Search

Background: Current guidelines recommend coronary artery calcium (CAC) scoring for stratification of atherosclerotic cardiovascular disease risk only in patients with borderline to intermediate risk score by the pooled cohort equation with low-density lipoprotein-cholesterol (LDL-C) of 70 to 190 mg/dL. It remains unknown if CAC or thoracic aorta calcification (TAC), detected on routine chest computed tomography, can provide further risk stratification in patients with LDL-C≥190 mg/dL. Methods: From a multisite medical center, we retrospectively identified all patients from March 2005 to June 2021 age ≥40 years, without established atherosclerotic cardiovascular disease and LDL-C≥190 mg/dL who had non-gated non-contrast chest computed tomography within 3 years of LDL-C measurement. Ordinal CAC and TAC scores were measured by visual inspection. Kaplan-Meier curves and multivariable Cox-regression models were built to ascertain the association of CAC and TAC scores with all-cause mortality. Results: We included 811 patients with median age 59 (53–68) years, 262 (32.3%) were male, and LDL-C median level was 203 (194–217) mg/dL. Patients were followed for 6.2 (3.29–9.81) years, and 109 (13.4%) died. Overall, 376 (46.4%) of patients had CAC=0 and 226 (27.9%) had TAC=0. All-cause mortality increased with any CAC and moderate to severe TAC. In a multivariate model, patients with CAC had a significantly higher mortality compared with those without CAC: mild hazard ratio (HR), 1.71 (1.03–2.83), moderate HR, 2.12 (1.14–3.94), and severe HR, 3.49 (1.94–6.27). Patients with moderate TAC (HR, 2.34 [1.19–4.59]) and those with severe TAC (HR, 3.02 [1.36–6.74]) had higher mortality than those without TAC. Conclusions: In patients without history of atherosclerotic cardiovascular disease and LDL-C≥190 mg/dL, the presence and severity of CAC and TAC are independently associated with all-cause mortality.

Summary Introduction Predigested, peptide-based enteral formulas are commonly used to promote GI tolerance in critically ill patients, but studies comparing these against polymeric enteral formulas are lacking. We performed a prospective, randomized clinical comparison pilot study to assess safety, tolerance and effectiveness of a peptide-based enteral product. Methods Critically ill patients from ICUs, including medical, surgical, and cardiothoracic, were randomized to either of two enteral feeding products: Group A: Peptide-based, high Protein, high omega-3 fat (Vital AF ® , Abbott Nutrition); Group B: high protein standard enteral formula (Osmolite ® , Abbott Nutrition). Tolerance and comorbidities as well as enteral feeding volume were collected at baseline and then daily for up to 21 days, or until the patient was discharged from the ICU. Results A total of 49 patients were included, 25 (51%) on group A, 24 (49%) on group B. Adverse events and undesired gastrointestinal events at baseline and mean intake (ml/d and percent of goal) post baseline were not different between the groups. There were significantly fewer days with adverse events (p = 0.0336, odds ratio = 3.02, standard error = 1.60, n = 24 per group) and undesired gastrointestinal events (p = 0.0489, odds ratio = 2.79, standard error = 1.48, n = 24 per group) in group A. There was no difference in other clinical outcomes. Conclusion This pilot study suggests that feeding a peptide-based formula to ICU patients may be associated with a statistically significant reduction in the number of days during which adverse events occurred as compared to a standard formula.

Functional and structural liver abnormalities may be found in patients with advanced heart failure (HF). The Model of End-Stage Liver Disease Excluding INR (MELD-XI) score allows functional risk stratification of HF patients on and off anti-coagulation awaiting heart transplantation (HTx), but these scores may improve or worsen depending on bridging therapies and during time on the waiting list. Liver biopsy is sometimes performed to assess for severity of fibrosis. Uncertainty remains whether biopsy in addition to MELD-XI improves prediction of adverse outcomes in patients evaluated for HTx.Sixty-eight patients suspected of advanced liver disease underwent liver biopsy as part of their HTx evaluation. A liver risk score (fibrosis-on-biopsy + 1) × MELD-XI was generated for each patient.Fifty-two patients were listed, of whom 14 had mechanical circulatory support (MCS). Thirty-six patients underwent transplantation and 27 patients survived ≥1 year post-HTx (74%, as compared with 88% average 1-year survival in HTx patients without suspected liver disease; p0.01). Survivors had a lower liver risk score at evaluation for HTx (31.0 ± 20.4 vs 65.2 ± 28.6, p0.01). A cut-point of 45 for liver risk score was identified by receiver-operating-characteristic (ROC) analysis. In the analysis using Cox proportional hazards models, a liver risk score ≥45 at evaluation for HTx was associated with greater risk of death at 1 year post-HTx compared with a score of45 in both univariable (HR 3.94, 95% CI 1.77-8.79, p0.001) and multivariable (HR 4.35, 95% CI 1.77-8.79, p0.001) analyses. Patients who died1 year post-HTx had an increased frequency of acute graft dysfunction (44.4% vs 3.7%, p = 0.009), longer ventilation times (55.6% vs 11.1%, p = 0.013) and severe bleeding events (44.4% vs 11.1%, p = 0.049). The liver risk score at evaluation for HTx also predicted 1-year mortality after HTx listing (p0.001).Patients with HF and advanced liver dysfunction are high-risk HTx candidates. Liver biopsy in addition to MELD-XI improves risk stratification of patients with advanced HF and suspected irreversible liver dysfunction.

Background: Proprotein convertase subtilisin/kexin type (PCSK9) inhibitors are promising new drugs for the treatment of hypercholesterolemia. They inhibit the binding of PCSK9 to the low density lipoprotein (LDL) receptor that, in turn, decreases lysosomal degradation of LDL receptors and increases their numbers on the cell surface. In Phase 2/3 studies, alirocumab significantly lowered plasma levels of LDL-cholesterol (C) and apolipoprotein B (apoB). The mechanism underlying the LDL-C lowering effects of PCSK9 inhibition has not been reported. Method: We enrolled 10 healthy volunteers (4 male, 6 female), into a Phase 1, placebo-controlled, single-blind, single-sequence study to examine the effects of alirocumab, 150 mg administered subcutaneously every two weeks, on lipid and lipoproteins levels and the metabolism of apoB in very low density (VLDL), intermediate density (IDL) and LDL. Subjects received 2 doses of placebo followed by 5 doses of alirocumab. At the end of each treatment period, fasting lipids and lipoprotein levels were measured, and stable isotope studies of the apoB turnover in VLDL, IDL and LDL were performed. Results: Alirocumab significantly reduced plasma levels of total-C by 37% (178.4±34 to 112.7±29 mg/dL), LDL-C by 59% (110.2±25 to 45.5±26 mg/dL), and apoB by 51% (93.6±25 to 45.5±13 mg/dL) compared to placebo. Plasma triglycerides (TG) and HDL-C did not change. Levels of LDL-C, LDL-TG, and LDL-apoB fell by 55.8±10%, 33.9±13%, and 56.0±11%, respectively (all p Summary: Alirocumab treatment significantly reduced the levels of IDL and LDL, and these changes were due to increases in the FCRs of these lipoproteins, particularly LDL.

procedural attempts at DPEJ, procedure duration, technical success rate, causes for failed DBE-DPEJ placement, and adverse events. Results: A total of 90 patients (55 women; mean age 55 18 years; mean BMI 22.9 6.3) underwent DBE-DPEJ placement (Table 1). Indications for DPEJ included: gastroparesis (nZ29), previous failed PEG (e.g., intrathoracic stomach, nZ16), nutritional support in altered gut anatomy unsuitable for PEG (nZ16), recurrent or high risk for aspiration (nZ13), gastric outlet obstruction (nZ11), and miscellaneous (e.g., nutritional support in setting of necrotizing pancreatitis, nZ5). Altered gut anatomy was noted in 35 (39%) patients. DBE-DPEJ was successful in all patients (nZ12) who had prior failed DPEJ attempts by extended push endoscopy or single balloon endoscopy. Mean duration of the DBE-DPEJ procedure was 31 minutes (range 10-49). DBE-DPEJ placement was successful in 83 (92%) patients. Reasons for failed DBE-DPEJ placement in 7 (8%) patients included: small bowel fixation from adhesions precluding endoscope advancement (nZ5), duodenal stenosis (nZ1), and lack of transillumination (nZ1). Post-procedural adverse events occurred in 8 (9%) patients and included: gastrointestinal bleed secondary to DPEJ site ulceration (nZ3), abdominal hematoma (nZ2), cellulitis (nZ1), kinking of the PEJ tube requiring replacement (nZ1) and gastric interposition (nZ1). Conclusion: Compared to published outcomes of DPEJ placement by conventional endoscopy, DBE-assisted DPEJ was technically successful in a high proportion of patients and with a relatively low rate of significant adverse events.