Randomized clinical trial on closure versus non-closure of mesenteric defects during laparoscopic gastric bypass surgery.

BACKGROUND: Internal herniation is a well known and potentially life-threatening complication of laparoscopic Roux-en-Y gastric bypass (LRYGB). The aim of this study was to evaluate the benefit and harm of closing the mesenteric defects with clips during LRYGB to prevent internal herniation. METHODS: This was a single-centre, single-blinded RCT. Patients eligible for LRYGB were randomized to surgery with or without closure of mesenteric defects with clips. The primary endpoint was the incidence of (intermittent) internal herniation after LRYGB with a minimum follow-up of 24 months. Secondary outcomes were duration of surgery, number of clips used, trocars and sutures used, postoperative pain measured by a visual analogue scale (VAS), and postoperative complications. RESULTS: Between 13 August 2012 and 18 May 2017, 401 patients were randomized to closure (201) or non-closure (200) of mesenteric defects. Median follow-up for both groups was 59 months (range 8-67 and 16-67 months in non-closure and closure groups respectively). The cumulated risk of internal herniation after 2 years was 8.0 per cent in the non-closure group compared with 4.5 per cent in the closure group (hazard ratio (HR) 1.81, 95 per cent c.i. 0.80 to 4.12; P = 0.231). At 5 years, rates were 15.5 and 6.5 per cent respectively (HR 2.52, 1.32 to 4.81; P = 0.005). Closure of mesenteric defects increased operating time by a median of 4 min (95 per cent c.i. 52 to 56 min for the non-closure group and 56 to 60 min for the closure group; P = 0.002). There was no difference in postoperative blood transfusion rates and VAS scores between the groups. CONCLUSION: Routine closure of the mesenteric defects in LRYGB with clips is associated with a lower rate of internal herniation. Registration number: NCT01595230 (http://www.clinicaltrials.gov).

Maternal mood disorders and lithium exposure in utero were not associated with poor cognitive development during childhood.

AIM: This study evaluated whether maternal mood disorders (MMD), particularly bipolar disorder, and lithium treatment during pregnancy influenced the neonatal health and cognition of children born from 2006 to 2010. METHODS: Our study at Karolinska University Hospital, Stockholm, Sweden, focused on women with and without mood disorders and their children. Information on pharmacotherapy, mental health, delivery and neonatal complications was retrospectively collected from electronic patient records. Children were tested in a blinded manner at four to five years of age with the Wechsler Preschool and Primary Scale of Intelligence, 3rd edition. Maternal health, child health and social situations were evaluated. RESULTS: Of the 39 children, 20 were exposed to lithium and MMD during pregnancy, eight were exposed to MMD but not lithium and 11 were not exposed to MMD or lithium. The children's full scale intelligence quotient (IQ), performance IQ and verbal IQ results did not differ significantly between the groups. The processing speed quotient was significantly lower in children exposed to mood disorders, but there was a high level of missing data for this subtest. CONCLUSION: This small, clinical cohort showed no significant association between mothers' prenatal exposure to lithium or mood disorders and their offspring's IQ.

Increased glucose-stimulated FGF21 response to oral glucose in obese nondiabetic subjects after Roux-en-Y gastric bypass.

OBJECTIVE: The positive metabolic outcome of Roux-en-Y gastric bypass (RYGB) surgery may involve fibroblast growth factor 21 (FGF21), in both the fasting state and postprandially. We measured the fasting levels of FGF21 before and after bariatric surgery as well as the postprandial FGF21 responses after a glucose load and after a mixed meal. DESIGN: Observational intervention trial. PATIENTS AND MEASUREMENTS: Eight obese, nondiabetic patients underwent RYGB. Plasma FGF21 was measured both before and after surgery on three different days during oral glucose loads (25 g or 50 g glucose) or a mixed meal. Blood samples were taken right before the meal and at 15-min intervals until 90 min and at 150 min and 210 min relative to the start of the meal. RESULTS: Overall, fasting plasma FGF21 did not change significantly before and after surgery (262 ± 71 vs 411 ± 119 pg/ml), but for three subjects, fasting plasma FGF21 increased significantly after surgery. Furthermore, FGF21 levels increased significantly at t = 90 and t = 150 min in response to 50 g glucose, but not after a mixed meal. CONCLUSIONS: In conclusion, the observed increase in postprandial plasma FGF21 in response to glucose and the lack of FGF21 response to a mixed meal may have important implications for the physiologic role of FGF21. The increase in postprandial FGF21 in response to glucose in the early postoperative period may contribute to the metabolic improvements observed after gastric bypass.

Reoperation risk following the first operation for internal herniation in patients with laparoscopic Roux-en-Y gastric bypass.

BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) is the most commonly used surgical procedure in the treatment of morbid obesity in Denmark. Internal herniation (IH) and intermittent internal herniation (IIH) are probably the most common late complications in patients with LRYGB. The aim of this study was to investigate a possible increased risk of subsequent operations after an initial IH or IIH event. METHODS: This long-term follow-up study of patients who had surgery for an initial IH or IIH event in 2006-2011, based on the Danish National Patient Registry (NPR), was performed to 2013. During this period, mesenteric defects were not closed routinely during LRYGB. RESULTS: Data were retrieved from 12 221 patients with LRYGB from the NPR. A total of 383 patients had surgery for an initial IH or IIH event. Some 102 patients (26·6 (95 per cent c.i. 22·5 to 31·3) per cent) had a second operation. Twenty-seven (26·5 (18·9 to 35·8) per cent) of these 102 patients had a third operation, and five (19 (8 to 37) per cent) of the 27 had a fourth operation. Of the 383 patients diagnosed with an initial IH or IIH event, 72 (18·8 per cent) had a second IH/IIH event, 14 (3·7 per cent) had a third event, and three (0·8 per cent) a fourth event requiring surgery. CONCLUSION: Patients who have surgery for IH or IIH have a substantial risk of needing further operations.

Acute and long-term effects of Roux-en-Y gastric bypass on glucose metabolism in subjects with Type 2 diabetes and normal glucose tolerance.

Our aim was to study the potential mechanisms responsible for the improvement in glucose control in Type 2 diabetes (T2D) within days after Roux-en-Y gastric bypass (RYGB). Thirteen obese subjects with T2D and twelve matched subjects with normal glucose tolerance (NGT) were examined during a liquid meal before (Pre), 1 wk, 3 mo, and 1 yr after RYGB. Glucose, insulin, C-peptide, glucagon-like peptide-1 (GLP-1), glucose-dependent-insulinotropic polypeptide (GIP), and glucagon concentrations were measured. Insulin resistance (HOMA-IR), ß-cell glucose sensitivity (ß-GS), and disposition index (D(ß-GS): ß-GS × 1/HOMA-IR) were calculated. Within the first week after RYGB, fasting glucose [T2D Pre: 8.8 ± 2.3, 1 wk: 7.0 ± 1.2 (P < 0.001)], and insulin concentrations decreased significantly in both groups. At 129 min, glucose concentrations decreased in T2D [Pre: 11.4 ± 3, 1 wk: 8.2 ± 2 (P = 0.003)] but not in NGT. HOMA-IR decreased by 50% in both groups. ß-GS increased in T2D [Pre: 1.03 ± 0.49, 1 wk: 1.70 ± 1.2, (P = 0.012)] but did not change in NGT. The increase in DI(ß-GS) was 3-fold in T2D and 1.5-fold in NGT. After RYGB, glucagon secretion was increased in response to the meal. GIP secretion was unchanged, while GLP-1 secretion increased more than 10-fold in both groups. The changes induced by RYGB were sustained or further enhanced 3 mo and 1 yr after surgery. Improvement in glycemic control in T2D after RYGB occurs within days after surgery and is associated with increased insulin sensitivity and improved ß-cell function, the latter of which may be explained by dramatic increases in GLP-1 secretion.

Impaired neutralizing activity by transplacental measles antibodies in infants born to HIV-1-infected mothers.

AIM: Growing numbers of newborns are saved from HIV infection through increased access to mother-to-child transmission prevention programmes. The maternally derived humoral immunity of these children might be impaired, both in terms of quantity and in terms of quality, with consequences for the timing of immunization against measles. METHODS: A cell-ELISA technique compared the neutralizing activity on Edmonston strain measles virus of sera from 1- to 4-month-old infants. Ten serum specimens came from noninfected infants of HIV-infected mothers and another 10 from infants of healthy mothers. The sera were matched for the level of conventional ELISA measles antibodies. RESULTS: Reflecting infection of the Vero cells by non-neutralized virus, optical density values were significantly higher for the sera from the children of the HIV-infected mothers than for those of the noninfected mothers (p < 0.001). CONCLUSION: Maternally derived protection against measles may be impaired by the mother's HIV infection, relating to the quality rather than to the quantity of transplacental antibodies. Selective, early immunization with live attenuated measles vaccine should be evaluated in noninfected children of HIV-1-infected mothers.

Neonatal intestinal colonization with extended-spectrum ß-lactamase-producing Enterobacteriaceae-a 5-year follow-up study.

OBJECTIVES: To analyse Klebsiella pneumoniae (KP) isolates from an outbreak of extended-spectrum ß-lactamase (ESBL)-producing KP and Escherichia coli (EC) among infants admitted to neonatal intensive care units and to determine the duration of the intestinal colonization. METHODS: We performed a prospective cohort study of intestinal ESBL-KP/ESBL-EC colonized neonates after a 5-month outbreak in two neonatal intensive care units. Whole genome sequencing, multilocus sequence typing, core genome multilocus sequence typing, pulsed-field electrophoresis and PCR for blaCTX-M were performed on the first isolates. Stool cultures were performed every second month after discharge until 2 years after discharge and at 5 years of age. The last positive samples were analysed with pulsed-field gel electrophoresis and PCR for blaCTX-M. The intestinal relative dominance of ESBL-producing Enterobacteriaceae was determined. RESULTS: Thirteen of 17 patients colonized with ESBL-KP/ESBL-EC survived. Isolates from 16 of 17 patients were available for analysis and featured the same strain type of ESBL-KP: sequence type 101. The strain had capsule type K29 and harboured blaCTX-M-15. The virulence genes irp1, irp2, iutA, kfu and mrk were detected in all isolates. The median length of colonization was 12.5 months (range, 5-68 months). After 2 years, two of 13 patients were carriers of ESBL-KP and one of 13 of ESBL-EC. At 5 years of age, one neonate was colonized with ESBL-EC. No infant experienced an ESBL-KP/EC-infection during follow-up. CONCLUSIONS: Two years after discharge, almost one fourth of the study participants were ESBL/KP-EC carriers. ESBL-KP sequence type 101 persisted in two of 13 children for 23 to 26 months. One patient was colonized with ESBL-EC at age 5 years.

The X4 phenotype of HIV type 1 evolves from R5 in two children of mothers, carrying X4, and is not linked to transmission.

Previously, we found that emergence of the X4 viral phenotype in HIV-1-infected children was related to the presence of X4 in their mothers (C.H. Casper et al., J Infect Dis 2002; 186:914-921). Here, we investigated the origin of the X4 phenotype in the child, analyzing two mother-child pairs (Ma-Ca, Mb-Cb) where the mothers carried X4 and their children developed X4 after an initial presence of R5. We used nested polymerase chain reaction of the env V3 region to generate 203 HIV-1 clones for sequencing (Ma, n = 44; Ca, n = 73; Mb, n = 61; Cb, n = 25) from DNA of peripheral blood mononuclear cell (PBMC) lysates, altogether 167 clones, or from cDNA of plasma RNA, 36 clones. PBMC and plasma isolate sequences from each time point enabled us to assign the probable phenotype to clone sequences in a phylogenetic tree. The transmission and evolution were reconstructed using the maximum likelihood method. In mother-child pair Ma-Ca, one maternal R5 isolate clustered with the child's R5 sequences, at the earliest time when R5 was isolated in the child, confirming this as a likely source of the transmitted R5 phenotype. At age 3, an X4 population was present in the child that had evolved from the child's own R5-associated population, clearly distinct from the maternal X4 sequences. The second mother-child pair (Mb-Cb) displayed a similar pattern. Amino acid substitution patterns corroborated the conclusions from the phylogenetic tree. Thus, in both children, the X4 virus developed from their own R5 population, and was not caused by transmission of X4.

Coreceptor change appears after immune deficiency is established in children infected with different HIV-1 subtypes.

Change of HIV-1 coreceptor use has been connected to progression of disease in children infected with HIV-1, presumably subtype B. It has not been possible to discern whether the appearance of new viral phenotypes precedes disease development or comes as a consequence of it. We studied the evolution of coreceptor use in HIV-1 isolates from 24 vertically infected children. Their clinical, virological, and immunological status was recorded and the env V3 subtype was determined by DNA sequencing. Coreceptor use was tested on human cell lines, expressing CD4 together with CCR5, CXCR4, and other chemokine receptors. The children carried five different env subtypes (nine A, five B, four C, three D, and one G) and one circulating recombinant form, CRF01_AE (n = 2). Of the 143 isolates, 86 originated from peripheral blood mononuclear cells (PBMCs) and 57 originated from plasma, received at 90 time points. In 52 of 54 paired plasma and PBMC isolates the coreceptor use was concordant. All 74 isolates obtained at 41 time points during the first year of life used CCR5. A change from use of CCR5 to use of CXCR4 occurred in four children infected with subtype A, D, or CRF01_AE after they had reached 1.5 to 5.8 years of age. There was a significant association with decreased CD4+ cell levels and severity of disease but, interestingly, the coreceptor change appeared months or even years after the beginning of the immunological deterioration. Thus CXCR4-using virus may emerge as a possible consequence of immune deficiency. The results provide new insights into AIDS development in children.

Avulsion of the popliteus tendon. A rare cause of chondral fracture and hemarthrosis.

A case of isolated avulsion of the popliteus tendon in a 20-year-old male athlete is reported. The avulsion was caused by forward gliding of the femur on the fixed tibia which produced a chondral fracture and hemarthrosis.

Tenosynovial chondroma of the hand.

A case of tenosynovial chondroma of the left middle finger is presented. The treatment of this benign lesion is local excision.

[Primary experiences with laparoscopic appendectomy]. / Primaere erfaringer med laparoskopisk appendektomi.

The material comprises 77 patients with suspected appendicitis seen in a district community hospital. In the presence of a surgeon with laparoscopic experience laparoscopy was performed in 23 patients. In two patients the laparoscopy was only diagnostic, and in two patients adhesions or friable gangrenous appendicitis necessitated conversion to conventional appendicectomy. Nineteen patients thus had a laparoscopic appendicectomy performed with a median operation time of 63 minutes and a median hospital stay of two days. One patient with gangrenous appendicitis and a periappendicular abscess was readmitted after three weeks because of deep infection, which resolved after antibiotic treatment. The remaining 54 patients had a conventional appendicectomy performed, with a median operation time of 40 minutes and a median hospital stay of three days. There were six complications in this group. We conclude that laparoscopic appendicectomy is a safe alternative to open operation with benefits for the patient in form of lesser pain, shorter hospital stay, fewer complications, better cosmetic outcome, and shorter time to normal activity.

[Laparoscopic cholecystectomy in patients with earlier laparotomy]. / Laparoskopisk kolecystektomi hos patienter med tidligere laparotomi.

Previous abdominal surgery has been reported as a relative contraindication to laparoscopic cholecystectomy. A retrospective analysis of 356 laparoscopic cholecystectomies was undertaken to determine whether previous abdominal surgery led to increased morbidity. The results of 116 patients who had had previous abdominal surgery were compared with those of 240 patients without previous abdominal surgery. The rate of conversion to open operation was not increased. The operating time was a little increased. There were no increases in either minor or major postoperative complications in patients with previous abdominal surgery, and the in-hospital stay time was the same. The median recovery time was respectively ten versus eight days in patients with and without previous surgery. We conclude that previous abdominal surgery is not a contraindication to laparoscopic cholecystectomy.

[Endoscopic treatment of colorectal obstruction with self-expandable metal endoprosthesis]. / Endoskopisk behandling af kolorektal obstruktion med selvekspanderende metal-endoprotese.

Relief of colo-rectal obstruction by means of self-expandable metal mesh stents (SEMS) has been suggested for palliation and acute decompression followed by optimization of the patients' general condition prior to definitive surgery. Twelve patients with high operative risk and/or metastatic disease were selected for stenting with a dedicated colorectal partly covered SEMS (Choo Colo-Rectal Stent, Solco Intermed Co., Seoul, Korea). Stent deployment was successful in nine, two of whom had total obstruction. In one a guidewire perforation was treated conservatively. In two patients (one benign stricture, and one rectal cancer) the stents migrated within three weeks. One re-obstructed. In the remaining six patients colonic decompression was achieved, and the stents have been patent until death (33-175 days, four patients) or are still patent (follow-up 35-80 days). These results are promising, but data from several centres should be compiled prospectively in a standardized fashion in order to allow for assessment of the method's safety and success rates before randomized trials can be initiated.

Fast pouch emptying, delayed small intestinal transit, and exaggerated gut hormone responses after Roux-en-Y gastric bypass.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) causes extensive changes in gastrointestinal anatomy and leads to reduced appetite and large weight loss, which partly is due to an exaggerated release of anorexigenic gut hormones. METHODS: To examine whether the altered passage of foods through the gastrointestinal tract after RYGB could be responsible for the changes in gut hormone release, we studied gastrointestinal motility with a scintigraphic technique as well as the secretion of the gut hormones glucagon-like peptide (GLP)-1 and peptide YY3-36 (PYY3-36 ) in 17 patients>1 year after RYGB and in nine healthy control subjects. KEY RESULTS: At meal completion, a smaller fraction of liquid and solid radiolabeled marker was retained in the pouch of RYGB patients than in the stomach of control subjects (P = 0.002 and P < 0.001, respectively). Accordingly, pouch emptying in patients was faster than gastric emptying in control subjects (P < 0.001 and P = 0.004, respectively liquid and solid markers). For the solid marker, small intestinal transit was slower in patients than control subjects (P = 0.034). Colonic transit rate did not differ between the groups. GLP-1 and PYY3-36 secretion was increased in patients compared to control subjects and fast pouch emptying of the liquid marker was associated with high gut hormone secretion. CONCLUSIONS & INFERENCES: After RYGB, the bulk of foods pass without hindrance into the small intestine, while the small intestinal transit is prolonged. The rapid exposure of the gut epithelium contributes to the exaggerated release of GLP-1 and PYY3-36 after RYGB.

Changes in gastrointestinal hormone responses, insulin sensitivity, and beta-cell function within 2 weeks after gastric bypass in non-diabetic subjects.

BACKGROUND: Roux-en-Y gastric bypass (RYGB) surgery causes profound changes in secretion of gastrointestinal hormones and glucose metabolism. We present a detailed analysis of the early hormone changes after RYGB in response to three different oral test meals designed to provide this information without causing side effects (such as dumping). METHODS: We examined eight obese non-diabetic patients before and within 2 weeks after RYGB. On separate days, oral glucose tolerance tests (25 or 50 g glucose dissolved in 200 mL of water) and a liquid mixed meal test (200 mL 300 kcal) were performed. We measured fasting and postprandial glucose, insulin, C-peptide, glucagon, total and intact glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-2 (GLP-2), peptide YY(3-36) (PYY), cholecystokinin (CCK), total and active ghrelin, gastrin, somatostatin, pancreatic polypeptide (PP), amylin, leptin, free fatty acids (FFA), and registered postprandial dumping. Insulin sensitivity was measured by homeostasis model assessment of insulin resistance. RESULTS: Fasting glucose, insulin, ghrelin, and PYY were significantly decreased and FFA was elevated postoperatively. Insulin sensitivity increased after surgery. The postprandial response increased for C-peptide, GLP-1, GLP-2, PYY, CCK, and glucagon (in response to the mixed meal) and decreased for total and active ghrelin, leptin, and gastrin, but were unchanged for GIP, amylin, PP, and somatostatin after surgery. Dumping symptoms did not differ before and after the operation or between the tests. CONCLUSIONS: Within 2 weeks after RYGB, we found an increase in insulin secretion and insulin sensitivity. Responses of appetite-regulating intestinal hormones changed dramatically, all in the direction of reducing hunger.