Poorly differentiated thyroid cancer: Clinical, pathological, mutational, and outcome analysis.

INTRODUCTION: Poorly differentiated thyroid cancer (PDTC) remains a challenge not only for pathologists and surgeons because of the difficulties associated with the diagnostic process and the compelling need for difficult thyroidectomy, but it is also of high clinical relevance because it is responsible for mortality in non-anaplastic follicular cell-derived thyroid cancer. MATERIALS AND METHODS: Cases of PDTC within a 30-year period were reviewed by two independent pathologists. Histological features like atypical mitosis, necrosis, capsular, and vascular invasion were studied. Mutation analysis was done for BRAF, RET/PTC, RAS, and PI3KCA, and P53 was performed using immunohistochemistry. RESULTS: There were 39 patients with a median age of 53 years; 14 patients were more than 55 years of age. At presentation, 38.4% had compressive features and the median tumor size was 9 cm. At presentation, 67.7% had an extrathyroidal extension (ETE). R0 resection was achieved in 41%, with 12 cases resulting in a difficult thyroidectomy. Necrosis was seen in 65.7% and mitosis in 73.3% with well-differentiated components in 41%. The commonest mutation was RAS (23.1%). Survival was higher in the operable group (54.26, 95% confidence interval [CI]: 30.83-77.70 vs. 20.25, 95% CI: 0-54.07) months, respectively; however, 10-year survival was only 5% and only the tumor size and presence of mitosis were independent risk factors. CONCLUSION: PDTC presents with worrisome features like large size, ETE, and rapid growth. Aggressive surgical resection with extended/radical thyroidectomy may result in better loco-regional control and improved survival. RAS was the frequent mutation detected. It is worthwhile to identify prognostic factors that can predict the course of PDTC.

Exome sequencing identified mutations in the WNT1 and COL1A2 genes in osteogenesis imperfecta cases.

BACKGROUND: Osteogenesis imperfecta (OI) is a heritable connective tissue disorder characterized by bone deformities, fractures and reduced bone mass. OI can be inherited as a dominant, recessive, or X-linked disorder. The mutational spectrum has shown that autosomal dominant mutations in the type I collagen-encoding genes are responsible for OI in 85% of the cases. Apart from collagen genes, mutations in more than 20 other genes, such as CRTAP, CREB3L1, MBTPS2, P4HB, SEC24D, SPARC, FKBP10, LEPRE1, PLOD2, PPIB, SERPINF1, SERPINH1, SP7, WNT1, BMP1, TMEM38B, and IFITM5 have been reported in OI. METHODS AND RESULTS: To understand the genetic cause of OI in four cases, we conducted whole exome sequencing, followed by Sanger sequencing. In case #1, we identified a novel c.506delG homozygous mutation in the WNT1 gene, resulting in a frameshift and early truncation of the protein at the 197th amino acid. In cases #2, 3 and 4, we identified a heterozygous c.838G > A mutation in the COL1A2 gene, resulting in a p.Gly280Ser substitution. The clinvar frequency of this mutation is 0.000008 (GnomAD-exomes). This mutation has been identified by other studies as well and appears to be a mutational hot spot. These pathogenic mutations were found to be absent in 96 control samples analyzed for these sites. The presence of these mutations in the cases, their absence in controls, their absence or very low frequency in general population, and their evaluation using various in silico prediction tools suggested their pathogenic nature. CONCLUSIONS: Mutations in the WNT1 and COL1A2 genes explain these cases of osteogenesis imperfecta.

Synthesis, crystal structure, Hirshfeld surface analysis, DFT and NBO study of ethyl 1-(4-fluoro-phen-yl)-4-[(4-fluoro-phen-yl)amino]-2,6-diphenyl-1,2,5,6-tetra-hydro-pyridine-3-carboxyl-ate.

The title com-pound, C32H28F2N2O2, a highly functionalized tetra-hydro-pyridine, was synthesized by a one-pot multi-com-ponent reaction of 4-fluoro-aniline, ethyl aceto-acetate and benzaldehyde at room temperature using sodium lauryl sulfate as a catalyst. The com-pound crystallizes with two mol-ecules in the asymmetric unit. The tetra-hydro-pyridine ring adopts a distorted boat conformation in both mol-ecules and the dihedral angles between the planes of the fluoro-substituted rings are 77.1 (6) and 77.3 (6)°. The amino group and carbonyl O atom are involved in an intra-molecular N-H⋯O hydrogen bond, thereby generating an S(6) ring motif. In the crystal, mol-ecules are linked by C-H⋯F hydrogen bonds forming a three-dimensional network and C-H⋯π inter-actions. A Hirshfeld surface analysis of the crystal structure indicates that the most important contributions to the crystal packing are from H⋯H (47.9%), C⋯H/H⋯C (30.7%) and F⋯H/H⋯F (12.4%) contacts. The optimized structure calculated using density functional theory (DFT) at the B3LYP/6-311+G(2d,p) level is compared with the experimentally determined molecular structure in the solid state. The HOMO-LUMO behaviour was used to determine the energy gap and the Natural Bond Orbital (NBO) analysis was done to study donor-acceptor interconnections.

A cross-sectional study to correlate antioxidant enzymes, oxidative stress and inflammation with prevalence of hypertension.

AIMS: Hypertension a multifactorial consequence of environmental factors, life style and genetics is the well-recognized risk factor contributing to coronary heart diseases. The antioxidant imbalance, excessive reactive oxygen species (ROS) leads to oxidative stress which is pivotal in progression of hypertension. The present study aims to understand the complex interaction between oxidative stress, inflammation and antioxidant system which is crucial to maintain cellular homeostasis which further can exaggerate hypertension pathophysiology. MATERIALS AND METHODS: The metabolic profile of hypertensive and normotensive subjects from Malwa region, Punjab was compared by estimating lipid profile, cardiac, hepatic and renal markers. The oxidative stress markers (protein carbonyls and lipid peroxidation), inflammatory markers (Nitric oxide, Myeloperoxidase and advanced oxygen protein products), and antioxidant enzymes (Superoxide Dismutase, Catalase, and Total Antioxidant Capacity) were analyzed. KEY FINDINGS: It is observed that the metabolic markers are altered in hypertensive subjects which further these subjects showed increased oxidative, inflammatory profile and compromised antioxidant status when compared with normotensive subjects. Co-relation analysis validated the involvement of inflammation and oxidative stress in impaired endothelial function and vital organ damage. SIGNIFICANCE OF STUDY: These markers may act as early indicators of hypertension which usually do not show any physical symptoms, thus can be diagnosed and treated at the earliest. The current study suggests that disturbed homeostasis, a consequence of altered interaction between antioxidant system and inflammatory events raises the oxidative stress levels which eventually leads to hypertension and associated complications. These indicators can serve as early indicators of future chronic complications of hypertension.

Growth and Neurodevelopmental Outcomes of Very Low Birth Weight Infants From Southern India at Corrected Age of One Year.

OBJECTIVE: To assess the growth and neurodevelopmental outcome of very low birth weight (VLBW) infants at corrected age of one year. METHODS: This prospective cohort study enrolled VLBW infants delivered in a tertiary care hospital, and followed up till one-year corrected age. The WHO Anthropo version 3.2.2 software was used to calculate weight for age, length for age, and head circumference z-score during follow up. Neuro-developmental assessment was done using Developmental Assessment Scale for Indian Infants (DASII) at the age of one year. RESULTS: The mean (SD) z-scores at one-year for weight for age, length for age and head circumference were -2.1 (1.1), -1.4 (1.03) and -2.2 (1.2), respectively. The mean (SD) DASII motor and mental scores were 90.8 (13.4) and 96.5 (13.2), respectively. Major and minor developmental abnormalities were noted in 9.4% and 18.2%, infants, respectively. Cerebral palsy was noted in 5.8% infants. CONCLUSION: VLBW infants showed impaired growth and significant developmental abnormalities at the corrected age of one year.

Applications of Gas Discharge Visualization Imaging in Health and Disease: A Systematic Review.

Context: Gas discharge visualization (GDV) works on the principle of the Kirlian effect. It's a noninvasive, quick, and safe biometric tool to investigate the psychophysiological state of an individual, with the potential to identify deviations from the healthy functioning of humans at early stages. Objective: The study intended to systematically document the scientific evidence pertaining to the use of GDV devices in human health and disease conditions. Design: The research team performed a systematic search for studies on GDV on research databases such as Google Scholar, PubMed, and PsychINFO, using the following inclusion criteria: (1) experimental studies dealing with a GDV device, (2) studies dealing with human participants related to health and disease, and (3) studies published in the English language. The study excluded: (1) review articles, (2) case studies, (3) letter to editors, (4) studies with unclear methodology, and (5) studies published before the year 2000. Setting: The study took place in the Department of Integrative Medicine at the National Institute of Mental Health and Neurosciences (NIMHANS) in Bengaluru, India. Results: After filtering, the research team obtained 108 publications that dealt with the application of a GDV device in human participants. Based on the selection criteria, 42 studies were included in the review. These 42 studies included eight randomized controlled trials (RCTs), five nonrandomized controlled studies, 17 cross-sectional studies, 10 single-group pre-post studies, and two correlational studies. Conclusions: More studies with a robust methodology are needed to make definitive conclusions. The literature reveals that the GDV technique has the potential to provide early diagnosis and screening, especially in disorders of the endocrine and immune systems. It might also be used to assess wellness in healthy subjects and monitor the effects of interventions, such as yoga-including pranayama and meditation, acupuncture, qigong, music therapy, and massage on the human energy system. Future studies should focus on the validation of GDV imaging in clinical settings.

PHPT with Pancreatitis: Atypical Presentation of PHPT.

Background: Primary hyperparathyroidism (PHPT) is rarely associated with the occurrence of acute or chronic pancreatitis, requiring complex perioperative management. This study aimed to assess the prevalence and disease characteristics of pancreatitis in PHPT. Materials and Methods: This study is a clinicopathological analysis of the medical records of patients who were diagnosed with PHPT with pancreatitis between 1989 and 2021 in the Endocrine Surgery department, SGPGI, Lucknow. Results: Out of 548 PHPT cases, 44 (8.03%) were found to be associated with pancreatitis. The mean age was 33.57 years (15-65 years); 5 were ≤20 years, while 26 were ≤30 years of age. There were 27 males and 17 females. Twenty-one cases were of acute (11 acute, nine recurrent acute, one acute on chronic), whereas 23 were of chronic pancreatitis (six chronic calcific pancreatitis). The major clinical presentation of PHPT with pancreatitis was abdominal pain (65.91%). The mean number of attacks per patient in recurrent acute pancreatitis was two. Mean PTH levels were 68.19 pmol/L. The mean tumor size (in the largest dimension) was 2.79 ± 1.4 cm while the mean tumor weight was 4.91 g. Nephrolithiasis was associated with 25 cases. An association with multiple endocrine neoplasia type 1 syndrome was seen in one case. The final histopathological diagnosis was parathyroid carcinoma in two, hyperplasia in three, and parathyroid adenoma in 39 cases. Normocalcemia was seen in 27.2%, hypercalcemic crisis in 15.9%, and 25% of patients required semi-emergency parathyroidectomy. The outcome was favorable in all, as none had any further attacks of pancreatitis. Conclusion: In our study, the prevalence of pancreatitis in PHPT cases was 8.03%. The majority of patients were young. Normocalcemia was seen in 12 patients, so even if calcium levels are normal, PHPT should be suspected in young patients with pancreatitis. Parathyroidectomy resulted in the complete resolution of symptoms of pancreatitis in all 44 patients.

Post-COVID-19 Vaccination and Thyrotoxicosis (ASIA Syndrome): Single-Centre Experience from India with Review of Literature.

Introduction: Thyrotoxicosis is not uncommon after immunization. It is known as 'autoimmune/autoinflammatory syndrome by adjuvants (ASIA syndrome)' and is caused by immunological reaction to adjuvants. However, there is insufficient information on thyrotoxicosis after COVID-19 vaccination in the Indian subcontinent. Aims/Objectives: To investigate the spectrum of thyrotoxicosis after COVID-19 immunization. Settings and Design: A single-centre retrospective study was conducted at a tertiary care academic institute in India. Materials and Methods: We studied the clinical symptoms, biochemical markers, imaging characteristics and treatment of every patient who was diagnosed with thyrotoxicosis within 60 days of receiving the COVID-19 vaccine. Results: Following COVID-19 vaccination, we diagnosed ten people (mean age 39.9 years, range 22-63 years) with thyrotoxicosis [Graves' disease (GD, n-6) and subacute thyroiditis (SAT, n-4)]. The typical duration for symptoms to appear was 2 to 60 days. The majority of patients (n-9) received the COVISHIELD™ vaccine, whereas only one received the COVAXIN® vaccine. After vaccination, two patients with GD developed mildly severe Graves' orbitopathy, with symptoms emerging two days and sixty days later, respectively. Anti-thyroid drugs (methimazole or carbimazole) were required for all GD patients. All SAT patients were treated conservatively with nonsteroidal anti-inflammatory medications and had positive outcomes. Conclusions: SAT, GD and GO may occur as a manifestation of ASIA syndrome, following immunization with COVISHIELD™ and COVAXIN®. Despite the obvious benefits of the COVID-19 vaccine, clinicians should be aware of any potential autoimmune and inflammatory thyroid problems.

Association of hyperglycaemia at-admission & diabetes mellitus with 28 day mortality in patients admitted with moderate-severe SARS-CoV-2 infection: A retrospective study.

Background & objectives: The association between hyperglycaemia at admission, diabetes mellitus (DM) status and mortality in hospitalized SARS-CoV-2 infected patients is not clear. The purpose of this study was to determine the relationship between DM, at-admission hyperglycaemia and 28 day mortality in patients admitted with moderate-severe SARS-CoV-2 infection requiring intensive care. Methods: All consecutive moderate-to-severe patients with SARS-CoV-2 infection admitted to the intensive care units (ICUs) over six months were enrolled in this single-centre, retrospective study. The predicators for 28 day mortality were analysed from the independent variables including DM status and hyperglycaemia at-admission. Results: Four hundred and fifty two patients with SARS-CoV-2 were admitted to the ICU, with a mean age of 58.5±13.4 yr, 78.5 per cent being male, HbA1c of 7.2 per cent (6.3-8.8) and 63.7 per cent having DM. Overall, 28 day mortality was 48.9 per cent. In univariate analysis, mortality in diabetes patients was comparable with non-diabetes (47.9 vs. 50.6%, P=0.58), while it was significantly higher in hyperglycaemic group (60.4 vs. 35.8%, P<0.001). In multivariate Cox regression analysis, after adjusting for age, sex and comorbidities, hyperglycaemia at-admission was an independent risk factor of mortality [hazard ratio (HR) 1.45, 95% confidence interval (CI) (1.06-1.99), P<0.05]. Interpretation & conclusions: This study showed that the presence of hyperglycaemia at-admission in critically ill SARS-CoV-2 patients was an independent predictor of 28 day mortality. However, the findings may be susceptible to unmeasured confounding, and more research from prospective studies is required.

Efficacy of Bacillus Calmette-Guérin (BCG) Vaccination in Reducing the Incidence and Severity of COVID-19 in High-Risk Population (BRIC): a Phase III, Multi-centre, Quadruple-Blind Randomised Control Trial.

INTRODUCTION: Universal coverage of vaccines alone cannot be relied upon to protect at-risk populations in lower- and middle-income countries against the impact of the coronavirus disease 2019 (COVID-19) pandemic and newer variants. Live vaccines, including Bacillus Calmette-Guérin (BCG), are being studied for their effectiveness in reducing the incidence and severity of COVID-19 infection. METHODS: In this multi-centre quadruple-blind, parallel assignment randomised control trial, 495 high-risk group adults (aged 18-60 years) were randomised into BCG and placebo arms and followed up for 9 months from the date of vaccination. The primary outcome was the difference in the incidence of COVID-19 infection at the end of 9 months. Secondary outcomes included the difference in the incidence of severe COVID-19 infections, hospitalisation rates, intensive care unit stay, oxygen requirement and mortality at the end of 9 months. The primary analysis was done on an intention-to-treat basis, while safety analysis was done per protocol. RESULTS: There was no significant difference in the incidence rates of cartridge-based nucleic acid amplification test (CB-NAAT) positive COVID-19 infection [odds ratio (OR) 1.08, 95% confidence interval (CI) 0.54-2.14] in the two groups, but the BCG arm showed a statistically significant decrease in clinically diagnosed (symptomatic) probable COVID-19 infections (OR 0.38, 95% CI 0.20-0.72). Compared with the BCG arm, significantly more patients developed severe COVID-19 pneumonia (CB-NAAT positive) and required hospitalisation and oxygen in the placebo arm (six versus none; p = 0.03). One patient belonging to the placebo arm required intensive care unit (ICU) stay and died. BCG had a protective efficacy of 62% (95% CI 28-80%) for likely symptomatic COVID-19 infection. CONCLUSIONS: BCG is protective in reducing the incidence of acute respiratory illness (probable symptomatic COVID-19 infection) and severity of the disease, including hospitalisation, in patients belonging to the high-risk group of COVID-19 infection, and the antibody response persists for quite a long time. A multi-centre study with a larger sample size will help to confirm the findings in this study. CLINICAL TRIALS REGISTRY: Clinical Trials Registry India (CTRI/2020/07/026668).

The Bacillus Calmette­Guérin (BCG) vaccine has been studied previously in several settings, including reducing childhood mortalities due to viral infections and induction of trained immunity and reducing upper respiratory tract infections and pneumonia in older adults. This multi-centre trial has tried to evaluate the efficacy of BCG revaccination in reducing the incidence and severity of COVID-19 infections in adults between 18 and 60 years of age belonging to the high-risk group owing to the presence of comorbidities including diabetes, chronic kidney disease, chronic liver disease and chronic lung diseases. A single dose of BCG vaccine produced significantly high titres of BCG antibodies lasting for six months. While there was no significant reduction in the incidence of COVID-19 infection, there was an 8.4% reduction in the incidence of symptomatic COVID-19 disease at the end of 9 months of follow-up. In addition, there were significantly fewer severe COVID-19 infections requiring hospital stay and oxygen support. However, the overall numbers of severe COVID-19 infections were low. Thus, the study shows that BCG can protect against symptomatic and severe COVID-19 disease. However, it might not reduce the incidence of new infections. The study results are significant for low- and middle-income countries without adequate coverage of primary doses of COVID-19 vaccination, let alone the booster doses. Future studies should evaluate the BCG vaccine's efficacy as a booster compared with routine COVID-19 vaccine boosters.

Proposing a clinical algorithm for better diagnosis of hypophosphatasia in resource-limiting situations.

Early diagnosis of hypophosphatasia (HPP) is challenging. Here, we propose to broaden the diagnostic criteria of HPP by reviewing published data on BMD and fractures in HPP patients. Non-osteoporotic fractures and higher than normal lumbar BMD were recurrent in HPP patients and could be included as diagnostic criteria. HPP is a genetic disorder caused by autosomal recessive or dominant loss-of-function mutations in the ALPL gene that encodes for tissue-nonspecific alkaline phosphatase (TNSALP). Expressive genetic heterogeneity and varying severity of TNSALP deficiency lead to a wide-ranging presentation of skeletal diseases at different ages that coupled with HPP's rarity and limitation of biochemical and mutational studies present serious hurdles to early diagnosis and management of HPP. To widen the scope of HPP diagnosis, we assessed the possibility of areal bone mineral density (BMD) as an additional clinical feature of this disease. PubMed, Web of Science, and ScienceDirect were searched with the following keywords: ("Hypophosphatasia OR HPP") AND ("Bone Mineral Density OR BMD") AND "Human". Studies and case reports of subjects with age ≥ 18 years and having BMD data were included. We pooled data from 25 publications comprising 356 subjects (90 males, 266 females). Only four studies had a control group. Biochemical hallmarks, pyridoxal 5'-phosphate (PLP) and phosphoethanolamine (PEA), were reported in fifteen and six studies, respectively. Twenty studies reported genetic data, nineteen studies reported non-vertebral fractures, all studies reported lumbar spine (LS) BMD, and nineteen reported non-vertebral BMD. Higher than normal and normal BMD at LS were reported in three and two studies, respectively. There was marked heterogeneity in BMD at the non-vertebral sites. Higher than normal or normal LS BMD in an adult with minimal or insufficient fractures, pseudofractures, non-healing fractures, fragility fractures, and stress fractures may be included in the diagnostic protocol of HPP. However, genetic testing is recommended for a definitive diagnosis.

Crystal structure, Hirshfeld surface analysis and DFT study of 2,2''-({[(1E,1'E)-(diselanedi-yl)bis-(2,1-phenyl-ene)]bis-(methane-ylyl-idene)}bis-(aza-neylyl-idene))bis-[3',6'-bis-(di-ethyl-amino)-4a',9a'-di-hydro-spiro-[isoindoline-1,9'-xanthen]-3-one].

The title compound, C70H70N8O4Se2, is a spiro bicyclic diselenide, made up of two [SeC6H4CH=N-N(CO)C6H4(C)C6H3NEt2(O)C6H3NEt2] units related by a twofold crystallographic symmetry element bis-ecting the diselenide bond. The compound crystallizes in a non-centrosymmetric polar space group (tetra-gonal, P b2) and the structure was refined as an inversion twin. The two diethyl amine groups and their attached phenyl groups of the xanthene ring are disordered over two orientations, with occupancies of 0.664 (19)/0.336 (19) and 0.665 (11)/0.335 (11), respectively. The dihedral angles between the mean planes of the central isoindoline and the phenyl rings are 26.8 (2) and 2.5 (4)°, respectively. The mean plane of the central xanthene ring forms dihedral angles of 2.0 (5), 8.8 (5), 1.7 (5) and 7.9 (6)° with the peripheral phenyl rings. The isoindoline and xanthene rings subtend a dihedral angle of 89.8 (2)°. The mol-ecular conformation is stabilized by an intra-molecular C-H⋯O hydrogen bond generating an S(6) ring motif. In the crystal, mol-ecules are linked by C-H⋯O hydrogen bonds together with C-H⋯π (ring) inter-actions, forming a three-dimensional network. A Hirshfeld surface analysis of the crystal structure indicates that the most important contributions to the crystal packing are from H⋯H (68.1%), C⋯H/H⋯C (21.2%) and O⋯H/H⋯O (8.7%) contacts. The optimized structure calculated using density functional theory (DFT) at the B3LYP/6 - 31 G(d) level is compared with the experimentally determined mol-ecular structure in the solid state. The HOMO-LUMO behaviour was used to determine the energy gap and the mol-ecular electrostatic potential (MEP) of the compound was investigated.

Prevalence of sleep apnea and lung function abnormalities in patients with acromegaly.

BACKGROUND: Sleep apnea (SA) is highly prevalent in acromegaly. Ethnicity influences the prevalence of SA in the general population. We studied the prevalence of SA and other respiratory comorbidities in North Indian patients with active acromegaly. DESIGN: Prospective, observational. MATERIALS AND METHODS: Consecutive adult patients with active acromegaly (n = 35, age 39.7 ± 13.2 years) and hypersomatotropism (nonsuppression of serum growth hormone after oral glucose and elevated serum insulin-like growth factor-1 [IGF-1]) were evaluated for respiratory symptoms, scoring for SA (Epworth Sleepiness Score [ESS] and STOP-BANG), pulmonary function tests (PFT), high-resolution computerized tomography (HRCT) of the thorax, polysomnography (PSG), and transthoracic echocardiography. Age- and sex-matched healthy individuals (n = 34) served as controls. RESULTS: Acromegaly subjects had dyspnea (34%), cough (37%), excessive daytime somnolence (43%), and fatigue (49%). Clinically significant ESS (>10) and STOP-BANG score (≥3) were present in 41% and 68.6% of subjects, respectively. PFT showed restrictive and obstructive patterns in 45.7% and 11.4% of acromegalics respectively; with higher total lung capacity (TLC), thoracic gas volume (TGV), and residual volume (RV). PSG revealed significantly higher SA events in acromegalics (central [acromegaly 24.63 ± 37.82 vs. control 3.21 ± 5.5], mixed [11 ± 19.46 vs. 3.50 ± 5.96], obstructive [34.86 ± 44.37 vs. 9.71 ± 10.48], and mean apnea-hypopnea index [AHI] [16.91 ± 18.0 vs. 7.86 ± 7.84]). Acromegalics had significantly higher prevalence of obstructive SA (71.4% [mild 31.4%, moderate 20%, severe 20%]) as compared to controls (38.2%). There was no correlation of AHI with serum IGF-1 and disease duration. CONCLUSION: Acromegaly subjects have a significantly higher prevalence of respiratory symptoms, SA, and abnormalities in PFT. Screening for respiratory comorbidities should be routinely recommended in all patients with acromegaly.

Clinical, Biochemical, Tumoural and Mutation Profile of VHL- and MEN2A-Associated Pheochromocytoma: A Comparative Study.

OBJECTIVE: To compare clinical, biochemical, tumoural and mutational characteristics of Von Hippel Lindau Syndrome (VHL)-associated pheochromocytoma (PCC) to multiple endocrine neoplasia 2A (MEN2A)-associated pheochromocytoma. DESIGN: Retrospective study design in a tertiary health care centre in Northern India. METHODS: A total of 47 patients with biochemical and histologically proven pheochromocytoma/paraganglioma (PCC/PGL): 29 associated with VHL and 18 with MEN2A, were divided in two cohorts, respectively. Analysis of their medical records along with a prospective follow-up was done. RESULTS: There were more children <19 years in VHL group (13 vs 1). Despite majority of VHL-PCC showing elevation of normetanephrine (NMN) (93%) as compared to MEN2A-PCC (22.2%), 75.8% presented with hypertension as compared to MEN2A (33.3%). The average size of VHL-PCC tumours was 5.66 cm. VHL-PCC as compared to MEN2A-PCC were multifocal (75% vs 61.1%), bilateral synchronous (72.4 vs 61.1%) and extra-adrenal (17.2% vs 0%). Both VHL (24%) and MEN2A-PCC (27.7%) showed multiple nodules, but more MEN2A PCC showed extra-tumoural hyperplasia (44.4% vs. 6.8%). In VHL, the commonest mutation (n = 17) was missense mutation with a hot spot on exon 3, while in MEN2A-PCC majority (66.6%) had 634 mutation in exon 11 and only 2 patients had the rare 611 mutation in exon 10. CONCLUSION: In contrast to world literature, our study suggests Indian VHL-PCC can be symptomatic in spite of noradrenergic phenotype, large in size and multifocal. Multiple nodules in VHL-PCC could increase risk of recurrence following subtotal adrenalectomy.

Genetic Diversity of Clinical Bordetella Pertussis ST2 Strains in comparison with Vaccine Reference Strains of India.

Objectives: Pertussis is a highly contagious disease of the respiratory tract caused by Bordetella pertussis, a bacterium that lives in the mouth, nose, and throat. Current study reports the highly accurate complete genomes of two clinical B. pertussis strains from India for the first time. Methods: Complete genome sequencing was performed for two B. pertussis strains using Ion Torrent PGM and Oxford nanopore sequencing method. Data was assembled de novo and the sequence annotation was performed through PATRIC and NCBI server. Downstream analyses of the isolates were performed using CGE server databases for antimicrobial resistance genes, plasmids, and sequence types. The phylogenetic analysis was performed using Roary. Results: The analysis revealed insertional elements flanked by IS481, which has been previously regarded as the important component for bacterial evolution. The two B. pertussis clinical strains exhibited diversity through genome degradation when compared to whole-cell vaccine reference strains of India. These isolates harboured multiple genetic virulence traits and toxin subunits, which belonged to sequence type ST2. Conclusion: The genome information of Indian clinical B. pertussis strains will serve as a baseline data to decipher more information on the genome evolution, virulence factors and their role in pathogenesis for effective vaccine strategies.

Acromegaly: Cardiovascular risk factors, cardiovascular manifestations and early vascular alterations in relation to disease activity.

Acromegaly is associated with increased cardiovascular morbidity and mortality. 49 acromegaly patients were evaluated for presence of cardiovascular risk factors and manifestations using 2D-Echocardiography, strain, strain-rate, carotid intima media thickness (CIMT) and flow mediated dilatation (FMD) and correlated with disease activity. 32 patients with growth hormone (GH) level >1 ng/ml were considered active. Patients with active disease have more LV dysfunction as assessed by strain(p-0.031) and strain rate(p-0.001); trend towards lower ejection fraction(p-0.11) with significant correlation to GH(cc -0.252,p-0.05). Patient with active disease have reduced FMD(p- 0.042); with no difference in prevalence of cardiovascular risk factors and CIMT inrelation to disease activity.

Diagnosis and Management Considerations in Steroid-Related Hyperglycemia in COVID-19: A Position Statement from the Endocrine Society of India.

The current coronavirus disease (COVID-19) pandemic is showing no signs of abatement and result in significant morbidity and mortality in the infected patients. Many therapeutic agents ranging widely between antivirals and anti-inflammatory drugs have been used to mitigate the disease burden. In the deluge of the drugs being used for COVID-19 infection, glucocorticoids (GCs) stand out by reducing mortality amongst in-hospital severe-to-critically ill patients. Health-care practitioners have seen this as a glimmer of hope and started using these drugs more frequently than ever in clinical practice. The fear of mortality in the short term has overridden the concern of adverse long-term consequences with steroid use. The ease of availability, low cost, and apparent clinical improvement in the short term have led to the unscrupulous use of the steroids even in mild COVID-19 patients including self-medication with steroids. The use of GCs has led to the increasing incidence of hyperglycemia and consequent acute complications of diabetic ketoacidosis and mucormycosis in COVID-19 patients. There is an urgent need to dissipate information about optimum management of hyperglycemia during steroid use. In view of this, the Endocrine Society of India has formulated this position statement about the diagnosis and management of hyperglycemia due to the use of GCs in patients with COVID-19 infection.