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 b-b  linkages when reacting tetra-meso-substituted porphyrins, the present findings highlight that multiple direct fusion (b-b/meso-meso/b-b or meso-b/b-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.

A Review on Recent Trends and Future Developments in Electrochemical Sensing.

Electrochemical methods and devices have ignited prodigious interest for sensing and monitoring. The greatest challenge for science is far from meeting the expectations of consumers. Electrodes made of two-dimensional (2D) materials such as graphene, metal-organic frameworks, MXene, and transition metal dichalcogenides as well as alternative electrochemical sensing methods offer potential to improve selectivity, sensitivity, detection limit, and response time. Moreover, these advancements have accelerated the development of wearable and point-of-care electrochemical sensors, opening new possibilities and pathways for their applications. This Review presents a critical discussion of the recent developments and trends in electrochemical sensing.

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.

Cytomorphologic and immunocytochemical characterization of pediatric pleuropulmonary blastoma with a comprehensive review of the literature.

INTRODUCTION: Pleuropulmonary blastoma (PPB) is a rare, aggressive, primary intrathoracic malignancy typically seen in infancy and early childhood. Accurate distinction from congenital cystic lung lesions is crucial due to significant prognostic and therapeutic differences. Cytologic features have rarely been described. Establishing a cytodiagnosis is challenging owing to its rarity, lack of awareness, and multiple morphologic mimics. MATERIALS AND METHODS: This was a retrospective study conducted over 8 years. The histopathology and cytopathology databases were searched for all pediatric PPB cases. The corresponding cytologic samples were reviewed to identify characteristic features that can help distinguish PPB from its mimics. RESULTS: There was a total of six cases of pediatric PPB reported during the study period. Of these, four (66.7%) presented as intrathoracic, and two (33.3%) as pleural-based masses. Cytology smears showed discretely scattered and perivascular arrangements of round-oval tumor cells with background eosinophilic stromal material. The tumor cells were mildly pleomorphic (n = 3) with round nuclei, fine chromatin, inconspicuous nucleoli, and scanty cytoplasm; however, three cases showed marked anaplasia, and one each showed necrosis and rhabdoid differentiation. On immunocytochemistry (4/6), these were positive for vimentin and desmin and negative for WT1, chromogranin, SALL4, cytokeratin, CD45, and CD99. FISH (1/6) did not show N-Myc amplification. CONCLUSIONS: Knowledge of the characteristic cytomorphological and immunocytochemical features of PPB is vital to establish a prompt and accurate cytodiagnosis with appropriate clinicoradiologic correlation.

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).

Decoding the rhabdoid riddle in liver: A rare case of primary hepatic malignant rhabdoid tumor with a comprehensive literature review.

Malignant rhabdoid tumor of the liver is a rare, highly aggressive primary hepatic malignancy occurring primarily in infants. Establishing a definitive diagnosis is challenging due to its rarity, non-specific clinicoradiologic findings, and overlapping morphologic features. Herein, we present the cytomorphologic and immunocytochemical characteristics of a rare case of primary hepatic Malignant rhabdoid tumor (MRT) in an infant. A 5-month-old female child presented with progressively increasing firm mass in the upper abdomen, progressive pallor, sudden onset respiratory distress, and difficulty feeding. On examination, the child had massive, firm nodular hepatomegaly. Ultrasonography of the abdomen revealed a heterogeneously hypoechoic lesion in the left lobe of the liver. Serum alpha-fetoprotein levels were within normal limits. An ultrasound-guided fine-needle aspiration cytology (FNAC) from the liver mass showed predominantly dispersed large, markedly pleomorphic tumor cells with round to oval eccentrically placed nuclei, prominent nucleoli, and moderate cytoplasm. On immunocytochemistry, tumor cells showed positivity for vimentin, cytokeratin, and EMA and demonstrated a loss of INI1, confirming the diagnosis of MRT. The index report highlights the distinctive clinicopathological features of a hepatic malignant rhabdoid tumor along with the key differential diagnoses, which may pose a diagnostic conundrum. A high index of clinical suspicion and a thorough understanding of its cytomorphological and immunochemical characteristics are crucial for an accurate diagnosis.

Effectiveness of Oral Cephalexin-Clavulanic Acid, Cefuroxime, and Amoxicillin-Clavulanic Acid in the Management of Dental Infections: A Real-World, Retrospective, Electronic Medical Record-Based Study in India.

BACKGROUND: Despite multiple antibiotics being available to manage dental infections (DI), there is lack of data comparing commonly prescribed antibiotics in India. OBJECTIVES: The aim of this study was to evaluate the real-world effectiveness and tolerability of cephalexin-clavulanic acid fixed-dose combination (cephalexin CV FDC) in contrast with amoxicillin-clavulanic acid (co-amoxiclav FDC) and cefuroxime among patients with dental infections (odontogenic) in India. METHODS: This retrospective, multi-centric, observational, real-world electronic medical record (EMR)-based study was conducted between January 2022 and December 2022. The EMRs of 355 adults with DI receiving oral cephalexin CV, co-amoxiclav, or cefuroxime were categorized into two distinct groups: Group I (Test Group) with patients prescribed cephalexin extended release 375/750 mg along with clavulanic acid 125 mg; and Group II (Comparator Group) with patients prescribed co-amoxiclav 625 mg (500 mg amoxicillin + 125 mg clavulanic acid) or cefuroxime (250 mg/500 mg). RESULTS: Toothache was the most common complaint, reported by 95.5% of patients, followed by swelling (46.8%), tooth sensitivity (35.5%), pus discharge (33.0%), redness and halitosis (30.4% each). Dental caries was observed in 81.1% of patients. Clinical improvement, defined as improvement/partial resolution of infection-related clinical signs and symptoms (composite measure of pain, swelling, fever, requirement of additional antimicrobial therapy) as per dentists' judgment, was recorded in 98.3% of patients with cephalexin CV, 96.8% of patients with co-amoxiclav, and 98.9% of patients treated with cefuroxime within 10 days. Time (days) to clinical improvement was numerically lesser among patients receiving cephalexin CV (4.6 ± 2.0) compared with cefuroxime (4.9 ± 2.1) and co-amoxiclav (5.0 ± 2.6). All treatments were well tolerated. CONCLUSION: Cephalexin CV was as effective as co-amoxiclav and cefuroxime, with faster clinical improvement and better resolution of certain symptoms.

A Polymer-Derived Co(Fe)Ox Oxygen Evolution Catalyst Benefiting from the Oxidative Dehydrogenative Coupling of Cobalt Porphyrins.

Thin films of cobalt porphyrin conjugated polymers bearing different substituents are prepared by oxidative chemical vapor deposition (oCVD) and investigated as heterogeneous electrocatalysts for the oxygen evolution reaction (OER). Interestingly, the electrocatalytic activity originates from polymer-derived, highly transparent Co(Fe)Ox species formed under operational alkaline conditions. Structural, compositional, electrical, and electrochemical characterizations reveal that the newly formed active catalyst greatly benefited from both the polymeric conformation of the porphyrin-based thin film and the inclusion of the iron-based species originating from the oCVD reaction. High-resolution mass spectrometry analyses combined with density functional theory (DFT) calculations showed that a close relationship exists between the porphyrin substituent, the extension of the π-conjugated system cobalt porphyrin conjugated polymer, and the dynamics of the polymer conversion leading to catalytically active Co(Fe)Ox species. This work evidences the precatalytic role of cobalt porphyrin conjugated polymers and uncovers the benefit of extended π-conjugation of the molecular matrix and iron inclusion on the formation and performance of the true active catalyst.

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.

A Well-Curated Cost-Effective Next-Generation Sequencing Panel Identifies a Diverse Landscape of Pathogenic and Novel Germline Variants in a Bone Marrow Failure Cohort in a Resource-Constraint Setting.

The current study is a 4-year experience in diagnosis and screening of inherited and immune bone marrow failure cases using a targeted sequencing panel. A total of 171 cases underwent targeted next-generation sequencing and were categorized as suspected inherited bone marrow failure syndrome (IBMFS) group (106; 62%) and immune/idiopathic aplastic anemia (IAA) group (65; 38%) based on clinical and laboratory criteria. A total of 110 (64%) were pediatric (aged 0 to 12 years) patients and 61 (36%) were adolescent and adult (aged 13 to 47 years) patients. In suspected IBMFS group, 47 (44%), and in IAA group, 8 (12%) revealed a likely germline pathogenic variation. Whole-exome sequencing performed in 15 of 59 suspected IBMFS group cases was negative on targeted panel, and revealed a clinically important variation in 3 (20%) cases. A total of 11 novel variants were identified. The targeted panel helped establish a diagnosis in 44% (27/61) of unclassified bone marrow failure syndrome cases and led to amendment of clinical diagnosis in 5 (4.7%) cases. Overall, diagnostic yield of this well-curated small panel was comparable to Western studies with larger gene panels. Moreover, this was achievable at a much lower cost, making it suitable for resource-constraint settings. In addition, high frequency (>10%) of cryptic pathogenic IBMFS gene variations in IAA cohort suggests routine incorporation of targeted next-generation sequencing screening in these cases.

Childhood pilomatrixoma mimicking malignant small round blue cell tumor with positivity for CD99: Potential pitfall in cytology.

Pilomatrixoma is a relatively rare benign skin appendageal tumor, often presenting in the pediatric age group as a nodular lesion and most commonly involving the head and neck, making it amenable to primary fine needle aspiration (FNA) diagnosis. We report the clinical and histopathological findings of two cases of pilomatrixoma in children, both of which were initially misdiagnosed as small round blue cell tumors due to high cellularity and misinterpretation of the proliferating basaloid cells. Histopathology revealed basal cell proliferation and mitoses indicating that they were progressive, early lesions. The first case showed membranous positivity for CD99 which prompted a diagnosis of Ewing sarcoma. Awareness of the morphological spectrum including positivity for CD99 and careful evaluation of cell block histology could have averted the misdiagnosis. Pilomatrixoma should be included as an important differential diagnosis when faced with primitive-appearing cells on FNA, especially in children with mass lesions in the head and neck region.

Profile of 193 pediatric cancer patients managed with radiation therapy: Challenges and lessons learned.

Background: Series on radiotherapy (RT) practice in pediatric malignancies are limited in India as only a few centers practice pediatric RT, particularly under anesthesia. We aimed to study the clinical profile of pediatric cancer patients treated with RT and to analyze various challenges in pediatric RT under anesthesia. Materials and Methods: The data were prospectively maintained in Microsoft Excel spreadsheets. Pediatric cancer patients aged 0-14 years, registered in the RT department between February 1, 2019 and July 30, 2021were analyzed. Results: A total of 193 pediatric cancer patients (noncentral nervous system) received RT during the said period. Median age at presentation was 5.2 years (range: 9 months to 14 years) with a male-to-female ratio of 1.8:1. The majority of the patients were in the age group of 0-4 years (52.8%) followed by 5-9 years (29.5%) and ≥10 years (17.6%). Most common indications for RT included bone and soft-tissue tumors, retinoblastoma, Wilms tumor, neuroblastoma, and hematological malignancies. One hundred and seventy-nine (92.7%) patients received RT with curative intent, while 14 (7.3%) patients received palliative RT. Thirty (15.5%) patients needed anesthesia for RT. Ten (5.18%) patients required RT interruption due to toxicities with a median gap of 3 days. Conclusions: RT is challenging yet an important aspect of multidisciplinary care in paediatric cancers. Estimating the burden of pediatric patients in the RT department may help in assessing unmet needs, resource development, and prioritization, which may improve the cure rates.

Correction to: Genetic Spectrum in F13A1 Detected by Next-Generation Sequencing Among North Indian Patients with FXIII Deficiency.

[This corrects the article DOI: 10.1007/s12288-022-01579-1.].

Isolation of Multidrug-Resistant Organisms in Surveillance Stool Culture at Diagnosis Fails to Predict Mortality or Subsequent Sepsis due to Multidrug-Resistant Organisms in Children with Acute Leukemia: A Single-Center, Prospective, Observational Study.

The utility of surveillance stool culture (SSC) to guide antibiotics for febrile neutropenia (FN) is unresolved in non-transplant settings. The prospective study explored the prevalence of multidrug-resistant organisms (MDRO) in SSCs, its correlation with mortality, and the concordance of SSCs with cultures obtained during subsequent episodes of FN amongst children with acute leukemia. SSCs were obtained at presentation and 2 mo into chemotherapy. Seventy-nine patients (mean age: 5.9±3.2 y) with acute lymphoblastic leukemia (ALL) (80%), acute myeloid leukemia (AML) (16%), or biphenotypic leukemia (4%) were enrolled. MDROs were isolated from 14 (17.5%) patients in the first SSCs, including E.coli (80%), K. pneumoniae (10%), and E. faecium (10%). Three (3.8%) patients developed MDRO sepsis; none concorded with the SSCs. Eleven (14%) patients died; 4/14 (28.5%) with MDRO-colonization vis-à-vis 7/66 (10.6%) without MDRO-colonization (OR: 3.37, 95% CI: 0.8-13.6; p = 0.095). MDRO-colonization failed to predict MDRO-sepsis, bloodstream infection, or mortality. SSC failed to guide the choice of antibiotics for FN in children with acute leukemia.

A Screening Approach for Inherited Erythrocytosis due to the VHL:c.598C > T Mutation (Chuvash Polycythemia).

Genetic work-up of unexplained erythrocytosis that is suspected to be inherited in nature currently requires either laborious exon-by-exon gene panel testing by Sanger sequencing or expensive next-generation sequencing. A high prevalence of Chuvash polycythemia (61%) has been previously reported among north Indian erythrocytosis patients. We assessed PCR-RFLP for VHL c.598C > T mutation as a first-line test in 99 persons with JAK2 V617F-negative, unexplained erythrocytosis. We enrolled two groups: Group A (n = 38) had erythrocytosis patients (n = 33) or their first-degree relatives (n = 5), and, Group B with 61 healthy blood donation volunteers who were deferred after the discovery of unexplained high hemoglobin levels. Detailed history and clinical examination, hemogram, erythropoietin levels and PCR-RFLP for the VHL:c.598C > T;p.R200W mutation were done. In Group A, three (8%) persons aged 9, 13 and 30-years were homozygous for VHL:c.598C > T. Two were heterozygous (parents of a known case of Chuvash polycythemia). None of the Group B subjects had the Chuvash mutation. Erythropoietin levels in group A were low in 5/26 cases (19%) and normal in 18/26 (69%). In Group B, seven (11%) donors had normal values while the remaining 54 (89%) had high erythropoietin levels. Despite a lower frequency (8%) compared to literature, our results suggest that the relatively simpler PCR-RFLP for VHL:c.598C > T mutation may be considered for the initial genetic screening of unexplained, suspected congenital erythrocytosis in regions where Chuvash polycythemia comprises a large proportion of inherited erythrocytosis, after polycythemia vera and common acquired secondary causes are excluded. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-023-01668-9.

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.