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.

Short Research Communication Anti-Spike Antibody Response to COVISHIELD™ (SII-ChAdOx1 nCoV-19) Vaccine in Patients with B-Cell and Plasma Cell Malignancies and Hematopoietic Cell Transplantation Recipients.

Introduction: There is limited data on the serologic antibody responses after the ChAdOx1 vaccine in patients with hematological malignancies and hematopoietic cell transplantation recipients. There is no data on the safety and efficacy of the Indian COVISHIELD™ vaccine in this population. Methods: This study reports the anti-S antibody response to the COVISHIELD™ vaccine in a prospective cohort of patients with B-cell and plasma cell malignancies and HCT recipients at a single center. The quantitative antibodies to the SARS-CoV-2 S protein receptor-binding domain in human plasma were determined by the validated Roche Elecsys Anti-SARS-CoV-2 S kit. Results: A total of 118 patients were included over the study period from April 2021 to August 2021. The seropositivity rate at baseline and after the first and second dose of the vaccine was 39%, 66%, and 79%, respectively (p < 0.0001). The seronegative cohort had a higher median age (65 vs. 60 years, p = 0.03), were more likely to be males (81% vs. 42%, p = 0.009), had a diagnosis of B-CLPD (100% vs. 42%, p < 0.001) and were more likely to be on ibrutinib therapy (56% vs. 15%, p = 0.001). Conclusions: This study confirms the safety and efficacy of the COVISHIELD™ vaccine in patients with hematological malignancies.

A novel ATRX splice variant causing acquired HbH disease in myelodysplastic syndrome with excess blasts-1.

A 60-year-old male with myelodysplastic syndrome with excess blasts-1 had unexplained microcytic hypochromic anemia. The cause of his anemia was revealed on supravital staining, hemoglobin studies and next-generation sequencing to be a novel hemizygous potentially pathogenic missense/splice site variant NM_000489.5:c.6848A>C, (p.Lys2283Thr) in exon 31 of the ATRX gene.

A 37-Year-Old Man With Bronchial Asthma and Unexplained Hypoxemia.

CASE PRESENTATION: A 37-year-old man presented with breathlessness and wheeze of 3 weeks' duration. There was no chest pain, cough, palpitation, pedal edema, or fever. For the past 12 years, he had been experiencing episodic breathlessness and wheeze, which improved with inhaled salbutamol. He also had symptoms of nasal obstruction, nasal discharge, and sneezing. There was no history of smoking, substance abuse, or the use of any over-the-counter medication. The current episode of bronchial asthma exacerbation was managed with bronchodilators and systemic glucocorticoids. Despite symptomatic relief and clinical improvement, his oxygen saturation remained at 75% to 80%, and he was referred to our facility for further evaluation.

Genetic basis of unexplained erythrocytosis in Indian patients.

OBJECTIVE: To evaluate the spectrum of genetic defects in Indian patients with unexplained erythrocytosis. METHODS: Fifteen families (18 patients) with unexplained erythrocytosis were enrolled after excluding polycythemia vera and secondary erythrocytosis. Focused Sanger sequencing from genomic DNA was performed for EPOR (exon 8), VHL (exons 2-3), EGLN1 (exons 2-5), EPAS1 (exon 12), and all exons of HBB, HBA1, and HBA2 genes. RESULTS: Eleven of the 18 patients (including two pairs of brothers) had Chuvash polycythemia, that is, homozygosity for VHL:c.598C > T (p.Arg200Trp). Three patients (two of whom were brothers) had HBB mutations associated with increased oxygen-affinity hemoglobin-one had a heterozygous Hb McKees Rocks HBB:c.438T > A (p.Tyr146*), and two brothers showed heterozygous Hb Rainier HBB:c.437A > G (p.Tyr146Cys). No pathogenic variants were found in the remaining four cases. CONCLUSION: A gene-by-gene Sanger sequencing approach could determine a genetic basis for erythrocytosis in 11 of the 15 (73%) Indian families, with homozygous VHL:c.598C > T (p.Arg200Trp) being the commonest pathogenic variant. This first study from the Indian subcontinent provides a rationale for analyzing this variant in patients with suspected congenital erythrocytosis from this region. Rare first occurrences of Hb McKees Rocks and Hb Rainier in Indians are also being reported.

Our experience with surgery in situs inversus: Open peptic perforation repair and laparoscopic cholecystectomy in 1 patient and 3 patients respectively.

INTRODUCTION: Situs inversus is a rare autosomal recessive condition associated with complete transposition of abdominal+/- thoracic organs. Surgical diagnosis and surgical procedures in patients with situs inversus is tricky because of the mirror image anatomy of intra-abdominal organs. MATERIALS AND METHODS: A retrospective analysis of 2152 and 1497 patients who underwent laparoscopic cholecystectomy and open peptic perforation repair respectively from June 2014-June 2016 was done. 1 patient and 3 patients with situs inversus underwent open peptic perforation repair and laparoscopic cholecystectomy respectively. A 10mm left para-median port 5cm caudally from xiphoid was used for grasping the infundibulum. Two 5mm ports placed 10cm caudally from costal margin in the mid-clavicular and anterior axillary line were used for dissecting and retracting fundus respectively. A 10mm supra-umbilical camera port was used. RESULTS: A 40year male with situs inversus totalis underwent open peptic perforation repair. Laparoscopic cholecystectomy was done in 3 female patients with situs inversus aged 33-46year (mean 41year). Mean operative time for laparoscopic cholecystectomy was 59min (39-93). There were no intraoperative or post-operative complications. Histopathology revealed chronic inflammation in peptic perforation and cholecystitis. CONCLUSION: Perforation peritonitis in situs inversus can cause diagnostic confusion with free gas under the left hemi diaphragm. Laparoscopic cholecystectomy in situs inversus is ergonomically inconvenient and technically difficult for right handed surgeons. We describe an ergonomically convenient port placement for right handed surgeons in situs inversus.

Primary hydatid cyst of pancreas: Case report and review of literature.

INTRODUCTION: Hydatid disease is caused by the larval stage of Echinococcus granulosus. It most commonly affects the liver and lung. Pancreatic hydatid cyst (PHC) is very rare with incidence of 0.14%-2%. PRESENTATION OF CASE: A 40year old lady presented with epigastric pain for last 3 months. A 5×5cm abdominal lump occupying the epigastric and left hypochondrial region was noted on physical examination. Ultrasonography (USG) and Contrast enhanced Computed Tomogrpahy (CT) revealed a 55×57mm cystic structure in the pancreatic body. Endoscopic ultrasound guided fluid aspiration cytology revealed normal Carcinoembryonic antigen and Amylase levels. Cytological examination was noncontributory. During open surgical exploration, it was found to be a hydatid cyst. After irrigation with scolicidal agent and evacuation of cystic contents, Partial cystectomy with external drainage was done. Histopathological biopsy revealed Hydatid cyst. Post-operative ELISA (Enzyme linked immunosorbent assay) for Echinococcal antigen was positive. DISCUSSION: PHC is a rare entity. Most common mode of spread is hematogenous. Cysts in pancreatic head can present as obstructive jaundice. Cysts in body and tail are usually asymptomatic. USG, CT and Hydaitd serology can help in diagnosis and monitoring recurrence. Surgical exploration is treatment of choice. Options include pericystectomy, partial cystectomy+/- external drainage/omentopexy, marsupialization or cysto-enterostomy. Preoperative and Post-operative anti helminthic (Albendazole) is recommended. CONCLUSION: PHC can masquerade as pseudocyst or cystic neoplasm of pancreas. It should always be considered in the differential diagnosis of cystic pancreatic lesion in patients from endemic regions.

Laparoscopic cholecystectomy in a 2 year old male child with choleilithiasis and recurrent right hypochondrial pain: Case report and review of literature.

INTRODUCTION: Gallstone disease has been considered an uncommon entity in children and infants, but its incidence is reportedly increasing which may be attributed to widespread use of diagnostic imaging (ultrasonography). PRESENTATION OF CASE: An apparently healthy 2 year old male child presented to our Outpatient department with chief complaint of recurrent abdominal pain. The episodes of pain were acute in onset and associated with vomiting. As per the complete examination and findings, a diagnosis of chronic calculous cholecystitis was made. A four port laparoscopic cholecystectomy was done. DISCUSSION: The incidence of gallstones in children in India has not been sufficiently studied. The incidence of gallstone disease in India was found to be 0.3% with the incidence in age group 0-10 being less than 0.1%. In contrast to adult gallstone disease, it has been found that there is no female preponderance in gallstone diseases of infancy. Also, the majority of children having increased haemoglobin turnover develop pigment stones only after 5 years of age. CONCLUSION: The probability of gallstone disease in infants and young children should not be ignored. Gall stones should always be considered as a differential diagnosis when young patients present with complaints of abdominal pain.