Diagnosis and treatment of hypertensive emergencies and urgencies among Italian emergency and intensive care departments. Results from an Italian survey: Progetto GEAR (Gestione dell'Emergenza e urgenza in ARea critica).

Hypertensive emergencies (HE) and urgencies (HU) are frequent causes of patients referral to Emergency Department (ED) and the approach may be different according to local clinical practice. Our aim was to explore awareness, management, treatment and counselling after discharge of HE and HU in Italy, by mean of an on-line survey. The young investigator research group of the Italian Society of Hypertension developed a 23-item questionnaire spread by e-mail invitation to the members of Italian Scientific societies in the field of Hypertension. 665 questionnaires were collected from EDs, Emergency and Urgency Medicine, Cardiology or Coronary Units, Internal Medicines, Intensive care, Stroke units. Symptoms considered suspicious of acute organ damage were: chest pain (89.0%), visual disturbances (89.8%), dyspnoea (82.7%), headache (82.1%), dizziness (52.0%), conjunctival haemorrhages (41.5%), tinnitus (38.2%) and epistaxis (34.4%). Exams more frequent prescribed were: electrocardiogram (97.2%), serum creatinine (91.4%), markers of cardiomyocyte necrosis (66.2%), echocardiography (65.1%). The use of intravenous or oral medications to treat HEs was 94.7% and 3.5%, while for HUs 24.4% and 70.8% respectively. Of note, a surprisingly high percentage of physicians (22 % overall, 24.5% in North Italy) used to prescribe sublingual nifedipine. After discharge, home blood pressure monitoring and general practitioner re-evaluation were more frequently suggested, while ambulatory blood pressure monitoring and hypertension specialist examination were less prescribed. The differences observed across the different macro-areas, regarded prescription of diagnostic test and drug administration. This survey depicts a complex situation of shades and lights in the real-life management of HE and HU in Italy.

Evolution of transmitted HIV-1 drug resistance and viral subtypes circulation in Italy from 2006 to 2016.

OBJECTIVES: The aim was to evaluate the evolution of transmitted HIV-1 drug resistance (TDR) prevalence in antiretroviral therapy (ART)-naïve patients from 2006 to 2016. METHODS: HIV-1 sequences were retrieved from the Antiviral Response Cohort Analysis (ARCA) database and TDR was defined as detection of at least one mutation from the World Health Organization (WHO) surveillance list. RESULTS: We included protease/reverse transcriptase sequences from 3573 patients; 455 had also integrase sequences. Overall, 68.1% of the patients were Italian, the median CD4 count was 348 cells/µL [interquartile range (IQR) 169-521 cells/µL], and the median viral load was 4.7 log10 HIV-1 RNA copies/mL (IQR 4.1-5.3 log10 copies/mL). TDR was detected in 10.3% of patients: 6% carried mutations to nucleos(t)ide reverse transcriptase inhibitors (NRTIs), 4.4% to nonnucleos(t)ide reverse transcriptase inhibitors (NNRTIs), 2.3% to protease inhibitors (PIs), 0.2% to integrase strand transfer inhibitors (INSTIs) and 2.1% to at least two drug classes. TDR declined from 14.5% in 2006 to 7.3% in 2016 (P = 0.003): TDR to NRTIs from 9.9 to 2.9% (P = 0.003) and TDR to NNRTIs from 5.1 to 3.7% (P = 0.028); PI TDR remained stable. The proportion carrying subtype B virus declined from 76.5 to 50% (P < 0.001). The prevalence of TDR was higher in subtype B vs. non-B (12.6 vs. 4.9%, respectively; P < 0.001) and declined significantly in subtype B (from 17.1 to 8.8%; P = 0.04) but not in non-B subtypes (from 6.1 to 5.8%; P = 0.44). Adjusting for country of origin, predictors of TDR were subtype B [adjusted odds ratio (AOR) for subtype B vs. non-B 2.91; 95% confidence interval (CI) 1.93-4.39; P < 0.001], lower viral load (per log10 higher: AOR 0.86; 95% CI 0.75-0.99; P = 0.03), site in northern Italy (AOR for southern Italy/island vs. northern Italy, 0.61; 95% CI 0.40-0.91; P = 0.01), and earlier calendar year (per 1 year more recent: AOR 0.95; 95% CI 0.91-0.99; P = 0.02). CONCLUSIONS: The prevalence of HIV-1 TDR has declined during the last 10 years in Italy.

Natural NS5A inhibitor resistance associated substitutions in hepatitis C virus genotype 1 infected patients from Italy.

OBJECTIVES: Genetic variability in NS5A is associated with different levels of resistance to the currently licensed NS5A inhibitors. The aim of this study was to detect NS5A inhibitor resistance associated substitutions (RASs) in hepatitis C virus (HCV) genotype 1 (GT1) patients who are naive to direct-acting HCV antivirals. METHODS: Amplification, Sanger sequencing and phylogenetic analysis of the HCV NS5A region were performed on plasma obtained from 122 consecutive patients with HCV chronic infection attending four different clinics in Italy. RESULTS: NS5A inhibitor RASs were detected in 14/61 (23.0%) HCV GT1b and 3/61 (4.9%) HCV GT1a infected patients (p 0.007). The pan-genotypic RAS Y93H was detected in 1 (1.6%) GT1a and 4 (6.6%) GT1b patients. GT1a sequences clustered into two different clades with RASs detected in 1/34 (2.9%) clade I and 2/27 (7.4%) clade II sequences. CONCLUSIONS: Although the impact of naturally occurring NS5A RASs might be limited with upcoming pan-genotypic treatment regimens, this information is still useful to map naturally occurring HCV variants in different geographic areas in the context of current HCV therapy.

Phosducin rs12402521 polymorphism predicts development of hypertension in young subjects with overweight or obesity.

BACKGROUND AND AIMS: The G-protein regulator phosducin has been shown to be associated with stress-dependent blood pressure, but whether obesity is a modulator of the relationship between phosducin and risk of hypertension is unknown. We studied the effect of two phosducin polymorphisms on risk of hypertension in 273 overweight or obese (Ov-Ob) young-to-middle-age participants from the HARVEST and 287 normal weight (NW) participants. METHODS AND RESULTS: Genotyping of phosducin SNPs rs12402521 and rs6672836 was performed by real time PCR. For rs12402521, 64.6% of the participants were homozygous for the G allele, 27.9% heterozygous, and 7.5% homozygous for the A allele. During 7.7 years of follow-up, 339 subjects developed hypertension. In a Cox multivariable model, carriers of the A allele had a 1.28 (95% CI,1.00-1.63, p = 0.046) increased risk of hypertension. However, increased incidence of hypertension associated with A allele (AA + AG, 79% and GG, 59%, p = 0.001) was observed only among Ov-Ob individuals with a hazard ratio of 1.60 (95% CI, 1.13-2.21, p = 0.007) whereas in NW subjects the incidence of hypertension did not differ by genotype (56% in both groups). In the whole cohort, there was a significant interaction of phosducin genotype with body mass index on the risk of hypertension (p = 0.012). For SNP rs6672836 no association was found with incident hypertension. No haplotype effect was detected on the risk of hypertension. CONCLUSION: These data suggest that phosducin rs12402521 polymorphism is an important genetic predictor of obesity-related hypertension. In Ov-Ob carriers of the A allele aggressive nonpharmacological measures should be implemented.

Obesity is a strong determinant of hypertensive target organ damage in young-to-middle-age patients.

OBJECTIVE: To examine the impact of overweight and obesity on development of target organ damage in the early stage of hypertension. SUBJECTS: Participants were 727 young-to-middle-age subjects screened for stage 1 hypertension and followed for 8 years. MEASUREMENTS: Ambulatory blood pressure (BP), albumin excretion rate and echocardiographic data were obtained at entry, every 5 years and/or before starting antihypertensive treatment. RESULTS: During the follow-up, hypertension needing treatment was developed by 54.7% of the subjects with normal weight, 66.6% of those with overweight and 73.0% of those with obesity (P<0.001). Kaplan-Meier curves showed that patients with obesity or overweight progressed to sustained hypertension earlier than those with normal weight (P<0.001). At study end, rate of organ damage was 10.7% in the normal weight, 16.4% in the overweight and 30.1% in the obese subjects (P<0.001). In a multivariable logistic regression analysis, overweight (P=0.008) and obesity (P<0.001) were significant predictors of final organ damage. Inclusion of changes in 24-h BP and body mass index, and of baseline organ damage did not virtually modify these associations (P=0.002 and <0.001, respectively). Obesity was a significant predictor of both left ventricular hypertrophy (P<0.001) and microalbuminuria (P=0.015) with an odds ratio (95% confidence interval) of 8.5 (2.7-26.8) and 3.5 (1.3-9.6), respectively. CONCLUSION: These data indicate that in hypertensive subjects obesity has deleterious effects on the cardiovascular system already at an early age. Preventive strategies addressed to achieve weight reduction should be implemented at a very early stage in young people with excess adiposity and high BP.

Prevalence of HIV-1 integrase mutations related to resistance to dolutegravir in raltegravir naïve and pretreated patients.

The prevalence of HIV-1 integrase mutations related to resistance to the next-generation integrase inhibitor (INI), dolutegravir (DTG), was assessed in 440 INI-naïve subjects and in 120 patients failing a raltegravir (RTG)-containing regimen. Of the mutations selected by DTG in vitro, S153FY was not detected in any isolate while L101I and T124A were highly prevalent in both groups and significantly associated with non-B subtype. RTG-selected double and triple mutants, mostly the G140S/Q148H variant, were detected in only 32 (26.7%) RTG-treated patients. As L101I and T124A do not appear to exert any major effect in vivo and double and triple mutants resistant to DTG are infrequently selected by RTG, DTG can be effectively used in INI-naïve patients and may retain activity in many patients failing RTG.

Changing patterns in HIV-1 non-B clade prevalence and diversity in Italy over three decades.

BACKGROUND: HIV-1 non-B subtypes have recently entered Western Europe following immigration from other regions. The distribution of non-B clades and their association with demographic factors, over the entire course of the HIV-1 epidemic, have not been fully investigated in Italy. METHODS: We carried out a phylogenetic analysis of HIV-1 pol sequences derived from 3670 patients followed at 50 Italian clinical centres over nearly three decades. RESULTS: Overall, 417 patients (11.4%) carried non-B subtypes. The prevalence of non-B strains increased from 2.6% in 1980-1992 to 18.9% in 1993-2008 (P<0.0001) in a subset of 2479 subjects with a known year of diagnosis. A multivariate analysis on a subset of 1364 patients for whom relevant demographic data were available indicated that African ethnicity, heterosexual route of infection and year of diagnosis were independently associated with non-B HIV-1 infection (P ≤ 0.0001). All pure subtypes, except for clade K, and seven circulating recombinant forms were detected, accounting for 56.6 and 34.1% of the non-B infections, respectively. The F1 subtype was the most prevalent non-B clade among Europeans and was acquired heterosexually in half of this patient population. Unique recombinant forms accounted for 9.4% of the non-B sequences and showed a B/F1 recombination pattern in one-third of cases. CONCLUSIONS: The circulation of non-B clades has significantly increased in Italy in association with demographic changes. Spread of the F1 subtype and B/F recombinants appears to predominate, which may result in a redistribution of the relative proportions of the different strains, and this could lead to overlapping epidemics. Thus, the HIV-1 landscape in Italy may in future be distinct from that of the rest of Europe.

Detection of residual human immunodeficiency virus type 1 reverse transcriptase K103N minority species in plasma RNA and peripheral blood mononuclear cell DNA following discontinuation of non-nucleoside therapy.

Non-nucleoside reverse transcriptase inhibitor (NNRTI) therapy failed in 30 patients with the typical human immunodeficiency virus type 1 reverse transcriptase K103N mutation, detected using standard genotyping. Following discontinuation of NNRTI therapy for a median of 55.9 weeks and a decrease of K103N mutant species to undetectable levels in plasma RNA, minority K103N species remained detectable, by allele-specific PCR, for longer periods of time and at higher frequency, in peripheral blood mononuclear cell (PBMC) DNA than in plasma RNA (76.7% and 46.7% of samples with residual K103N species detected at median frequencies of 18.0% and 3.8%, respectively). Analysis of PBMC DNA should be considered when searching for residual K103N mutant species in patients previously exposed to NNRTIs.