Directly-Fused Ni(II)Porphyrin Conjugated Polymers with Blocked meso-Positions: Impact on Electrocatalytic Properties.

The oxidative coupling reaction of two Ni(II) porphyrins meso-substituted with three and four phenyl groups, Ni(II) 5,10,15-(triphenyl)porphyrin (NiPh3P) and Ni(II) 5,10,15,20-(tetraphenyl)porphyrin (NiPh4P) respectively, was investigated in a oxidative chemical vapor deposition (oCVD) process. Irrespective of the number of meso-substituents, high-resolution mass spectrometry evidences the formation of oligomeric species containing up to five porphyrin units. UV-Vis-NIR and XPS analyses of the oCVD films highlighted a strong dependence of the intermolecular coupling reaction with the substrate temperature. Specifically, higher substrate temperatures yield lowering of valence band maxima and reduction of the band gap. The formation of conjugated polymeric assemblies results in increased conductivities as compared to their sublimed counterparts. Yet, electrocatalytic measurements exhibit water oxidation onset overpotentials (308 mV for pNiPh3P and 343 mV for pNiPh4P) comparatively higher than the onset overpotential measured for the oCVD film from Ni(II) 5,15-(diphenyl)porphyrin (pNiPh2P), i. e. 283 mV. Although DFT and comparative oCVD studies suggest the formation of directly fused porphyrins involving 'phenyl-mediated' and ß-ß linkages when reacting tetra-meso-substituted porphyrins, the present findings highlight that multiple direct fusion (ß-ß/meso-meso/ß-ß or meso-ß/ß-meso) is essential for Ni(II) porphyrin-based conjugated polymers to enable a dinuclear radical oxo-coupling operating mechanism for water oxidation at low overpotential and durable catalytic activity.

Unearthing the genotype-inhibitor phenotype association in severe haemophilia A: A north Indian cohort study.

INTRODUCTION: Various risk factors for inhibitor development in haemophilia A (HA) have been described but Indian data remains scanty. AIM: We aimed to evaluate the genetic changes in Indian HA-patients that are associated with the development of inhibitors. METHODS: All HA-patients with inhibitors who availed coagulation-laboratory services from January-2015 till December-2021 and had their samples preserved for DNA extraction were included in this study. An equal number of severity-matched HA patients without inhibitors were also included as controls. Intron 22 and intron 1 inversions in Factor VIII gene were identified using inverse-shifting-PCR. Inversion-negative patients were further assessed by targeted NGS, MLPA. RESULTS: Thirty HA-patients with inhibitors were identified. All had severe-HA. Thirty severe-HA-patients without inhibitors were also included as controls. Intron 22 inversion (63.3%) and large deletions (15%) were the commonest variants identified. There was no difference in genetic variants in patients with low and high titre inhibitors. A3, A2 and C2 were the most common domains involved in inversion-negative patients with inhibitors. However, there was no significant difference in domain involvement among inversion-negative patients with and without inhibitors. Seven novel-variants were identified, including three large deletions, one large duplication and two nonsense variants in inhibitor-positive patients, and one frameshift variant in inhibitor-negative patient. After adjusting for clinical risk-factors, large deletions were independently associated with the presence of inhibitors [aOR:6.1 (1.41-56.3)]. CONCLUSION: Intron 22 inversions are the commonest variant in Indian patients with severe-HA. Large deletions predispose to inhibitor development independent of clinical risk factors.

Autoimmune anti-D in an RhD-positive young infant: Learning from a rare case.

BACKGROUND AND OBJECTIVES: Anti-D is usually immune in nature and is formed in individuals lacking D antigen or having variants/altered D phenotypes. In the Indian population, 93.8% are RhD positive, and R1 R1 is the commonest Rh phenotype. Here we report a rare and interesting case of autoimmune anti-D in an RhD-positive 3-month-old infant leading to warm autoimmune haemolytic anaemia. STUDY DESIGN AND METHODS: Auto-anti-D was detected serologically by immunohaematological techniques such as direct antiglobulin test, antibody detection and identification, dithiothreitol, enzyme treatment, antibody titration and elution. Molecular studies were performed to rule out genetic variants of RhD. RESULTS: Anti-D was confirmed in eluate and blood group post elution was B RhD positive. On genotyping using the Indian-specific RHD genotyping assay, the sample was found to be negative for the RHD*01W.150 (most common RhD variant in Indians) but positive for RHD exon 5 and RHD exon 10 along with glyceraldehyde-3-phosphate dehydrogenase (GAPDH). The sample was further sequenced for RHD exons 1-10 by Sanger sequencing and found to be a wild type, thus, ruling out the presence of an RhD variant. CONCLUSION: This case is of interest because of the rare occurrence of autoimmune anti-D in an RhD-positive patient of such a young age (3 months). To the best of our knowledge, only two case reports have been published on autoimmune anti-D in infancy (in 1961 and 1964).

Clinical spectrum, phenotypic and molecular characterization, and antifungal susceptibility of an emerging human pathogen, Acrophialophora, from India.

Acrophialophora is implicated in superficial and invasive infections, especially in immunosuppressed individuals. The present study was undertaken to provide clinical, microbiological, phylogenetic, and antifungal susceptibility testing (AFST) profile of Acrophialophora isolated from India. All the isolates identified as Acrophialophora species at National Culture Collection for Pathogenic Fungi, Chandigarh, India were revived. Phenotypic and molecular characterization was performed, followed by temperature studies, scanning electron microscopy (SEM) and AFST. We also performed systematic review of all the cases of Acrophialophora species reported till date. A total of nine isolates identified as Acrophialophora species were identified by molecular method as A. fusispora (n = 8) and A. levis (n = 1), from brain abscess (n = 4), respiratory tract (n = 3) and corneal scraping (n = 2). All patients but two had predisposing factors/co-morbidities. Acrophialophora was identified as mere colonizer in one. Temperature studies and SEM divulged variation between both species. Sequencing of the ITS ribosomal DNA and beta-tubulin loci could distinguish species, while the LSU ribosomal DNA locus could not. AFST showed lowest MICs for triazoles and highest for echinocandins. Systematic literature review revealed 16 cases (11 studies), with ocular infections, pulmonary and central nervous system infections, and A. fusispora was common species. All the patients except three responded well. High MICs were noted for fluconazole, micafungin and caspofungin. This is the first study delineating clinical, phenotypic, and genotypic characteristics of Acrophialophora species from India. The study highlights microscopic differences between both species and emphasizes the role of molecular methods in precise identification. Triazoles appear to be the most effective antifungals for managing patients.

We describe clinical, phenotypic, and genotypic characteristics of Acrophialophora species. This species causes mild infection to fatal infection in immunosuppressed individuals. Triazoles are effective in treating such infections.

Molecular spectrum of inherited FVII deficiency in North India revealed a recurrent variant with a founder effect.

INTRODUCTION: Inherited Factor VII (FVII) deficiency is commonest among the rare bleeding disorders. A small number of patients present in infancy with severe bleeding, and many may remain asymptomatic but detected before surgery/invasive procedures. Genetic testing may be helpful in predictive testing/prenatal diagnosis in severe cases. AIM: Characterisation of clinical and genotypic spectrum of patients with inherited FVII deficiency. METHODS: Retro-prospectively, 35 cases with prolonged prothrombin time and FVII activity (FVII:C) <50 IU/dl were subjected to targeted resequencing. After in-silico analysis, variant/s were validated by Sanger sequencing in index cases and family members. Haplotype analysis was done for F7 polymorphisms. RESULTS: Severe FVII deficiency was found in 50% of patients (FVII:C ≤1 IU/dl), and 42.9% were asymptomatic. Clinical severity assessment revealed 17% severe, 17% moderate and 22.9% patients with mild bleeds. FVII levels ranged from .3 to 38 IU/dl. Molecular analysis revealed variants in 30/35 cases, of which 17 were homozygous, 10 were compound heterozygous and 3 were heterozygous. Twelve genetic variants were identified, one promoter variant c.-30A>C; seven missense (c.215C>G, c.244T>C, c.253G>C, c.904G>A, c.961C>T, c.1109G>T, c.1211G>A), two deletions (c.21delG, c.868_870delATC), and one each of nonsense c.634C>T and splice-site variant c.316+1G>A. Recurrent variants c.1109G>T and c.215C>G were found in 17 and 8 cases, 12 of the former cases were homozygous. They had the same haplotype, indicating the founder effect in North Indians. CONCLUSION: This is the largest cohort of FVII genotyping from India, confirming heterogeneity in terms of clinical manifestations, FVII activity and zygosity of the variants with a limited genotypic phenotypic correlation.

SIOP PODC adapted risk stratification and treatment guidelines: Recommendations for acute myeloid leukemia in resource-limited settings.

In low- and middle-income countries (LMICs), limited resources, suboptimal risk stratification, and disproportionate patient-to-infrastructure ratio result in low survival of patients with acute myeloid leukemia (AML). A high incidence of relapse, inherent to the biology, renders management arduous. The challenge of treating AML in LMICs is of balancing the intensity of myelosuppressive chemotherapy, which appears necessary for cure, with available supportive care, which influences treatment-related mortality. The recommendations outlined in this paper are based on published evidence and expert opinion. The principle of this adapted protocol is to tailor treatment to available resources, reduce preventable toxic death, and direct limited resources toward those children who are most likely to be cured.

A single-blinded, randomized controlled trial of standard versus higher dose carboplatin-based intravenous chemotherapy for group D and E retinoblastoma.

BACKGROUND: Access to intra-arterial chemotherapy for retinoblastoma in low- and middle-income countries (LMICs) is limited. There is a need to optimize the efficacy of systemic chemotherapy for advanced intraocular retinoblastoma, particularly in LMICs. The aim was to compare the efficacy of standard versus higher dose carboplatin-based intravenous chemotherapy for group D and E retinoblastoma. METHODS: The single-center, single-blinded, randomized study was conducted during 2019-2021. Patients with newly diagnosed group D or E retinoblastoma were randomized to receive vincristine, etoposide, and standard versus higher dose (<36 months: 18.6 vs. 28 mg/kg; ≥36 months: 560 vs. 840 mg/m2 ) carboplatin. Examination under anesthesia and ultrasonography was performed at diagnosis and following three cycles of chemotherapy. Group E eyes with poor likelihood of globe/vision salvage at diagnosis were excluded. RESULTS: Thirty-two eyes of 30 patients were analyzed: 17 group D and 15 group E eyes. The tumor response to chemotherapy with regards to regression pattern (p = .72), tumor shrinkage (diameter: p = .11, height: p = .96), subretinal seeds (p = .91), and vitreous seeds (p = .9) were comparable between the two treatment arms. The globe salvage (group D [82% vs. 67%; p = .58]; group E [12.5% vs. 29%; p = .57]) and salvage of meaningful vision (group D [100% vs. 75%; p = .13]; group E [100% vs. 50%; p = .48]) were comparable between standard and higher dose arms. No excess treatment-related toxicity was observed in the higher dose arm. CONCLUSIONS: Higher dose carboplatin-based intravenous chemotherapy did not result in superior globe or vision salvage in group D or E retinoblastoma.

Common queries in managing rhabdomyosarcoma in low- and middle-income countries: An Indo-North American collaboration.

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma among children and adolescents. The management of RMS involves risk stratification of the patients based on various clinicopathological characteristics. The multimodality treatment approach requires chemotherapy, surgery, and/or radiation. The treatment of RMS necessitates the involvement of multiple disciplines, such as pathology, pediatric oncology, surgery, and radiation oncology. The disease heterogeneity, molecular testing, evolving treatment regimens, and limited resources are some of the challenges faced by clinicians while treating a patient with RMS in low- and middle-income countries (LMICs). In this review, we endeavor to bring experts from varying fields to address clinicians' common questions while managing a child or adolescent with RMS in LMICs. This review is most applicable to level 2 centers in LMICs as per the levels of services described by the Adapted Treatment Regimens Working Group of the Pediatric Oncology in Developing Countries committee of the International Society of Pediatric Oncology.

Remediation of contaminants from wastewater using algal nanoparticles via green chemistry approach: an organized review.

Bio-nanotechnology is one of the new and sound techniques that have various advantages over conventional methods of wastewater treatment. The utilization of nanomaterials like nanoparticles for wastewater treatment is emerging field of research. Both physical and chemical methods can be used for nanoparticle synthesis, but synthesis based on algae (biological method) has numerous advantages over others as it is environmentally friendly and sustainable. Top-down and bottom-up are the two approaches used for nanoparticle synthesis, generally, bio-reduction (bottom-up approach) is used to synthesize nanoparticles. Nanoparticles can be synthesized inside the cell of algae called intracellular synthesis and outside on the surface of the cell called extracellular synthesis. Temperature, pH, and reaction time are some of the factors that can influence the synthesis, size, and properties of nanoparticles. Characterization of nanoparticles is carried out with the help of the techniques like UV-visible spectroscopy (UV-vis), x-ray diffraction, Fourier transfer infrared spectroscopy, etc. Algal nanoparticles are highly efficient in the remediation of contaminants like heavy metals and dyes from wastewater. In the present review, the utilization of algal nanoparticles for wastewater treatment containing contaminants like heavy metals, and dye, and various methods of synthesis of nanoparticles from algae are discussed. Moreover, the challenges and opportunities present in this field are also highlighted. As this field is in its initial stage, therefore, a lot of research gaps are present, which can only be filled by further new research.

Early mortality continues to be a barrier to excellent survival in childhood acute promyelocytic leukemia: a retrospective study of 62 patients spanning 17 years.

Data on childhood acute promyelocytic leukemia (APL) from low-and middle-income countries is limited. Early mortality is a concern and often not highlighted in clinical trials. The retrospective study was conducted on patients (≤12 years) with APL from 2003 to 2021 at a single center in India. Patients were treated with all-trans-retinoic acid (ATRA) and chemotherapy. Induction and three courses of consolidation were followed by maintenance for 2 years. In 2015, the protocol was updated with following modifications: (a) obtaining diagnostic cerebrospinal fluid at end-of-induction rather than at diagnosis, (b) administering intrathecal cytarabine regardless of risk-category, (c) risk-stratified administration of chemotherapy, and (d) inclusion of ATRA in all the cycles of consolidation. Sixty-two patients were diagnosed over the 17 years. The median age was 8 years (range: 0.9-12). Half had high-risk disease. Differentiation syndrome was observed in 32%, none being fatal. Eighteen (29%) patients died due to hemorrhage (83%) or septicemia (17%). Thirteen (21%) had early mortality (≤15 days), all due to hemorrhage. A platelet count <20 × 109/L predicted early mortality (odds ratio: 4.5; 95% CI: 0.9-22, p = 0.06). Treatment abandonment reduced from 23.5% during 2003-2015 to nil during 2015-2021 (p = 0.006). Three (8%) patients relapsed. The 4-year OS of all patients and the patients who survived >15 days was 70.1% and 89.6%, respectively. The 4-year EFS, including abandonment and early mortality, before and following updated protocol, was 61.4% and 65.5%, respectively (p = 0.77). Early mortality continues to be a barrier to an otherwise excellent survival in childhood APL. A significant reduction in treatment abandonment in recent years is gratifying.

Estimation of iron overload with T2*MRI in children treated for hematological malignancies.

Iron overload may contribute to long-term complications in childhood cancer survivors. There are limited reports of assessment of tissue iron overload in childhood leukemia by magnetic resonance imaging (MRI). A cross-sectional, observational study in children treated for hematological malignancy was undertaken. Patients ≥6 months from the end of therapy who had received ≥5 red-cell transfusions were included. Iron overload was estimated by serum ferritin (SF) and T2*MRI. Forty-five survivors were enrolled among 431 treated for hematological malignancies. The median age at diagnosis was 7-years. A median of 8 red-cell units was transfused. The median duration from the end of treatment was 15 months. An elevated SF (>1,000 ng/ml), elevated liver iron concentration (LIC) and myocardial iron concentration (MIC) were observed in 5 (11.1%), 20 (45.4%), and 2 (4.5%) patients, respectively. All survivors with SF >1,000 ng/ml had elevated LIC. The LIC correlated with SF (p < 0.001). MIC lacked correlation with SF or LIC. Factors including the number of red-cell units transfused and duration from the last transfusion were associated with elevated SF (p = 0.001, 0.002) and elevated LIC (p = 0.012, 0.005) in multiple linear regression. SF >595 ng/ml predicted elevated LIC with a sensitivity of 85% and specificity of 91.6% (AUC 91.2%). A cutoff >9 units of red cell transfusions had poor sensitivity and specificity of 70% and 75% (AUC 76.6%) to predict abnormal LIC. SF >600 ng/ml is a robust tool to predict iron overload, and T2*MRI should be considered in childhood cancer survivors with SF exceeding 600 ng/ml.

A higher tumor volume and undernutrition at diagnosis adversely affect the survival of children with Wilms tumor: A study of 200 patients.

BACKGROUND: Distinct prognostic factors for Wilms tumor (WT) in low- and middle-income countries need identification. METHODS: Retrospective study of patients with WT managed by the International Society of Pediatric Oncology (SIOP) approach for over 11 years (2005-2016) at a single center in Chandigarh, India. RESULTS: The study included 200 patients (median age: 33.5 months). The tumor stage (SIOP) distribution included stage I (30%), II (36%), III (14%), IV (17%), and V (3%). The histology-risk groups were low (8%), intermediate (84%), and high risk (9%). At diagnosis, 68 out of 190 (36%) patients were underweight. The median tumor volume at diagnosis was 481 ml (interquartile ratio [IQR]: 306.9, 686.8, n = 146). Following neoadjuvant chemotherapy, it reduced to 110 ml (IQR: 151.2, 222, n = 77). Treatment was abandoned in 20.5% of the patients. Treatment-related mortality occurred in 13 of 179 (7.2%) patients. Relapse occurred in 26 of 158 (16.5%) patients. The 3-year overall survival (OS) and event-free survival (EFS) of patients who completed therapy were 78.3 and 72%, respectively. The stage (p = .013) and histology (p = .023) influenced OS. A lower OS in stage II (75.4%) versus stage III disease (83.7%) suggested understaging. Patients with a higher tumor volume at diagnosis (p = .005; odds ratio [OR]: 0.99; 95% confidence interval [CI]: 0.99-1.00) or a lower weight-for-age z-score (p = .002; OR: 1.68; 95% CI: 1.21-2.33) had an increased risk of death or relapse. CONCLUSIONS: The 3-year OS and EFS of children who completed therapy were 78.3 and 72%, respectively. A higher tumor volume and lower weight-for-age z-score at diagnosis were identified as distinct adverse prognostic factors. A likely suboptimal lymph node assessment (intraoperative and histopathology) contributed to the understaging of stage III to II disease and reduced survival.

Comparative Analysis of Mononuclear 1:1 and 2:1 Tetravalent Actinide (U, Th, Np) Complexes: Crystal Structure, Spectroscopy, and Electrochemistry.

Six mononuclear tetravalent actinide complexes (1-6) have been synthesized using a new Schiff base ligand 2-methoxy-6-(((2-methyl-1-(pyridin-2-yl)propyl)imino)methyl)phenol (HLpr). The HLpr is treated with tetravalent actinide elements in varied stoichiometries to afford mononuclear 1:1 complexes [MCl3-Lpr·nTHF] (1-3) and 2:1 complexes [MCl2-L2pr] (4-6) (M = Th4+ (1 and 4), U4+ (2 and 5), and Np4+ (3 and 6)). All complexes are characterized using different analytical techniques such as IR, NMR, and absorption spectroscopy as well as crystallography. UV-vis spectroscopy revealed more red-shifted absorption spectra for 2:1 complexes as compared to 1:1 complexes. 1H NMR of Th(IV) complexes exhibit diamagnetic spectra, whereas U(IV) and Np(IV) complexes revealed paramagnetically shifted 1H NMR. Interestingly, NMR signals are paramagnetically shifted between -70 and 40 ppm in 2 and 3 but are confined within -35 to 25 ppm in 2:1 complexes 5 and 6. Single-crystal structures for 1:1 complexes revealed an eight-coordinated Th(IV) complex (1) and seven-coordinated U(IV) (2) and Np(IV) (3) complexes. However, all 2:1 complexes 4-6 were isolated as eight-coordinated isostructural molecules. The geometry around the Th4+ center in 1 is found to be trigonal dodecahedral and capped trigonal prismatic around U(IV) and Np(IV) centers in 2 and 3, respectively. However, An4+ centers in 2:1 complexes are present in dodecahedral geometry. Importantly, 2:1 complexes exhibit increased bond distances in comparison to their 1:1 counterparts as well as interesting bond modulation with respect to ionic radii of An(IV) centers. Cyclic voltammetry displays an increased oxidation potential of the ligand by 300-500 mV, after coordination with An4+. CV studies indicate Th(IV)/Th(II) reduction beyond -2.3 V, whereas attempts were made to identify redox potentials for U(IV) and Np(IV) centers. Spectroscopic binding studies reveal that complex stability in 1:1 stoichiometry follows the order Th4+ ≈ U4+ > Np4+.

Outcome of pediatric germ cell tumor with comparison of carboplatin and cisplatin based regimens: A 10-year analysis.

Carboplatin is being advocated more frequently for treatment of childhood germ cell tumors (GCT), due to less long-term toxicity, and demonstrable equivalence in outcome as compared to cisplatin. This analysis presents the survival of GCT in a low middle-income country and compares two different chemotherapeutic regimens. A retrospective analysis of patient case records was carried out over 10-years (January 2007-December 2016). Chemotherapy regimen used was bleomycin, etoposide, and cisplatin (PEb) for initial 6-½ years and carboplatin, etoposide, and bleomycin (CEb) subsequently. Ninety patients with GCT were treated over 10-years. Malignant GCT was diagnosed in 69 (77%) patients, with 21(23%) having teratoma. The chemotherapy protocol was PEb in 38 (42%), CEb in 28 (31%) patients, while 24 patients were treated with surgery only. Stage 4 tumor was observed in 19 (21%) patients. Relapse or disease progression was seen in 11(12%). Overall and event-free survival at 5-years for the entire cohort was 77% and 73%, being similar with PEb (OS:77%; EFS:72.5%) vs. CEb (OS:69%; EFS: 69%). Significantly better overall survival was noted for patients with gonadal GCT) and non-stage 4 disease, while event-free survival was significantly better in patients with non-stage 4 disease. The chemotherapeutic regimen (PEb vs. CEb), very high AFP (value ≥10,000 IU/L), and risk stratification (low, intermediate, or high-risk disease) did not affect survival significantly. Carboplatin-based strategy was equivalent in our cohort to cisplatin-based strategy, and could be used safely in the LMIC set-up. The overall survival is suboptimal, with delayed presentation, abandonment, and relapse being barriers to survival.

Retrospective single-center experience with OEPA/COPDAC and PET-CT based strategy for pediatric Hodgkin lymphoma in a LMIC setting.

ABVD regimen for Hodgkin lymphoma (HL) is frequently used in children and young adults in low-middle income countries (LMIC). The feasibility and safety data for 'non-ABVD' protocols from LMIC is limited. The retrospective study was conducted in a single center in India. The Euronet PHL-C1 based protocol was administered during 2010-19. A PET-CT was performed at diagnosis and following two OEPA cycles. Radiotherapy was administered for inadequate PET response. During the 10-year period, 143 patients with HL were treated. The mean age was 7.8 ± 2.5 years. Bulky disease was observed in 82 (59%). Treatment abandonment was recorded in 13 (9.1%). The median follow-up duration was 46.4 months. An inadequate PET response was observed in 41/119 (34.4%), of which 56.1% received radiotherapy. Twelve (29.3%) patients who were supposed to receive radiotherapy received 2-cycles of COPDAC instead. Sixty-nine episodes of febrile neutropenia were observed in 54 patients. Treatment-related mortality (TRM) was observed in 7 (5.3%). The majority of episodes of febrile neutropenia (61%) and TRM (86%) occurred in the first cycle of OEPA. The 4-year event-free survival (EFS) and overall survival (OS) were 86.2 ± 3.4% and 93.5 ± 2.2%, respectively. Nine (6.3%) patients relapsed. Bulky disease lacked association with inadequate PET response (p = .800) or relapse (p = 1.000). OEPA/COPDAC regimen and response assessment by PET-CT permitted therapy reduction, including radiotherapy. Febrile neutropenia and resultant TRM (5.3%) are concerning and occurred frequently in the first cycle of OEPA. The support system for managing febrile neutropenia should be optimized for administering OEPA in LMIC.

Infantile Inflammatory Myofibroblastic Tumor of Spleen.

Background: 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 (ALK) gene with the majority expressing ALK protein. ALK-negative IMTs harbor alteration in ROS1 gene in a subset of cases. Few reports have shown association of IMT with Epstein-Barr virus (EBV). Case report: 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. Conclusions: IMT can arise in an infant spleen.

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

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.

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.

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).

Diagnostic values of 68Ga-labelled DOTANOC PET/CT imaging in pediatric patients presenting with paraneoplastic opsoclonus myoclonus ataxia syndrome.

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 68Ga DOTANOC PET/CT for detecting neuroblastic tumors in patients with OMA syndrome. METHODS: We retrospectively evaluated the 68Ga-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 68Ga-DOTANOC PET/CT were also compared with 131I 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: 68Ga-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. • 123I/131I MIBG imaging has a proven role for functional imaging in neuroblastoma or patients with OMA, but the role of 68Ga-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.

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

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.