Effectiveness and safety of PCSK9 inhibitor therapy in patients with familial hypercholesterolemia within a therapeutic program in Poland: Preliminary multicenter data.

BACKGROUND: In Poland, treatment with proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors has become available free of charge in a therapeutic program. Assessed herein, is the efficacy and safety of alirocumab and evolocumab in patients with heterozygous familial hypercholesterolemia (FH). METHODS: Data of 55 adult FH patients who participated in the program were analyzed upon meeting the criteria established by the Ministry of Health (low density lipoprotein cholesterol [LDL-C] above 160 mg/dL on max. tolerated statin dose and ezetimib). The efficacy of PCSK9 inhibitors in reducing LDL-C with drug administration every 2 weeks was assessed after 3 months and 1 year of therapy. A safety profile evaluation was performed at each visit. 48 patients completed the 3-month and 21 for the 1-year observation periods (34 patients treated with alirokumab and 14 with evolocumab). RESULTS: The mean concentration of direct-measured LDL-C decreased from the initial level of 215.1 ± 74.5 mg/dL to 75.3 ± 64.1 mg/dL, i.e., by 65 ± 14% following 3 months of treatment. This effect was stable in 1-year observation (77.7 ± 72.8 mg/dL). Adverse effects were flu-like symptoms (13.0%), injection site reactions (11.1%), fatigue (5.6%) and musculoskeletal symptoms (5.6%). Seven patients failed to complete the 3-month treatment period due to side effects or non-compliance, and 1 patient failed to complete the 1-year treatment due to myalgia. CONCLUSIONS: This study confirmed high effectiveness of PCSK9 inhibitors in reducing LDL-C levels in patients with FH. Due to restrictive inclusion criteria with LDL-C threshold level > 160 mg/dL (> 4.1 mmol/L) required for participation in the therapeutic program, a relatively small number of FH patients were eligible for treatment.

Head/neck paragangliomas: focus on tumor location, mutational status and plasma methoxytyramine.

Head and neck paragangliomas (HNPGLs) are tumors of parasympathetic origin that occur at variable locations and are often secondary to germline mutations in succinate dehydrogenase (SDH) subunit genes. Occasionally, these tumors produce catecholamines. Here, we assessed whether different locations of HNPGLs relate to the presence of SDHx mutations, catecholamine production and other presentations. In this multicenter study, we collected clinical and biochemical data from 244 patients with HNPGLs and 71 patients without HNPGLs. We clarified that jugulotympanic HNPGLs have distinct features. In particular, 88% of jugulotympanic HNPGLs arose in women, among whom only 24% occurred due to SDHx mutations compared to 55% in men. Jugulotympanic HNPGLs were also rarely bilateral, were of a smaller size and were less often metastatic compared to carotid body and vagal HNPGLs. Furthermore, we showed that plasma concentrations of methoxytyramine (MTY) were higher (P < 0.0001) in patients with HNPGL than without HNPGL, whereas plasma normetanephrine did not differ. Only 3.7% of patients showed strong increases in plasma normetanephrine. Plasma MTY was positively related to tumor size but did not relate to the presence of SDHx mutations or tumor location. Our findings confirm that increases in plasma MTY represent the main catecholamine-related biochemical feature of patients with HNPGLs. We expect that more sensitive analytical methods will make biochemical testing of HNPGLs more practical in the future and enable more than the current 30% of patients to be identified with dopamine-producing HNPGLs. The sex-dependent differences in the development of HNPGLs may have relevance to the diagnosis, management and outcomes of these tumors.

Plasma Steroid Profiling in Patients With Adrenal Incidentaloma.

CONTEXT: Most patients with adrenal incidentaloma have nonfunctional lesions that do not require treatment, while others have functional or malignant tumors that require intervention. The plasma steroid metabolome may be useful to assess therapeutic need. OBJECTIVE: This work aimed to establish the utility of plasma steroid profiling combined with metanephrines and adrenal tumor size for the differential diagnosis of patients with adrenal incidentaloma. METHODS: This retrospective cross-sectional study, which took place at 7 European tertiary-care centers, comprised 577 patients with adrenal incidentaloma, including 19, 77, 65, 104 and 312 respective patients with adrenocortical carcinoma (ACC), pheochromocytoma (PHEO), primary aldosteronism (PA), autonomous cortisol secretion (ACS), and nonfunctional adrenal incidentaloma (NFAI). Mesaures of diagnostic performance were assessed (with [95% CIs]) for discriminating different subgroups of patients with adrenal incidentaloma. RESULTS: Patients with ACC were characterized by elevated plasma concentrations of 11-deoxycortisol, 11-deoxycorticosterone, 17-hydroxyprogesterone, androstenedione, and dehydroepiandrosterone-sulfate, whereas patients with PA had elevations of aldosterone, 18-oxocortisol, and 18-hydroxycortisol. A selection of those 8 steroids, combined with 3 others (cortisol, corticosterone, and dehydroepiandrosterone) and plasma metanephrines, proved optimal for identifying patients with ACC, PA, and PHEO at respective sensitivities of 83.3% (66.1%-100%), 90.8% (83.7%-97.8%), and 94.8% (89.8%-99.8%); and specificities of 98.0% (96.9%-99.2%), 92.0% (89.6%-94.3%), and 98.6% (97.6%-99.6%). With the addition of tumor size, discrimination improved further, particularly for ACC (100% [100%-100%] sensitivity, 99.5% [98.9%-100%] specificity). In contrast, discrimination of ACS and NFAI remained suboptimal (70%-71% sensitivity, 89%-90% specificity). CONCLUSION: Among patients with adrenal incidentaloma, the combination of plasma steroid metabolomics with routinely available plasma free metanephrines and data from imaging studies may facilitate the identification of almost all clinically relevant adrenal tumors.

Left Ventricular Structural and Functional Alterations in Patients With Pheochromocytoma/Paraganglioma Before and After Surgery.

OBJECTIVES: This study sought to evaluate left ventricular (LV) structure and function in pheochromocytoma and paraganglioma (PPGL) patients before and after curative surgery. BACKGROUND: Data on catecholamine-induced effects on LV structure and function in patients with PPGL are limited and conflicting. METHODS: The study evaluated 81 consecutive patients with a PPGL, among whom 66 were evaluated 12 months after tumor removal. Fifty patients matched for age, sex, hypertension presence, and blood pressure (BP) levels served as a control group (non-PPGL group). Echocardiography was employed to assess the LV mass index (LVMI), systolic function including speckle tracking echocardiography, and diastolic function. RESULTS: Patients with PPGL were characterized by higher LVMI (median 103 [interquartile range (IQR): 88 to 132] g/m2 vs. median 94 [IQR: 74 to 106] g/m2; p = 0.006) and frequency of LV hypertrophy (44.4% vs. 24.0%; p = 0.018) compared with the non-PPGL group. Patients with PPGLs were characterized by lower global longitudinal strain (GLS) and early diastolic mitral annular velocity compared with patients in the non-PPGL group (median -17.2% [IQR: 15.6% to 18.9%] vs. median -19.3% [IQR: 17.7% to 20.6%]; p < 0.001; and median 11.1 [IQR: 8.3 to 13.0] cm/s vs. median 12.3 [IQR: 10.6 to 14.6] cm/s; p = 0.018, respectively). Presence of LV hypertrophy and GLS were independently associated with plasma free metanephrine concentrations. In operated patients, there were lower frequencies of LV hypertrophy (39.4% vs. 22.7%; p = 0.003), LVMI (median 98 [IQR: 85 to 115] g/m2 vs. median 90 [IQR: 76 to 109] g/m2; p < 0.001), and the ratio of transmitral early diastolic velocity to early diastolic mitral annular velocity (median 6.8 [IQR: 5.5 to 8.6] vs. median 6.0 [IQR: 5.0 to 7.6]; p = 0.005) but higher values for GLS (median -17.4 [IQR: -15.8 to 19.1] vs. median -18.5 [IQR: -17.1 to 20.1] p < 0.001) after compared with before surgery. CONCLUSIONS: Catecholamine excess in patients with PPGLs can lead not only to LV hypertrophy, but also to impairment of systolic LV function and subclinical alterations of diastolic LV function, independently of BP levels. These structural and functional changes are reversible after surgical intervention.

Clinical and echocardiographic parameters as risk factors for atrial fibrillation in patients with hypertrophic cardiomyopathy.

BACKGROUND: Atrial fibrillation (AF) is a common complication in patients with hypertrophic cardiomyopathy (HCM) and may contribute to high cardiovascular morbidity and mortality. Therefore, it is important to assess parameters associated with AF in HCM patients. HYPOTHESIS: The aim of the study was to evaluate AF prevalence in patients with HCM and to investigate risk factors for AF. METHODS: Five hundred and forty-six HCM patients aged below 65 were included into analysis. Clinical and echocardiographic parameters were analyzed. RESULTS: In 141 patients (25.8%) AF episodes were recorded. The following factors were identified as risk factors for AF in patients with HCM: age ≥ 45 years (OR 2.38, CI 1.40-4.05, P = 0.001), past history of presyncope or syncope (OR 2.25, CI 1.35-3.74, P = 0.002), non-sustained ventricular tachycardia (nsVT) (OR 2.70, CI 1.60-4.57, P < 0.001), left atrium diameter during first assessment (OR 1.065, CI 1.03-1.11, P = 0.001), left atrium diameter at the last assessment before AF occurrence (OR 1.10, CI 1.06-1.14, P < 0.001) and left ventricular ejection fraction at the last assessment before AF occurrence (CI 0.96, CI 0.94-0.98, P = 0.001). CONCLUSIONS: We confirm that AF is a common complication for patients with HCM. Identification of patients with high risk for AF and implementation of preventive strategies may reduce AF occurrence and its complications.

Consumption of sweetened beverages as a risk factor of colonization of oral cavity by fungi - eating habits of university students.

Foods rich in sugar are an excellent substrate for the microorganisms that inhabit the initial sections of the gastrointestinal tract, and one of the most commonly available sources of sugar is the sweetened drink. Students represent an interesting sub-population; the large number of classes and associated stress levels promote fixing of unhealthy behaviors, e.g. tendency to consume a lot of sweetened drinks, for example cola-type or energetic drinks. Aim of this study was to determine the relationship between the amount of sugar consumed in beverages and the prevalence of fungi in the oral cavity. The investigated material consisted of oral washings. Participants completed original questionnaire regarding beverages consumed. The relationship between the consumption of sweetened beverages and risk of the presence of fungi in the oral cavity was determined. Fungi were isolated from 68.1% of examined subjects. Seven species of the genus Candida were observed. Higher prevalence of fungi was seen in the oral cavity of subjects who declared consumption of beverages containing sugar. 37.8% of respondents were found to consume with beverages doses of sugar exceeding the recommended daily requirement. Significantly greater prevalence of oral cavity fungi was noted in those exceeding the recommended GDA (76.3%), compared to of those who were not (68.7%). There were positive correlations between occurrence of fungi and consumption of sweetened carbonated drinks or adding sugar to coffee and tea. The addition of sugar to coffee/tea and sugar consumption above the recommended daily amount significantly increases the risk of colonization of the oral cavity by fungi. Students, due to invalid nutritional habits especially excessive consumption of beverages containing large amounts of sugar, belong to a group with a predisposition to the occurrence of fungi in the oral cavity.