Laparoscopic Sleeve Gastrectomy Improves Reproductive Hormone Levels in Morbidly Obese Males -A Series of 28 Cases

Rezumat Gastrectomia longitudinalã laparoscopicã îmbunãtãåeaete nivelul hormonilor reproductivi la bãrbaåii cu obezitate morbidã -o serie de 28 cazuri Introducere: Bãrbaåii obezi prezintã frecvent reduceri ale hormonilor androgeni ce pot fi modificate dupã scãderea ponderalã obåinutã prin chirurgie bariatricã. Gastrectomia longitudinalã laparoscopicã (GLL) a fost folositã frecvent în ultimul deceniu pentru tratarea obezitãåii severe. Scopul studiului a fost evaluarea modificãrilor hormonilor reproductivi dupã GLL

Early Improvement in Glycemic Metabolism after Laparoscopic Sleeve Gastrectomy in Obese Patients -A Prospective Study

Rezumat Ameliorarea rapidã a metabolismului glucidic dupã gastrectomia longitudinalã laparoscopicã la pacienåii cu obezitate -studiu prospectiv Introducere: Conform Organizaåiei Mondiale a Sãnãtãåii, existau în 2014 peste 600 de milioane de adulåi cu obezitate (mai mult decât dublu faåã de anul 1980) care prezintã un risc crescut de dezvoltare a sindromului metabolic, deci inclusiv pentru diabetul zaharat de tip 2. Datoritã controlului slab glicemic în urma tratamentului conservator al DZ tip 2, chirurgia metabolicã a fost capabilã sã câaetige un rol important în managementul pacientului cu DZ tip 2 aei obezitate, cu remisii sau îmbunãtãåiri semnificative raportate în literatura de specialitate. Obiectiv: studierea efectelor gastrectomiei longitudinale laparoscopice (LSG) asupra metabolismului glucidic la pacienåii cu obezitate, cu sau fãrã DZ tip 2. Metodã: 60 de pacienåi consecutivi, operaåi în spitalul Ponderas pentru obezitate prin gastrectomie longitudinalã laparoscopicã, au fost incluaei într-un studiu prospectiv, în perioada FebruarieMartie 2013. IMC-ul (indicele de masã corporalã), circumferinåã abdominalã aei parametrii glicemici au fost studiaåi pre-operator, la 10 zile aei 6 luni postoperator. Rezultate: controlul glicemic a fost semnificant îmbunãtãåit începând cu ziua 10 postoperatorie. Imbunãtãåiri semnificative statistic au fost notate la 6 luni postoperator în valorile IMCului (p<0.0001), circumferinåa abdominalã (p<0.0001), glicemie (p<0.0001), insulinemie (p<0.0001), peptid C (p<0.0001) aei HOMA. Concluzii: o îmbunãtãåire rapidã a metabolismului glucidic, atât la pacienåii cu obezitate aei DZ tip 2 cât aei la cei fãrã DZ tip 2, se regãseaete înaintea scãderii ponderale semnificative (10 zile postoperator). La 6 luni postoperator, când se asociazã aei o scãdere ponderalã semnificativã, atât pacienåii diabetici cât aei cei nediabetici prezintã o îmbunãtãåire suplimentarã a metabolismului glicemic, care poate susåine ideea ca gastrectomia longitudinalã laparoscopicã este o metodã eficientã pentru tratamentul pacienåilor cu obezitate aei sindrom metabolic. Aceste modificãri benefice pot explica atât remisia DZ tip 2 dar aei prevenåia acestuia la pacienåii cu obezitate supuaei tratamentului chirurgical metabolic. Cuvinte cheie: obezitate, metabolism glucidic, gastrectomie longitudinalã laparoscopicã, remisia aei prevenåia diabetului zaharat tip 2 Abstract Background: according to W.H.O. in 2014 more than 600 million adults were obese, (more than doubled since 1980), and face a major risk for the onset of metabolic syndrome, including T2DM. Due to the poor control of glycemic imbalance for the conservative treatment of T2DM, the metabolic surgery was able to gain an important role in modern management of T2DM, with significant reported improvements or remissions for these patients. Objective: to study the effects of laparoscopic sleeve gastrec- BMI, waist circumference and glycemic parameters were studied at the moment of entering the study, 10 days after surgery and at 6 months follow up. Results: the glycemic control was significantly improved starting with postoperative day 10. Statistically significant improvements were noticed after six months postoperatively in BMI values (p<0,0001), waist circumference (p<0,0001), glycemic levels (p<0,0001), insulin (p<0,0001), C-peptide (p<0,0001) and HOMA. Conclusions: a rapid induced improvement of glucose metabolism in both diabetic and non-diabetic patients occurs before a significant weight loss (POD 10). At 6 months, when associated with an important weight loss, both diabetic and non-diabetic patients present a furthermore improvement in glycemic metabolism, that enables us to consider that sleeve gastrectomy is an efficient method for a sustained improvement in the metabolic status of patients with obesity. These beneficial changes that can explain the remission of T2DM can also explain the prevention of T2DM after metabolic surgery

De novo variants in the RNU4-2 snRNA cause a frequent neurodevelopmental syndrome

Around 60% of individuals with neurodevelopmental disorders (NDD) remain undiagnosed after comprehensive genetic testing, primarily of protein-coding genes1. Large genome-sequenced cohorts are improving our ability to discover new diagnoses in the non-coding genome. Here we identify the non-coding RNA RNU4-2 as a syndromic NDD gene. RNU4-2 encodes the U4 small nuclear RNA (snRNA), which is a critical component of the U4/U6.U5 tri-snRNP complex of the major spliceosome2. We identify an 18 base pair region of RNU4-2 mapping to two structural elements in the U4/U6 snRNA duplex (the T-loop and stem III) that is severely depleted of variation in the general population, but in which we identify heterozygous variants in 115 individuals with NDD. Most individuals (77.4%) have the same highly recurrent single base insertion (n.64_65insT). In 54 individuals in whom it could be determined, the de novo variants were all on the maternal allele. We demonstrate that RNU4-2 is highly expressed in the developing human brain, in contrast to RNU4-1 and other U4 homologues. Using RNA sequencing, we show how 5′ splice-site use is systematically disrupted in individuals with RNU4-2 variants, consistent with the known role of this region during spliceosome activation. Finally, we estimate that variants in this 18 base pair region explain 0.4% of individuals with NDD. This work underscores the importance of non-coding genes in rare disorders and will provide a diagnosis to thousands of individuals with NDD worldwide

Significant benefits of AIP testing and clinical screening in familial isolated and young-onset pituitary tumors

Context Germline mutations in the aryl hydrocarbon receptor-interacting protein (AIP) gene are responsible for a subset of familial isolated pituitary adenoma (FIPA) cases and sporadic pituitary neuroendocrine tumors (PitNETs). Objective To compare prospectively diagnosed AIP mutation-positive (AIPmut) PitNET patients with clinically presenting patients and to compare the clinical characteristics of AIPmut and AIPneg PitNET patients. Design 12-year prospective, observational study. Participants & Setting We studied probands and family members of FIPA kindreds and sporadic patients with disease onset ≤18 years or macroadenomas with onset ≤30 years (n = 1477). This was a collaborative study conducted at referral centers for pituitary diseases. Interventions & Outcome AIP testing and clinical screening for pituitary disease. Comparison of characteristics of prospectively diagnosed (n = 22) vs clinically presenting AIPmut PitNET patients (n = 145), and AIPmut (n = 167) vs AIPneg PitNET patients (n = 1310). Results Prospectively diagnosed AIPmut PitNET patients had smaller lesions with less suprasellar extension or cavernous sinus invasion and required fewer treatments with fewer operations and no radiotherapy compared with clinically presenting cases; there were fewer cases with active disease and hypopituitarism at last follow-up. When comparing AIPmut and AIPneg cases, AIPmut patients were more often males, younger, more often had GH excess, pituitary apoplexy, suprasellar extension, and more patients required multimodal therapy, including radiotherapy. AIPmut patients (n = 136) with GH excess were taller than AIPneg counterparts (n = 650). Conclusions Prospectively diagnosed AIPmut patients show better outcomes than clinically presenting cases, demonstrating the benefits of genetic and clinical screening. AIP-related pituitary disease has a wide spectrum ranging from aggressively growing lesions to stable or indolent disease course

Gonadectomy in conditions affecting sex development: a registry-based cohort study

Objectives To determine trends in clinical practice for individuals with DSD requiring gonadectomy. Design Retrospective cohort study. Methods Information regarding age at gonadectomy according to diagnosis; reported sex; time of presentation to specialist centre; and location of centre from cases reported to the International DSD Registry and who were over 16 years old in January 2019. Results Data regarding gonadectomy were available in 668 (88%) individuals from 44 centres. Of these, 248 (37%) (median age (range) 24 (17, 75) years) were male and 420 (63%) (median age (range) 26 (16, 86) years) were female. Gonadectomy was reported from 36 centres in 351/668 cases (53%). Females were more likely to undergo gonadectomy (n = 311, P < 0.0001). The indication for gonadectomy was reported in 268 (76%). The most common indication was mitigation of tumour risk in 172 (64%). Variations in the practice of gonadectomy were observed; of the 351 cases from 36 centres, 17 (5%) at 9 centres had undergone gonadectomy before their first presentation to the specialist centre. Median age at gonadectomy of cases from high-income countries and low-/middle-income countries (LMIC) was 13.0 years (0.1, 68) years and 16.5 years (1, 28), respectively (P < 0.0001) with the likelihood of long-term retention of gonads being higher in LMIC countries. Conclusions The likelihood of gonadectomy depends on the underlying diagnosis, sex of rearing and the geographical setting. Clinical benchmarks, which can be studied across all forms of DSD will allow a better understanding of the variation in the practice of gonadectomy

Preoperative medical treatment in Cushing&apos;s syndrome : frequency of use and its impact on postoperative assessment : data from ERCUSYN

Background: Surgery is the definitive treatment of Cushing's syndrome (CS) but medications may also be used as a first-line therapy. Whether preoperative medical treatment (PMT) affects postoperative outcome remains controversial. Objective: (1) Evaluate how frequently PMT is given to CS patients across Europe; (2) examine differences in preoperative characteristics of patients who receive PMT and those who undergo primary surgery and (3) determine if PMT influences postoperative outcome in pituitary-dependent CS (PIT-CS). Patients and methods: 1143 CS patients entered into the ERCUSYN database from 57 centers in 26 countries. Sixty-nine percent had PIT-CS, 25% adrenal-dependent CS (ADR-CS), 5% CS from an ectopic source (ECT-CS) and 1% were classified as having CS from other causes (OTH-CS). Results: Twenty per cent of patients took PMT. ECT-CS and PIT-CS were more likely to receive PMT compared to ADR-CS (P < 0.001). Most commonly used drugs were ketoconazole (62%), metyrapone (16%) and a combination of both (12%). Median (interquartile range) duration of PMT was 109 (98) days. PIT-CS patients treated with PMT had more severe clinical features at diagnosis and poorer quality of life compared to those undergoing primary surgery (SX) (P < 0.05). Within 7 days of surgery, PIT-CS patients treated with PMT were more likely to have normal cortisol (P < 0.01) and a lower remission rate (P < 0.01). Within 6 months of surgery, no differences in morbidity or remission rates were observed between SX and PMT groups. Conclusions: PMT may confound the interpretation of immediate postoperative outcome. Follow-up is recommended to definitely evaluate surgical results