Thyrotoxicosis Due to Acute Suppurative Thyroiditis in a Pediatric Patient: A Case Report.

Acute suppurative thyroiditis is a rare and potentially life-threatening cause of thyroid inflammation requiring prompt recognition and management. There are few reported cases of thyrotoxicosis due to acute suppurative thyroiditis. We are reporting the case of a 9-year-old boy who presented to the emergency room with fevers, neck pain and swelling, night terrors, and emotional lability. He was hemodynamically stable with initial lab work remarkable for neutrophilia without leukocytosis, elevated inflammatory markers, and hyperthyroidism. Imaging of the neck revealed a heterogenous collection in the region of the left thyroid concerning for suppurative thyroiditis and adenitis. He was admitted to the hospital and initiated on intravenous antibiotics. Given lack of significant improvement in pain, he was taken to the operating room for drainage on hospital day 4 with remarkable clinical improvement in pain. He was discharged on oral antibiotics. Lab work obtained on postoperative day 15 showed resolution of hyperthyroidism and decreasing inflammatory markers. Subsequent imaging following resolution of the acute illness did not reveal any anatomic abnormality that may have predisposed him to developing acute suppurative thyroiditis. Thyrotoxicosis as a complication of acute suppurative thyroiditis is a rare occurrence, and is thought to be due to the release of preformed thyroid hormone from damaged thyroid follicles. The thyrotoxic state is often transient and resolves with appropriate management of acute suppurative thyroiditis. This complication is important to recognize, as failure to appropriately diagnose and treat acute suppurative thyroiditis can lead to poor outcomes, such as airway compromise and death.

Alternating exosomes and their mimetics as an emergent strategy for targeted cancer therapy.

Exosomes, a subtype of the class of extracellular vesicles and nano-sized particles, have a specific membrane structure that makes them an alternative proposition to combat with cancer through slight modification. As constituents of all most all the primary body fluids, exosomes establish the status of intercellular communication. Exosomes have specific proteins/mRNAs and miRNAs which serve as biomarkers, imparting a prognostic tool in clinical and disease pathologies. They have efficient intrinsic targeting potential and efficacy. Engineered exosomes are employed to deliver therapeutic cargos to the targeted tumor cell or the recipient. Exosomes from cancer cells bring about changes in fibroblast via TGFß/Smad pathway, augmenting the tumor growth. These extracellular vesicles are multidimensional in terms of the functions that they perform. We herein discuss the uptake and biogenesis of exosomes, their role in various facets of cancer studies, cell-to-cell communication and modification for therapeutic and diagnostic use.

Dysglycemia screening with oral glucose tolerance test in adolescents with polycystic ovary syndrome and relationship with obesity.

BACKGROUND: Adolescents with polycystic ovary syndrome (PCOS) are at increased risk of impaired glucose tolerance (IGT) and type 2 diabetes mellitus. The aim of this study is to evaluate dysglycemia and biochemical differences based on BMI status and assess the prognostic ability of elevated hemoglobin A1c (HbA1c) in predicting an abnormal 2 hour oral glucose tolerance test (OGTT). METHODS: Retrospective cohort of female patients aged 11-18 years who underwent 75-g OGTT and were evaluated for PCOS at an urban tertiary care hospital between January 2002 to December 2017. RESULTS: In 106 adolescents with PCOS who had OGTT results available, IGT was markedly pronounced in the ≥95th percentile BMI group (17 out of 72; 23.6%) compared with <95th percentile BMI group (4 out of 34; 11.7%). One patient with obesity met the criteria for type 2 diabetes. Patients with obesity had significantly higher homeostasis model assessment (HOMA-IR) and lower whole body insulin sensitivity index (WBISI) (p < 0.001) compared to patients without obesity. Free testosterone levels were also higher in patients with obesity (p< 0.03) and were significantly associated with HOMA-IR when controlling for body mass index (BMI). HbA1c did not demonstrate a strong ability to predict abnormal OGTT on receiver operating characteristic (ROC) curve analysis [Area under the curve (AUC) = 0.572, 95% CI: 0.428, 0.939]). CONCLUSIONS: In a study to assess glucose abnormalities in adolescents with PCOS, IGT was found to be markedly increased in patients with obesity, with abnormal glucose metabolism identified in over one-fifth of the patients. HbA1c alone may be a poor test to assess IGT and we recommend that adolescents diagnosed with PCOS and obesity undergo formal oral glucose tolerance testing.

Effect of Mo and space holder content on microstructure, mechanical and corrosion properties in Ti6AlxMo based alloy for bone implant.

The porous alloys of Ti6Al(3-15)Mo were developed to replace the fractured bone; the alloy consists of 6 wt% of Al which was taken as α the phase stabilizer and (3-15) wt% Mo with an increment of 3 wt% was taken as ß phase stabilizer. The porosity of these fabricated porous alloys was controlled by adjusting volume% of the ammonium bicarbonate (SH). These porous samples were characterized in terms of their microstructure, compressive strength, elastic modulus, energy absorption, ion release and corrosion rate in simulated body fluid (SBF) and these properties are compared with the existing alloys and human bone. The fabricated porous samples were characterized, and the obtained results were analysed as a function of Mo concentration and the volume% of space holder content. Three phases were found in the microstructure: α, α2 and ß phase of titanium. Increase in Mo content from 3 to 15 wt% has increased the volume fraction of ß phase from 7.45% to 64.09% and Kirkendall pores also are observed to be increased with increase in Mo content. α and α2 phase was differentiated by the TEM and phase map of EBSD images. The plateau stress, elastic modulus and energy absorption are observed to be decreased, and the densification strain is observed to be increased with the addition of Mo and SH content. The released ion concentration and corrosion rate are far below the tolerance limits of Ti, Al and Mo elements, in the static immersion test conducted in SBF solution.

Emerging trends from COVID-19 research registered in the Clinical Trials Registry - India.

Since the beginning of the year, the deadly coronavirus pandemic, better known as coronavirus disease 2019 (COVID-19), brought the entire world to an unprecedented halt. In tandem with the global scenario, researchers in India are actively engaged in the conduct of clinical research to counter the pandemic. This review attempts to provide a comprehensive overview of the COVID-19 research in India including design aspects, through the clinical trials registered in the Clinical Trials Registry - India (CTRI) till June 5, 2020. One hundred and twenty two registered trials on COVID-19 were extracted from the CTRI database. These trials were categorized into modern medicine (n=42), traditional medicine (n=67) and miscellaneous (n=13). Of the 42 modern medicine trials, 28 were on repurposed drugs, used singly (n=24) or in combination (n=4). Of these 28 trials, 23 were to evaluate their therapeutic efficacy in different severities of the disease. There were nine registered trials on cell- and plasma-based therapies, two phytopharmaceutical trials and three vaccine trials. The traditional medicine trials category majorly comprised Ayurveda (n=45), followed by homeopathy (n=14) and others (n=8) from Yoga, Siddha and Unani. Among the traditional medicine category, 31 trials were prophylactic and 36 were therapeutic, mostly conducted on asymptomatic or mild-to-moderate COVID-19 patients. This review would showcase the research being conducted on COVID-19 in the country and highlight the research gaps to steer further studies.

Clinical Trials Registry - India: A decadal perspective.

OBJECTIVE: To present a descriptive analysis of the clinical studies registered in the Clinical Trials Registry - India (CTRI) and deduce its impact. METHODS: We searched the CTRI databease for all registered clinical studies from July 20, 2007 to May 31, 2018. Extracted data were analyzed in three time periods i.e., Periods 1, 2, and 3 based on the major activities and milestones of the CTRI. In addition, comparative registrations of the various Primary Registries of the WHO were compiled and registration policy of Indian journals with regard to trial registration assessed. RESULTS: A total of 20,160 clinical studies were submitted to the CTRI in the designated study period. Of the registered 14,341 clinical studies, 10,485 (76.3%) were interventional trials which were either regulatory (n = 2004), academic non-regulatory (n = 3855), or those conducted as part of PG thesis (n = 4626) trials. Regulatory trials registration numbers varied according to the Indian regulatory scenario. PG thesis trial registrations showed a steep rise, although unlike regulatory trials, these were mostly retrospective registrations. CTRI registration numbers were comparable to that in other Primary Registries. Instructions to authors of 48% indexed Indian journals made a mention of trial registration. CONCLUSIONS: The CTRI has a strong global presence and has enhanced the transparency of regulatory trials as well as academic research particularly thesis-based work. The latter is expected to help improve standard of research and prevent repetitive research. Additional support from Indian journal editors by strict implementation of prospective registration is crucial for increasing compliance by researchers.

Van Wyk-Grumbach syndrome in a female pediatric patient with trisomy 21: a case report.

BACKGROUND: Children with hypothyroidism typically present with delayed growth and development, but on rare occasions can present with signs of precocious puberty. This presentation is called Van Wyk-Grumbach syndrome. Van Wyk-Grumbach syndrome has seldom been described in patients with trisomy 21. CASE PRESENTATION: We present the case of a 4-year-old girl with trisomy 21, who recently moved to the United States from Guyana, and presented to the emergency room with recurrent vaginal bleeding. She was eventually diagnosed with hypothyroidism and Van Wyk-Grumbach syndrome. She was noted to have Tanner I breasts and pubic hair. A pelvic ultrasound was performed, which showed a simple cyst in the right adnexa. Subsequent laboratory evaluation revealed a thyroid stimulating hormone (TSH) of > 150 mIU/ml along with low free thyroxine of 0.3 ng/dl, suggesting longstanding untreated hypothyroidism. Estradiol and alpha-fetoprotein (AFP) levels were elevated. Bone age was delayed. The patient was diagnosed with Van Wyk-Grumbach syndrome and was started on levothyroxine therapy with subsequent resolution of vaginal bleeding. Estradiol and AFP both normalized after initiating levothyroxine therapy. CONCLUSION: This case emphasizes the importance of recognizing the presence of precocious puberty, delayed bone age and ovarian cyst as a manifestation of primary hypothyroidism. In addition, it highlights the need for thyroid function screening in patients with Trisomy 21. Tumor markers may be elevated in Van Wyk-Grumbach syndrome with subsequent normalization after treatment.

Letter on: "An analysis of deficiencies in the data of interventional drug trials registered with Clinical Trials Registry - India".

An article published in this journal analyses the deficiencies in the data of interventional drug trials registered with Clinical Trials Registry - India. We wish to rebut some of the inferences and highlight the pitfalls of a purely automated analysis of registry data as posited by the authors.

Racial Differences in Performance-Based Function and Potential Explanatory Factors Among Individuals With Knee Osteoarthritis.

OBJECTIVE: In individuals with knee osteoarthritis (OA), self-reported physical function is poorer in African Americans than in whites, but whether this difference holds true for objective assessments is unclear. The purpose of this study was to examine racial differences in performance-based physical function as well as potential underlying factors contributing to these racial differences. METHODS: Participants with knee OA from a randomized controlled trial completed the 2-minute step test (2MST), timed-up-and-go (TUG), and 30-second chair stand (30s-CST) at baseline. Race differences in performance-based function were assessed by logistic regression. Separate models were adjusted for sets of demographic, socioeconomic, psychological health, and physical health variables. RESULTS: In individuals with knee OA (n = 322; 72% women, 22% African American, mean ± SD age 66 ± 11 years, mean ± SD body mass index 31 ± 8 kg/m2 ), African Americans (versus whites) had greater unadjusted odds of poorer function (30s-CST odds ratio [OR] 2.79 [95% confidence interval (95% CI) 1.65-4.72], 2MST OR 2.37 [95% CI 1.40-4.03], and TUG OR 3.71 [95% CI 2.16-6.36]). Relationships were maintained when adjusted for demographic and psychological health covariates, but they were either partially attenuated or nonsignificant when adjusted for physical health and socioeconomic covariates. CONCLUSION: African American adults with knee OA had poorer unadjusted performance-based function than whites. Physical health and socioeconomic characteristics diminished these differences, emphasizing the fact that these factors may be important to consider in mitigating racial disparities in function.

Overview of Ayurveda trials registered with Clinical Trial Registry-India: Need for customized data set items.

Background: Lack of research data is one of the major challenges identified in traditional medicine (TM). Further, there is an urgent need to strengthen and streamline clinical research processes as well as develop research databases in TM. The Clinical Trials Registry-India (CTRI), a free, online primary register of the WHO's International Clinical Trials Registry Platform, undertakes registration of all clinical trials being conducted in India, including TM trials. However, as the CTRI data set items are primarily designed to capture information of interventional trials of the conventional system of medicine, key fields relevant to the TM system are not adequately captured in the CTRI. Aims and Objectives: The current study was conceptualized with the objective to review the type and quality of trials registered in the CTRI as well as identify the specific data set items in CTRI which may be customized as per Ayurveda studies. Materials and methods: The trials registered from July 1, 2018, to March 31, 2020, were analyzed to decipher the kind of research being undertaken in the field of Ayurveda. These trials were manually reviewed independently by two Ayurveda reviewers to gain insights into the discrepancies. Along with these analysis, brainstorming sessions with Ayurveda experts were also held. Results: The fields which were identified and need tweaking and customization were the fields "health condition" and "intervention/comparator agent." Conclusions: These modifications in the CTRI would enable the capture of more effective Ayurveda-specific information which would in turn help to standardize and streamline research practices as well as raise the standard of research.

An overview of primary registries of WHO's international clinical trial registry platform.

INTRODUCTION: WHO's International Clinical Trials Registry Platform (ICTRP) has 17 primary registries that collect the information on the minimum set of items of trial information that appear in the register and these registries are also endorsed by the International Committee of Medical Journal Editors. OBJECTIVE: The objective of this study is to describe the profile of all the primary registries including Clinical Trial Registry­India (CTRI), through features such as magnitude, domain of registration, flagging, audit trail, language, mandatory requirements, and result disclosure. METHODOLOGY: The profiling of all registries was based on countries and zones, year of establishment, registrant, flagging, conflict of interest, language, documents, result disclosure, type of study, mode of registration, mandate of registration, quality check method, individual patient data statement and translation of content facility. The mode of search used was online which included advanced search, basic search and also from the audio/video manual on their website. RESULTS: There are 17 primary registries of ICTRP, the first one International Standard Randomised Controlled Trial Number (ISRCTN) of England being initiated in year 2000 and the most recent being Lebanese registry, in September 2019. The trials registered with these registries range from 301 in Cuba to 53972 in European union's EU Clinical Trials Register. The primary registries in WHO registry network are diverse in functionalities and practices. The characteristics of online registers vary in content and features and to achieve coordinated level of data quality, across all the different registries and to keep a balance in standards of the data collected and validation of that data, the registries are adhering to the minimum data set items laid down by ICTRP. CONCLUSION: The very process of registering the clinical studies helps in promoting the research methods and also raising the standards of research, especially among young researchers. It also helps in reducing the duplicity of research.

Clinical Trials Registry - India: An overview and new developments.

The Clinical Trials Registry - India (CTRI), launched over 10 years ago, is a free, searchable online platform for registration of clinical trials being conducted in India and as well as countries which do not have a Primary Registry of their own. The objective of the present article is to appraise the current status and the new developments of CTRI, which registers all types of clinical studies, including postgraduate theses. The CTRI which was until now allowing both prospective and retrospective registration is moving towards only prospective trial registration. From April 1, 2018, only those trials where the first patient enrollment has not yet commenced will be registered. Further, the CTRI is in the process of implementing structured summary results disclosure of all interventional clinical trials in the near future.

Increased GVHD-related mortality with broad-spectrum antibiotic use after allogeneic hematopoietic stem cell transplantation in human patients and mice.

Intestinal bacteria may modulate the risk of infection and graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Allo-HSCT recipients often develop neutropenic fever, which is treated with antibiotics that may target anaerobic bacteria in the gut. We retrospectively examined 857 allo-HSCT recipients and found that treatment of neutropenic fever with imipenem-cilastatin and piperacillin-tazobactam antibiotics was associated with increased GVHD-related mortality at 5 years (21.5% for imipenem-cilastatin-treated patients versus 13.1% for untreated patients, P = 0.025; 19.8% for piperacillin-tazobactam-treated patients versus 11.9% for untreated patients, P = 0.007). However, two other antibiotics also used to treat neutropenic fever, aztreonam and cefepime, were not associated with GVHD-related mortality (P = 0.78 and P = 0.98, respectively). Analysis of stool specimens from allo-HSCT recipients showed that piperacillin-tazobactam administration was associated with perturbation of gut microbial composition. Studies in mice demonstrated aggravated GVHD mortality with imipenem-cilastatin or piperacillin-tazobactam compared to aztreonam (P < 0.01 and P < 0.05, respectively). We found pathological evidence for increased GVHD in the colon of imipenem-cilastatin-treated mice (P < 0.05), but no difference in the concentration of short-chain fatty acids or numbers of regulatory T cells. Notably, imipenem-cilastatin treatment of mice with GVHD led to loss of the protective mucus lining of the colon (P < 0.01) and the compromising of intestinal barrier function (P < 0.05). Sequencing of mouse stool specimens showed an increase in Akkermansia muciniphila (P < 0.001), a commensal bacterium with mucus-degrading capabilities, raising the possibility that mucus degradation may contribute to murine GVHD. We demonstrate an underappreciated risk for the treatment of allo-HSCT recipients with antibiotics that may exacerbate GVHD in the colon.

Exploring Indian women's reproductive decision-making regarding prenatal testing.

Pregnant women in large cities and small towns of India are increasingly undergoing prenatal testing (PNT) on the advice of medical practitioners to ensure foetal health and to prevent the birth of disabled children. In the last two decades, several studies have been conducted in India to determine the extent of proliferation of PNT for sex selection, the profile of women/couples who avail themselves of it and their attitudes towards it, but hardly any research exists which studies women's use of PNT for genetic purposes. Drawing on empirical research, this paper aims to identify factors and actors that influence women's decision-making regarding testing and whether to continue a pregnancy after PNT and how informed their choice is. The research shows that once placed in the role of autonomous and responsible decision-makers, women are making very pragmatic decisions, although the information they possess is highly inadequate and incomplete and their life circumstances too constraining.