Medullary carcinoma of the thyroid - an unusual case of hyalinizing trabecular adenoma - like variant (encapsulated)

Medullary thyroid carcinoma is a neoplasm occurring in sporadic and familial patterns. A rare variant of medullary thyroid carcinoma shows microscopic features similar to hyalinizing trabecular adenoma of thyroid. Detection of this variant requires a high index of suspicion and immunohistochemical confirmation by calcitonin positivity. We present a 36 years old female patient with a thyroid nodule, which, on microscopy, displayed an encapsulated tumor with elongated cells arranged in trabecular pattern separated by hyalinized fibrous septae simulating a hyalinizing trabecular adenoma. Also present were spindle cells arranged in an organoid fashion. Most of the cells showed salt and pepper chromatin pattern. The lesion was negative for amyloid but showed diffuse calcitonin positivity indicative of a tumor of C-cell origin i.e. medullary carcinoma of thyroid – hyalinizing trabecular variant

Maximum Likelihood Estimation of Parameters in a Mixture Model

The estimation of parameters of the log normal distribution based on complete and censored samples are considered in the literature. In this article, the problem of estimating the parameters of log normal mixture model is considered. The Expectation Maximization algorithm is used to obtain maximum likelihood estimators for the parameters, as the likelihood equation does not yield closed form expression. The standard errors of the estimates are obtained. The methodology developed here is then illustrated through simulation studies. The confidence interval based on large-sample theory is obtained

Domain specific architecture development for enterprise systems based on common object request broker architecture (CORBA)

Large business organizations with enterprise wide systems have followed an ad hoc incremental growth pattern. They are either monolithic, that are difficult to replace and maintain, or are components with little or no interoperability between them. Such systems suffer from lack of uniformity and definition in their information technology infrastructure. To migrate from this state, to systems that are extensible, interoperable and non-redundant in functionality it is very important to focus on the architecture. We use the healthcare enterprise system as a case study for the purpose of this thesis. It is indeed difficult, if not impossible to construct the overall architecture of the system without identifying the individual components of the system. Hence we follow an incremental methodology in identifying and developing each component. One such component is Order management, which is an essential component of a healthcare information system that offers enterprise wide functionality

Outcome of laparoscopic surgeries during pregnancy for non-obstetric emergencies

Background: This study was conducted to evaluate the surgical and obstetric outcome, safety and feasibility of various laparoscopic surgeries for non-obstetric indications in pregnancy.Methods: We did a retrospective analysis of 18 pregnant patients who underwent laparoscopic surgeries. Study period was from October 2013 till September 2015 conducted in Radhakrishna multispeciality hospital /IVF center Bangalore. Patients operated are 6 cases cholicystectomy, 6 cases appendicectomy, 5 adnexal mass removals, one salpingectomy for heterotopic pregnancy resulted from ART. All patients were between 11 to 32 weeks of gestation, with mean gestational age 21±6.5 weeks at the time of surgery and mean duration of surgery was 46±16.3 minutes.Results: All eighteen pregnant patients had uneventful hospital courses after laparoscopic procedures. Mean duration of hospital stay after surgery was 43±8.5 hours. One pregnancy was terminated at 11 weeks for suspected ovarian malignancy and 16 delivered full-term babies without complications, one patient delivered preterm at 35 weeks with NICU admission. The mean birth weight at the time of delivery was 2.8±550 gms. There was no maternal morbidity or mortality, or any identifiable neonatal birth defect. No conversion to laparotomy required in any case.Conclusions: Laparoscopic surgeries can be done in any trimester of pregnancy, but more safe and feasible during the second and early third trimester of pregnancy. Laparoscopic surgeries are as safe as laparotomy in the hands of experienced laparoscopic surgeon with no deleterious effects on either mother or fetus

Efficacy and safety of ferric carboxymaltose in Indian pregnant women with iron deficiency anemia

Background: Iron deficiency anemia (IDA) is a significant problem worldwide particularly in women. The aim of the study was to evaluate the effectiveness of intravenous ferric carboxymaltose (FCM) in in Indian pregnant women with anemia.Method: This was a single centre, prospective, observational, open label, clinical study at real life scenario with 4 weeks follow up. Fifty pregnant women with IDA and visiting to the Radhakrishna multispecialty hospital, Bangalore, for antenatal care were enrolled for the study. IV FCM was given as per the standard protocol. Change in the laboratory parameters such as hemoglobin, mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), packed cell volume (PCV) level at baseline and after 4 weeks of completion of parenteral iron therapy was recorded and fatigue score was assessed. The pregnant women were monitored for the adverse events. Results: All pregnant women received a single IV infusion of FCM 1000 mg. A significant increase in the hemoglobin of 2.37±0.51 g/dl (p<0.001) was noted at 4 weeks, MCV rise of 19.89±21.94 (p<0.001) was noted at 4 weeks, MCHC rise was of 2.56±5.65 and PCV rise was of 4.45±2.67 (p<0.011) at over 4 weeks. Significant improvement in fatigue score was observed at 4 weeks after single FCM infusion. No adverse effects were observed in any pregnant woman throughout the duration of the study.Conclusions: This real-life observational study highlights IV FCM is effective in management of IDA in pregnant women and well tolerated. Trial registration number: CTRI/2021/02/030874

Efficacy of growth hormone in improving the pregnancy rate in poor responders in ART

Background: Poor responders impose a great challenge to ART clinicians. Research to improve their pregnancy rate is going on. This study was conducted to analyze the effect of growth hormone in poor responders in ART.Methods: This study was done from January 2015 to December 2015. It was a retrospective, single centre, cohort study in which 36 poor responders were selected and allotted into group A (18) with growth hormone and group B (18) without growth hormone. High dose of gonadotrophins was used for ovarian stimulation and antagonist protocol was followed in all patients. Group A received 4 IU of growth hormone along with usual treatment from day 2 till ovulation trigger with HCG injection, group B usual protocol.Results: Statistical analysis was done with independent T test, and p value <0.05 was considered significant. Higher number of mature oocytes and pregnancy rates were observed in growth hormone group. Number of MII oocytes was 5.8, on an average in group A and 3.7 in group B, the difference was statistically significant (p 0.0000001).  Clinical pregnancy rates were 27.7% in group A and 16.6% in group B, statistical significance (p 0.02).Conclusions: Addition of growth hormone shows increase in number of oocytes retrieved and pregnancy rates in poor responders in ART patients

Effect of myo-inositol and di-chiro inositol plus vitamin D supplementation during pregnancy on prevention of gestational diabetes: a multi-centric, prospective, randomized, double-blind clinical trial

Background: Aim of study was to evaluate the impact of myoinositol and D-chiro inositol plus vitamin D supplementation on the prevention of gestational diabetes mellitus (GDM) in pregnant women. Methods: In the multi-centric, prospective, randomised, double-blind clinical trial, either vitamin D alone (group I) or myoinositol and D-chiro inositol plus Vitamin D (group II) were administered to pregnant women from 12 weeks of gestation. The administration was continued until delivery to primigravids who were normoglycemic at 12 weeks of gestation and consented. From October 2018 to December 2019. A total of 1250 women were enrolled, and randomly allocated to either of the groups: 630 women in Group I and 620 in Group II. The allocation was blinded. The primary outcome was the rate of GDM as assessed by oral glucose tolerance test (OGTT) recommended by diabetes in pregnancy Study Group India (DIPSI), International Federation of Gynecology and Obstetrics (FIGO) and the Government of India, at first antenatal visit followed by at weeks 24 to 28 in both the groups. Results: The rate of GDM was found more in group I as compared to group II treated with myoinositol and D-chiro Inositol plus vitamin D, but the difference was not statistically significant (5.08% in group I and 3.22% in group II). Conclusions: In conclusion, an improved trend has been noticed in the reduction of the rate of GDM with myoinositol and D-chiro inositol plus vitamin D as compared to vitamin D alone. Myoinositol and D-chiro inositol plus vitamin D supplementation may be a good option for pregnant women to prevent the GDM occurrence especially in women having positive risk factors for GDM.

CERT1 mutations perturb human development by disrupting sphingolipid homeostasis

Neural differentiation, synaptic transmission, and action potential propagation depend on membrane sphingolipids, whose metabolism is tightly regulated. Mutations in the ceramide transporter CERT (CERT1), which is involved in sphingolipid biosynthesis, are associated with intellectual disability, but the pathogenic mechanism remains obscure. Here, we characterize 31 individuals with de novo missense variants in CERT1. Several variants fall into a previously uncharacterized dimeric helical domain that enables CERT homeostatic inactivation, without which sphingolipid production goes unchecked. The clinical severity reflects the degree to which CERT autoregulation is disrupted, and inhibiting CERT pharmacologically corrects morphological and motor abnormalities in a Drosophila model of the disease, which we call ceramide transporter (CerTra) syndrome. These findings uncover a central role for CERT autoregulation in the control of sphingolipid biosynthetic flux, provide unexpected insight into the structural organization of CERT, and suggest a possible therapeutic approach for patients with CerTra syndrome

CERT1 mutations perturb human development by disrupting sphingolipid homeostasis

Neural differentiation, synaptic transmission, and action potential propagation depend on membrane sphingolipids, whose metabolism is tightly regulated. Mutations in the ceramide transporter CERT (CERT1), which is involved in sphingolipid biosynthesis, are associated with intellectual disability, but the pathogenic mechanism remains obscure. Here, we characterize 31 individuals with de novo missense variants in CERT1. Several variants fall into a previously uncharacterized dimeric helical domain that enables CERT homeostatic inactivation, without which sphingolipid production goes unchecked. The clinical severity reflects the degree to which CERT autoregulation is disrupted, and inhibiting CERT pharmacologically corrects morphological and motor abnormalities in a Drosophila model of the disease, which we call ceramide transporter (CerTra) syndrome. These findings uncover a central role for CERT autoregulation in the control of sphingolipid biosynthetic flux, provide unexpected insight into the structural organization of CERT, and suggest a possible therapeutic approach for patients with CerTra syndrome.This work was supported by the National Institute of Neurological Disorders and Stroke (NINDS), NIH (R01NS109858, to VAG); the Paul A. Marks Scholar Program at the Columbia University Vagelos College of Physicians and Surgeons (to VAG); a TIGER grant from the TAUB Institute at the Columbia Vagelos College of Physicians and Scientists (to VAG); the Swiss National Science Foundation (SNF 31003A-179371, to TH); the European Joint Program on Rare Diseases (EJP RD+SNF 32ER30-187505, to TH); the Swiss Cancer League (KFS-4999-02-2020, to GD); the EPFL institutional fund (to GD); the Kristian Gerhard Jebsen Foundation (to GD); the Swiss National Science Foundation (SNSF) (310030_184926, to GD); the Swiss Foundation for Research on Muscle Disease (FSRMM, to MAL); the Natural Science and Engineering Research Council of Canada (Discovery Grant 2020-04241, to JEB); the Italian Ministry of Health Young Investigator Grant (GR-2011-02347754, to EL); the Fondazione Istituto di Ricerca Pediatrica – Città della Speranza (18-04, to EL); the Wroclaw Medical University (SUB.E160.21.004, to RS); the National Science Centre, Poland (2017/27/B/NZ5/0222, to RS); Telethon Undiagnosed Diseases Program (TUDP) (GSP15001); the Temple Street Foundation/Children’s Health Foundation Ireland (RPAC 19-02, to IK); the Deutsche Forschungsgemeinschaft (DFG) (PO2366/2–1, to BP); the Instituto de Salud Carlos III, Spain (to ELM, EBS, and BMD); the National Natural Science Foundation of China (81871079 and 81730036, to HG and KX); and the National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK), NIH (R01 DK115574, to SSC).The DEFIDIAG study is funded by grants from the French Ministry of Health in the framewok of the national French initiative for genomic medicine. The funders were not involved in the study design, data acquisition, analysis, or writing of the manuscript. Funding for the DECIPHER project was provided by Wellcome. The DDD study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between Wellcome and the Department of Health, and the Wellcome Sanger Institute (grant number WT098051). The views expressed in this publication are those of the author(s) and not necessarily those of Wellcome or the Department of Health. The study has UK Research Ethics Committee approval (10/H0305/83, granted by the Cambridge South REC, and GEN/284/12, granted by the Republic of Ireland REC). The research team acknowledges the support of the National Institute for Health Research, through the Comprehensive Clinical Research Network.S

The impact of surgical delay on resectability of colorectal cancer: An international prospective cohort study

AIM: The SARS-CoV-2 pandemic has provided a unique opportunity to explore the impact of surgical delays on cancer resectability. This study aimed to compare resectability for colorectal cancer patients undergoing delayed versus non-delayed surgery. METHODS: This was an international prospective cohort study of consecutive colorectal cancer patients with a decision for curative surgery (January-April 2020). Surgical delay was defined as an operation taking place more than 4 weeks after treatment decision, in a patient who did not receive neoadjuvant therapy. A subgroup analysis explored the effects of delay in elective patients only. The impact of longer delays was explored in a sensitivity analysis. The primary outcome was complete resection, defined as curative resection with an R0 margin. RESULTS: Overall, 5453 patients from 304 hospitals in 47 countries were included, of whom 6.6% (358/5453) did not receive their planned operation. Of the 4304 operated patients without neoadjuvant therapy, 40.5% (1744/4304) were delayed beyond 4 weeks. Delayed patients were more likely to be older, men, more comorbid, have higher body mass index and have rectal cancer and early stage disease. Delayed patients had higher unadjusted rates of complete resection (93.7% vs. 91.9%, P = 0.032) and lower rates of emergency surgery (4.5% vs. 22.5%, P < 0.001). After adjustment, delay was not associated with a lower rate of complete resection (OR 1.18, 95% CI 0.90-1.55, P = 0.224), which was consistent in elective patients only (OR 0.94, 95% CI 0.69-1.27, P = 0.672). Longer delays were not associated with poorer outcomes. CONCLUSION: One in 15 colorectal cancer patients did not receive their planned operation during the first wave of COVID-19. Surgical delay did not appear to compromise resectability, raising the hypothesis that any reduction in long-term survival attributable to delays is likely to be due to micro-metastatic disease