Targeted next generation sequencing approach identifies nineteen new candidate genes in normosmic hypogonadotropic hypogonadism and Kallmann Syndrome, Molecular and Cellular Endocrinology (2016), doi: 10.1016/ j.mce.2016 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
AbstractThe genetic basis is unknown for ~60% of normosmic hypogonadotropic hypogonadism (nHH)/Kallmann syndrome (KS). DNAs from (17 male and 31 female) nHH/KS patients were analyzed by targeted next generation sequencing (NGS) of 261 genes involved in hypothalamic, pituitary, and/or olfactory pathways, or suggested by chromosome rearrangements. Selected variants were subjected to Sanger DNA sequencing, the gold standard. The frequency of Sanger-confirmed variants was determined using the ExAC database. Variants were classified as likely pathogenic (frameshift, nonsense, and splice site) or predicted pathogenic (nonsynonymous missense). Two novel FGFR1 mutations were identified, as were 19 new candidate genes including:
The incidence of cholecystectomy in children has increased considerably since the early 1990s.Management of gallbladder disease in children must include an awareness of choledocholithiasis treatment strategies. Both endoscopic retrograde cholangiopancreatography (ERCP) and common bile duct exploration (open or laparoscopic) are accepted management techniques for choledocholithiasis. Laparoscopic cholecystectomy with preoperative or postoperative ERCP is at least a two-procedure process while cholecystectomy with laparoscopic common bile duct exploration (LCBDE) can provide definitive treatment in a single procedure under one anesthetic. Despite this, the trend over the last decade continues towards less LCBDE utilization in favor of ERCP. This trend has resulted in decreased familiarity with LCBDE by adult and pediatric surgeons and their trainees. Access to the necessary tools and education on the technical aspects can allow for successful single-stage treatment of choledocholithiasis by surgeons during laparoscopic cholecystectomy. This may include a pre-defined stepwise algorithm and understanding of all the equipment and resources necessary to perform a LCBDE. Ultimately, increased understanding of the equipment and procedural steps necessary for LCBDE will result in widened adoption of the technique and thus confer advantages to the patient such as decreased length of stay and fewer required anesthetics.
Laparoscopic cholecystectomy (LC) with laparoscopic common bile duct exploration (LCBDE) is gaining traction for the management of choledocholithiasis. Liver function tests (LFTs) are often used to determine the success of ductal clearance, yet the impact of differing therapeutic interventions, endoscopic retrograde cholangiopancreatography (ERCP) or LCBDE, have on postprocedure LFT is insufficiently described. We hypothesize that these interventions have different postoperative LFT profiles. The preprocedural and postprocedural total bilirubin (Tbili), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) were analyzed of 167 patients who had successful ERCPs (117) or LCBDEs (50). Endoscopic retrograde cholangiopancreatography patients demonstrated a significant decrease in all LFTs postprocedure (n = 117; P = <0.001 for all) with a continued downtrend when a second set of LFTs was obtained (n = 102; P = <0.001 for all). For successful LC+LCBDEs, there was no significant change between preoperative and 1st postoperative Tbili, AST, ALT, and ALP and the 2nd postoperative labs.
Background Biliary dyskinesia (BD) is a poorly understood functional gallbladder disorder. Diagnosis is made with abdominal pain and an intact gallbladder without signs of anatomical obstruction on imaging or pathology. Our aim was to assess whether laparoscopic cholecystectomy (LC) resolves hyperkinetic BD symptoms. Methods Records of patients ≥18 years of age, who underwent LC by four surgeons at a tertiary care center between 2012 and 2020, were retrospectively reviewed. Patients were excluded if they had a documented gallbladder ejection fraction (GBEF) <80% or had biliary stones or sludge on pathology or imaging. Demographic information, HIDA results, preoperative testing, operative details, gallbladder pathology, and symptom status at follow-up were collected from electronic medical records. Improvement in BD symptoms was assessed using McNemar’s test. Risk differences with standard errors were employed to estimate percent reduction in symptoms. Results Ninety-eight patients met inclusion criteria. Of those who presented for follow-up (n = 91), 92.3% (n = 84) reported partial or complete resolution of symptoms. Preoperative symptoms, including back pain (16.7%, 95% CI: [7.9%, 25.5%]; P < .0001), epigastric pain (31.1% [21.3%, 41.3%]; P < .0001), nausea (56.7% [45.0%, 65.8%]; P < .0001), RUQ pain (57.8% [46.1%, 66.9%]; P < .0001), and vomiting (27.8% [18.4%, 37.7%]; P < .0001) showed significant improvement after LC. Chronic cholecystitis and/or cholesterolosis were present on pathology in 79.8% of gallbladders. Discussion Our study currently represents the largest cohort of patients with hyperkinetic BD. Laparoscopic cholecystectomy appears to result in resolution of symptoms for this clinical entity.
A 25-year-old man presented with right lower quadrant abdominal wall erythema, a punctum of purulence, and localized pain at the site of a previous appendicostomy. Cross-sectional imaging revealed appendicitis at his previous appendicostomy with a fecalith near the skin. He was managed with appendectomy. The surgical approach mimicked a loop ileostomy reversal by circumferentially dissecting the tissue around the appendicostomy to the level of the fascia and then dividing the appendix at the base of the cecum through a small two-centimeter incision. Appendicitis in a previous appendicostomy is uncommon and has only been described in three previous case reports (two adults and one child) and was surgically approached through a low-midline laparotomy. Our case is unique as it is an uncommon presentation of a common disease managed with a minimally invasive approach not previously described.
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