Publications by authors named "Deepak Bansal"

225 Publications

Next-Generation Sequencing Based Approach to Identify Underlying Genetic Defects of Glanzmann Thrombasthenia.

Indian J Hematol Blood Transfus 2021 Jul 24;37(3):414-421. Epub 2020 Oct 24.

Department of Hematology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012 India.

Glanzmann thrombasthenia (GT) is an autosomal recessive platelet function disorder characterized by mucocutaneous bleeding as the most common clinical phenotype. Patients with GT have normal platelet counts, platelet morphology but reduced platelet aggregation in response to various agonists. Homozygosity or compound heterozygosity for variants in the genes is the genetic basis for GT. Establishing a molecular diagnosis is definitive and is important for predictive testing. Using multi-gene panels is an accurate, faster, and cost-effective mode as compared to Sanger sequencing in large genes. We used a targeted resequencing based approach to identify pathogenic variants in eight cases in seven families. These variants were validated using Sanger sequencing in patients as well as family members and were predicted probably pathogenic using prediction tools. The variants include three missense (3/7 = 43%) (c.1028 T > C, c.1186G > A, c.1388G > C), two deletions (c.559delG, c.3092delT), one duplication (c.1424_1427dupAGGT) and nonsense variant (c.2578C > T, p.Gln860Ter). Except for one case which was compound heterozygous, the rest of the cases were homozygous. We found two novel variants that are reported for the first time in GT. The targeted resequencing based approach revealed varied genetic variants in North Indian patients, including two novels ones. The high yield of our panel indicates its suitability for usage in larger cohorts for the genetic diagnosis of GT patients. This approach is cost-effective and less cumbersome as compared to Sanger sequencing for these large size genes with multiple exons. The information so obtained is helpful in prenatal testing, carrier analysis, and genetic counseling.
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http://dx.doi.org/10.1007/s12288-020-01368-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8239080PMC
July 2021

A comparative study between light transmission aggregometry and flow cytometric platelet aggregation test for the identification of platelet function defects in patients with bleeding.

Blood Res 2021 Jun;56(2):109-118

Department of Hematology, Advanced Pediatric Centre, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Background: Platelet aggregation studies using conventional light transmission aggregometry (LTA) have several disadvantages and require strict pre-analytical measures for reliable results. We aimed to examine the utility of flow cytometric platelet aggregation (FCA) assay in detecting platelet function defects (PFDs) in patients with a history of bleeding symptoms.

Methods: Sixty-four participants (24 patients and 40 healthy controls) were included in this study. LTA and FCA assay were performed simultaneously in patients and healthy controls. In the FCA assay, two portions of platelets from the same individual were labeled separately with CD31-FITC and CD31-PE. After mixing and stimulation with agonists, the double- colored platelet aggregates were visualized using a flow cytometer. The results generated using the two techniques were compared and correlated.

Results: The patients' median age was 17 years (range, 3‒72 yr) with a male-to-female ratio of 1:1.7. There was substantial agreement between LTA and FCA assay in detecting a PFD (=0.792). Four patients showing a Glanzmann thrombasthenia-like pattern on LTA exhibited an abnormal FCA. A functional defect in collagen binding was detected on the FCA assay conducted in two immune thrombocytopenic patients with severe bleeding.

Conclusion: FCA assay can be used to identify functional defects in platelets, with potential applications in thrombocytopenic individuals. It also facilitates the diagnosis of inherited bleeding disorders with platelet defects.
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http://dx.doi.org/10.5045/br.2021.2020232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8246037PMC
June 2021

An Autopsy Case of β-Thalassemia Major Illuminating the Pathological Spectrum of the Disease.

Hemoglobin 2021 Jun 30:1-6. Epub 2021 Jun 30.

Department of Pediatrics, Pediatric Hematology-Oncology Unit, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

Despite declining rates worldwide, autopsy studies remain invaluable tools to expand existing knowledge on the pathophysiology of diseases, especially those with multisystem involvement. β-thalassemia major (β-TM) is a relatively common hemoglobinopathy in India and is characterized by a regular requirement for life-sustaining transfusions and chelation. The iron overload is an invariable side effect. This secondary hemosiderosis leads to several complications, primarily in the heart, liver, pancreas, and endocrine organs. Despite adequate transfusion and chelation, untransplanted patients may show early mortality for several reasons. We report a 10-year-old boy with β-TM who died with clinical possibilities of iron overload-related cardiac failure and pulmonary arterial hypertension. His autopsy revealed certain unique disease pathologies in the form of minimal cardiac fibrosis in the presence of significant cardiac siderosis and widespread endocrine damage due to iron-overload. A null-cell pituitary microadenoma, previously undescribed in thalassemia syndromes, was found. This report highlights the importance of the diminishing art of autopsy, without which these histopathological insights would not have emerged.
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http://dx.doi.org/10.1080/03630269.2021.1941080DOI Listing
June 2021

A case series highlighting structured hematological, biochemical and molecular approach to clinical oral iron refractoriness in children: A pressing need for a 3-tier system for classification of variants in TMPRSS6 gene.

Blood Cells Mol Dis 2021 07 16;89:102569. Epub 2021 Apr 16.

Pediatric Hematology-Oncology Unit, Department of Pediatrics, India. Electronic address:

In current study, we discuss clinical oral iron refractoriness cases and highlight need for a classification system to define TMPRSS6 gene variants. Out of 231 cases of microcytic hypochromic anemia screened (Sept 2019-Dec 2020), 17 cases (7.35%) with unexplained iron refractoriness (URIDA) phenotype were enrolled after ruling out secondary causes and compliance related issues. 11 (65%) had absent/negligible response (0-0.4 g/dl Hb rise) while 6 (35%) partial (0.5-0.9 g/dl Hb rise) response to initial iron trial at 4-8 weeks. Of these 17 cases, inappropriate hepcidin levels (normal-high) were noted in 11/15 (73%) tested. TSAT/Hepcidin ratio was low in 13/15 (87%). Genetic analysis of TMPRSS6 gene by NGS revealed variations in 15/17 (88%) cases. 10/15 cases with variations harbored a common splice site INDEL that was noted to be pathogenic SNP (MAF-0.19) on case-control association study in combination with other known missense SNPs with an odds ratio of 6.38 and relative risk 2.66 (p- < 0.01).
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http://dx.doi.org/10.1016/j.bcmd.2021.102569DOI Listing
July 2021

Diagnostic accuracy and cytomorphological spectrum of Wilms tumour in fine needle aspiration biopsy cytology samples supplemented with cell blocks.

Pediatr Blood Cancer 2021 Jul 21;68(7):e28996. Epub 2021 Mar 21.

Department of Cytology and Gynaecological Pathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Objective: Paediatric malignant renal neoplasms are subjected to neoadjuvant chemotherapy as per Societe Internationale d'Oncologie Pediatrique; International Society of Pediatric Oncology (SIOP) protocol. An accurate tissue diagnosis is required prior to institution of chemotherapy, and hence the aim of this study was to evaluate the diagnostic accuracy of fine needle aspiration biopsy cytology (FNABC) along with cell block histology.

Materials And Methods: A retrospective audit of all paediatric renal neoplasms diagnosed by FNABC between 2015 and 2019 was performed. Histopathology correlation was done wherever available. WT cases were subjected to detailed cytomorphological evaluation.

Results: A total of 121 cases of paediatric renal neoplasms including 109 WT, four clear cell sarcoma, one malignant rhabdoid tumour and three mesoblastic nephroma were evaluated. The age range was 4 weeks to 8 years. FNABC samples were adequate for diagnosis in 120 of 121 cases (99.18%) and a definitive cytological diagnosis was achieved in 117 cases (96.7%). The specificity and sensitivity for a cytopathological diagnosis of WT were 98.7% and 97.4%, respectively. On detailed cytomorphological analysis of 68 histopathology-proven WT, 40 (58.8%) cases were triphasic, 23 (35.3%) were biphasic and four were composed of blastema only. The corresponding cell blocks provided additional information over the conventional smears in 23 (33.8%) cases, with epithelial or mesenchymal elements recognised and evidence of rhabdomyoblastic differentiation.

Conclusion: FNABC along with cell block histology is highly accurate for diagnosis of WT and other malignant paediatric renal neoplasms and is recommended as the technique of choice in centres with cytopathology expertise for establishing a cellular diagnosis prior to commencement of neoadjuvant chemotherapy.
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http://dx.doi.org/10.1002/pbc.28996DOI Listing
July 2021

Role of Stereotactic Radiosurgery in Intracranial Histiocytosis: a Systematic Review of Literature of an Emerging Modality for Localized Disease.

World Neurosurg 2021 06 17;150:64-70. Epub 2021 Mar 17.

Department of Radiation Therapy, Postgraduate Institute of Medical Education and Research, Chandigarh. Electronic address:

Background: A histiocytosis is a group of immunoproliferative disorders of clonal cells. The management protocols are still evolving, with chemotherapy as the mainstay of treatment.

Objective: This study aims to evaluate the feasibility, safety, efficacy, and complication profile of stereotactic radiosurgery for intracranial histiocytosis.

Methodology: The authors reviewed PubMed, Scopus, Web of Science, and Embase for "radiosurgery" and "histiocytosis" in the English/Japanese language following preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. The patient profile, radiosurgical parameters (dose and isodose), target volume, and mode of radiosurgery (Gamma knife, LINAC radiosurgery, etc.) were collected. Its use as primary or adjuvant therapy, clinical and radiological outcome was also evaluated.

Results: We identified 7 studies (9 patients); mean age: 41.9 years (24-57 years). Six patients received Gamma-knife radiosurgery, whereas 3 received CyberKnife radiosurgery. The Langerhans cell histiocytosis variants were eosinophilic granuloma in 3, whereas 4 were not defined. Two cases had Rosai-Dorfman disease, and 2 different yet pathogenetically related histiocytic disorders. Four patients harbored lesions in the pituitary stalk and posterior pituitary, 2 patients in the petrous region, 1 patient had a pontine lesion, and 2 patients had multiple lesions. The dose delivered ranged from 8 to 28 Gy. A total of 18 lesions (9 patients) were followed for 81.67 patient-years: 7 (39%) disappeared, 8 (44.4%) showed radiological reduction, and 2 (11%) remained stable. One lesion (5%) showed an increase in size needed surgical excision. There were no adverse effects.

Conclusion: The role of stereotactic radiosurgery needs to be further evaluated as the current cohort with only 9 cases (2 are Rosai-Dorfman disease) is insufficient to make conclusions. It may be a viable alternative in localized disease, along with chemotherapy and targeted surgery.
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http://dx.doi.org/10.1016/j.wneu.2021.03.047DOI Listing
June 2021

Clinical insights and molecular study of three foetuses with DYNC2H1 gene mutation causing short rib thoracic dystrophy.

Clin Genet 2021 Jun 11;99(6):853-854. Epub 2021 Mar 11.

Department of Radiology, Sir Ganga Ram Hospital, New Delhi, India.

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http://dx.doi.org/10.1111/cge.13953DOI Listing
June 2021

Dual Oral Iron Chelation in Thalassemia: Need for Robust Evidence.

Indian J Pediatr 2021 04 8;88(4):319-321. Epub 2021 Mar 8.

Pediatric Hematology-Oncology Unit, Department of Pediatrics, Advanced Pediatrics Center, Postgraduate Institute of Medical Education and Research, Chandigarh, 160012, India.

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http://dx.doi.org/10.1007/s12098-021-03698-5DOI Listing
April 2021

Towards sustainable agriculture with carbon sequestration, and greenhouse gas mitigation using algal biochar.

Chemosphere 2021 Jul 10;275:129856. Epub 2021 Feb 10.

Department of Environmental Sciences, J.C. Bose University of Science and Technology YMCA, Faridabad, India. Electronic address:

With the increase in the world's population, demand for food and other products is continuously rising. This has put a lot of pressure on the agricultural sector. To fulfill these demands, the utilization of chemical fertilizers and pesticides has also increased. Consequently, to overcome the adverse effects of agrochemicals on our environment and health, there has been a shift towards organic fertilizers or other substitutes, which are ecofriendly and help to maintain a sustainable environment. Microalgae have a very high potential of carbon dioxide (CO) capturing and thus, help in mitigating the greenhouse effect. It is the most productive biological system for generating biomass. The high growth rate and higher photosynthetic efficiency of the algal species compared to the terrestrial plants make them a wonderful alternative towards a sustainable environment. Moreover, they could be cultivated in photobioreactors or open ponds, which in turn reduce the demand for arable land. Biochar derived from algae is high in nutrients and exhibits the property of ion exchange. Therefore, it can be utilized for sustainable agriculture by partial substituting the chemical fertilizers that degrade the fertility of the soil in the long run. This review provides a detailed insight on the properties of algal biochar as a potential fertilizer for sustainable agriculture. Application of algal biochar in bio-refinery and its economic aspects, challenges faced and future perspective are also discusses in this study.
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http://dx.doi.org/10.1016/j.chemosphere.2021.129856DOI Listing
July 2021

Survival in patients with high-risk neuroblastoma treated without autologous stem cell transplant or dinutuximab beta.

Pediatr Hematol Oncol 2021 May 23;38(4):291-304. Epub 2021 Feb 23.

Pediatric Hematology-Oncology Unit, Department of Pediatrics, Advanced Pediatrics Center, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

The majority of patients with high-risk neuroblastoma (HR-NB) in low- and middle-income countries (LMIC) do not have access to autologous stem cell transplant (ASCT) and dinutuximab. Consolidation with nonmyeloablative chemotherapy is not well-defined, and the outcomes are variable. We report a single-center outcome of patients with HR-NB, treated with nonmyeloablative consolidation. A tabulated compilation of similar reports is included. A retrospective chart review of patients with HR-NB was performed from January 2009 till June 2016. Patients were treated on the backbone of HR-NBL1/SIOPEN protocol. Treatment included induction with rapid-COJEC, surgery, followed by consolidation. Consolidation involved 4 cycles of topotecan, vincristine, and doxorubicin (TVD) instead of ASCT. Infusion of vincristine and doxorubicin were modified for ease and to enable administration in the clinic. Subsequent treatment included radiotherapy to the primary tumor and differentiation therapy with isotretinoin. Over 7½ years, 28 patients with HR-NB were treated. Two (7%) patients had therapy-related mortality. A relapse or disease progression occurred in 11 (39%) patients at a median duration of 17 months (IQR: 5, 18). Treatment abandonment was observed in 4 (14%) patients. The median follow-up of disease-free patients was 49 months (IQR: 45, 79). Patients with relapse were not treated further. A 4-year EFS of 29.3% was observed when 4-cycles of TVD were administered instead of ASCT in patients with HR-NB. The study and the review will aid decision-making for care of patients in LMIC while considering the options of treatment for HR-NB if access to ACST and dinutuximab is lacking.
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http://dx.doi.org/10.1080/08880018.2020.1850955DOI Listing
May 2021

Metastatic, Bilateral Adrenal Neuroblastoma Presenting With Blindness Without Proptosis.

J Pediatr Hematol Oncol 2021 Jan 27. Epub 2021 Jan 27.

Pediatric Hematology-Oncology Unit Department of Pediatrics, Advanced Pediatrics Center Departments of Cytology and Gynaecological Pathology Radiodiagnosis and Imaging, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

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http://dx.doi.org/10.1097/MPH.0000000000002084DOI Listing
January 2021

Diagnostic values of Ga-labelled DOTANOC PET/CT imaging in pediatric patients presenting with paraneoplastic opsoclonus myoclonus ataxia syndrome.

Eur Radiol 2021 Jul 6;31(7):4587-4594. Epub 2021 Jan 6.

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

Objectives: Opsoclonus myoclonus ataxia (OMA) syndrome, also known as "Kinsbourne syndrome" or "dancing eye syndrome," is a rare, paraneoplastic entity which may be associated with pediatric neuroblastic tumors and carry a grave prognosis. We aimed to evaluate the role of Ga DOTANOC PET/CT for detecting neuroblastic tumors in patients with OMA syndrome.

Methods: We retrospectively evaluated the Ga-DOTANOC PET/CT data of pediatric patients presenting with OMA syndrome from March 2012 to November 2018. A somatostatin receptor (SSTR)-expressing lesion with corresponding morphological change on CT image was considered PET-positive, while no abnormal SSTR expression or lesion was noticed in PET-negative patients. Histopathology and/or clinical/imaging follow-up (minimum one year) was considered a reference standard for comparing the PET/CT findings. The results of Ga-DOTANOC PET/CT were also compared with I MIBG whole-body scintigraphy, which was available in five patients.

Results: Of 38 patients (13 males, 25 females, aged 3-96 months), 18 (47.3%) had SSTR-expressing lesions (PET-positive), and histopathology revealed neuroblastic tumors in 17/18 lesions (neuroblastoma 14, ganglioneuroblastoma 2, and ganglioneuroma 1) and reactive hyperplasia in 1/18. The remaining 20/38 (52.6%) patients did not demonstrate SSTR-expressing lesions (PET-negative) and had an uneventful follow-up. The average SUVmax of the PET-positive lesions was 10.3 (range 2.8-34.5). The PET/CT results revealed 17 true-positive, one false-positive, 20 true-negative, and zero false-negative. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy were 100%, 95.2%, 94.4%, 100%, and 97.3% respectively.

Conclusions: Ga-DOTANOC PET/CT identified neuroblastic tumors with a high diagnostic accuracy in our cohort compared to histology and follow-up.

Key Points: • Opsoclonus myoclonus ataxia (OMA) syndrome or "dancing eye syndrome" is a rare paraneoplastic entity which may be associated with pediatric neuroblastic tumors with a grave prognosis. • I/I MIBG imaging has a proven role for functional imaging in neuroblastoma or patients with OMA, but the role of Ga-DOTANOC PET/CT is not yet studied. • 68Ga-labelled DOTANOC PET/CT (SSTR) imaging, in our cohort, was able to positively identify neuroblastic tumors with high diagnostic accuracy when compared with histology.
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http://dx.doi.org/10.1007/s00330-020-07587-xDOI Listing
July 2021

Multisystemic Pediatric Langerhans cell histiocytosis: a comprehensive clinico-pathological and BRAF V600E mutation study at autopsy.

Autops Case Rep 2020 Apr 23;10(2):e2020154. Epub 2020 Apr 23.

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

Langerhans cell histiocytosis (LCH), a disorder of antigen-presenting cells, is the commonest disorder of the mononuclear phagocytic system. Diagnosis is always challenging due to heterogeneous clinical presentation. However, with the evolution and better understanding of its biology, many of these children are being diagnosed early and offered appropriate therapy. Despite these advances, in developing countries, an early diagnosis is still challenging due to resource constraints for specialized tests. As a result, many patients succumb to their disease. Autopsy data on LCH is notably lacking in the literature. We sought to analyze the clinical (including mutational) and morphologic features at autopsy in six proven cases of LCH. This study includes a detailed clinico-pathological and mutational analysis of 6 proven cases of LCH. Presence of BRAF V600E mutation was assessed by both Real Time PCR and Sanger sequencing. A varied spectrum of organ involvement was noted with some rare and novel morphological findings, like nodular bronchiolocentric infiltration of LCH cells, lymphovascular emboli of LCH cells, and paucity of eosinophils within the infiltrate; these features have not been described earlier. Surprisingly, all cases were negative for BRAF V600E mutation on both RQ-PCR and Sanger sequencing. The present study is perhaps the first autopsy series on LCH. This extensive autopsy analysis represents a correlation of pathological features with clinical symptoms which provides clues for a timely diagnosis and appropriate therapeutic intervention. Also, our findings hint at the low frequency of BRAF V600E mutation in our LCH patients.
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http://dx.doi.org/10.4322/acr.2020.154DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7703466PMC
April 2020

Pediatric bone marrow failure: Clinical, hematological and targeted next generation sequencing data.

Blood Cells Mol Dis 2021 03 5;87:102510. Epub 2020 Nov 5.

Pediatric Hematology Oncology Unit, Department of Pediatrics, Postgraduate Institute of Medical Education & Research, Chandigarh, India.

Objective: In this study, clinico-hematological, genetic and outcome profile of children with BMF was evaluated to delineate the underlying genotype and phenotype.

Design: Cases were evaluated as two groups: Group 1 (n = 56; DBA-23, FA-18, DC-2, UBMFS-13) included children with suspected IBMFS based on clinical phenotype and accessible lab investigations and Group 2 (n = 53) included children with IAA treated with IST. Targeted NGS was carried out in a subset of these children (n = 42) and supplemented with WES wherever required.

Results: We identified causative mutation in overall 15 of 27 tested children (55.5%) in group 1 and 2 of 15 tested children (13.3%) in group 2. In DBA, a mutation was noted in 50% cases with involvement of RPS 19 (75%) and RPL5 (25%) genes. Phenotypic abnormalities were present in 69.5% and response to steroids in 68.4% of cases at a median follow up of 33 months. In children with IAA, overall response (complete + partial) was present in 51% at a median follow up of 23 months. The 3-year OS and FFS for the cohort of IAA were 68% and 48% respectively. Targeted sequencing could also pick up germline mutations in 50% of UBMFS cases and nearly 19% of IAA cases.
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http://dx.doi.org/10.1016/j.bcmd.2020.102510DOI Listing
March 2021

Infantile Inflammatory Myofibroblastic Tumor of Spleen.

Fetal Pediatr Pathol 2020 Oct 23:1-5. Epub 2020 Oct 23.

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

Inflammatory myofibroblastic tumor (IMT) is a mesenchymal neoplasm with unknown etiology and recurrent potential. They are widely reported in children and young adults. Nearly 50% of inflammatory myofibroblastic tumor harbor rearrangement in anaplastic lymphoma kinase () gene with the majority expressing ALK protein. ALK-negative IMTs harbor alteration in gene in a subset of cases. Few reports have shown association of IMT with Epstein-Barr virus (EBV). We report a case of IMT of the spleen in an 18-month-old infant presenting with abdominal distention and failure to thrive. Workup for ALK-1, ROS1, and EBV small-encoded RNA in-situ hybridization using immunohistochemistry was negative. IMT can arise in an infant spleen.
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http://dx.doi.org/10.1080/15513815.2020.1836098DOI Listing
October 2020

Hemophagocytic Lymphohistiocytosis in a PICU of a Developing Economy: Clinical Profile, Intensive Care Needs, Outcome, and Predictors of Mortality.

Pediatr Crit Care Med 2021 01;22(1):e44-e57

Division of Pediatric Critical Care, Department of Pediatrics, Advanced Pediatrics Centre, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, India.

Objectives: To describe the clinical profile, intensive care needs, outcome, and predictors of mortality in critically ill children with hemophagocytic lymphohistiocytosis.

Design: Retrospective case series.

Setting: PICU of a tertiary care teaching hospital in North India.

Patients: Children 2 months to 12 years old with the diagnosis of hemophagocytic lymphohistiocytosis admitted to PICU from January 2012 to April 2019 (7¼ yr).

Interventions: None.

Measurements And Main Results: Sixty-two children with hemophagocytic lymphohistiocytosis (60 secondary and two primary) were enrolled. The median (interquartile range) age of the study group was 82 months (50.5-124 mo). The median (interquartile range) Pediatric Risk of Mortality III score was 16 (10-23). Majority of hemophagocytic lymphohistiocytosis was infection-associated (n = 51; 82.3%). Among these, scrub typhus accounted for 29% of cases (n = 18), dengue 17.7% (n = 11), bacterial sepsis 14.5% (n = 9), enteric fever 6.5% (n = 4), and other infections 14.5% (n = 9). Systemic-onset juvenile idiopathic arthritis accounted for 9.7% of cases (n = 6) and malignancy for 4.8% patients (n = 3). Majority of cases were treated with steroids (77.4%) and IV immunoglobulin (25.8%). Various complications noted were shock (71%), acute kidney injury (66.1%), acute respiratory distress syndrome (41.9%), disseminated intravascular coagulation (54.8%), CNS dysfunction (54.8%), multiple organ dysfunction syndrome (82.3%), and healthcare-associated infections (14.5%). Intensive care needs for primary illness and/or hemophagocytic lymphohistiocytosis included mechanical ventilation (74.2%); packed RBC (72.3%), fresh frozen plasma (40.3%), and platelet (48.4%) transfusion; vasoactive drugs (71%); and renal replacement therapy (24.2%). The median duration of PICU stay was 5 days (2.5-9.5 d) and mortality was 59.7% (n = 37). On univariate analysis, nonsurvivors had higher Pediatric Risk of Mortality III score; higher proportion of shock, acute kidney injury, acute respiratory distress syndrome, disseminated intravascular coagulation, and multiple organ dysfunction syndrome; the need for blood and blood components, mechanical ventilation, vasoactive drugs, and renal replacement therapy; higher Vasoactive-Inotropic Score; and prolonged duration of mechanical ventilation compared with survivors.

Conclusions: Hemophagocytic lymphohistiocytosis in PICU is commonly secondary to tropical infections and associated with high mortality. Higher severity of illness; shock and multiple organ dysfunction syndrome; need for blood and blood products, mechanical ventilation, vasoactive drugs, and renal replacement therapy; higher Vasoactive-Inotropic Score; and prolonged mechanical ventilation predicted death. Treatment of underlying infection and a less intense immunosuppressive therapy (steroids ± IV immunoglobulin) are suggested options. A high index of suspicion for complicating hemophagocytic lymphohistiocytosis is required in children with prolonged fever, cytopenias, organomegaly, and organ dysfunction not responding to conventional treatment.
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http://dx.doi.org/10.1097/PCC.0000000000002539DOI Listing
January 2021

An Evaluation of a Fluorescence In Situ Hybridization Strategy Using Air-dried Blood and Bone-marrow Smears in the Risk Stratification of Pediatric B-Lineage Acute Lymphoblastic Leukemia in Resource-limited Settings.

J Pediatr Hematol Oncol 2021 05;43(4):e481-e485

Unit of Paediatric Haemato-oncology, Department of Paediatrics, Advanced Paediatric Centre, Post Graduate Institute of Medical Education and Research, Chandigarh, India.

Cytogenetic abnormalities (CAs), one of the strongest influencers of therapeutic outcome in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL), can be identified by different techniques. Despite several technological advances, many centers with resource-limited settings continue to use either reverse-transcriptase polymerase chain reaction (RT-PCR) and/or fluorescence in situ hybridization (FISH) to identify prognostically relevant CAs. We evaluated a simple and cost-effective triple-probe FISH strategy on air-dried blood and bone-marrow smears and compared its performance with a multiplex RT-PCR-based approach in the prognostication of pediatric BCP-ALL patients. Three hundred twenty BCP-ALL patients were tested prospectively and in parallel by FISH on air-dried blood or bone-marrow smears and RT-PCR. The FISH strategy correctly diagnosed all genetic abnormalities identified by RT-PCR. Prognostically relevant genetic abnormalities were missed by RT-PCR in 24 (8.1%) patients. In another 20 children (6%), with samples inadequate for RT-PCR testing (dry taps or due to poor sample quality), a successful FISH testing could be performed on bone-marrow aspirate or trephine-imprint smears. In addition, FISH detected ploidy changes, which could be confirmed by FxCycle Violet-based flow-cytometry. FISH testing on air-dried smears identified more prognostically relevant CAs, provided information on the ploidy status, and could be successfully performed in children with difficulty in bone-marrow sampling.
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http://dx.doi.org/10.1097/MPH.0000000000001892DOI Listing
May 2021

Small Cell Carcinoma of Ovary, Hypercalcemic Type: Cytologic, Histopathologic, and Immunohistochemical Landscapes of a Rare Case.

J Pediatr Adolesc Gynecol 2021 Feb 1;34(1):98-102. Epub 2020 Aug 1.

Department of Histopathology, PGIMER, Chandigarh, India.

Background: Small cell carcinoma of ovary, hypercalcemia type (SCCOHT), also known as the malignant rhabdoid tumor of the ovary, is a rare and highly aggressive malignancy affecting younger women. The pathogenesis involves mutations in SWI/SNF-related, matrix-associated, actin-dependent regulator chromatin group A4 (SMARCA4)/Brahma-related gene 1 (BRG1) and/or SWI/SNF-related, matrix-associated, actin-dependent regulator chromatin group A2 (SMARCA2)/Brahma homolog (BRM).

Case: A 10-year-old girl presented with lower abdominal pain and a mass for the past 2 weeks. She underwent ultrasound-guided fine needle aspiration and core needle biopsy from the pelvic mass followed by surgery. On the basis of the characteristic morphologic and immunohistochemical features, a diagnosis of SCCOHT was rendered. Chemotherapy was started, however, she succumbed to the disease.
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http://dx.doi.org/10.1016/j.jpag.2020.07.017DOI Listing
February 2021

A high frequency of Gilbert syndrome (UGT1A1*28/*28) and associated hyperbilirubinemia but not cholelithiasis in adolescent and adult north Indian patients with transfusion-dependent β-thalassemia.

Ann Hematol 2020 Sep 16;99(9):2019-2026. Epub 2020 Jul 16.

Department of Hematology, PGIMER, Level 5, Research Block A, Sector 12, Chandigarh, 160012, India.

Hyperbilirubinemia and pigment gallstones are frequent complications in transfusion-dependent β-thalassemia (TDβT) patients. Bilirubin production and clearance are determined by genetic as well as environmental variables like ineffective erythropoiesis, hemolysis, infection-induced hepatic injury, and drug- or iron-related toxicities. We studied the frequency of the Gilbert syndrome (GS), a common hereditary cause of hyperbilirubinemia in 102 TDβT patients aged 13-43 years (median 26 years). Total and unconjugated hyperbilirubinemia were frequent (81.4% and 84.3% patients respectively). Twenty (19.6%) patients showed total bilirubin > 3.0 mg/dL; 53 (51.9%) had an elevation of either alanine or aspartate aminotransferase, or alkaline phosphatase liver enzymes. Nineteen (18.6% of the 92 tested) were positive for hepatitis B or C, or HIV. The mean total and unconjugated bilirubin levels and AST, ALT, and ALP levels in patients positive for hepatitis B or C were not significantly different from negative cases. Eighteen patients (17.7%) had GS: homozygous (TA)7/7 UGT1A1 promoter motif (the *28/*28 genotype), 48 (47.1%) were heterozygous (TA)6/7. Total + unconjugated bilirubin rose significantly with the (TA)7 allele dose. Fourteen (13.7%) patients had gallstones. There was no significant difference in total/unconjugated bilirubin in patients with/without gallstones and no significant differences in frequencies of gallstones within the three UGT1A1 genotypes. This largest study in Indian TDβT patients suggests that GS should be excluded in TDβT cases where jaundice remains unexplained after treatable causes like infections, chelator toxicity, or transfusion-related hemolysis are excluded. GS was not associated with gallstones, possibly due to a lower incidence of cholelithiasis overall, a younger age cohort, or other environmental factors.
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http://dx.doi.org/10.1007/s00277-020-04176-2DOI Listing
September 2020

Ataxia as Forme Fruste of Opsoclonus Myoclonus Ataxia Syndrome.

Ann Indian Acad Neurol 2020 May-Jun;23(3):415-417. Epub 2020 Jun 10.

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

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http://dx.doi.org/10.4103/aian.AIAN_111_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7313590PMC
June 2020

Challenges in the management of localized Ewing sarcoma in a developing country.

Pediatr Hematol Oncol 2020 Oct 19;37(7):610-619. Epub 2020 Jun 19.

Paediatric Haematology Oncology unit, Department of Paediatrics.

Survival in pediatric Ewing sarcoma (ES) lags in low- and middle-income countries (LMICs). This study analyzed factors contributing to a lower outcome in an LMIC center. A retrospective case review of children with localized ES treated from January 2011 till December 2017 was performed. Neoadjuvant chemotherapy with alternating cycles of vincristine, doxorubicin, cyclophosphamide; and ifosfamide, etoposide was administered 3-weekly for 48 weeks. Reassessment was planned for week 12, followed by local therapy (surgery/radiotherapy or both) tailed by adjuvant chemotherapy. Forty-eight patients with mean age 8 years (range: 0.7-14) were evaluated. Extremity and central axis tumors were seen in 25 (52%) and 23 (48%) patients. Three patients died of neutropenic sepsis and five abandoned therapy. Local therapy included primary surgery, radiotherapy and a combination of surgery and radiotherapy in 7 (16%), 20 (45%) and 17 (39%) patients. The 3-year event-free survival (EFS) and disease-free survival (DFS) for the cohort were 47.7 ± 11% and 57.6 ± 11.2%. Time to local therapy >16 weeks was associated with inferior DFS local therapy administered within 16 weeks [46.6 ± 12.4 63.9 ± 19.4, =.046]. Older age, axial site, large size and incomplete surgical resection did not predict relapse/progression. Patients who received wide local excision, as local therapy, had 100% DFS. Coordinated efforts to ensure timely therapy can improve outcome in pediatric ES. Abandonment and treatment-related mortality (TRM) are additional challenges that need to be tackled in LMICs.
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http://dx.doi.org/10.1080/08880018.2020.1772912DOI Listing
October 2020

Oncology care in a lower middle-income country during the COVID-19 pandemic.

Pediatr Blood Cancer 2020 08 15;67(8):e28438. Epub 2020 Jun 15.

Pediatric Hematology Oncology Unit, Department of Pediatrics, Advanced Pediatrics Center, Postgraduate Institute of Medical Education and Research, Chandigarh, India.

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http://dx.doi.org/10.1002/pbc.28438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7323035PMC
August 2020

Halogen-Bonded Assemblies of Arylene Imides and Diimides: Insight from Electronic, Structural, and Computational Studies.

Chemistry 2020 Aug 20;26(46):10607-10619. Epub 2020 Jul 20.

Supramolecular and Material Chemistry Lab, School of Physical Sciences, Jawaharlal Nehru University, Delhi, 110067, India.

Halogen-bonding interactions in electron-deficient π scaffolds have largely been underexplored. Herein, the halogen-bonding properties of arylene imide/diimide-based electron-deficient scaffolds were studied. The influence of scaffold size, from small (phthalimide) to moderately sized (pyromellitic diimide or naphthalenediimides) to large (perylenediimide), axial-group modification, and number of halo substituents on the halogen bonding and its self-assembly was probed in a set of nine compounds. The structural modification leads to tunable optical and redox properties. The first reduction potential ranges between -1.09 and -0.17 V (vs. SCE). Two of the compounds, that is, 6 and 9, have deep-lying LUMOs with values reaching -4.2 eV. Single crystals of all nine systems were obtained, which showed Br⋅⋅⋅O, Br⋅⋅⋅Br, or Br⋅⋅⋅π halogen-bonding interactions, and a few systems are capable of forming all three types. These interactions lead to halogen-bonded rings (up to 12-membered), which propagate to form stacked 1D, 2D, or corrugated sheets. A few outliers were also identified, for example, molecules that prefer C-H⋅⋅⋅O hydrogen bonding over halogen bonding, or noncentrosymmetric rather than centrosymmetric organization. Computational studies based on Atoms in Molecules and Natural Bond Orbital analysis provided further insight into the halogen-bonding interactions. This study can lead to a predictive design tool-box to further explore related systems on surfaces reinforced by these weak directional forces.
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http://dx.doi.org/10.1002/chem.202001706DOI Listing
August 2020

Inherited Bleeding Disorders in North Indian Children: 14 years' Experience from a Tertiary Care Center.

Indian J Hematol Blood Transfus 2020 Apr 21;36(2):330-336. Epub 2019 Nov 21.

1Division of Pediatric Hemato-Oncology, Department of Pediatrics, Post Graduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012 India.

Inherited bleeding disorders are not uncommon in pediatric practice: most of them being chronic, require lifelong replacement therapy. To frame a management policy, it is essential to assess the load and pattern of bleeding disorders in the local population. However, there is paucity of data reporting the clinical spectrum of coagulation and platelet function disorders in Indian children. Hence to find out the exact burden and clinico-investigational profile of these patients we conducted this study. In this retrospective case review, detailed clinical information was extracted from case records in 426 children with a suspected diagnosis of hereditary bleeding disorder registered in the Pediatric Hematology clinic of a tertiary referral centre over a period of 14 years (1998-2011) and pooled for analysis. In our cohort prevalence of hemophilia A, hemophilia B, platelet function disorders, von Willebrand disease and other rare factor deficiencies were 72%, 11%, 7%, 4% and 4% respectively. Common clinical spectrum included skin bleeds, arthropathy, mucosal bleeds. 10% had deeper tissue bleeding and 16% received replacement therapy at the first visit. Nearly 3/4th of cases were lost for follow up after the initial visit. Hemophilia A was the commonest inherited bleeding disorder in our population. Skin bleeds and arthropathy were common clinical presentations. Factor replacement therapy was restricted to a minority. There is an urgent need for establishing centres of excellence with administrative commitment for factor replacement therapy for comprehensive management of such children in resource-limited countries.
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http://dx.doi.org/10.1007/s12288-019-01233-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7229128PMC
April 2020

Imatinib-Induced Hypogammaglobulinemia in Children and Adolescents with Chronic Myeloid Leukemia.

Pediatr Hematol Oncol 2020 Sep 4;37(6):539-544. Epub 2020 May 4.

Pediatric Hematology-Oncology Unit, Dept. of Pediatrics, Advanced Pediatrics Center, Chandigarh, India.

Imatinib-induced tyrosine kinase inhibition extends beyond the BCR-ABL mutation, resulting in adverse effects. We evaluated hypogammaglobulinemia as a potential 'off-target' action of imatinib in children with CML. A cross-sectional, observational study was performed. Patients with CML in chronic phase, age <18-years at diagnosis, receiving imatinib for a duration exceeding 6-months were enrolled. Serum immunoglobulin G, A, and M were measured by end-point nephelometry. Thirty patients were enrolled. The mean age at diagnosis was 10.4 ± 3.1 years (range: 5-18). The mean age at enrollment was 16.4 ± 4.1 years (range: 9-23). The median dose of imatinib was 287.5 mg/m (IQR: 267.3, 345.0). The median duration of imatinib-therapy was 6-years (IQR: 3.0, 10.3). The median (IQR) normalized levels of IgG, IgA, and IgM were 33.0% (IQR: -12.8, 58.7), 28.1% (IQR: -17.0, 90.1) and 15.9% (IQR: -9.3, 40.5), respectively. The IgG, IgA, and IgM levels were reduced in 9 (30%), 8 (27%), and 10 (33%) patients, respectively. Five (17%) patients had pan-hypogammaglobulinemia. We suggest checking immunoglobulin levels in patients with CML receiving imatinib with recurrent/unusual infections.
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http://dx.doi.org/10.1080/08880018.2020.1759739DOI Listing
September 2020

Green technology for sustainable biohydrogen production (waste to energy): A review.

Sci Total Environ 2020 Aug 12;728:138481. Epub 2020 Apr 12.

Innovative Green Product Synthesis and Renewable Environment Development Research Group, Faculty of Environment and Labour Safety, Ton Duc Thang University, Ho Chi Minh City, Viet Nam. Electronic address:

Perceiving and detecting a sustainable source of energy is very critical issue for current modern society. Hydrogen on combustion releases energy and water as a byproduct and has been considered as an environmental pollution free energy carrier. From the last decade, most of the researchers have recommended hydrogen as one of the cleanest fuels and its demand is rising ever since. Hydrogen having the highest energy density is more advantageous than any other fuel. Hydrogen obtained from the fossil fuels produces carbon dioxide as a byproduct and creates environment negative effect. Therefore, biohydrogen production from green algae and cyanobacteria is an attractive option that generates a benign renewable energy carrier. Microalgal feedstocks show a high potential for the generation of fuel such as biohydrogen, bioethanol and biodiesel. This article has reviewed the different methods of biohydrogen production while also trying to find out the most economical and ecofriendly method for its production. A thorough review process has been carried out to study the methods, enzymes involved, factors affecting the rate of hydrogen production, dual nature of algae, challenges and commercialization potential of algal biohydrogen.
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http://dx.doi.org/10.1016/j.scitotenv.2020.138481DOI Listing
August 2020

Congenital dyserythropoietic anemia type IV with high fetal hemoglobin caused by heterozygous KLF1 p.Glu325Lys: first report in an Indian infant.

Ann Hematol 2021 Jan 27;100(1):281-283. Epub 2020 Mar 27.

Department of Hematology, Post Graduate Institute of Medical Education and Research, Chandigarh, 160012, India.

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http://dx.doi.org/10.1007/s00277-020-03982-yDOI Listing
January 2021
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