Notes

Endoscopic Treatment of Large Bile Air duct Rocks: An organized Assessment as well as Circle Meta-analysis.
MEKP and MEK were successfully detected in blood samples even with less-than-ideal storage conditions. Knowledge of MEKP dangerousness and good work practices can prevent accidental MEKP poisoning.
Although NAC treatment was successful, supervision after the hospitalization period was required according to the prognosis. Workplace conditions promoted anosmia, explaining the accident. MEKP and MEK were successfully detected in blood samples even with less-than-ideal storage conditions. Knowledge of MEKP dangerousness and good work practices can prevent accidental MEKP poisoning.
The European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) initiated the CArdiac MARker Guidelines Uptake in Europe (CAMARGUE) Study to survey if current biomarker testing for heart failure (HF) in Europe is in accordance with up-dated guidelines.

A web-based questionnaire was distributed to clinical laboratories via European biochemical societies in 2019. Questions covered the type of natriuretic peptide (NP) assays performed, decision limits for HF, and opinion concerning requirement of different thresholds in patients with renal failure or obesity.

There were 347 participating laboratories mostly from European countries with 266 offering NP testing. NP testing was increased from 67% to 77% between 2013 and 2019. NT-proBNP remained the preferred biomarker. Recommended decision limits were implemented for BNP (85%) and better focused for NT-proBNP (40%) than in the previous survey. The survey revealed that laboratorians are willing to support the translation of adjusted cut-off values for age, gender and for patients with conditions like renal insufficiency.

Guidelines stimulate clinical laboratories to offer NP testing with high value for the diagnosis and management of HF, and to present adjusted medical decision limits. Future guidelines should encourage the use of personalized cut-offs for some confounding factors.
Guidelines stimulate clinical laboratories to offer NP testing with high value for the diagnosis and management of HF, and to present adjusted medical decision limits. Future guidelines should encourage the use of personalized cut-offs for some confounding factors.Dyslipidaemia is associated with numerous health problems that include the combination of insulin resistance, hypertension and obesity, ie, metabolic syndrome. Although the use of statins to decrease serum low density lipoprotein cholesterol (LDL-C) has been an effective therapeutic in treating atherosclerosis, the persistence of high atherosclerotic risk, ie, residual risk, is notable and is not simply explained as a phenomenon of dyslipidaemia. As such, it is imperative that we identify new biomarkers to monitor treatment and more accurately predict future cardiovascular events. This athero-protective strategy includes the assessment of novel inflammatory biomarkers such as YKL-40. Recent evidence has implicated YKL-40 in patients with inflammatory diseases and cardio-metabolic disorders, making it potentially useful to evaluate disease severity, prognosis and survival. In this review, we summarize role of YKL-40 in the pathogenesis of cardio-metabolic disorders and explore its use as a novel biomarker for monitoring athero-protective therapy.
The legal implications associated with illicit drug use during pregnancy are significant, as providers are required to notify child protective services when a drug-exposed infant is identified.

The case presented involves possible specimen mishandling in two infants at risk for in utero drug exposure and describes alternative methodologies available to confirm specimen identity.

It is critical that institutions establish and adhere to stringent procedures when screening newborns.
It is critical that institutions establish and adhere to stringent procedures when screening newborns.Analytical methods must be qualified as part of the method development lifecycle for product characterization of biotherapeutics. For higher order structure characterization methods, such as near ultraviolet circular dichroism spectroscopy, qualification is performed to determine the expected variability of the method and to establish criteria for analytical product comparability, reference standard qualification, and analytical similarity evaluations. Typical method qualifications require a single product to be tested across several days with multiple replicates, essential to establish a quantitative limit for future product evaluation studies, which may be burdensome with respect to time, instrumentation, and material requirements. In this note, a methodology is proposed to expedite the qualification process for the near ultraviolet circular dichroism spectroscopy method, decreasing the number of required qualification runs, in many cases, to just one for each product. The significant reduction in the number of assays for qualification is achieved by utilizing historical data that applies universally across products of variable classification, size, and test date. Despite their differences, the products exhibit comparable method performance when compared to a product-specific reference standard, and a universal detection threshold is established for application to future product evaluations that meet pre-determined method suitability criteria following a single verification run.NSAIDs such as celecoxib and sulindac play a critical role in the treatment of colorectal cancer, yet it is not understood how sufficiently high concentrations are reached in colonic tissue. We previously demonstrated that an incomplete small intestinal absorption of celecoxib enables gut driven drug accumulation in caecal tissue, which is most likely needed for inducing remission. However, a multistage dissolution experiment suggested a more extensive absorption of sulindac relative to celecoxib, though still incomplete. learn more To study whether caecal accumulation of sulindac is solely plasma driven or also gut driven, we performed an exploratory clinical study in healthy volunteers. After intake of a tablet of sulindac (200 mg; Arthrocine), two colonoscopies (1.0-2.5 h, and 6.0-7.5 h after drug intake) were performed to assess concentrations of sulindac and metabolites in plasma, caecal tissue and caecal contents. We observed that sulindac, even without the use of a colon-targeted delivery strategy, can arrive at the colonic lumen due to incomplete absorption and biliary excretion, and that the microbiota can catalyse the production of sulindac sulfide, which then accumulates in a high and local manner in the colonic tissue. These data can be relevant for drug development in the treatment of colorectal adenomas and cancer.This review presents my early exploration in the area of prodrugs and specifically prodrugs of the anticonvulsant, phenytoin, also called diphenylhydantoin. My journey started in graduate school with an introduction to the prodrug concept and continued for much of my career as I remain fascinated by the topic/technique. I have also included some backstories that the reader might find noteworthy. Prodrug intervention is now recognized as one of the better tools for taking a challenging small molecule drug from un-developable to developable.Low levels of high-density lipoprotein (HDL) have been associated with adverse cardiovascular events in epidemiologic studies. Evidence regarding its role in patients who underwent percutaneous coronary intervention (PCI) is scarce. We evaluated consecutive patients who underwent PCI with drug-eluting stents from 2012 to 2017, excluding those with unavailable baseline HDL, age less then 18 years, presentation with ST-segment elevation myocardial infarction (MI) or shock, and coexisting neoplastic disease. The final population was stratified according to baseline HDL levels into reduced and nonreduced HDL cohorts, with cut-off value 40 mg/dl in males and 50 mg/dl in females. The primary end point was 1-year major adverse cardiovascular events (MACE), defined as the composite of death, MI, or target vessel revascularization (TVR). Among 10,843 patients included, 6,511 (60%) had reduced HDL, and 4,332 (40%) nonreduced HDL. The rate of 1-year MACE was similar between the 2 groups (7.5% vs 6.6%; p = 0.14). Although mortality and MI rates were comparable, reduced HDL was associated with significantly higher TVR 5.2% vs 4.0%; p = 0.02, a finding that attenuated after multivariable adjustment (adjusted hazard ratio 1.18, p = 0.14). Sex subgroup analysis included 7,718 (71.2%) males and 3,125 (28.8%) females. Among men, there was a trend toward higher MACE in those with reduced HDL (7.4% vs 6.0%; p = 0.08) mostly driven by TVR (5.4% vs 3.7%; p = 0.005). No association between HDL and 1-year outcomes was evident in females. Assessment for interaction between sex and reduced HDL did not reach statistical significance. In conclusion, reduced baseline HDL was not associated with increased risk of MACE in a contemporary PCI population.Due to limited real-world data, the aim of this study was to explore the impact of catheter ablation (CA) for atrial fibrillation (AF) in heart failure (HF). This retrospective cohort study identified 119,694 patients with AF and HF from the Nationwide Readmissions Database (NRD) from 2016 to 2017. Propensity-matching was generated using demographics, comorbidities, hospital and other characteristics through multivariate logistic regression. Greedy's propensity score match (115) algorithm was used to create matched data. The primary end point was a composite of HF readmission and mortality at 1 year. Secondary outcomes include HF readmission, mortality, AF readmission, and any-cause readmission at 1 year. Of the 119,694 patients, 63,299 had HF with reduced ejection fraction (HFrEF), and 56,395 had HF with preserved ejection fraction (HFpEF). In the overall HFrEF cohort, the primary outcome was similar (HR, 95% confidence interval, p-value) (1.01, 0.91 to 1.13, 0.811). AF readmission (0.41, 0.33 to 0.49, less then 0.001) and any readmission (0.87, 0.82 to 0.93, less then 0.001) were reduced with CA. In the propensity-matched HFrEF cohort, results were unchanged (primary outcome 1.10, 0.95 to 1.27, 0.189; AF readmission 0.46, 0.36 to 0.59, less then 0.001; any readmission 0.89, 0.82 to 0.98, 0.015). In the overall HFpEF cohort, the primary outcome was similar (0.90, 0.78 to 1.04, 0.154). AF readmission was reduced with CA (0.54, 0.44 to 0.65, less then 0.001). In the propensity-matched HFpEF cohort, results were unchanged (primary outcome 1.10, 0.92 to 1.31, 0.289; AF readmission 0.44, 0.33 to 0.57, less then 0.001). CA did not reduce mortality and HF readmission at one year irrespective of the type of HF, but significantly reduce readmission due to AF.The role of central sleep apnea (CSA) in pacing-induced cardiomyopathy (PICM) remains speculative. In a prospective trial entitled UPGRADE, the presence of CSA was assessed by single-night polysomnography (PSG) in 54 PICM patients within 1 month after left ventricular lead implantation (with biventricular stimulation still not activated). CSA was diagnosed in half of patients (n = 27). Patients with moderate or severe CSA were randomized to cardiac resynchronization therapy (CRT) versus right ventricular pacing (RVP) in a double-blinded cross-over design and re-scheduled for a follow-up PSG within 3 to 5 months. After crossing-over of stimulation mode another PSG was conducted 3 to 5 months later. CRT led to a significant increase in left ventricular ejection fraction and significant reduction in left ventricular end systolic volumes and N-terminal pro brain natriuretic peptide plasma levels, whereas no significant effects were observed with ongoing RVP. CSA was significantly improved after 3.9 (3.2 to 4.4) months of CRT apnea-hypopnea index decreased from 39.
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