New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

BHPR research: qualitative1. Complex reasoning determines patients' perception of outcome following foot surgery in rheumatoid arhtritis

Background: Foot surgery is common in patients with RA but research into surgical outcomes is limited and conceptually flawed as current outcome measures lack face validity: to date no one has asked patients what is important to them. This study aimed to determine which factors are important to patients when evaluating the success of foot surgery in RA Methods: Semi structured interviews of RA patients who had undergone foot surgery were conducted and transcribed verbatim. Thematic analysis of interviews was conducted to explore issues that were important to patients. Results: 11 RA patients (9 ♂, mean age 59, dis dur = 22yrs, mean of 3 yrs post op) with mixed experiences of foot surgery were interviewed. Patients interpreted outcome in respect to a multitude of factors, frequently positive change in one aspect contrasted with negative opinions about another. Overall, four major themes emerged. Function: Functional ability & participation in valued activities were very important to patients. Walking ability was a key concern but patients interpreted levels of activity in light of other aspects of their disease, reflecting on change in functional ability more than overall level. Positive feelings of improved mobility were often moderated by negative self perception ("I mean, I still walk like a waddling duck”). Appearance: Appearance was important to almost all patients but perhaps the most complex theme of all. Physical appearance, foot shape, and footwear were closely interlinked, yet patients saw these as distinct separate concepts. Patients need to legitimize these feelings was clear and they frequently entered into a defensive repertoire ("it's not cosmetic surgery; it's something that's more important than that, you know?”). Clinician opinion: Surgeons' post operative evaluation of the procedure was very influential. The impact of this appraisal continued to affect patients' lasting impression irrespective of how the outcome compared to their initial goals ("when he'd done it ... he said that hasn't worked as good as he'd wanted to ... but the pain has gone”). Pain: Whilst pain was important to almost all patients, it appeared to be less important than the other themes. Pain was predominately raised when it influenced other themes, such as function; many still felt the need to legitimize their foot pain in order for health professionals to take it seriously ("in the end I went to my GP because it had happened a few times and I went to an orthopaedic surgeon who was quite dismissive of it, it was like what are you complaining about”). Conclusions: Patients interpret the outcome of foot surgery using a multitude of interrelated factors, particularly functional ability, appearance and surgeons' appraisal of the procedure. While pain was often noted, this appeared less important than other factors in the overall outcome of the surgery. Future research into foot surgery should incorporate the complexity of how patients determine their outcome Disclosure statement: All authors have declared no conflicts of interes

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

A genome-wide association search for type 2 diabetes genes in African Americans.

African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations

Laparoscopic vs open pyloromyotomy: a systematic review and meta-analysis

The aim of the study was to determine whether laparoscopic pyloromyotomy (LP) or open pyloromyotomy (OP) is the most effective intervention in infants with hypertrophic pyloric stenosis. A systematic review of the published literature was undertaken in February 2009. Prospective studies comparing LP and OP were selected. Age, weight, complications, duration of operation, time to full feedings, postoperative vomiting, and postoperative length of stay (LOS) data were extracted. Six prospective studies (5 level I, 1 level II) with 625 (303 LP, 322 OP) participants met selection criteria. Combined estimates indicated that LP had a lower total complication rate (odds ratio [OR], 0.58 [0.35, 0.97]; P = .04), mostly due to a lower wound complication rate (OR, 0.42 for LP [0.20, 0.91]; P = .03). Patients who underwent LP also had shorter time to full feedings (mean difference [MD], −11.52 hours [−12.77, −10.27]; P < .00001) and shorter postoperative LOS (MD, −5.71 hours [−8.90, −2.52]; P = .0005). No statistically significant differences were noted in the rates of mucosal perforation, wound infection, postoperative emesis, or operating time. Incomplete pyloromyotomy occurred in 6 patients who underwent LP (OR, 7.74 [0.94, 63.38]; P = .06). This meta-analysis favors the laparoscopic approach with significantly reduced rate of total complications, which is mostly due to a lower wound complication rate

Pediatric surgical wound infections

Postoperative wound infections are one of the most common nosocomial infections in surgical patients and the third most common nosocomial infection in all hospitalized patients. Surgical wound infections commonly increase the need for antibiotics and increase the length of stay and hospital costs. Although this subject has been discussed frequently in the adult literature, fewer than 10 articles exist on the subject in the pediatric patient population, despite the rate of surgical wound infection, which ranges from 3 to 20 percent. Surgical site infections are potentially preventable complications that increase hospital costs as well as patient morbidity and discomfort. Recognizing the patient who is at high risk for a surgical site infection and providing appropriate antibiotic prophylaxis to those patients is an important step in decreasing surgical site infections. This article discusses the risks of surgical site infection specific to pediatric surgical procedures, as well as appropriate antibiotic prophylaxis and treatment. Copyright © 2001 by W.B. Saunders Compan

Pediatric neurofibrosarcoma

Neurofibrosarcoma is rare in children, and the natural history and prognostic factors are not well described. The authors present a 57-year review of their experience. The charts of children with neurofibrosarcoma were reviewed retrospectively. Statistical analysis was performed using the Chi2 and unpaired t tests. From 1944 to 2001, 38 patients under the age of 21 were diagnosed with neurofibrosarcoma. Twenty-two were boys. The average age at diagnosis was 13.8 years (range, 3 to 19.9 years). Nineteen patients (50%) had neurofibromatosis. The tumor site was as follows: extremity, 19 patients; trunk, 9 patients; head and neck, 7 patients; and retroperitoneum, 3 patients. The average tumor size was 10 cm. The margins after resection were as follows: grossly positive, 9; microscopically positive, 5; negative, 21; and unknown, 3. Patients with positive margins had a 22% survival rate, whereas those with negative or unknown margins had a 34% survival rate. Thirty-two patients achieved a complete response, 2 a partial response, and 4 progressed while on therapy. Twenty-six patients relapsed after a complete response (11 local, 10 distant, 5 both). Of the 15 patients with a distant relapse, 73% (11) relapsed in the lung. Twelve (32%) patients survived with an average follow-up of 14 years (range, 0.3 to 28 years). Nine patients were treated with chemotherapy, 9 with radiation, and 9 with both chemotherapy and radiation. Outcome was not significantly affected by gender, presence of neurofibromatosis, site, margin, or use of adjuvant therapy. Neurofibrosarcoma remains a rare disease in children with insufficient contemporary numbers to assess efficacy of therapy. Prognosis remains poor with a high incidence of relapse, particularly in the lungs, suggesting that more aggressive therapies to control both local and distant relapses are needed

Emergent abdominal decompression with patch abdominoplasty in the pediatric patient

Background/Purpose: Abdominal compartment syndrome (ACS) is the cardiac, pulmonary, and renal dysfunction that occurs as a result of elevated intraabdominal pressure. The authors present their experience with patch abdominoplasty (PA) in pediatric patients as a means to treat and prevent ACS. Methods: The charts of patients who underwent PA were reviewed retrospectively. ACS was defined as the increased oxygen requirements and elevation of peak inspiratory pressures (PIP) associated with abdominal distension and worsening renal and or cardiac function. Results: A total of 23 patients (13 boys) were treated (average age, 23 months). Diagnoses included necrotizing enterocolitis (NEC, n = 13), trauma (n = 3), Hirschsprung's enterocolitis (n = 2), perforated bowel (n = 4), and bilateral Wilms' tumor with bowel obstruction (n = 1). Oxygen requirements decreased after patch abdominoplasty (mean preoperative FIO2, 0.87 ± 24, mean postoperative, 0.67 ± 24 [P =.01]). The PIP decreased significantly in the 13 patients who survived (mean preoperative PIP, 33 ± 8, mean postoperative PIP, 27 ± 7 [P =.01]). These PIPs failed to respond in the 8 nonsurvivors (mean preoperative PIP, 35 ± 10, mean postoperative PIP, 33 ± 14 [P value not significant]). Six of the 8 nonsurvivors had NEC. Complications of intraabdominal abscess and enterocutaneous fistula were seen in 5 patients, all of who had NEC. Conclusions: Patch abdominoplasty effectively decreases airway pressures and oxygen requirements associated with ACS. Complications with PA occur primarily in patients with NEC. Failure to respond with a decrease in PIP and FIO2 requirements is an ominous sign. J Pediatr Surg 35:705-708. Copyright © 2000 by W.B. Saunders Company

Pacifier-induced bowel obstruction—not so soothing

Pacifiers are nearly ubiquitous among children in the United States, and although safety regulations exist, the responsibility to choose and maintain a safe pacifier generally falls on the parents, many of whom are unaware of potential hazards. We report a case of a complete bowel obstruction because of an ingested pacifier nipple and recommend increased awareness among practitioners as well as education of parents