Genetic Testing for Hypertriglyceridemia in Academic Lipid Clinics: Implications for Precision Medicine-Brief Report.

BACKGROUND: Severe hypertriglyceridemia is often caused by variants in genes of triglyceride metabolism. These variants include rare, heterozygous pathogenic variants (PVs), or multiple common, small-effect single nucleotide polymorphisms that can be quantified using a polygenic risk score (PRS). The role of genetic testing to examine PVs and PRS in predicting risk for pancreatitis and severity of hypertriglyceridemia is unknown. METHODS: We examined the relationship of PVs and PRSs associated with hypertriglyceridemia with the highest recorded plasma triglyceride level and risk for acute pancreatitis in 363 patients from 3 academic lipid clinics who underwent genetic testing (GBinsight's Dyslipidemia Comprehensive Panel). Categories of hypertriglyceridemia included: normal triglyceride (<200 mg/dL), moderate (200-499 mg/dL), severe (500-999 mg/dL), or very severe (≥1000 mg/dL). RESULTS: PVs and high PRSs were identified in 37 (10%) and 59 (16%) individuals, respectively. Patients with both had increased risk for very severe hypertriglyceridemia compared with those with neither genetic risk factor. Risk for acute pancreatitis was also increased in individuals with both genetic risk factors (odds ratio, 5.1 [P=0.02] after controlling for age, race, sex, body mass index, and highest triglyceride level), but not in individuals with PV or high PRS alone. CONCLUSIONS: The presence of both PV and high PRS significantly increased risk for very severe hypertriglyceridemia and acute pancreatitis, whereas PV or PRS alone only modestly increased risk. Genetic testing may help identify patients with hypertriglyceridemia who have the greatest risk for developing pancreatitis and may derive the greatest benefit from novel triglyceride-lowering therapies.

Effect of Lipoprotein Apheresis on Progression of Carotid Intima-Media Thickness in Patients with Severe Hypercholesterolemia.

The extent of intervention effects on carotid intima-media thickness (CIMT) can predict the degree of atherosclerotic cardiovascular risk-reduction. We hypothesized that regular lipoprotein apheresis over the course of 10 years might slow down progression of CIMT in patients with severe hypercholesterolemia. This case series describes 10 Caucasian patients (mean age 60 ± 9 years, 70% female, 80% statin intolerant) with a severe hypercholesterolemia phenotype treated with lipoprotein apheresis between 2005 and 2020 (mean duration, 10 ± 4 years). The median pretreatment low-density lipoprotein cholesterol (LDL-C) level was 214 mg/100 ml (95% confidence interval, 145 to 248), lipoprotein(a) (Lp[a]), 26 mg/100 ml (15 to 109; 40% with Lp(a)>60 mg/100 ml). Three patients were diagnosed with a monogenic cause. The baseline mean CIMT was 850 ± 170 µm, and maximum CIMT was 1,040 ± 220 µm across the age range of 46 to 70 years. Acute effects of lipoprotein apheresis determined as a difference before and immediately after the procedure were estimated as a median of 72 ± 8% and 75 ± 7% reduction in the LDL-C and Lp(a) levels, respectively. Using the imputed trajectories, period-specific on-treatment time-weighted averages for LDL-C and Lp(a) were 141 mg/100 ml (interquartile range, 89 to 152; 38% reduction from the baseline) and 24 mg/100 ml (interquartile range, 12 to 119; 19% reduction from baseline), respectively. The number of patients with CIMT above their "vascular age" decreased from 80% to 30% over the treatment course. In conclusion, an increase in CIMT seen with advanced age and severe hypercholesterolemia was halted with lipoprotein apheresis with an estimated annual rate of change in mean common CIMT of -4 µm/y and maximum CIMT of -3 µm/y.

The Management of Women's Health Care by Internists With a Focus on the Utility of Ultrasound.

Adult women require routine care for the acute and chronic health problems found in both sexes, and they require specialized care for women's health problems, including disease prevention, disease screening, and disease management. Internists should direct primary care and participate in specialized care and to the extent possible follow guidelines published by various professional organizations. They should understand the use of ultrasound in breast cancer screening, the management of pregnancy, and other gynecologic problems, including vaginal bleeding, pelvic pain, and investigation for pelvic malignancy. Finally, all management decisions need discussions on the potential benefit or harm in each step of a woman's care with an emphasis on personal preferences.

Zika Virus: Epidemiology, Pathogenesis and Human Disease.

The Zika virus is a positive sense, single-stranded RNA arbovirus in the Flaviviridae family, genus Flavivirus. This virus was initially isolated in Africa and is transmitted to nonhuman primates and humans by mosquitoes. Initial reports describe sporadic mild viral infection with fever, arthralgia, myalgia and conjunctivitis in Africa and Asia. However, its geographic distribution has significantly increased, and it has caused large outbreaks in the Yap Islands in 2007, in French Polynesia in 2013 and in Brazil in 2015. Multiple cases of Guillain-Barre´ syndrome occurred in French Polynesia and Columbia during outbreaks, and infections in pregnant women in Brazil have been associated with microcephaly and fetal loss. The viremic phase in humans is short, and diagnosis usually depends on positive immunoglobulin M titers with serum neutralization tests for confirmation. Treatment is directed at symptoms; there are no antiviral drugs available. Transmission can also occur through sexual contact with infected men and through blood transfusion. Prevention is important in women and includes limiting travel to endemic areas when possible, control of mosquito populations and condom use when appropriate. The Centers for Disease Control and Prevention is actively involved in tracking these infections and providing up-to-date information.