Unraveling, contributing factors to the severity of postprandial hypoglycemia after gastric bypass surgery.

BACKGROUND: Despite the increasing prevalence of postbariatric hypoglycemia (PBH), a late metabolic complication of bariatric surgery, our understanding of its diverse manifestations remains incomplete. OBJECTIVES: To contrast parameters of glucose-insulin homeostasis in 2 distinct phenotypes of PBH (mild versus moderate hypoglycemia) based on nadir plasma glucose. SETTING: University Hospital (Bern, Switzerland). METHODS: Twenty-five subjects with PBH following gastric bypass surgery (age, 41 ± 12 years; body mass index, 28.1 ± 6.1kg/m2) received 75g of glucose with frequent blood sampling for glucose, insulin, C-peptide, and glucagon-like peptide 1 (GLP)-1. Based on nadir plasma glucose (

Multiplexed Assay to Quantify the PP-Fold Family of Peptides in Human Plasma Using Microflow Liquid Chromatography-Tandem Mass Spectrometry.

BACKGROUND: Peptide Tyr-Tyr (PYY1-36), pancreatic polypeptide (PP1-36) and neuropeptide Y (NPY1-36) constitute the PP-fold family of peptides that is involved in metabolic regulation. Very low plasma concentrations and cleavage into active 3-36 fragments challenge bioanalytical assays used for the quantification of these peptides. METHODS: We developed a multiplexed isotopic dilution assay to quantify PYY1-36, PP1-36, and NPY1-36 and their dipeptidyl peptidase-4 (DPP4)-derived metabolites PYY3-36, PP3-36 and NPY3-36. All peptides were immunocaptured from plasma using a monoclonal antibody and quantified by micro-ultra-HPLC-MS/MS. Blood samples from healthy volunteers were collected fasting and 30 min after nutrient stimulation. Method comparison was performed with commercial immunoassays. RESULTS: Linearity was shown in the measured intervals (r2 > 0.99). The lower limit of quantification (LLOQ) with a CV at 20% was 1.5 pM for PYY1-36 and PYY3-36, 3.0 pM for PP1-36 and PP3-36, 0.8 pM for NPY1-36 and 0.5 pM for NPY3-36. In all cases, intra- and inter-assay bias and imprecision were <21%. Pre-analytical stability required addition of a protease inhibitor cocktail. Physiological concentrations of PYY3-36, NPY3-36, PP1-36 and PP3-36 were above the LLOQ in 43% to 100% of the samples. PYY1-36 and NPY1-36 were above the LLOQ in 9% and 0% of the samples, respectively. Immunoassays showed higher concentrations of measurands and poor agreement when compared with micro-UHPLC-MS/MS. CONCLUSIONS: The assay allowed for specific multiplexed analysis of the PP-fold family of peptides and their DPP4-cleaved fragments in a single sample, thereby offering new perspectives to study the role and therapeutic potential of these essential peptide hormones in health and metabolic disease.

Effect of fully automated closed-loop insulin delivery using faster aspart versus standard aspart on gluco-regulatory hormones in type 2 diabetes.

We retrospectively assessed gluco-regulatory hormones over 10 h (including two meals) of fully automated closed-loop insulin delivery using faster (FA) versus standard insulin aspart (IAsp) in adults with type 2 diabetes [n = 15, age 59 ± 10 years, body mass index 34.5 ± 9.1 kg/m2 , glycated haemoglobin 7.7 ± 1.2% (60 ± 13 mmol/mol)]. Plasma concentration of human insulin, IAsp, C-peptide, glucagon, glucagon-like peptide 1, glucose-dependent insulinotropic peptide and peptide tyrosine tyrosine were measured every 15-30 min. Endogenous insulin secretion was calculated using C-peptide deconvolution and exposures to hormones were compared using their mean plasma concentrations. Ten-hour exposure of IAsp was higher with FA versus IAsp (P = .037) in line with the 10% higher insulin requirements to achieve similar glucose control. No significant difference was found for total insulin exposure and endogenous insulin secretion. Similarly, other gluco-regulatory hormones did not significantly differ. In conclusion, the faster pharmacokinetic profile and slightly higher aspart exposure of FA versus IAsp remained without significant effects on endogenous insulin secretion or other gluco-regulatory hormones. Further studies are warranted to explore the metabolic and endocrine effects of novel insulins with accelerated pharmacokinetic properties.

Recurrent nonbacterial thrombotic endocarditis and stroke on anticoagulation.

We present a rare case of recurrent nonbacterial thrombotic endocarditis (NBTE) and stroke despite anticoagulation. A 48-year-old man with history of antiphospholipid syndrome, prior nonbacterial aortic valve endocarditis status post valve replacement and prior stroke was found to have acute ischemic stroke while on apixaban and nonbacterial thrombotic endocarditis of mitral valve. This was initially managed conservatively with therapeutic dose of enoxaparin, but the patient later underwent mitral valve replacement. Unfortunately, the patient later passed away with hemorrhagic stroke while on enoxaparin.

The "ICE" study: feasibility of inexpensive commercial coolers on mobile EMS units.

INTRODUCTION: Prehospital postresuscitation induced hypothermia (IH) has been shown to reduce neurological complications in comatose cardiac-arrest survivors. Retrofitting ambulances to include equipment appropriate to initiate hypothermia, such as refrigeration units for cooled saline, is expensive. The objective of this nonhuman subject research study was to determine if inexpensive, commercially available coolers could, in conjunction with five reusable ice packs, keep two 1 L bags of precooled 0.9% normal saline solution (NSS) at or below 4°C for an average shift of eight to 12 hours in a real-world environment, on board in-service Emergency Medical Service (EMS) units, over varying weather conditions in all seasons. METHODS: The coolers were chosen based on availability and affordability from two nationally available brands: The Igloo MaxxCold (Igloo Products Corp., Katy, Texas USA) and Coleman (The Coleman Company, Wichita, Kansas USA). Both are 8.5 liter (nine-quart) coolers that were chosen because they adequately held two 1 L bags of saline solution, along with the reusable ice packs designated in the study design, and were small enough for ease of placement on ambulances. Initial testing of the coolers was conducted in a controlled environment. Thereafter, each EMS unit was responsible to cool the saline to less than 4°C prior to shift. Data were collected by emergency medical technicians, paramedics, and resident physicians working in seven different ambulance squads. Data analysis was performed using repeated measurements recorded over a 12-hour period from 19 individual coolers and were summarized by individual time points using descriptive statistics. RESULTS: Initial testing determined that the coolers maintained temperatures of 4°C for 12 hours in a controlled environment. On the ambulances, results based on the repeated measurements over time revealed that the saline solution samples as defined in the protocol, remained consistently below 4°C for 12 hours. Utilizing the lower bound of the 2-sided 95% exact binomial confidence intervals, there was less than a five percent chance that saline samples could not be maintained below 4°C for 12 hours, even during the summer months. CONCLUSIONS: Simple, commercially available coolers can maintain two 1 L bags of 0.9% NSS at 4°C for 12 hours in ambulances in varying environmental conditions. This suggests that EMS agencies could inexpensively initiate prehospital IH in appropriate cases.

Quadricyclane hydration kinetics in natural waters.

Hydration rates of quadricyclane were measured over a pH range of 3 to 8 in phosphate buffer, carbonate buffer, and nitric acid solutions. Norbornadiene was a minor impurity in the quadricyclane, and its hydration rate was also measured. Hydration products were exo-5-norbornen-2-ol (bicyclo[2.2.1]hept-5-ene-2-ol) and nortricyclyl alcohol (tricyclo[2.2.1.03,5 ]heptane-2-ol). Diol formation was not detected. Quadricyclane hydration in solutions containing chloride ions formed the alcohols and their chlorinated analogs. A mechanism consistent with observed kinetics and reaction products involving two carbocation intermediates is proposed. Comparison of reaction rates was used to determine the role of buffer catalysis and chlorination reactions in natural waters. Phosphate buffer catalysis was shown to be important, and rate constants for all phosphate species were calculated. Comparison of hydration rates in nitric acid and carbonate buffer indicated that catalysis by carbonate species for this reaction is unimportant in surface waters. Catalytic effects of other buffers in some natural waters appear possible. Proper buffer selection is important if laboratorymeasured hydration rates of quadricyclane are to be applied to natural water systems.