Role of bisphosphonates in hypertrophic osteoarthropathy: a systematic review.

BACKGROUND: The role of bisphosphonates (BP) in hypertrophic osteoarthropathy (HPOA) is unclear. We presented a case of primary HPOA and performed a systematic review of literature on the effect of BP on treatment response in primary and secondary HPOA. METHODS: The study was prospectively registered in PROSPERO (CRD42022343786). We performed a PubMed literature search that restricted to the English language. We included patients diagnosed with primary or secondary HPOA who received BP. The primary endpoint assessed was the effectiveness of BP on response to pain or arthritis. Secondary outcomes included timing, degree, and duration of response, comparison to other HPOA therapies, impact of BP on radiology, bone scan, bone turnover markers, and adverse effects of BP. RESULTS: Literature search retrieved only case reports. Forty-five patients (21 primary, 24 secondary HPOA) had received BP. Majority(88.3%) experienced improvement in pain or arthritis. Response was gradual for primary HPOA and within a median of 3 to 7 days for secondary HPOA after treatment with BP. Most patients had reduced bone scan uptake after BP. When other HPOA therapies were tried, half responded to BP after not having previously responded to other therapies, while a third received the treatments concurrently, making it difficult to attribute treatment response to a drug. Reporting of other secondary outcomes was very heterogenous and qualitative to draw conclusions. No major adverse effects have been reported for BP in HPOA. CONCLUSION: Bisphosphonates provide an effective and safe treatment option for primary and secondary HPOA. However, there is a lack of randomized controlled trials.

Advancements in medical treatment for pancreatic neuroendocrine tumors: A beacon of hope.

This editorial highlights the remarkable advancements in medical treatment strategies for pancreatic neuroendocrine tumors (pan-NETs), emphasizing tailored approaches for specific subtypes. Cytoreductive surgery and somatostatin analogs (SSAs) play pivotal roles in managing tumors, while palliative options such as molecular targeted therapy, peptide receptor radionuclide therapy, and chemotherapy are reserved for SSA-refractory patients. Gastrinomas, insulinomas, glucagonomas, carcinoid tumors and VIPomas necessitate distinct thera-peutic strategies. Understanding the genetic basis of pan-NETs and exploring immunotherapies could lead to promising avenues for future research. This review underscores the evolving landscape of pan-NET treatment, offering renewed hope and improved outcomes for patients facing this complex disease.

Insulin Sensitivity, Islet Cell Function, and Incretin Axis in Pregnant Women With and Without Gestational Diabetes Mellitus.

Introduction: The aim of this study was to compare insulin sensitivity, islet cell function, and incretin axes in pregnant subjects with GDM and normal healthy controls. Methods: Pregnant women at 24 to 28 weeks of gestation were subjected to a 75 g oral glucose tolerance test (OGTT). Samples for glucose, insulin, glucagon, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) were collected at 0, 30, 60, and 120 min during the OGTT. The Matsuda index (MI) and insulin secretion and sensitivity index-2 (ISSI-2) were assessed. The glucagon suppression index (GSI) was calculated along with the area under the curve (AUC) for glucose, insulin, glucagon, GLP-1, and GIP. Results: A total of 48 pregnant women (25 GDM and 23 controls) were finally analysed. The MI and ISSI-2 were low in the GDM group [4.31 vs. 5.42; P = 0.04], [1.99 vs. 3.18, P ≤ 0.01] respectively). Total AUCglucagon was higher in the GDM group (7411.7 vs. 6320.1, P = 0.02). GSI30 was significantly lower in the GDM group (-62.6 vs. -24.7, P = 0.03). Fasting GLP-1 levels were low in GDM women (17.3 vs. 22.2, P = 0.04). The total AUCGLP-1 positively correlated with total GSI in the GDM group. Conclusion: Asian-Indian GDM women have high insulin insensitivity, islet cell dysfunction, and low fasting GLP-1. Incretin axis dysfunction plays a potential role in their islet cell dysfunction.

Bone mineral density, turnover, and microarchitecture assessed by second-generation high-resolution peripheral quantitative computed tomography in patients with Sheehan's syndrome.

Sheehan's syndrome (SS) is a rare but well-characterized cause of hypopituitarism. Data on skeletal health is limited and on microarchitecture is lacking in SS patients. PURPOSE: We aimed to explore skeletal health in SS with bone mineral density (BMD), turnover, and microarchitecture. METHODS: Thirty-five patients with SS on stable replacement therapy for respective hormone deficiencies and 35 age- and BMI-matched controls were recruited. Hormonal profile and bone turnover markers (BTMs) were measured using electrochemiluminescence assay. Areal BMD and trabecular bone score were evaluated using DXA. Bone microarchitecture was assessed using a second-generation high-resolution peripheral quantitative computed tomography. RESULTS: The mean age of the patients was 45.5 ± 9.3 years with a lag of 8.3 ± 7.2 years prior to diagnosis. Patients were on glucocorticoid (94%), levothyroxine (94%), and estrogen-progestin replacement (58%). None had received prior growth hormone (GH) replacement. BTMs (P1NP and CTX) were not significantly different between patients and controls. Osteoporosis (26% vs. 16%, p = 0.01) and osteopenia (52% vs. 39%, p = 0.007) at the lumbar spine and femoral neck (osteoporosis, 23% vs. 10%, p = 0.001; osteopenia, 58% vs. 29%, p = 0.001) were present in greater proportion in SS patients than matched controls. Bone microarchitecture analysis revealed significantly lower cortical volumetric BMD (vBMD) (p = 0.02) at the tibia, with relative preservation of the other parameters. CONCLUSION: Low areal BMD (aBMD) is highly prevalent in SS as compared to age- and BMI-matched controls. However, there were no significant differences in bone microarchitectural measurements, except for tibial cortical vBMD, which was lower in adequately treated SS patients.

Male Hypogonadism After Recovery from Acute COVID-19 Infection: A Prospective Observational Study.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 can affect the hypothalamic-pituitary-gonadal axis (HPG) due to the expression of the angiotensin-converting enzyme 2 receptor. OBJECTIVES: To assess the prevalence of hypogonadism and Sertoli cell dysfunction in coronavirus disease 2019 (COVID-19) male survivors. METHOD: Male subjects recovered from acute COVID-19 infection were prospectively observed. The primary outcomes included the proportion of hypogonadism, defined biochemically as serum testosterone<230 ng/dL or CFT of<6.4 ng/mL if the total testosterone is between 230-320 ng/m. Sertoli cell dysfunction was defined as inhibin-B level<54.5 pg/mL. Subjects with hypogonadism were followed up at 12 months to assess the recovery of the HPG axis. RESULTS: Eighty-three subjects aged≥18 years were evaluated at a median of 120 (±35) days post-recovery. Their mean age was 49.50±12.73 years, and the mean BMI was 26.84±5.62 kg/m2. Low testosterone was detected in 21 (24.71%) and low inhibin-B was detected in 14 (19.71%) out of 71 subjects at 3 months. Subjects with low testosterone were younger, with a mean age of 43.29±12.03 years (P-0.08) and higher BMI (P-0.012). The severity of COVID-19 infection, duration of hospitalization, and other factors were not significantly associated with low testosterone. At 12 months, 18 out of 21 subjects came for follow-up, of which 9 (50%) showed persistently low testosterone, suggestive of hypogonadism. CONCLUSION: Following COVID-19 infection, testosterone levels recovered over time; however, a significant proportion of subjects had low levels at 12-month follow-up. These findings have long-term implications for the management of COVID-19 subjects.

Effect of daily zinc supplementation for 12 weeks on serum thyroid auto-antibody levels in children and adolescents with autoimmune thyroiditis - a randomized controlled trial.

OBJECTIVES: To assess the effect of daily zinc supplementation for 12 weeks on thyroid auto-antibodies - thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb), and oxidative stress in children with autoimmune thyroid disease (AITD) compared to standard therapy. METHODS: This open-labeled, parallel, randomized controlled trial was done in a tertiary care teaching institute in south India. Children aged 3-18 years with AITD were randomized to receive 25 mg elemental zinc daily for 12 weeks or standard therapy alone. The change in thyroid function tests (thyroid stimulating hormone, free T3, free T4), thyroid auto-antibody (TPOAb, TgAb) titers, oxidative stress markers (glutathione peroxidase, malondialdehyde, superoxide dismutase, and total antioxidant capacity) were compared. RESULTS: Forty children, 20 in each arm, were recruited in the study. We observed a female-to-male ratio of 7:1. Median duration of disease was 2 (0.25, 4.25) years. A total of 37 (92.5 %) children were hypothyroid, two hyperthyroid, and one euthyroid at enrolment. A total of 13 children (32.5 %) had associated co-morbidities, most commonly type 1 diabetes mellitus and systemic lupus erythematosus, three (7.5 %) each. We did not find any significant change in thyroid function tests, thyroid auto-antibody titers, and oxidative stress markers. However, the requirement of levothyroxine dose was significantly increased in the control arm, compared to the zinc group (p=0.03). Only four (20 %) children had minor adverse effects like nausea, metallic taste, and body ache. CONCLUSIONS: Zinc supplementation did not have any effect on thyroid auto-antibodies and oxidative stress. Zinc-supplemented children did not require escalation in levothyroxine dose.

Clinical Features of Unrecognized Congenital Adrenal Hyperplasia Due to 17α-hydroxylase Deficiency Since Adolescence: A Case Report.

The majority of patients with congenital adrenal hyperplasia (CAH) present with a deficiency of 21-hydroxylase or 11-beta-hydroxylase, which account for 90% and 7% of cases, respectively. However, CAH due to 17α-hydroxylase deficiency (17OHD) is an extremely rare form of CAH (<1% of all CAH cases) that leads to a deficiency of cortisol and sex steroids, along with features of aldosterone excess. This is a case of a 51-year-old single female who was referred to us for the evaluation of new-onset hypertension and hypokalaemia of one-year duration. She was born out of a second-degree consanguineous marriage and reared as a female. She was diagnosed to have testicular feminization syndrome when she presented with a history of primary amenorrhea, absence of secondary sexual characteristics, and bilateral labial swellings at pubertal age. Subsequently, she underwent gonadectomy at the age of 16. Due to the presence of hypertension, metabolic alkalosis and bilaterally enlarged adrenals on CT scan, 46, XY disorders of sexual development (DSD) was considered. A karyotype confirmed the presence of 46, XY chromosomal sex, and genetic analysis revealed a mutation in the CYP17A1 gene, thus confirming the diagnosis of 17α-hydroxylase deficiency.

The Association of Dyslipidemia and Atherogenic Indices With Glycemic Control in Diabetic Dyslipidemia Patients: A Real-World Landscape.

BACKGROUND: Dyslipidemia is an important comorbid factor of type 2 diabetes mellitus (T2DM) that increases the risk of cardiovascular diseases. This study aimed to assess the pattern of dyslipidemia and atherogenic indices and determine its relation with glycemic control. METHODS: A cross-sectional study enrolled 382 patients with diabetic dyslipidemia. The socio-demographics data, clinical features, and laboratory parameters were collected. The baseline lipid parameters such as total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and glycated hemoglobin (HbA1C) were measured. Atherogenic indices such as TC/HDL-C ratio, TG/HDL-C ratio, LDL-C/HDL-C ratio, non-HDL-C/HDL-C and atherogenic index of plasma (AIP) [log10 (TG/HDL-C)] were calculated. T2DM patients were classified into three groups based on the degree of glycemic control: Good glycemic control (HbA1C<7%), fair control (HbA1C 7-8%), and poor control (HbA1C>8%). RESULTS: The population's mean age was 48.60±6.15 years, with 145 (38%) males. We found mixed dyslipidemia as the most prevalent (36.1%) form of dyslipidemia in our patients. The most common pattern in atherogenic indices was AIP (94.2%). HbA1c was positively correlated with duration of diabetes (r=0.253, p<0.001). In multivariate logistic regression analysis, duration of diabetes (>10 years) was significantly associated with poor glycemic control with an odds ratio (OR) of 2.31(95% CI; 1.25-4.24, p=0.007). CONCLUSION: The present study indicated that neither the pattern of dyslipidemia nor the atherogenic indices were markers of poor glycemic control among South Indian patients attending our tertiary care institute. However, duration of diabetes was significantly associated with poor glycemic control.

Thyroid Dysfunction in Patients with and Without Venous Thromboembolism: a Case Control Study.

Recent studies report an association between thyroid dysfunction and venous thromboembolism (VTE). Considering the high prevalence of thyroid diseases in India, identification of thyroid dysfunction as a risk factor for VTE will have implications in management. The aim of study was to determine if thyroid dysfunction could be considered as risk factor for unprovoked VTE. The study was conducted on 102 patients with unprovoked VTE and 102 age and gender matched controls in a tertiary care centre. Clinical profile and thyroid function tests (Free T3, Free T4, TSH) including antibody profile (Anti TPO and Anti TG) were compared between two groups. Thyroid disease was identified in 34 cases and 14 controls (33.1% vs. 13.7%, P = 0.001) Out of 34 cases with thyroid dysfunction, 17 had subclinical hypothyroidism (SCH) while 6 out of 14 controls had SCH. Both thyroid dysfunction and SCH were found to be associated with unprovoked VTE, as compared with controls; [Odds ratio (OR) = 3.14, 95% CI 1.56-6.33, P = 0.001] and (OR = 3.71; 95% CI 1.4-9.9; P = 0.01) respectively. Thyroid dysfunction was significantly higher among patients with unprovoked VTE. Thyroid dysfunction, SCH were associated with unprovoked VTE.

Hypothalamic-Pituitary Adrenal Axis Status 3 Months After Recovery From COVID-19 Infection.

CONTEXT: Coronavirus disease 2019 (COVID-19) predominantly involves the lungs, albeit many other organ systems, including the hypothalamic-pituitary-adrenal (HPA) axis, can be affected due to the expression of the angiotensin-converting enzyme 2 (ACE2) binding receptor. Few studies have reported the involvement of adrenal gland and the HPA axis during the acute phase of COVID-19; however, the data on the long-term effect of COVID-19 on the HPA axis after acute infection is scarce. OBJECTIVE: To assess and compare the changes in HPA axis in mild, moderate and severe COVID-19 categories at ≥ 3 months after acute infection. METHODS: A prospective, observational study was conducted to assess the HPA axis status among COVID-19 subjects at least 3 months after recovery from acute infection. The study was conducted from June 2021 to May 2022. Subjects visited the hospital in the fasting state (8.00-9.00am), serum cortisol levels were measured at baseline, 30 and 60 minutes after a 1-µg short Synacthen test (SST). RESULTS: A total of 66 subjects ≥ 18 years of age were included in the study. The mean age (SD) was 49.13 ± 11.9 years, 45(68.18%) were male and 21 (31.81%) were female subjects. The mean BMI in the study was 25.91 ± 4.26 kg/m2. Seventeen (25.8%) subjects had mild, twelve (18.2%) had moderate and thirty-seven (56.1%) subjects had severe COVID-19 infection. Out of the sixty-six subjects with COVID-19, nine subjects (9/66, 13.63%) had peak serum cortisol < 496.62 nmol/L suggestive of adrenal insufficiency (AI). SST peak serum cortisol levels did not differ significantly across the disease severity [Mild, (628.50 ± 214.65 nmol/L) vs moderate, [603.39 ± 161.95 nmol/L) vs severe, (597.59 ± 163.05 nmol/L), P = 0.617]. Six subjects with AI came for follow-up at 12 months, and all had normal HPA axis. CONCLUSION: HPA axis is affected in 13.63% (9/66) of subjects at least 3 months after recovery from COVID-19 infection. AI in COVID-19 might be transient and would recover spontaneously. These findings have important implications for the clinical care and long-term follow-up of subjects after COVID-19 infection.

Effect of a single dose of zoledronic acid on bone mineral density and trabecular bone score in Indian postmenopausal osteoporotic women with and without type 2 diabetes mellitus - A prospective cohort pilot study.

PURPOSE: The objectives were to study the effect of a single dose of intravenous (IV) zoledronic acid (ZA) on changes in bone mineral density (BMD) (lumbar spine (LS), hip, & distal forearm), trabecular bone score (TBS) and bone turnover markers (BTMs) in postmenopausal osteoporotic women with and without diabetes over 12 months. METHODS: Patients were divided into two groups: type 2 diabetes mellitus (T2DM) (n = 40) and non-DM (n = 40). Both groups received a single dose of 4 mg IV ZA at baseline. The BMD with TBS and BTMs (ß-CTX, sclerostin, P1NP) were measured at baseline, six months, and 12 months. RESULTS: At baseline, BMD in all three sites was similar in both groups. T2DM patients were older and had lower BTMs than non-DM patients. The mean increase in LS-BMD (gram/cm2) at 12 months in T2DM and the non-DM group was 3.6 ± 4.7% and 6.2 ± 4.7 %, respectively (P = 0.01). However, the age adjusted mean difference in LS BMD increment between two groups at one year was - 2.86 % (-5.02% to -0.69%), P = 0.01. There was a comparable change in BMD at other two sites, BTMs, and TBS in both the groups over one year follow-up. CONCLUSION: The gain in the LS-BMD was significantly lower in T2DM group compared to non-DM subjects over 12 months after a single IV infusion of 4 mg ZA. The explanation for this could be low bone turnover in diabetes subjects at baseline.

Peroxisome Proliferator-Activated Receptor α and γ Gene Polymorphisms among South Indian Patients with Diabetic Dyslipidaemia.

Background: Peroxisome proliferator-activated receptors (PPAR) α and γ genes play an important role in dyslipidaemia of T2DM. Aims: To estimate the frequency distribution of PPAR α and γ gene polymorphisms in South Indian T2DM patients with dyslipidaemia compared to healthy controls. Normative frequencies of SNPs were established and compared with data for 1000 genome populations. Methods: Eligible 382 cases and 336 age and sex-matched controls were enrolled. Six SNPs in PPARα [rs1800206 C>G (Leu162Val), rs4253778 G>C, rs135542 T>C] and PPARγ [rs3856806 (C>T), rs10865710 (C>G), rs1805192 C>G (Pro12Ala)] genes were selected for genotyping. Results: The allele and gene frequencies did not significantly differ between the diabetic dyslipidaemia cases and healthy controls. However, they were significantly different from that of 1000 genome populations except for rs1800206 C>G (Leu162Val) and rs1805192 C>G (Pro12Ala). Conclusion: The studied polymorphisms in PPARα and PPARγ genes are not associated with diabetic dyslipidaemia among South Indian patients.

Treatment on Nature's lap: Use of herbal products in the management of hyperglycemia.

Diabetes mellitus (DM) is characterized by persistently elevated blood glucose concentration that lead to multisystem complications. There are about 400 medicinal plants cited to have a beneficial effect on DM. We must choose products wisely based on data derived from scientific studies. However, a major obstacle in the amalgamation of herbal medicine in modern medical practices is the lack of clinical data on its safety, efficacy and drug interaction. Trials of these herbal products often underreport the side effects and other crucial intervention steps deviating from the standards set by Consolidated Standards of Reporting Trials. Due to a lack of knowledge of the active compounds present in most herbal medicines, product standardization is difficult. Cost-effectiveness is another issue that needs to be kept in mind. In this mini-review, we focus on the anti-hyperglycemic effect of herbal products that are commonly used, along with the concerns stated above.

Deficiency of the mitochondrial ribosomal subunit, MRPL50, causes autosomal recessive syndromic premature ovarian insufficiency.

Premature ovarian insufficiency (POI) is a common cause of infertility in women, characterised by amenorrhea and elevated FSH under the age of 40 years. In some cases, POI is syndromic in association with other features such as sensorineural hearing loss in Perrault syndrome. POI is a heterogeneous disease with over 80 causative genes known so far; however, these explain only a minority of cases. Using whole-exome sequencing (WES), we identified a MRPL50 homozygous missense variant (c.335T > A; p.Val112Asp) shared by twin sisters presenting with POI, bilateral high-frequency sensorineural hearing loss, kidney and heart dysfunction. MRPL50 encodes a component of the large subunit of the mitochondrial ribosome. Using quantitative proteomics and western blot analysis on patient fibroblasts, we demonstrated a loss of MRPL50 protein and an associated destabilisation of the large subunit of the mitochondrial ribosome whilst the small subunit was preserved. The mitochondrial ribosome is responsible for the translation of subunits of the mitochondrial oxidative phosphorylation machinery, and we found patient fibroblasts have a mild but significant decrease in the abundance of mitochondrial complex I. These data support a biochemical phenotype associated with MRPL50 variants. We validated the association of MRPL50 with the clinical phenotype by knockdown/knockout of mRpL50 in Drosophila, which resulted abnormal ovarian development. In conclusion, we have shown that a MRPL50 missense variant destabilises the mitochondrial ribosome, leading to oxidative phosphorylation deficiency and syndromic POI, highlighting the importance of mitochondrial support in ovarian development and function.

Observation of negative terahertz photoconductivity in strongly correlated electron-doped CaMnO3thin film.

Electron-doped Ca0.96Ce0.04MnO3(CCMO) possesses a unique band structure and exhibits a giant topological Hall effect contrary to other correlation-driven manganites known for insulator-to-metal transition, magnetoresistance, complex magnetic order, etc. The interaction mechanisms among the fundamental entities and their dynamical evolutions responsible for this unusual topological phase are yet to be understood. Here, we employ time-averaged and sub-picosecond time-resolved terahertz (THz) spectroscopy to explore the low-energy steady-state and ultrafast carrier dynamics, respectively, to unravel the complexity of charge carriers during their transition from a non-equilibrium state to the ground state in CCMO thin film. The THz optical conductivity confirms the presence of dichotomic charge carriers, i.e. heavy and light carriers throughout the temperature range of 15-300 K. A rare observation of both positive and negative photoconductivities along with a sharp crossover between the two resolved to a few picoseconds of illumination confirms the formation of polaron with a lifetime of a few nanoseconds. These optical evidences of dichotomic charge carriers, along with manipulation of the sign of photoconductivity induced by dynamics of related quasiparticles could facilitate a new mechanism for ultrafast optoelectronic switching devices.

Growth hormone and gastrointestinal malignancy: An intriguing link.

Growth hormone (GH) excess is associated with several systemic complications, one of which is the increased risk of neoplastic processes particularly of the gastrointestinal (GI) tract. Among the GI neoplasms, the most reported association is with benign and malignant neoplasms of the colon. In the majority of published literature, an increased incidence of GI neoplasms, both colonic adenomas as well as colorectal carcinoma is reported. However, the studies on colon cancer-specific mortality rate are conflicting with recent studies reporting similar cancer-specific mortality rates in comparison to controls. Many studies have reported an association of colorectal neoplasms with GH levels. Pathogenic mechanisms put forward to explain this association of GH excess and GI neoplasms primarily involve the increased GH-insulin-like growth factor 1 (IGF-1) signaling. Both GH and IGF-1 have proliferative, anti-apoptotic, and angiogenic effects on the systemic tissues leading to cellular proliferation. Other contributing factors to the increased risk of GI neoplasms include slow intestinal transit with a redundant large bowel, altered bile acids, deranged local immune response, shared genetic susceptibility factors and hyperinsulinemia. In view of the increased risk association, most guidelines for the care of acromegaly patients recommend an initial screening colonoscopy. Recommendations for further follow-up colonoscopy differ but broadly, the guidelines agree that it depends on the findings at first colonoscopy and state of remission of GH excess. Regarding the concern about the risk of colorectal cancers in patients receiving recombinant GH therapy, most cohort studies do not show an increased risk.

Thyroid Function Abnormalities and Outcomes in Hospitalized Patients with COVID-19 Infection: A Cross-Sectional Study.

Thyroid gland can be affected by the COVID-19 infection. The pattern of thyroid function abnormality reported in COVID-19 is variable; in addition, some drugs used in COVID-19 patients like glucocorticoids and heparin can affect the thyroid function tests (TFT). We conducted an observational, cross-sectional study of thyroid function abnormalities with thyroid autoimmune profile in COVID-19 patients with varying severity from November 2020 to June 2021. Serum FT4, FT3, TSH, anti-TPO, and anti-Tg antibodies were measured before the initiation of treatment with steroids and anti-coagulants. A total of 271 COVID-19 patients were included in the study, of which 27 were asymptomatic and remaining 158, 39, and 47 were classified to mild, moderate and severe categories, respectively, according to MoHFW, India criteria. Their mean age was 49±17 years and 64.9% were males. Abnormal TFT was present in 37.2% (101/271) patients. Low FT3, low FT4, and low TSH were present in 21.03%, 15.9% and 4.5% of patients, respectively. Pattern corresponding to sick euthyroid syndrome was the most common. Both mean FT3 and FT3/FT4 ratio decreased with increasing severity of COVID-19 illness (p=0.001). In multivariate analysis, low FT3 was associated with increased risk of mortality (OR 12.36, 95% CI: 1.23-124.19; p=0.033). Thyroid autoantibodies were positive in 58 (27.14%) patients; but it was not associated with any thyroid dysfunction. Thyroid function abnormality is common among COVID-19 patients. Both low FT3 and FT3/FT4 ratio are indicators of disease severity while low FT3 is a prognostic marker of COVID-19 associated mortality.

Correlation among Poincare plot and traditional heart rate variability indices in adults with different risk levels of metabolic syndrome: a cross-sectional approach from Southern India.

OBJECTIVES: Heart rate variability (HRV) is an important marker of cardiac autonomic modulation. Metabolic syndrome (MetS) can alter cardiac autonomic modulation, raising the risk of cardiovascular disease (CVD). Poincaré plot analysis (PPA) is a robust scatter plot-based depiction of HRV and carries similar information to the traditional HRV measures. However, no prior studies have examined the relationship between PPA and traditional HRV measures among different risk levels of MetS. We evaluated the association between the Poincare plot and traditional heart rate variability indices among adults with different risk levels of MetS. METHODS: We measured anthropometric data and collected fasting blood samples to diagnose MetS. The MetS risk was assessed in 223 participants based on the number of MetS components and was classified as control (n=64), pre-MetS (n=49), MetS (n=56), and severe MetS (n=54). We calculated the Poincaré plot (PP) and traditional HRV measures from a 5 min HRV recording. RESULTS: Besides the traditional HRV measures, we found that various HRV indices of PPA showed significant differences among the groups. The severe MetS group had significantly lower S (total HRV), SD1 (short-term HRV), SD2 (long-term HRV), and higher SD2/SD1. The values of S, SD1, SD2, and SD2/SD1 were significantly correlated with most traditional HRV measures. CONCLUSIONS: We found gradual changes in HRV patterns as lower parasympathetic and higher sympathetic activity alongside the rising number of MetS components. The HRV indices of PPA integrating the benefits of traditional HRV indices distinguish successfully between different risk levels of MetS and control subjects.

Early Markers of Atherosclerosis in Children and Adolescents with Type 1 Diabetes Mellitus.

OBJECTIVES: To detect early atherosclerosis changes using flow-mediated dilation (FMD) of the brachial artery, carotid intima-media thickness (CIMT), inflammatory markers (hs-CRP, IL-6), and endothelial markers (sICAM and sVCAM). METHODS: The authors recruited 4 to 18-y-old children with type 1 diabetes mellitus (T1DM) and age- and sex-matched normal children, excluding those with familial hypercholesterolemia, syndromic disorders, and cardiovascular disease. CIMT and FMD were measured in both the groups. Biomarkers hs-CRP, IL-6, sICAM, and sVCAM, were analyzed in the T1DM group. RESULTS: Forty T1DM children and 40 controls with 27 (67.5%) girls were enrolled in each group. The mean age was 9.68 y. The T1DM group had 4 (10%) obese and 4 (10%) overweight children. Among cases, 9 (22.5%) had diabetes for > 5 y, 24 (60%) required daily insulin between 0.8 and 1.2 IU/kg/d and 26 (65%) had HbA1c > 10 g/dL. The CIMT values were significantly higher in cases (0.69 mm) than in controls (0.59 mm); 29 (72.5%) cases had abnormal combined CIMT values. FMD was lesser in cases than in controls but not significant. The median values of hs-CRP, IL-6, sICAM, sVCAM were 0.81 mg/L, 6.27 pg/mL, 46.33 ng/mL and 668.81 ng/mL, respectively. A significant correlation of IL-6 with CIMT (r = 0.543, p = < 0.001) and sICAM with FMD (r = -0.397, p = 0.011) was observed. VCAM was low in the obese and overweight children. CONCLUSION: Children with type 1 diabetes had higher CIMT than normal children, whereas FMD did not differ. The association between elevated inflammatory markers with high CIMT and low FMD indicates that inflammation plays an essential role in endothelial dysfunction.