Citations

AbstractBackgroundAlthough the process of reclassification of a variant of uncertain significance can be complex, they are commonly detected through molecular testing. It often takes years before enough clinical data are acquired, and it can be costly and time‐consuming to perform functional analysis of a single variant. It is important that other tools are developed to aid in clarifying how a specific genetic variant impacts a protein's function, and ultimately the health of the patient.MethodsTwo more newly characterized, suspected pathogenic variants in NBN and PTEN were analyzed through personalized protein modeling. Comparisons between the wild‐type and altered protein were studied using simulations, genomic exome analysis, and clinic study.ResultsModeling of the new NBN and PTEN protein structures suggested loss of essential domains important for normal enzymatic function for these personalized genomic examples which matched the clinical findings.ConclusionThe defects detected through modeling were consistent with the expected clinical effect. Personalized protein modeling is another tool for determination of correct variant classification, which can become further useful through construction of deposition archive.

AbstractParenteral nutrition (PN) is a complex therapeutic modality provided to neonates, children, and adults for various indications. Surveys have shown that current electronic health record (EHR) systems are in need of functionality enhancement for safe and optimal delivery of PN. This is a consensus statement from the American Society for Parenteral and Enteral Nutrition, the Academy of Nutrition and Dietetics, and the American Society of Health‐System Pharmacists outlining some of the key challenges to prescribing, order review/verification, compounding, and administration of PN using EHRs today and is a call to action for clinicians and vendors to optimize their EHRs regarding the PN build and workflow.

AbstractBackgroundEnteral nutrition (EN) is a safe and cost‐effective intervention with significant morbidity and mortality benefit that can also be associated with complications. Peristomal infections can occur in 5%–30% of cases after percutaneous endoscopic gastrostomy placement. Despite this common occurrence, widespread use of objective diagnostic criteria is not prevalent, possibly leading to overuse of antibiotics.MethodsAll patients who were reporting symptoms consistent with peristomal infection were evaluated. Criteria based on erythema, induration, and exudates were applied with cumulative score ≥8 indicating peristomal infection. All patients were followed, with additional factors being collected if available.ResultsForty‐three patients noted complaints consistent with peristomal infection. In patients with a score <8 (n = 16), only 2 required antibiotics (12.5%) and 1 patient was hospitalized (6.3%). In patients with a score ≥8 (n = 27), 16 had a score of 8 or 9; all patients responded to antibiotics (100%), and 1 was hospitalized (6.3%). In patients with a score ≥10, all (100%) were treated with antibiotics. Five of 11 (45%) patients were hospitalized, with the most common diagnosis being sepsis. Of the baseline variables analyzed, higher body mass index correlated with score ≥10 (26.36 ± 2.94 vs 22.91 ± 4.35 in score <9, P = .0128).ConclusionsObjective criteria were effective in risk stratifying patients who presented with reports of peristomal infection. Patients with a score <8 tended to be at low risk, scores of 8–9 were of moderate risk, and patients with a score ≥10 were at high risk and required very close monitoring or hospitalization.

DPP (dipeptidyl peptidase)-4 inhibitors are antidiabetic drugs that may increase heart failure in high-risk patients. NPY (neuropeptide Y) is coreleased with norepinephrine, causes vasoconstriction via the Y1 receptor, and is degraded by DPP4 to NPY (3–36) in vitro. NPY (3–36) decreases release of norepinephrine via the Y2 receptor. We tested the hypothesis that DPP4 inhibition would potentiate the vasoconstrictor effect of NPY. Eighteen nonsmokers (12 healthy controls and 6 with type 2 diabetes mellitus) participated in 1 of 2 randomized, double-blind, placebo-controlled crossover studies. First, subjects were randomized to order of treatment with sitagliptin 100 mg/d versus placebo for 7 days separated by 4-week washout. On the last day of treatment, NPY was infused by brachial artery and forearm blood flow was measured using plethysmography. Blood samples were collected after each dose. NPY infusions were repeated after 90-minute washout and intra-arterial enalaprilat. Second, 5 healthy subjects were randomized to crossover treatment with sitagliptin 100 mg/d plus valsartan 160 mg/d versus placebo plus valsartan. NPY infusions were performed on the seventh day of treatment. NPY caused dose-dependent vasoconstriction. During enalaprilat, sitagliptin significantly potentiated NPY-induced vasoconstriction in controls and diabetics ( P ≤0.02 for forearm blood flow in either group). Baseline norepinephrine release was increased during sitagliptin and enalaprilat, but not further by NPY. Sitagliptin increased the ratio of NPY to NPY (3–36). During valsartan, sitagliptin also significantly potentiated NPY-induced vasoconstriction ( P =0.009 for forearm blood flow). Potentiation of endogenous NPY could contribute to cardiovascular effects of DPP4 inhibitors in patients taking an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker.