Laparoscopic adjustable gastric banding in adolescents: Results at two years including psychosocial aspects

BACKGROUND/PURPOSE: Obesity now affects 3%-4% of the pediatric population and contributes to the increase in cardiac mortality in adulthood. Bariatric surgery is the best treatment for weight loss and the obesity-associated comorbidities in adults. We report here our experience of laparoscopic adjustable gastric banding (LAGB) in adolescents. METHODS: The medical charts of the first 16 patients operated on in our center were reviewed. Data were compiled concerning weight loss, physical and biological comorbidities, health-related quality of life (QOL) and surgical complications before surgery and during 24months of follow-up. RESULTS: The maximal pre-operative median body mass index was 43.0kg·m(-2), decreasing to 33.0kg·m(-2) at 2years post-LAGB, which corresponded to a 49.2% excess body weight loss (p<0.001). Most comorbidities (glucose intolerance, hypertension and sleep apnea) resolved within the first year post-LAGB and QOL was improved on the PedsQL™ scales. No severe surgical complications were noted, with only three re-interventions for device failure (2) or band removal (1). CONCLUSION: LAGB is well tolerated in adolescents and shows a beneficial impact on weight loss and obesity-related comorbidities. Associated with global management, it may have a positive impact on patients\u27 QOL and social and psychological status

A new case of pcsk1 pathogenic variant with congenital proprotein convertase 1/3 deficiency and literature review

Issue: To report a homozygous pathogenic variant in PCSK1 in a boy affected with proprotein convertase 1/3 (PC1/3) deficiency. Case description and literature review: A male infant born to consanguineous Turkish parents presented in the first week of life with transient central diabetes insipidus, watery diarrhea, micropenis due to hypogonadotropic hypogonadism and GH deficiency, and transient asymptomatic hypoglycemia. Further endocrine defects gradually appeared, including central hypothyroidism and mild central hypocortisolism (at 1 yr), central diabetes insipidus that reappeared progressively (at 2.5 yr), and obesity (at 2 yr). Whole exome sequencing revealed a homozygous nonsense pathogenic variant (NM_000439.4) c. 595 C>T in exon 5 of PCSK1, not yet reported in cases of proprotein convertase 1/3 (PC1/3) deficiency. To date, 26 cases of PC1/3 deficiency have been reported in the literature. All individuals had early and severe malabsorptive diarrhea and 83% had polyuria-polydipsia syndrome (before 5 yr). Most (79%) had early-onset obesity. Various endocrine disorders were present, including growth hormone deficiency (44%), mild central hypothyroidism (56%), central hypogonadism (44%), central hypocortisolism (57%), and postprandial hypoglycemia (52%). When described (n=15), proinsulin levels were consistently high: between 8 and 154 times the upper limit of normal (mean 74). Conclusion: We described a homozygous nonsense pathogenic variant (NM_000439.4) c. 595 C>T in exon 5 of PCSK1 in a boy with congenital proprotein convertase 1/3 deficiency. Elevated proinsulin could be useful in the diagnosis of this condition

SmartPilot® view-guided anaesthesia improves postoperative outcomes in hip fracture surgery: a randomized blinded controlled study

Background Both under-dosage and over-dosage of general anaesthetics can harm frail patients. We hypothesised that computer-assisted anaesthesia using pharmacokinetic/pharmacodynamic models guided by SmartPilot® View (SPV) software could optimise depth of anaesthesia and improve outcomes in patients undergoing hip fracture surgery. Methods This prospective, randomized, single-centre, blinded trial included patients undergoing hip fracture surgery under general anaesthesia. In the intervention group, anaesthesia was guided using SPV with predefined targets. In the control group, anaesthesia was delivered by usual practice using the same agents (propofol, sufentanil and desflurane). The primary endpoint was the time spent in the “appropriate anaesthesia zone” defined as bispectral index (BIS) (blinded to the anaesthetist during surgery) of 45–60 and systolic arterial pressure of 80–140 mm Hg. Postoperative complications were recorded for one month in a blinded manner. Results Of 100 subjects randomised, 97 were analysed (n=47 in SPV and 50 in control group). Anaesthetic drug consumption was reduced in the SPV group (for propofol and desflurane). Intraoperative duration of low BIS (<45) was similar, but cumulative time of low systolic arterial pressure (<80 mm Hg) was significantly shorter in the SPV group (median (Q1-Q3); 3 (0–40) vs 5 (0–116) min, P=0.013). SPV subjects experienced fewer moderate or major postoperative complications at 30-days (8 (17)% vs 18 (36)%, P=0.035) and shorter length of hospitalisation (8 (2–20) vs 8 (2–60) days, P=0.017). Conclusions SmartPilot® View-guided anaesthesia reduces intraoperative hypotension duration, occurrence of postoperative complications and length of stay in hip fracture surgery patients

Circulating adrenomedullin estimates survival and reversibility of organ failure in sepsis: the prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock-1 (AdrenOSS-1) study

Background: Adrenomedullin (ADM) regulates vascular tone and endothelial permeability during sepsis. Levels of circulating biologically active ADM (bio-ADM) show an inverse relationship with blood pressure and a direct relationship with vasopressor requirement. In the present prospective observational multinational Adrenomedullin and Outcome in Sepsis and Septic Shock 1 (, AdrenOSS-1) study, we assessed relationships between circulating bio-ADM during the initial intensive care unit (ICU) stay and short-term outcome in order to eventually design a biomarker-guided randomized controlled trial. Methods: AdrenOSS-1 was a prospective observational multinational study. The primary outcome was 28-day mortality. Secondary outcomes included organ failure as defined by Sequential Organ Failure Assessment (SOFA) score, organ support with focus on vasopressor/inotropic use, and need for renal replacement therapy. AdrenOSS-1 included 583 patients admitted to the ICU with sepsis or septic shock. Results: Circulating bio-ADM levels were measured upon admission and at day 2. Median bio-ADM concentration upon admission was 80.5 pg/ml [IQR 41.5-148.1 pg/ml]. Initial SOFA score was 7 [IQR 5-10], and 28-day mortality was 22%. We found marked associations between bio-ADM upon admission and 28-day mortality (unadjusted standardized HR 2.3 [CI 1.9-2.9]; adjusted HR 1.6 [CI 1.1-2.5]) and between bio-ADM levels and SOFA score (p < 0.0001). Need of vasopressor/inotrope, renal replacement therapy, and positive fluid balance were more prevalent in patients with a bio-ADM > 70 pg/ml upon admission than in those with bio-ADM ≤ 70 pg/ml. In patients with bio-ADM > 70 pg/ml upon admission, decrease in bio-ADM below 70 pg/ml at day 2 was associated with recovery of organ function at day 7 and better 28-day outcome (9.5% mortality). By contrast, persistently elevated bio-ADM at day 2 was associated with prolonged organ dysfunction and high 28-day mortality (38.1% mortality, HR 4.9, 95% CI 2.5-9.8). Conclusions: AdrenOSS-1 shows that early levels and rapid changes in bio-ADM estimate short-term outcome in sepsis and septic shock. These data are the backbone of the design of the biomarker-guided AdrenOSS-2 trial. Trial registration: ClinicalTrials.gov, NCT02393781. Registered on March 19, 2015

Current and Calcium Responses to Local Activation of Axonal NMDA Receptors in Developing Cerebellar Molecular Layer Interneurons

In developing cerebellar molecular layer interneurons (MLIs), NMDA increases spontaneous GABA release. This effect had been attributed to either direct activation of presynaptic NMDA receptors (preNMDARs) or an indirect pathway involving activation of somato-dendritic NMDARs followed by passive spread of somatic depolarization along the axon and activation of axonal voltage dependent Ca2+ channels (VDCCs). Using Ca2+ imaging and electrophysiology, we searched for preNMDARs by uncaging NMDAR agonists either broadly throughout the whole field or locally at specific axonal locations. Releasing either NMDA or glutamate in the presence of NBQX using short laser pulses elicited current transients that were highly sensitive to the location of the spot and restricted to a small number of varicosities. The signal was abolished in the presence of high Mg2+ or by the addition of APV. Similar paradigms yielded restricted Ca2+ transients in interneurons loaded with a Ca2+ indicator. We found that the synaptic effects of NMDA were not inhibited by blocking VDCCs but were impaired in the presence of the ryanodine receptor antagonist dantrolene. Furthermore, in voltage clamped cells, bath applied NMDA triggers Ca2+ elevations and induces neurotransmitter release in the axonal compartment. Our results suggest the existence of preNMDARs in developing MLIs and propose their involvement in the NMDA-evoked increase in GABA release by triggering a Ca2+-induced Ca2+ release process mediated by presynaptic Ca2+ stores. Such a mechanism is likely to exert a crucial role in various forms of Ca2+-mediated synaptic plasticity

Insulin resistance and its association with the components of the metabolic syndrome among obese children and adolescents

<p>Abstract</p> <p>Background</p> <p>Insulin resistance is the primary metabolic disorder associated with obesity; yet little is known about its role as a determinant of the metabolic syndrome in obese children. The aim of this study is to assess the association between the degree of insulin resistance and the different components of the metabolic syndrome among obese children and adolescents.</p> <p>Methods</p> <p>An analytical, cross-sectional and population-based study was performed in forty-four public primary schools in Campeche City, Mexico. A total of 466 obese children and adolescents between 11-13 years of age were recruited. Fasting glucose and insulin concentrations, high density lipoprotein cholesterol, triglycerides, waist circumference, systolic and diastolic blood pressures were measured; insulin resistance and metabolic syndrome were also evaluated.</p> <p>Results</p> <p>Out of the total population studied, 69% presented low values of high density lipoprotein cholesterol, 49% suffered from abdominal obesity, 29% had hypertriglyceridemia, 8% presented high systolic and 13% high diastolic blood pressure, 4% showed impaired fasting glucose, 51% presented insulin resistance and 20% metabolic syndrome. In spite of being obese, 13% of the investigated population did not present any metabolic disorder. For each one of the components of the metabolic syndrome, when insulin resistance increased so did odds ratios as cardiometabolic risk factors.</p> <p>Conclusions</p> <p>Regardless of age and gender an increased degree of insulin resistance is associated with a higher prevalence of disorders in each of the components of the metabolic syndrome and with a heightened risk of suffering metabolic syndrome among obese children and adolescents.</p