Transmission of resistant HIV type 1 variants and epidemiological chains in Italian newly diagnosed individuals

Transmission of HIV-1 and drug resistance continue to occur at a considerable level in Italy, influenced mainly by changes in modality of infection. However, the long period of infectivity makes difficult the interpretation of epidemiological networks, based on epidemiological data only. We studied 510 naive HIV-1-infected individuals, of whom 400 (78.4%) were newly diagnosed patients with an unknown duration of infection (NDs), with the aim of identifying sexual epidemiological networks and transmitted drug resistance (TDR) over a 7-year period. Clusters were identified by Bayesian methods for 412 patients with B subtype; 145 individuals (35.2%) clustered in 34 distinct clades. Within epidemiological networks males were 93.1% (n=135); the same proportion of patients has been infected by the sexual route; 62.1% (n=90) were men having sex with men (MSM) of whom 67.8% (n=61) were NDs. Among heterosexuals (n=44), males were predominant (79.5%, n=35) and 77.3% (n=34) were NDs. TDR in clusters was 11.7 % (n=17), of whom 76.5% (n=13) was found in MSM. TDR was predominantly associated with NRTI resistance in individuals with chronic infection (n=11). A high prevalence of epidemiological networks has been found in the metropolitan area of Milan, indicating a high frequency of transmission events. The cluster analysis of networks suggested that the source of new infections was mainly represented by males and MSM who have long lasting HIV-1 infection. Notably, the prevalence of resistance-conferring mutations was higher in chronically infected patients, carrying mainly resistance to thymidine analogs, the backbone of first antiretroviral (ARV) generation. Intervention strategies of public health are needed to limit HIV-1 transmission and the associated TDR.     

Donor compatibility and performance status affect outcome of allogeneic haematopoietic stem cell transplant in patients with relapsed or refractory acute myeloid leukaemia

We retrospectively analysed 78 patients with relapsed (n?=?38), primary refractory (n?=?34) or untreated (n?=?6) acute myeloid leukaemia (AML) who underwent allogeneic HSCT at our Institution between 2002 and 2011, to verify outcome and to identify factors that can affect long-term outcome. Myeloablative conditioning regimens were used in 48 patients (24 siblings, 24 matched unrelated donor (MUD)), while 30 patients (18 siblings, 12 MUD) received reduced-intensity conditioning. Acute graft versus host disease (GVHD) developed in 37 (47?%) patients, while chronic GVHD occurred in 19 of the 65 evaluable patients (29?%). With a median follow-up time of 5?years, 13 of 78 patients (17?%) are alive and in complete remission (CR), while 64 have died. Cause of death was disease recurrence in 37 patients (58?%), infection in ten patients (16?%) and GVHD in six (9?%). One-year non-relapse mortality was 35?%. In multivariate analysis, performance status ≥80?% WHO and a full-matched donor were associated with a better outcome: these two variables allowed for risk stratification, identifying three groups with significantly different survival after transplant (P?=?0.0001). Considering post-transplant variables, only CR at recovery and development of cGVHD were correlated with a longer survival. Our data confirm the capacity of allogeneic transplant to prolong survival in a significant proportion of extremely high-risk AML patients.     

Ablation of perimitral flutter following catheter ablation of atrial fibrillation: impact on outcomes from a randomized study (PROPOSE)

MVI Block vs Trigger Ablation in PMFL . Introduction: Patients with previous ablation for atrial fibrillation (AF) may experience recurrence of perimitral flutter (PMFL). These arrhythmias are usually triggered from sources that may also induce AF. This study aims at determining whether ablation of triggers or completing mitral valve isthmus (MVI) block prevents more arrhythmia recurrences. Methods and Results: Sixty‐five patients with recurrent PMFL after initial ablation of long standing persistent AF were included in this study. Thirty‐two patients were randomized to MVI ablation only (Group 1) and 33 were randomized to cardioversion and repeat pulmonary vein (PV) isolation plus ablation of non‐PV triggers (Group 2). MVI bidirectional block was achieved in all but 1 patient from Group 1. In Group 2, reconnection of 17 PVs was detected in 14 patients (42%). With isoproterenol challenge, 44 non‐PV trigger sites were identified in 28 patients (85%, 1.57 sites per patient). At 18‐month follow‐up, 27 patients (84%) from Group 1 had recurrent atrial tachyarrhythmias, of whom 15 remained on antiarrhythmic drug (AAD); however, 28 patients from Group 2 (85%, P < 0.0001 vs Group 1) were free from arrhythmia off AAD. The ablation strategy used in Group 2 was associated with a lower risk of recurrence (hazard ratio = 0.10, 95% CI 0.04–0.28, P < 0.001) and an improved arrhythmia‐free survival (log rank P < 0.0001). Conclusion: In patients presenting with PMFL after ablation for longstanding persistent AF, MVI block had limited impact on arrhythmia recurrence. On the other hand, elimination of all PV and non‐PV triggers achieved higher freedom from atrial arrhythmias at follow‐up. (J Cardiovasc Electrophysiol, Vol. 23, pp. 137‐144, February 2012)     

Selexipag: an oral, selective prostacyclin receptor agonist for the treatment of pulmonary arterial hypertension

In this phase 2 proof-of-concept study we examined the safety and efficacy of selexipag, an orally available, selective prostacyclin receptor (IP receptor) agonist, as a treatment for pulmonary arterial hypertension (PAH). 43 adult patients with symptomatic PAH (receiving stable endothelin receptor antagonist and/or a phosphodiesterase type-5 inhibitor therapy) were randomised three to one to receive either selexipag or placebo. Dosage was up-titrated in 200-μg increments from 200 μg twice daily on day 1 to the maximum tolerated dose by day 35 (maximum allowed dose of 800 μg twice daily). Change in pulmonary vascular resistance at week 17 expressed as a percentage of the baseline value was the primary efficacy end-point, and was analysed in the per protocol set first and then in the all-treated set to assess robustness of results. A statistically significant 30.3% reduction in geometric mean pulmonary vascular resistance was observed after 17 weeks' treatment with selexipag compared with placebo (95% confidence limits -44.7- -12.2; p=0.0045, Wilcoxon rank sum test). This was supported by a similar result from the all-treated set. Selexipag was well tolerated with a safety profile in line with the expected pharmacological effect. Our results encourage the further investigation of selexipag for the treatment of PAH.     

Multicentre European study for the treatment of advanced emphysema with bronchial valves

This multicentre, blinded, sham-controlled study was performed to assess the safety and effectiveness of bronchial valve therapy using a bilateral upper lobe treatment approach without the goal of lobar atelectasis. Patients with upper lobe predominant severe emphysema were randomised to bronchoscopy with (n = 37) or without (n = 36) IBV Valves for a 3-month blinded phase. A positive responder was defined as having both a ≥ 4-point improvement in St George's Respiratory Questionnaire (SGRQ) and a lobar volume shift as measured by quantitative computed tomography. At 3 months, there were eight (24%) positive responders in the treated group versus none (0%) in the control group (p = 0.002). Also, there was a significant shift in volume in the treated group from the upper lobes (mean ± SD -7.3 ± 9.0%) to the non-treated lobes (6.7 ± 14.5%), with minimal change in the control group (p<0.05). Mean SGRQ total score improved in both groups (treatment: -4.3 ± 16.2; control: -3.6 ± 10.7). The procedure and devices were well tolerated and there were no differences in adverse events reported in the treatment and control groups. Treatment with bronchial valves without complete lobar occlusion in both upper lobes was safe, but not effective in the majority of patients.     

Influence of upper airway size on volume exhaled under negative pressure during evaluation of upper airway collapsibility

Study objectives  

It has been shown that volume exhaled in the first 0.5 s after application at the mouth of 5 cmH₂O negative pressure (V,NEP_0.5) during wakefulness strongly reflects critical pressure (Pcrit) during sleep but only in males with neck circumference (NC) >37 cm. The aim of this study was to establish the relationship between upper airway (UA) size and V,NEP_0.5, to obtain V,NEP_0.5 values as percent predicted and then correlate them with Pcrit obtained in the same subjects.     

Post-load insulin resistance does not predict virological response to treatment of chronic hepatitis C patients without the metabolic syndrome

Background and aimThe role of insulin resistance in predicting virological response to therapy of chronic hepatitis C is debated. We assessed the association between basal (defined as homeostasis model assessment of insulin resistance (HOMA-IR) > 2) and post-load insulin resistance (as oral glucose insulin sensitivity index < 9.8 mg/kg/min) with the rapid and sustained virological responses in chronic hepatitis C.MethodsObservational prospective study of 124 treatment-naïve patients with chronic hepatitis C not fulfilling the metabolic syndrome criteria, adherent to a standard treatment with pegylated interferon alpha plus ribavirin.ResultsInsulin resistance was detected in 50% (by HOMA-IR) and 29% (by oral glucose insulin sensitivity index) of patients. Independent predictors of rapid virologic response were hepatitis C virus (HCV) genotype 2 (odds ratio 5.66; 95% confidence interval 1.88–17.01), HCV genotype 3 (odds ratio 5.23; 95% confidence interval 1.84–14.84) and lower basal ferritin levels (odds ratio 0.99; 95% confidence interval 0.993–0.998). Independent predictors of sustained virologic response were HCV genotype 2 (odds ratio 19.54; 95% confidence interval 2.29–166.41) and HCV genotype 3 (odds ratio 3.24; 95% confidence interval 1.10–9.58). Rapid virologic response was by itself predictive of sustained virologic response (odds ratio 40.90; 95% confidence interval 5.37–311.53).ConclusionsInsulin resistance, measured by both static and dynamic methods, does not predict rapid or sustained virologic response in chronic hepatitis C patients without the metabolic syndrome.     

Gender differences in benign renal masses

Purpose

To examine gender-specific differences in benign renal tumors.

Methods

This retrospective study included 135 adult Caucasian patients with 143 benign renal tumors, which were treated surgically at a single institution. Demographics, comorbidity, histology, renal function, and management were compared by gender. A systematic review and meta-analysis of the literature were performed.

Results

A total of 73 women were compared with 62 men. The female-to-male ratio was significantly higher in patients with benign renal tumors than in those with renal cell carcinoma (1.18:1 vs. 0.57:1, p < 0.001). Only 17 % of benign renal tumors were correctly classified by preoperative computed tomography. The most frequently observed histological types were oncocytoma (44 %) and angiomyolipoma (37 %). Angiomyolipoma occurred more than twice as often in women than in men (72 vs. 28 %), while oncocytoma was more frequently found in men (59 vs. 41 %, p = 0.001). Men with benign renal tumors were older (p = 0.002) and had higher body mass indices (p = 0.019), higher comorbidity indices (p < 0.001), lower ECOG performance status (p < 0.001), and smaller tumors (p = 0.045). No differences were seen in pack years, mode of diagnosis, bilaterality, renal function, use of laparoscopic surgery, and the rate of radical nephrectomy. In the meta-analysis of 9,665 renal tumors, women had a 2.55-fold increased chance of benign pathology and a greater chance of angiomyolipoma (OR 4.66) than men.

Conclusions

This study demonstrated several gender-specific differences in benign renal tumors, especially in the histological types. Despite this, clinical–pathological features and management of benign renal tumors in men and women appear more alike than different.