Long Term Impact of Adeno-tonsillectomy on Immunity Against Respiratory Viral Infections; Evidence Deduced During COVID-19 Pandemic.

OBJECTIVES: To evaluate the risk of acquiring COVID-19 infection in patients who have undergone adeno-tonsillectomy (AT) as compared to their siblings. METHODS: In this bidirectional cohort control study, 36 cohorts, younger than 18 y, who underwent AT, and 27 controls (siblings of the enrolled cohorts, younger than 18 y) were recruited. Incidence of COVID-19 was analyzed by symptoms suggestive of COVID-19 infection, COVID-19 testing, and SARS-CoV-2 specific antibody measurement. RESULTS: In the cohort group, the overall COVID-19 positivity rate was 80.5% (n = 29/36) and symptomatic COVID-19 positivity rate was 68.9% (n = 20/29). Among the controls, the overall COVID-19 positivity rate was 44% (n = 12/27) and symptomatic COVID-19 positivity rate was 16% (n = 2/12). The cohorts had 1.8 times higher risk of contracting COVID-19 infection and the relative risk of symptomatic COVID-19 infections as compared to controls was 4.14. CONCLUSIONS: This pilot study indicates that adeno-tonsillectomy poses children at a significantly higher risk of COVID-19 infections and likely other viral upper respiratory tract infections.

Calotropis procera extract inhibits prostate cancer through regulation of autophagy.

Current treatment options available for prostate cancer (PCa) patients have many adverse side effects and hence, new alternative therapies need to be explored. Anticancer potential of various phytochemicals derived from Calotropis procera has been studied in many cancers but no study has investigated the effect of leaf extract of C. procera on PCa cells. Hence, we investigated the effect of C. procera leaf extract (CPE) on cellular properties of androgen-independent PC-3 and androgen-sensitive 22Rv1 cells. A hydroalcoholic extract of C. procera was prepared and MTT assay was performed to study the effect of CPE on viability of PCa cells. The effect of CPE on cell division ability, migration capability and reactive oxygen species (ROS) production was studied using colony formation assay, wound-healing assay and 2',7'-dichlorodihydrofluorescein diacetate assay, respectively. Caspase activity assay and LDH assay were performed to study the involvement of apoptosis and necrosis in CPE-mediated cell death. Protein levels of cell cycle, antioxidant, autophagy and apoptosis markers were measured by western blot. The composition of CPE was identified using untargeted LC-MS analysis. Results showed that CPE decreased the viability of both the PCa cells, PC-3 and 22Rv1, in a dose- and time-dependent manner. Also, CPE significantly inhibited the colony-forming ability, migration and endogenous ROS production in both the cell lines. Furthermore, CPE significantly decreased NF-κB protein levels and increased the protein levels of the cell cycle inhibitor p27. A significant increase in expression of autophagy markers was observed in CPE-treated PC-3 cells while autophagy markers were downregulated in 22Rv1 cells after CPE exposure. Hence, it can be concluded that CPE inhibits PCa cell viability possibly by regulating the autophagy pathway and/or altering the ROS levels. Thus, CPE can be explored as a possible alternative therapeutic agent for PCa.

Anti-SARS-CoV-2 antibody kinetics up to 6 months of follow-up: Result from a nation-wide population-based, age stratified sero-epidemiological prospective cohort study in India.

Repeated serological testing tells about the change in the overall infection in a community. This study aimed to evaluate changes in antibody prevalence and kinetics in a closed cohort over six months in different sub-populations in India. The study included 10,000 participants from rural and urban areas in five states and measured SARS-CoV-2 antibodies in serum in three follow-up rounds. The overall seroprevalence increased from 73.9% in round one to 90.7% in round two and 92.9% in round three. Among seropositive rural participants in round one, 98.2% remained positive in round two, and this percentage remained stable in urban and tribal areas in round three. The results showed high antibody prevalence that increased over time and was not different based on area, age group, or sex. Vaccinated individuals had higher antibody prevalence, and nearly all participants had antibody positivity for up to six months.

Role of Procalcitonin as a Biomarker in Early Identification of Adverse Events Following Esophageal Atresia Surgery.

Introduction: Surgical complication following esophageal atresia repair is one of the several factors known to influence the final outcomes. Early identification of such complications may help in timely institution of therapeutic measures and translate into improved prognosis. Objective: The objective of this study was to evaluate the role of procalcitonin in early prediction of the adverse events after surgery in patients of esophageal atresia and the temporal relationship with clinical manifestations and other inflammatory biomarkers such as C-reactive protein (CRP). Materials and Methods: This was a prospective study on consecutive patients of esophageal atresia (n = 23). Serum procalcitonin and CRP levels were assessed at baseline (prior to surgery) and on postoperative days (POD) 1, 3, 5, 7, and 14. The trends in the biomarker values and temporal relationships of deviation in trend with the clinical and conventional laboratory parameters and patient outcomes were analyzed. Results: Baseline serum procalcitonin was elevated (n = 23; 1.7 ng/ml: min: 0.07 ng/ml-max: 24.36 ng/ml) in 18/23 (78.3%) patients. Procalcitonin nearly doubled on POD-1 (n = 22; 3.28 ng/ml: min: 0.64 ng/ml-max: 16.51 ng/ml) followed by a gradual decline. CRP was also elevated on POD-1 (three times the baseline) and depicted a delayed peak at POD-3. POD-1 procalcitonin and CRP levels correlated with survival. POD-1 procalcitonin cutoff at 3.28 ng/ml predicted mortality with a sensitivity and specificity of 100% and 57.9% (P = 0.05). Serum procalcitonin and CRP were higher for patients who sustained complications, so was the time required for hemodynamic stabilization. Procalcitonin (baseline and POD-5) and CRP (POD-3 and POD-5) values correlated with the clinical course after surgery. Baseline procalcitonin cutoff at 2.91 ng/ml predicted the possibility of a major complication with a sensitivity of 71.4% and a specificity of 93.3%. POD-5 procalcitonin cutoff at 1.38 ng/ml predicted the possibility of a major complication with a sensitivity of 83.3% and a specificity of 93.3%. Patients who sustained major complications depicted a change in serum procalcitonin trend 24-48 h ahead of clinical manifestation of an adverse event. Conclusions: Procalcitonin is a good indicator to identify the adverse events in neonates after surgery for esophageal atresia. The procalcitonin levels in patients who sustained a major complication depicted a reversal in trend 24-48 h of clinical manifestation. POD-1 procalcitonin correlated with survival while the baseline and POD-5 serum procalcitonin predicted the clinical course.

Lung water estimation on cardiac magnetic resonance imaging for predicting adverse cardiovascular outcomes in patients with heart failure.

OBJECTIVES: Pulmonary congestion is a central feature of heart failure (HF) seen in acute decompensated state as well as in chronic stable disease. The present study sought to determine whether simplified cardiac magnetic resonance imaging (CMR)-derived lung water density (LWD) measurement has prognostic relevance in predicting adverse cardiovascular outcomes in patients with HF and left ventricular ejection fraction (LVEF)<50%. METHODS: Eighty consecutive patients referred for CMR with HF and LVEF<50% along with 22 healthy age- and sex-matched controls were prospectively recruited. LWD was the lung-to-liver signal intensity ratio multiplied by 70% (estimated hepatic water density). The primary endpoint was composite of all-cause mortality or HF-related hospitalization within 6 months from CMR. RESULTS: The mean LWD was significantly higher in HF patients compared to healthy controls (19.78 ± 6.1 vs 13.6 ± 2.3; p < 0.001). The mean LWD was significantly different among patients with NYHA class I/II and NYHA class III/IV (17.88 ± 4.8 vs 21.77 ± 1.08; p = 0.004). At 6 months, the primary endpoint was reached in 12 (15%) patients. Patients with "wet lungs" (LWD > 18.1%) had higher incidence of adverse cardiovascular outcomes compared to patients with "dry lungs". LWD was an independent predictor of adverse cardiovascular outcomes in multivariable analysis. At the optimal cut-off of LWD > 23.38%, the sensitivity and specificity were 91.67 and 91.18%, respectively, to predict adverse cardiovascular outcomes. CONCLUSION: LWD on CMR is independently associated with increased risk of mortality and HF-related hospitalization in HF patients with LVEF<50%. ADVANCES IN KNOWLEDGE: Non-invasive quantitative estimation of LWD on CMR can improve risk stratification and guide management in HF patients.

Association of vitamin D status with disease severity and outcome in Indian patients with IgA nephropathy.

BACKGROUND: Vitamin D deficiency has been examined as a risk factor for severity and progression of kidney disease due to its immunomodulatory effects. There is paucity of data about its impact in IgA nephropathy (IgAN). METHODS: In a retrospective cohort study, 25 (OH) vitamin D assay was performed in bio-banked baseline serum samples collected during kidney biopsy of 105 adult patients with primary IgAN diagnosed between 2015 and 2019. A level of < 10 ng/mL was defined as Vitamin D deficiency. RESULTS: Mean age of patients was 34 ± 10.6 years, 69.5% were males. Mean baseline 25(OH) Vitamin D levels was 15.9 ± 11.9 ng/mL and 41(39%) patients had vitamin D deficiency. Serum albumin level was lower in vitamin D deficient patients compared to those who had higher vitamin D levels (3.7 ± 0.9 vs 4.1 ± 0.7 g/dl, p = 0.018)but there was no significant difference in baseline proteinuria and eGFR. Crescentic lesions were more frequent in vitamin D deficient group (19.5% vs 6.3%, p = 0.022). At median follow up of 21.5 months (6 - 56 months), there was no difference in remission (68.3% vs 65.6%, p = 0.777) and disease progression (12.5% vs 9.4%, p = 0.614) in those with and without Vitamin D deficiency respectively. On multivariate cox proportional hazard analysis, vitamin D deficiency was not a significant risk factor for renal survival (HR-1.79, 95% confidence interval:0.50-6.34, p = 0.368). CONCLUSION: There was no association between vitamin D deficiency and disease profile as well as renal outcome in Indian patients with IgAN.

Serological prevalence of SARS-CoV-2 antibody among children and young age group (between 2 and 17 years) in India: An interim result from a large multicentric population-based seroepidemiological study.

Background: Estimating seroepidemiolgical prevalence of SARS-CoV-2 antibody is an essential public health strategy. There is insufficient evidence of prevalence among those belonging to young age population in India. Objective: To compare the SARS-CoV-2 seropositivity rate between children and adults in selected sites from India. Materials and Methods: This was a multicentric population-based seroepidemiological study conducted in selected urban and rural areas of five sites selected from four states (Delhi, Odisha, Uttar Pradesh, Tripura) of India. Participants aged ≥1 year were included from different clusters of each area. Total serum antibody against SARS-CoV-2 virus was assessed qualitatively by using a standard enzyme-linked immunosorbent assay (ELISA) kit. Results: Data collection period was from 15 March 2021 to 10 June 2021. Total available data was of 4509 participants, of whom 700 were <18 years of age and 3809 were ≥18 years of age. The site-wise number of available data among those aged 2-17 years was 92, 189, 165, 146 and 108 for the sites of Delhi urban, Delhi rural, Bhubaneswar rural, Gorakhpur rural and Agartala rural area, respectively. The seroprevalence was 55.7% in the <18 years age group and 63.5% in the ≥18 years age group. The prevalence among female children was 58% and among male children was 53%. Conclusion: SARS-CoV-2 seropositivity rate among children was high and comparable to that of the adult population. Hence, it is unlikely that any future third wave by prevailing SARS-CoV-2 variant would disproportionately infect children 2 years or older.

Epigenetic regulation of epithelial to mesenchymal transition: a trophoblast perspective.

Epigenetic changes alter the expression of genes at both pre- and post-transcriptional levels without changing their DNA sequence. Accumulating evidence suggests that such changes can modify cellular behavior and characteristics required during development and in response to various extracellular stimuli. Trophoblast cells develop from the outermost trophectoderm layer of the blastocyst and undergo many phenotypic changes as the placenta develops. One such phenotypic change is differentiation of the epithelial natured cytotrophoblasts into the mesenchymal natured extravillous trophoblasts. The extravillous trophoblasts are primarily responsible for invading into the maternal decidua and thus establishing connection with the maternal spiral arteries. Any dysregulation of this process can have adverse effects on the pregnancy outcome. Hence, tight regulation of this epithelial-mesenchymal transition (EMT) is critical for successful pregnancy. This review summarizes the recent research on the epigenetic regulation of the EMT occurring in the trophoblast cells during placental development. The functional significance of chemical modifications of DNA and histone, which regulate transcription, as well as non-coding RNAs, which control gene expression post-transcriptionally, is discussed in relation to trophoblast biology.

The role of Plasma Renin Activity in prenatally diagnosed non-obstructed hydronephrosis at risk for surgery-an observational study.

BACKGROUND: Patients with asymptomatic prenatally diagnosed hydronephrosis may progress to needing surgery; no biomarker supporting the identification of these cases is currently available. The aim of the study was to assess the role of Plasma Renin Activity (PRA) as a discriminatory factor to identify patients with asymptomatic prenatally diagnosed hydronephrosis who require close monitoring and are at-risk for surgery. METHODS: The study group consists of 30 children prenatally diagnosed with asymptomatic unilateral hydronephrosis, initially managed with medical follow-up. Pyeloplasty was indicated if patients became symptomatic or if there was a significant drop in split renal function (SRF) during follow-up. An association was sought between PRA and renal parameters in post-hoc analysis. RESULTS: During the mean follow-up of 55.5 ± 8.2 months, 13/30 (43.3%) patients developed delayed drainage and 8/30 (26.6%) underwent pyeloplasty. Mean PRA was higher at presentation in the group which later presented with a drop in differential kidney function ≥ 10%, while it was within the normal range for age in the other patients. Before pyeloplasty, progression to delayed drainage coincided with a drop in SRF and a rise in PRA. While PRA levels normalized after pyeloplasty, SRF improved but did not reach initial values. A mean rise of 68.9% in PRA preceded current indications for surgery by 27.5 ± 9.5 months. CONCLUSIONS: A progressive increase in PRA in children with asymptomatic prenatally diagnosed hydronephrosis reflects obstructive stress in the tubulo-interstitial compartment. This stress is relieved by pyeloplasty and is reflected by a drop in PRA after surgery. PRA can, thus, serve as the discriminatory factor to identify hydronephrosis patients 'at-risk' for surgery even before the current criteria for pyeloplasty are met.

Analysis OF C677T polymorphism in methylene tetrahydrofolate reductase (MTHFR) gene as a risk factor for congenital talipes equino varus (CTEV).

BACKGROUND: Clubfoot is a common congenital foot deformity. Low folate status in mothers has been associated with CTEV. Folate metabolism might be affected by Methylene Tetrahydrofolate Reductase (MTHFR) gene polymorphism. The present study was aimed to investigate MTHFR C677T polymorphism and its association with CTEV. METHODS: This is a Case-mother-Dyad study with 30 pairs of cases and controls. Single Nucleotide Polymorphism (SNP) analysis of the MTHFR gene was done in this hospital-based study by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP). RESULTS: In this study, we observed less relative risk of CTEV in presence of C allele as compared to T allele in children, with Relative Risk- 0.6281 and likelihood ratio of 0.5714. While analysing the correlation of genotype variation in cases (CC = 8(26.66%) and CT = 22(73.33%)) with there biological mother (CC = 13(43.33%) and CT = 17(56.66%)), no significant correlation (p = 0.3110) was found between cases and their biological mother genotype. CONCLUSION: Among the enrolled cases, there was a significant association of increased CTEV risk with 677T variant allele of MTHFR gene. Also, maternal MTHFR genotype was not found to influence CTEV risk of offspring.

A prospective randomized comparison of sexual function and semen analysis following laparoscopic totally extraperitoneal (TEP) and transabdominal pre-peritoneal (TAPP) inguinal hernia repair.

BACKGROUND: With standardization of laparoscopic technique of groin hernia repair, the focus of surgical outcome has shifted to lesser studied parameters like sexual function and fertility. METHODS: This prospective randomized study was conducted in a single surgical unit at a tertiary care hospital. A sample size of 144 was calculated with 72 in each group (Group 1 TEP and Group 2 TAPP). Primary outcomes measured included comparison of sexual function using BMFSI, qualitative semen analysis and ASA levels between patients undergoing TEP or TAPP repair. Semen analysis and ASA was measured pre-operatively and 3 months post-operatively. RESULTS: A total of 145 patients were randomized into two groups, TAPP (73) and TEP (72) patients. Both the groups were comparable in terms of demographic profile and hernia characteristics with majority of the patients in both the groups having unilateral inguinal hernia (89.0% in TAPP group and 79.2% in TEP group). Both the groups showed statistically significant improvement in overall sexual function score (BMFSI) at 3 months; however, there was no inter group difference. Both the groups were also comparable in terms of ASA and qualitative semen analysis. CONCLUSION: Both TEP and TAPP repair are comparable in terms of sexual function and effect on semen analysis. Laparoscopic repair improves the overall sexual functions in patients with groin hernia.

A three-arm randomized study to compare sexual functions and fertility indices following open mesh hernioplasty (OMH), laparoscopic totally extra peritoneal (TEP) and transabdominal preperitoneal (TAPP) repair of groin hernia.

BACKGROUND: With evolving technology, the focus of groin hernia repair has shifted to sexual function and fertility outcomes. METHODS: This three-arm randomized study was conducted in tertiary care hospital from 1st July 2017 to 30th March 2019. Consecutive patients of groin hernia were randomized into 3 groups, TAPP (Group 1), TEP (Group 2), and OMH (Group 3). Demographic profile and hernia characteristics were assessed preoperatively. Sexual functions (using BMSFI) and fertility (using surrogate fertility indices, viz., semen analysis and anti-sperm antibodies (ASA)) were assessed preoperatively at 3 months after the surgery. RESULTS: A total of 121 patients were included in the study with 41 patients in TAPP (Group 1) and 40 each in TEP (Group 2) and OMH (Group3) group. All the 3 groups were comparable in terms of demographic profile, hernia characteristics, intra-operative and early post-operative outcomes. Significant improvement was found in most of the domains of BMSFI score in the study population (p value < 0.001) with no intergroup difference. There was significant increase of anti-sperm antibody level in OMH group as compared to TAPP and TEP (p = 0.001), however, the levels were within normal limit. CONCLUSIONS: In conclusion, this study has shown that inguinal hernia repair whether open or laparoscopic (TEP or TAPP) leads on to improvement in sexual functions and fertility indices and can have a significant impact on pre-op counseling of the patient in terms of choice of repair, depending on the available expertise in a given center.

Comparison of CRP and procalcitonin for etiological diagnosis of fever during febrile neutropenia in hematology patients- an experience from a tertiary care center in Northern India.

INTRODUCTION: Febrile neutropenia is a common cause in morbidity and mortality during treatment of hematological neoplasms. METHODS: Subjects included all cases admitted under hematology department with febrile neutropenia from February to June 2018. Each febrile episode was investigated by standard investigations (Blood culture, Chest x ray etc.); Procalcitonin (PCT) and c reactive protein (CRP) was sent at fever onset 0, 24, 48 h, day 7 and day 14. RESULTS: Data was analyzed for 52 febrile episodes in 50 patients. PCT cut off value at 24 h of ≤1.2 ng/ml had a sensitivity and specificity of 62.5% and 87.5% for discriminating Invasive fungal infection (IFI) and Microbiologically documented infection (MDI) (p = 0.033). PCT had a negative predictive value of 70% for the diagnosis of IFI as compared to MDI. CRP cut off >160 mg/dl at 48 h was suggestive of fever due to fungal infection with a sensitivity of 100%, specificity of 48%, PPV of 33.3% and NPV of 100%. CRP at 24 and 48 h of fever was useful to distinguish non-infectious causes of fever from infectious causes. CONCLUSION: PCT at 24 h and CRP at 48 h was useful in identifying fungal infection. CRP was a better marker when compared to PCT for identifying disease fever.

Prevalence of thyroid autoimmunity in first-degree relatives of patients with celiac disease.

AIM: Patients with celiac disease (CeD) are prone to develop other autoimmune diseases such as autoimmune thyroid disease and type 1 diabetes. While 7.5% of first-degree relatives (FDRs) of patients with CeD develop CeD, it is not clear whether FDRs of patients with CeD are at higher risk of developing autoimmune thyroid disease. METHODS: In this prospective case-control study, we recruited 194 FDRs (males 53.1%) of 91 patients with CeD and 140 age-matched healthy controls (males 76.4%). They were screened for CeD using anti-tissue transglutaminase antibodies (anti-tTG Ab) and thyroid disease using a symptom questionnaire, anti-thyroid peroxidase antibodies (anti-TPO) and serum thyroid-stimulating hormone (TSH). Subjects having positive anti-TPO but a normal TSH were classified as having thyroid autoimmunity and those with elevated TSH with or without positive anti-TPO Ab were classified as having autoimmune thyroid dysfunction. RESULTS: The prevalence of thyroid autoimmunity and autoimmune thyroid dysfunction in FDRs was significantly higher than that in healthy controls (17.5% vs. 5.0%, p < 0.01; 11.8% vs. 3.5%, p < 0.01), respectively. A significantly higher number of FDRs had a positive anti-tTG Ab in comparison with controls (13.9% vs. 2.2%, p < 0.001). Amongst FDRs having thyroid autoimmunity, 44.1%, 47.0% and 8.8% were siblings, parents and children of patients with CeD, respectively. Familial clustering was seen only in 1 family. CONCLUSION: FDRs of patients with CeD have 3-fold higher risk of developing autoimmune thyroid disorders and associated thyroid dysfunction. Therefore, it is advisable for early screening of FDRs for CeD and associated thyroid autoimmune through screening measures.

Mechanobiology of Cancer Stem Cells and Their Niche.

Though the existence of cancer stem cells remained enigmatic initially, over the time their participation in tumorigenesis and tumor progression has become highly evident. Today, they are also appreciated as the causal element for tumor heterogeneity and drug-resistance. Cancer stem cells activate a set of molecular pathways some of which are triggered by the unique mechanical properties of the tumor tissue stroma. A relatively new field called mechanobiology has emerged, which aims to critically evaluate the mechanical properties associated with biological events like tissue morphogenesis, cell-cell or cell-matrix interactions, cellular migration and also the development and progression of cancer. Development of more realistic model systems and biophysical instrumentation for observation and manipulation of cell-dynamics in real-time has invoked a hope for some novel therapeutic modalities against cancer in the future. This review discusses the fundamental concepts of cancer stem cells from an intriguing viewpoint of mechanobiology and some important breakthroughs to date.

Association of raised levels of IL-4 and anti-TPO with hyperprolactinemia.

BACKGROUND AND OBJECTIVE: The modulatory role of prolactin in autoimmune regulation is well established. Hyperprolactinemia is often associated with autoimmune disease like systemic lupus erythematosus and autoimmune thyroid diseases. The objective was to compare levels of direct and indirect autoimmune factors in different categories of hyperprolactinemia cases and predict the direction of association between hyperprolactinemia and autoimmune factors, if any. METHODS: A total of 102 hyperprolactinemia cases (>100 ng/mL serum prolactin level) were included along with 24 controls. Among 102 hyperprolactinemia cases, there were 36 idiopathic cases, 19 pituitary adenoma cases, 36 drug-induced cases, and 11 cases associated with other secondary/systemic diseases (chronic renal failure, chronic hepatic failure, etc). MEASUREMENTS: Direct autoimmune markers, IL-2, IFN-γ, IL-4, and IL-5, were measured in serum by ELISA. Indirect autoimmune markers, anti-TPO, anti-tg, anti-CCP, VDRL, platelet count, and aPTT, were measured as per laboratory-defined protocol. RESULTS: Serum levels of IL-4 and anti-TPO were significantly high in idiopathic hyperprolactinemia cases. Serum IL-4 levels were also significantly high in pituitary adenoma cases, drug-induced cases, and in cases with other secondary causes of hyperprolactinemia. Serum anti-TPO levels were also significantly high in drug-induced hyperprolactinemia cases. CONCLUSION: No significant difference in autoimmune factors is observed between macroprolactinemia and true hyperprolactinemia. Serum IL-4 and anti-TPO were high in all categories of hyperprolactinemia. This suggests a possible association of hyperprolactinemia with autoimmune conditions (high IL-4 and anti-TPO), mostly subclinical. Thus, hyperprolactinemia case with serum prolactin level >100 ng/mL may require long-term follow-up for the development of autoimmune disease in future.

A Comparative Analysis of the Metabolic and Coagulative Profiles in Patients with Idiopathic Scoliosis, Congenital Scoliosis and Healthy Controls: A Case-Control Study.

STUDY DESIGN: Single-center, observational, case-control study. PURPOSE: Comparison and analysis of the metabolic and coagulative profiles in patients with idiopathic scoliosis, patients with congenital scoliosis, and healthy controls. OVERVIEW OF LITERATURE: Serum melatonin deficiency has been a controversial topic in the etiopathogenesis of scoliosis. Low bone mineral density, low vitamin D3 levels, and high parathyroid hormone levels are common metabolic abnormalities associated with scoliosis that may be responsible for its pathogenesis. In addition to metabolic defects, several studies have shown coagulation defects that either persist from the preoperative period or occur during surgery and usually lead to more than the expected amount of blood loss in patients undergoing deformity correction for scoliosis. METHODS: The study population (n=73) was classified into those having congenital scoliosis (n=31), those with idiopathic scoliosis (n=30), and healthy controls (n=12). After detailed clinicoradiological evaluation of all the subjects, 10-mL blood samples were collected, measured, and analyzed for various metabolic and coagulation parameters. RESULTS: The mean serum melatonin levels in patients with idiopathic scoliosis were significantly lower than those in the healthy controls. Although the mean serum melatonin level in the congenital group was also low, the difference was not statistically significant. Serum alkaline phosphatase and parathyroid hormone levels were higher in the scoliosis groups, whereas the vitamin D level was lower. No differences were observed in the coagulation profiles of the different groups. CONCLUSIONS: Low serum melatonin levels associated with scoliosis can be a cause or an effect of scoliosis. Moreover, low bone mineral density, high bone turn over, and negative calcium balance appear to play an important role in the progression, if not the onset, of the deformity.

Oral thyroxin supplementation in infants undergoing cardiac surgery: A double-blind placebo-controlled randomized clinical trial.

BACKGROUND: Decreases in serum total thyroxin and total triiodothyronine occurs after cardiopulmonary bypass, and is reflected as poor immediate outcome. We studied effects of oral thyroxin supplementation in infants who underwent open-heart surgery. METHODS: In this prospective study, 100 patients were randomized into 2 groups: 50 in the thyroxin group (TH) and 50 in the placebo group (PL). Patients in the TH group received oral thyroxin (5 µg/kg) 12 hours before surgery and once daily for the remainder of their intensive care unit (ICU) stay. Data on intraoperative and postoperative variables were recorded. Cardiac index (CI) was measured. Perioperative serum thyroid hormone levels and serum interleukin-6 and tumor necrosis factor-α were measured. Secondary analysis was performed by dividing patients into simple and complex subcategories. RESULTS: Results of the primary analysis indicated a higher CI in the TH compared with the PL. In the complex category, the mean duration of mechanical ventilation was 3.85 ± 0.93 and 4.66 ± 1.55 days in the TH and PL, respectively (P = .001). Mean ICU stay was 6.79 ± 2.26 and 8.33 ± 3.09 days (P = .03), and mean hospital stay was 15.70 ± 4.77 and 18.90 ± 4.48 days (P = .01) in the TH and PL, respectively. There were no significant differences between the TH and the PL in the simple category. CI was higher in the TH at all time points (P = .004). The average therapeutic intervention scoring system scores for the first 2 days were higher in the PL in the complex category. CONCLUSIONS: Oral thyroxin supplementation improves the CI and reduces the inotropic requirement. In addition, it reduces the duration of mechanical ventilation, ICU and hospital stay, and therapeutic intervention scoring system in infants after surgery for complex congenital heart defects.

Posterior urethral valves: Persistent renin angiotensin system activation after valve ablation and role of pre-emptive therapy with angiotensin converting enzyme-inhibitors on renal recovery.

AIM: To study renin angiotensin system (RAS) activity after posterior urethral valve ablation and the role of early induction of angiotensin converting enzyme-inhibitors (ACE-I) on the outcome of renal function. MATERIALS AND METHODS: Thirty four children underwent valve ablation in which therapy with ACE-I was started 40.5 ± 4.1 (range 32-47 months) formed the study group. Post-ACE-I data were collected after mean duration of 18.2 ± 4.0 (12-28 months). Plasma renin activity (PRA), urinary micro albumin, glomerular filtration rate (GFR), and serum creatinine, before and after therapy were monitored. RESULTS: Therapy with ACE-I resulted in a fall in micro albuminuria by 45.7% and 42.0% in patients without and with vesico ureteral reflux, respectively, and improvement in split renal function by 6.6% and 5.9% GFR respectively. A similar response was noted in patients without and with renal scars. CONCLUSION: The decline in renal function after valve ablation is accompanied by activation of RAS reflected in a gradual rise in PRA. Therapy with ACE-I stabilizes and then improves renal function, thereby, retarding the pace of renal damage.

Obesity, and not obstructive sleep apnea, is responsible for metabolic abnormalities in a cohort with sleep-disordered breathing.

OBJECTIVE: To assess the profile of metabolic abnormalities in subjects with obstructive sleep apnea (OSA). PATIENTS AND METHODS: In a case-control study conducted in two years, from April 2003 to March 2005, data obtained from polysomnography study, lipid profile, fasting blood sugar, serum insulin, insulin resistance, leptin and adiponectin levels, were compared between the various groups. Included in the study were OSA subjects from a sleep laboratory and matched controls from the community. Those with recent myocardial infarction, upper airway surgery, class III/IV heart failure, pregnancy, acromegaly, chronic renal failure, or who were on treatment for hyperthyroidism, on systemic steroid treatment, or on hormonal replacement therapy, were excluded from the study. RESULTS: Forty apneic obese subjects (AHI=32.19, range 13-52.75) were compared with 40 non-apneic obese controls (AHI=1.3, range 0-2.45) and 40 normal weight control subjects (AHI=0.7, range 0-1). No significant difference was noted in levels of fasting blood sugar, insulin resistance (obese apneics 61.9, obese controls 47.8, non-obese controls 19.1), leptin (obese apneics 10.65 microg/L, obese controls 8.52 microg/L, non-obese controls 2.83 microg/L) or adiponectin (obese apneics 4959.3 ng/ml, obese controls 5706 ng/ml, non-obese controls 7412 ng/ml) in the OSA group compared to obese controls. CONCLUSIONS: OSA has no independent association with lipid abnormalities, insulin resistance, serum leptin and adiponectin levels. In multivariate analysis, obesity was the major determinant of metabolic abnormalities in this cohort.