunits and IF for cytochrome b558 were performed.

Results: All 4 cases with pathogenic variation of NCF2 gene showed loss of expression for p67phox subunit. Two cases with pathogenic variation of NCF1 gene showed loss of expression for p47phox subunit. Five cases, except a single case with CYBB gene pathogenic variation, showed loss of expression for cytochrome b558 on IF. Thus, loss of expression consistently matched with the underlying genetic defects assessed by sequencing.

Conclusions: Our results confirm our hypothesis that IHC and IF are two rapid, economical, pathologist-friendly techniques providing pertinent information regarding the underlying pathogenic variants and such immuno-analysis can be easily performed on the tissue.
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http://dx.doi.org/10.1007/s10875-021-01148-7DOI Listing
January 2022

Correlation of dual energy computed tomography electron density measurements with cerebral glioma grade.

Neuroradiol J 2022 Jun 3;35(3):352-362. Epub 2021 Oct 3.

Department of Histopathology PGIMER, India.

Objective: To correlate dual energy computed tomography electron density measurements with histopathological cerebral glioma grading to determine whether it can be used as a non-invasive predictor of cerebral glioma grade.

Materials And Methods: Fifty patients with suspected cerebral gliomas on imaging scheduled to undergo resection were included. We tested our hypothesis that with increasing glioma grade, increased tumor cellularity should translate into increased electron density and if a statistically significant difference between electron density of low-grade gliomas and high-grade gliomas is seen, we may have a clinical use of dual energy computed tomography as a non-invasive tool to predict cerebral glioma grade.A pre-operative dual energy computed tomography scan of the brain was performed, and electron density measurements calculated from the solid part of the tumor. Obtaining a ratio with electron density of contralateral normal brain parenchyma normalized these values. The minimum, maximum and mean electron density and their normalized values recorded between high-grade gliomas and low-grade gliomas were compared for presence of statistical significance.

Results: A statistically significant difference was found between all six parameters recorded (minimum electron density and normalized values, mean electron density and normalized values, maximum electron density and normalized values) between low-grade gliomas and high-grade gliomas. The predictivity ranged from 75% (for minimum electron density and maximum normalized values) to 81.25% (for mean normalized values). All six parameters were found to have statistically significant positive correlation with Ki-67 index.

Conclusion: Dual energy computed tomography electron density measurements in cerebral gliomas are predictive of pre-operative differentiation of low-grade gliomas from high-grade gliomas and show a linear, statistically significant positive correlation with Ki-67 index.
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http://dx.doi.org/10.1177/19714009211047455DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9244748PMC
June 2022

Hepatic cirrhosis in a 15-month-old boy.

J Clin Pathol 2021 Nov 28;74(11):686-689. Epub 2021 Jul 28.

Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

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http://dx.doi.org/10.1136/jclinpath-2020-207006DOI Listing
November 2021

Course and outcomes of pregnancy in women treated for acromegaly: Discerning a contemporary cohort.

Growth Horm IGF Res 2021 Oct-Dec;60-61:101417. Epub 2021 Jul 8.

Department of Obstetrics and Gynecology, PGIMER, Chandigarh, India. Electronic address:

Objective: To analyze pregnancy course and outcomes in women treated for acromegaly and compare outcomes based on disease activity at the time of conception.

Design: Retrospective study.

Patients: Women with acromegaly diagnosed prior to or during pregnancy from 2010 to 2019, representing cases (14 pregnancies in 12 cases), were later stratified based on active (n = 5) or controlled disease (n = 9) at time of conception. Female acromegalic patients over the same period constituted the 'acromegaly cohort' (AC) (n = 75).

Results: All cases had macroadenomas with nadir GH of 15.06 ng/ml (IQR 9-30), IGF-I index of 3.04 (1.96-3.82), for which they had undergone pituitary surgery; except two patients diagnosed during pregnancy, who received pharmacotherapy followed by surgery 4 months postpartum. Adjuvant pharmacotherapy was required in 71.4% patients and radiotherapy in 35.7%. Pregnancy occurred at a median of 2 (0.8-5.1) years after surgery and 21.4% required assisted reproduction. All had term delivery with normal APGAR except one case with gestational hypertension, who delivered a preterm baby. None had congenital malformations. Despite higher baseline IGF-I, GH and tumor volume in those with pre-conceptional active acromegaly, materno-fetal outcomes were not different from those with controlled disease (p > 0.05). Similar or greater proportion of cases had normal GH and no residual tumor postpartum, even in those with pre-conceptional active acromegaly.

Conclusion: The current study showed conducive outcomes of gestation in women treated for acromegaly and no higher rates of pregnancy parameters or complications than non-acromegaly pregnancies in the same population. Active acromegaly does not seem to have an adverse bearing on outcomes.
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http://dx.doi.org/10.1016/j.ghir.2021.101417DOI Listing
February 2022

A 7-month-old boy with failure to thrive.

Brain Pathol 2021 09 14;31(5):e12998. Epub 2021 Jul 14.

Department of Pediatrics, Post Graduate Institute of Medical Education & Research, Chandigarh, India.

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http://dx.doi.org/10.1111/bpa.12998DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8412114PMC
September 2021

Roflumilast improves resolution of sepsis-induced acute kidney injury by retarding late phase renal interstitial immune cells infiltration and leakage in urinary sediments.

Fundam Clin Pharmacol 2022 Feb 6;36(1):114-132. Epub 2021 Aug 6.

Department of Pharmacology, ISF College of Pharmacy, Moga, India.

Some evidence has demonstrated that both inflammation and immune cell dysregulation are coincident at late phase (post 24 h) of sepsis. The present study was designed to determine the pathological role of hyperinflammation and renal immune cells mobilization during late phase of sepsis induced acute kidney injury (S-AKI) and tests the pharmacological effects of PDE-4 inhibitor on these events. Sepsis was induced by cecal ligation puncture and renal function, oxidative-inflammatory stress biomarkers were assessed after 24 h. PDE-4 inhibitor was administered for 7 days prior to induction of S-AKI. Renal immune cells infiltration during sepsis was analyzed by H&E staining and papanicolaou staining method was used for detecting leukocytes and cast in urinary sediments, periodic acid schiff (PAS) staining was used for detection of brush border loss. AKI developed 24 h post sepsis insult as depicted by increase in serum creatinine, blood urea nitrogen (BUN), renal oxidative stress, and elevated inflammatory biomarkers levels. Moreover, septic rats displayed increased bacterial load, renal expression of phosphodiesterase-4B, 4D isoforms, enhanced vascular permeability, caspase-3 and myeloperoxidase activity, electrolyte imbalance, reduced Na K ATPase activity, declined cAMP levels, increased interstitial leukocyte infiltration, and leakage in urinary sediments along with histological alterations. Pre-treatment with roflumilast at high dose completely prevented the various AKI associated manifestations in septic rats. Renal hyper-inflammation and leukocyte infiltration was detected in late phase of S-AKI. Roflumilast pre-treatment resolved sepsis induced renal dysfunction and histological damage by suppressing late phase renal immune cells invasion and anti-inflammatory effects mediated by up-regulation of renal cAMP levels.
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http://dx.doi.org/10.1111/fcp.12711DOI Listing
February 2022

Basal Cell Carcinoma with Flexural Predilection in Basal Cell Nevus Syndrome.

Indian Dermatol Online J 2021 May-Jun;12(3):469-471. Epub 2021 May 12.

Department of Dermatology, Venereology, and Leprology, Postgraduate Institute of Medical Education and Research, Sector 12, Chandigarh, India.

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http://dx.doi.org/10.4103/idoj.IDOJ_593_20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8202479PMC
May 2021

Customising the surgical management for intraventricular meningiomas - 'one size doesn't fit all'.

Br J Neurosurg 2021 Oct 21;35(5):633-638. Epub 2021 Jun 21.

Department of Neurosurgery, PGIMER, Chandigarh, India.

Background: Intraventricular meningiomas are uncommon and gross total resection is the recommended treatment. However, total resection may not always be possible, especially in locations in which the lesions are adherent to veins and neural structures. We share our experience with intraventricular meningiomas, focusing on the management strategies and outcomes.

Patients And Methods: We describe the data of 7 patients with intraventricular meningiomas operated at our institute over the last 9 years. Three patients had a third ventricular tumor of which two had lesions straddling across the foramen of Monro. The remaining 4 patients had trigonal mass. The clinico-radiological features, management strategies and outcomes have been elaborated with a mean follow-up of 57 months.

Results: The common clinical presentations were raised intracranial pressure symptoms, visual field defects and memory deficits. One patient had multiple meningiomas. Total excision was achieved in all except in 2 patients in whom the lesion straddled across the foramen of Monro with dense adhesions to veins and neural structures. Staged resection was required in one patient with a large trigonal mass. All patients had a low-grade lesion. The tumor recurred in one patient (post-pregnancy) after partial resection. All the patients improved neurologically, and none had added deficits.

Conclusions: Gross total resection of intraventricular meningiomas although desirable may not be possible in certain cases in which the risks outweigh the benefits. These tumors often are of low histological grade and the treatment strategies should be individualized. Regular follow-up is warranted as these tumors may recur despite a low histological grade.
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http://dx.doi.org/10.1080/02688697.2021.1940858DOI Listing
October 2021

Impact of Immunohistochemical profiling of Glioblastoma multiforme on clinical outcomes: Real-world scenario in resource limited setting.

Clin Neurol Neurosurg 2021 08 4;207:106726. Epub 2021 Jun 4.

Department of Radiotherapy& Oncology, PGIMER, Chandigarh, India. Electronic address:

Objective: Intuition into the molecular pathways of glioblastoma multiforme (GBM) has changed the diagnostic, prognostic, and therapeutic approaches. We investigated the influence of various clinical and molecular prognostic factors on survival outcomes in radically treated GBM patients.

Methods: Medical records of 160 GBM patients treated between January-2012 and December-2018 with surgery followed by post-operative external beam radiotherapy (EBRT) with/without temozolomide (TMZ) were reviewed. Immunohistochemical (IHC) assays were performed for IDH1mutation, ATRX loss, TP53 overexpression and Ki-67% index. Apart from disease and treatment-related factors' influence on clinical outcomes, the impact of IHC markers in prognostication was analyzed using appropriate statistical tests.

Results: The median overall survival (OS) was 14 months. EBRT with concurrent TMZ was given to 60% of patients and 42.5% completed the standard Stupp-protocol. Significant improvements in OS was observed in patients aged ≤ 50years (2-year OS: 22.1% vs. 12.5%, p = 0.001), those who underwent gross total resection (2-year OS: 21.8% vs. 12.8%, p = 0.002), received concurrent TMZ (21.9% vs. 12.5%, p = 0.005), completed the entire Stupp-protocol (2-year OS: 23.4% vs. 6.5%, p = 0.000), and with Ki-67 index <20% (2-year OS: 23.3% vs. 11.6%, p = 0.015). On multivariate analysis, IDH1 mutation, ATRX loss, TP53 expression, and Ki-67 ≤ 20% were significant prognosticators of outcomes.

Conclusion: GBM patients treated with concurrent chemoradiation and those who completed the full Stupp-protocol experienced better survival outcomes. Molecular biology significantly impacts clinical outcomes and plays a key deterministic role in newer management strategies.
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http://dx.doi.org/10.1016/j.clineuro.2021.106726DOI Listing
August 2021

Adrenal histoplasmosis presenting as life-threatening adrenal insufficiency.

BMJ Case Rep 2021 06 10;14(6). Epub 2021 Jun 10.

Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

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http://dx.doi.org/10.1136/bcr-2021-243181DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8194325PMC
June 2021
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