Effects of PCSK9 inhibitors on LDL cholesterol, cardiovascular morbidity and all-cause mortality: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND AND AIMS: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors determine a wide reduction of LDL cholesterol, greater than other lipid-lowering agents. The present meta-analysis is aimed at the assessment of PCSK9 inhibitors effect on LDL Cholesterol, cardiovascular morbidity and all-cause mortality. METHODS AND RESULTS: A Medline and Clinicaltrials.gov search for eligible studies until December 1, 2017, was performed. All randomized trials (> 12 weeks) comparing PCSK-9 inhibitors with placebo or active drugs were retrieved. Primary endpoints: (a) LDL cholesterol at endpoint; (b) Major cardiovascular events (MACE); (c) All-cause mortality. Data extraction was performed independently by two of the authors, and conflicts resolved by a third investigator. A total of 38 trials fulfilling the inclusion criteria were identified, with mean duration of 36.4 weeks. The reduction of LDL cholesterol at endpoint, versus placebo, ezetimibe, and high-dose statins was - 65.3 [- 69.6, - 60.9]%, - 57.7 [- 68.3;- 47.0]%, and - 34.5 [- 40.8;- 28.1]%, respectively, with alirocumab possibly showing a smaller effect than the other drugs of the class. Treatment with PCSK9 inhibitors was associated with a reduction in the incidence of MACE (Mantel-Haenszel Odds Ratio [MH-OR] 0.83 [0.78, 0.88]), with significant effects of alirocumab and evolocumab only. The number needed to treat for 2 years for preventing one event was 89. All-cause mortality and cardiovascular mortality were not reduced by treatment with PCSK-9 inhibitors (MH-OR 0.94 [0.84, 1.04] and 0.97[0.86;1.09]). CONCLUSIONS: PCSK-9 inhibitors are effective in reducing LDL cholesterol and the incidence of major cardiovascular events in high-risk patients. Bococizumab does not show significant effects on MACE. REGISTRATION NUMBER: PROSPERO-CRD42018087640.

Bringing the body of the iceberg to the surface: the Female Sexual Dysfunction Index-6 (FSDI-6) in the screening of female sexual dysfunction.

PURPOSE: Female Sexual Dysfunction (FSD) is a still poorly studied and underdiagnosed condition. The aim of the study was to produce an improved version of FSFI-6 (6-Item Version of the Female Sexual Function Index), entitled Female Sexual Dysfunction Index-6 (FSDI-6), and to estimate its accuracy as a screening instrument for FSD. METHODS: In the new version, an item related to the personal interest in having a satisfying sex life was added, while the item rating the entity of sexual arousal was removed. We administered FSDI-6 in a consecutive series of female adult patients not consulting for sexual problems (n = 120, Cohort 1), and in another series of patients specifically consulting for sexual problems, which were considered as the control group (n = 160, Cohort 2). RESULTS: FSDI-6 score was significantly higher in patients in Cohort 2 (p < 0.0001). Cronbach's alpha for FSDI-6 was 0.784, indicating a high level of reliability. The estimated area under the ROC curve for FSDI-6 was 0.657 (p < 0.0001, 95 % CI 0.584-0.730). The proportion of subjects with a pathological FSDI-6 score (≥16.5) was 29.9 (n = 32) and 59.4 % (n = 95) in Cohort 1 and 2, respectively (p < 0.0001). Among subjects with a pathological FSDI-6 (score ≥16.5), those consulting for FSD had been postmenopausal for fewer years, had a higher level of education, a lower BMI and a lower prevalence of chronic diseases than those not consulting for FSD (p < 0.05). CONCLUSIONS: Although a lower educational level, overweight/obesity, menopause and chronic diseases are risk factors for FSD, they are often associated with the failure in medical consultation for FSD. We propose that FSDI-6 should be performed by health care providers in non-specialist settings to detect potential FSD, which otherwise could remain under-diagnosed.

Fasting and post-prandial glucose and diabetic complication. A meta-analysis.

BACKGROUND: The reduction of hemoglobin A1c (HbA1c) levels is recognized as a useful means of preventing diabetic complications. HbA1c results from both fasting and post-prandial glycemia, and therefore FPG and PPG could provide different, and independent, contributions to long-term outcomes. Aim of the present meta-analysis is the assessment of the effects of reduction of FPG and PPG on cardiovascular outcomes in randomized controlled trials. METHODS: An extensive search of Medline was performed for all randomized trials with a duration of at least 52 weeks and performed on glucose-lowering agents. Differences in the incidence of cardiovascular events, and all-cause and cardiovascular mortality were assessed in trials comparing different treatments with a between-group difference in FPG or PPG at endpoint greater than 1 mmol/l. RESULTS: The Mantel-Haenszel Odds Ratio (MH-OR) for cardiovascular events and all-cause and cardiovascular mortality in patients on more intensive treatments, in trials with a between-group difference of PPG greater than 1 mmol/l, was not significantly different from controls (MH-OR [95%CI] 0.90 [0.51-1.58] for MACE); on the contrary, more intensive treatment of FPG produced a significantly lower all-cause (MH-OR 0.90 [0.81-0.99], p = 0.03) and cardiovascular (MH-OR 0.86 [0.76-0.97], p = 0.012) mortality, with no significant effect on the incidence of major cardiovascular events. CONCLUSIONS: In conclusion, reduction of FPG is associated with reduced cardiovascular mortality. Data on PPG are still scarce, but they point in the same direction.

Evaluation of the anterior pituitary function in the acute phase after spontaneous subarachnoid hemorrhage.

BACKGROUND: Subarachnoid hemorrhage (SAH) is a potential cause of hypopituitarism. Most of the studies regarding the relationship between SAH and anterior pituitary function were retrospective and hormonal assessment was performed several months after SAH. AIM: To prospectively evaluate the prevalence of anterior pituitary hormone deficiencies in the acute phase after spontaneous SAH and their possible correlation with clinical and radiological parameters. METHODS: Pituitary function was tested in 60 patients within 72 h after spontaneous SAH. RESULTS: 56.9% of the patients showed at least one anterior pituitary hormone deficiency: gonadotropin and GH secretion failure represented the most prevalent hormonal deficiencies (33.3 and 22.0%, respectively), whereas ACTH and TSH deficiency was less frequent (7.1 and 1.8%, respectively). With the exception of secondary hypogonadism, the prevalence of other pituitary hormone deficiencies is in agreement with previous studies, which evaluated pituitary function on longterm follow up after SAH. No correlation was found between hypopituitarism and clinical status, as assessed with Hunt-Hess and Glascow Coma Scales. Moreover, no correlation was found between hypopituitarism and bleeding severity evaluated with Fisher's scale. CONCLUSIONS: We demonstrated a high prevalence of anterior pituitary hormone deficiencies acutely after SAH. Although part of GH and gonadotropin deficiencies might be a consequence of functional alteration due to SAH itself, the finding of low cortisol levels in this stressful condition strongly suggests the presence of true hypocortisolism. Therefore, an evaluation of pituitary function shortly after SAH might be useful to identify a subset of patients who deserve a more accurate follow-up.

Follicular nodules (THY3) of the thyroid: we recommend surgery.

OBJECTIVE: To determine the need of total thyrodectomy for patients with follicular nodules of thyroid. SUBJECTS AND METHODS: From January 2005 through June 2008, 2249 consecutive patients (438 males, 1811 females; mean age 54 yr, range 9-87) with thyroid nodules were submitted to 2518 ultrasound-guided fine-needle aspiration (USgFNA) for cytological examination. USgFNA were performed by experienced surgeon (RP) and endocrinologist (RGG) under ultra- sonographyc guidance, using a 10-MHz linear transducer. Liquid-based cytology was used. RESULTS: All cytological samples were classified in 5 diagnostic classes (THY1, THY2, THY3, THY4, THY5) in agreement with the British Thyroid Association (BTA); 1.4% specimen were classified as THY5, 2.1% as THY4, 7.6% as THY3, 79.5% as THY2 and 9.4% as THY1. In 97% of THY5 patients, malignancy was found. Among THY4 patients, 95.5% were positive for thyroid tumor. Among THY3 patients, malignancy was found in 29.1%. THY3 patients with thyroid tumors were younger than those with benign lesions (46 ± 14.1 yr vs 50 ± 13.8 yr; p<0.05, t test). No statistical difference was found neither in malignancy frequency among men and women nor in mean size of nodules (24 ± 11.8 mm malignant vs 23 ± 9.4 mm benign). CONCLUSIONS: this study provides evidence that USgFNA offers a very sensitive and accurate method in reducing THY1 samples and in detecting malignancy (>95% both in THY5 and THY4, and >29% in THY3 lesions). Our proposal is to submit to total thyroidectomy all patients with THY5 and THY4 lesions and THY3 thyroid nodule >1 cm.