Immunological evidence of an early seroconversion to oncogenic Merkel cell polyomavirus in healthy children and young adults

Oncogenic Merkel cell polyomavirus (MCPyV) provokes a widespread and asymptomatic infection in humans. Herein, sera from healthy children and young adults (HC, n = 344) aged 0–20 years old were evaluated for anti-MCPyV immunoglobulin G (IgG) and IgM antibodies employing a recently developed immunoassay. Serum MCPyV IgG data from healthy subjects (HS, n = 510) and elderlies (ES, n = 226), aged 21–65/66–100 years old, from our previous studies, were included. The anti-MCPyV IgG and IgM rates in HC sera were 40.7% and 29.7%, respectively. A lower prevalence of anti-MCPyV IgGs was found in HC aged 0–5 years old (13%) compared to 6–10 (52.3%), 11–15 (60.5%) and 16–20 years old (61.6%) cohorts. Age-stratified HCs exhibited similar anti-MCPyV IgM rates (27.9%–32.9%). Serological profiles indicated that anti-MCPyV IgGs and IgMs had low optical densities (ODs) during the first years of life, while IgM ODs appeared to decrease throughout young adulthood. A lower anti-MCPyV IgGs rate was found in HC (40.7%) than HS (61.8%) and ES (63.7%). Upon the 5-years range age-stratification, a lower anti-MCPyV IgGs rate was found in the younger HC cohort aged 0–5 years old compared to the remaining older HC/HS/ES cohorts (52.3%–72%). The younger HC cohort exhibited the lowest anti-MCPyV IgG ODs than the older cohorts. Low anti-MCPyV IgMs rates and ODs were found in the 21–25 (17.5%) and 26–30 (7.7%) years old cohorts. Our data indicate that, upon an early-in-life seroconversion, the seropositivity for oncogenic MCPyV peaks in late childhood/young adulthood and remains at high prevalence and relatively stable throughout life.     

An open-randomized clinical trial of selegiline in amyotrophic lateral sclerosis

Based on the hypothesis that free radicals play a general role in the neurodegenerative process in motor neuron disease, we tested selegiline in a group of patients affected by amyotrophic lateral sclerosis (ALS) to examine whether it might modify the progression of the disease. Patients were admitted if they were 25–80 years old and had a confirmed diagnosis of ALS with symptoms lasting no longer than 24 months. Patients with familial ALS, pure progressive bulbar palsy, primary lateral sclerosis or progressive muscle atrophy were excluded; a total of 111 patients were recruited. Fifty-three patients were randomly assigned to receive the drug (selegiline 10 mg/day orally for 6 months) and the remaining 58 were considered ALS controls. Mortality was similar in the two groups (4 and 5 patients respectively), though the difference was not statistically significant. Among the survivors, mean MRC and Norris disability scores and forced vital capacity were fairly similar in the two groups at all times and no statistically significant difference between treated and untreated patients was found. The results did not change when the data were related to age, duration and characteristics of onset of the disease. The rate of progression was significantly more rapid in patients with bulbar symptoms in both groups. Our data do not show any significant effect of selegiline in modifying the progression of ALS.     

Evidence based assessment of long-term results of plaque incision and vein grafting for Peyronie's disease

PURPOSE: We assessed the long-term outcome of plaque incision and vein grafting in select patients with Peyronie's disease by extensive preoperative and postoperative subjective and objective analysis. MATERIALS AND METHODS: From January 1995 to June 1998, 50 men 28 to 62 years old (mean age 44) underwent surgery. Patients were evaluated preoperatively, 3 months after surgery and at a mean long-term followup of 32 months by sexual history, physical examination, determination of penile length and degree of curvature, dynamic color power Doppler sonography of the penile vessels and nocturnal RigiScan* evaluation for 3 nights. Study inclusion criteria were penile curvature 45 degrees or greater that made vaginal intromission impossible, stable disease for at least 6 months, patient reported normal penile rigidity, normal penile hemodynamics on color power Doppler ultrasound, normal nocturnal penile rigidity with at least 1 erection nightly (including base and tip rigidity greater than 60%, and a duration of 10 minutes) and absent base-tip discrepancies. Plaque was usually approached via a combined subcoronal and midline sagittal scrotal incision. Maximal rigidity was created intraoperatively and 1 to 3 plaque incisions were made. Saphenous vein patches were then grafted at the incision sites. Postoperatively patients were systemically treated with neurotrophic factors and low molecular weight heparin. Local vacuum supported corporeal stretching was done and weekly alprostadil injections were given to optimize corporeal oxygenation. RESULTS: At long-term followup complete penile straightening was achieved in 40 cases (80%), minor residual curvature of 30 degrees or less persisted in 7 (14%) and significant disease recurred in 3 (6%). Penile rigidity was equal to that preoperatively in 47 patients (94%), while 3 (6%) reported clinically significant decreased potency. Penile length was equal to that preoperatively in 30 patients (60%), while 20 (40%) noticed slight penile shortening. Postoperatively penile color power Doppler sonography showed vascular impairment in 5 men (10%) and nocturnal RigiScan testing revealed a significant decrease in nightly erections in 5 (10%). Surgical complications included penile hypoesthesia in 1 case (2%), penile hematoma in 2 (4%), wound infection in 1 (2%) and glandular ischemia in 1 (2%). CONCLUSIONS: Plaque incision and vein grafting achieved satisfactory clinical results in the majority of patients with severe and stable Peyronie's disease, intact penile rigidity preoperatively, normal penile color power Doppler ultrasound and normal nocturnal RigiScan testing.     

Saporin-S6: A Useful Tool in Cancer Therapy

Thirty years ago, the type 1 ribosome-inactivating protein (RIP) saporin-S6 (also known as saporin) was isolated from Saponaria officinalis L. seeds. Since then, the properties and mechanisms of action of saporin-S6 have been well characterized, and it has been widely employed in the construction of conjugates and immunotoxins for different purposes. These immunotoxins have shown many interesting results when used in cancer therapy, particularly in hematological tumors. The high enzymatic activity, stability and resistance to conjugation procedures and blood proteases make saporin-S6 a very useful tool in cancer therapy. High efficacy has been reported in clinical trials with saporin-S6-containing immunotoxins, at dosages that induced only mild and transient side effects, which were mainly fever, myalgias, hepatotoxicity, thrombocytopenia and vascular leak syndrome. Moreover, saporin-S6 triggers multiple cell death pathways, rendering impossible the selection of RIP-resistant mutants. In this review, some aspects of saporin-S6, such as the chemico-physical characteristics, the structural properties, its endocytosis, its intracellular routing and the pathogenetic mechanisms of the cell damage, are reported. In addition, the recent progress and developments of saporin-S6-containing immunotoxins in cancer immunotherapy are summarized, including in vitro and in vivo pre-clinical studies and clinical trials.     

Self-reported influenza vaccination uptake in people with chronic diseases: data from Progressi delle Aziende Sanitarie per la Salute in Italia (PASSI)

BackgroundInfluenza is an important public health problem, with potential severe consequences among people with chronic diseases. The aim of this study was to obtain reliable measures of seasonal influenza vaccine uptake in this population, otherwise not available in Italy.MethodsProgressi delle Aziende Sanitarie per la Salute in Italia (PASSI) is a nationwide surveillance system of health-related behaviours and acceptance of preventive interventions (including influenza immunisation) offered by the Italian National Health Service. Data are collected with telephone interviews at local health unit level for supporting local activities. The survey sample is randomly selected from local health unit lists of adult residents. The trend of annual vaccine coverage since 2008 was estimated for people aged 18–64 years who reported having at least one chronic disease. To obtain a sufficient sample size in subgroups, we analysed the characteristics of vaccinated people in the 2010–13 cumulative dataset. Univariate, multivariate, and logistic regression analyses were undertaken.FindingsIn 2008–13, 13 659 individuals with at least one chronic disease were interviewed. Vaccination coverage fell significantly from 29·7% (95% CI 27·2–32·4) in 2007–08 to 19·9% (18·0–22·1) in 2012–13. During 2010–13, the overall proportion of vaccinated people with a chronic disease was 25·6% (24·5–26·7). Vaccine coverage of people with diabetes (34·3%, 31·7–36·9) or cardiovascular diseases (31·8%, 29·6–34·2) was greater than that of people affected by renal failure, respiratory diseases, tumours, or chronic liver diseases (26·5% [22·5–30·7], 24·9% [23·2–26·7], 22·2% [20·0–24·6], and 20·6% [17·5–24·6], respectively). Vaccination coverage increased with age (from 13·1% [11·0–15·5] in the 18–34 year age group to 33·4% [31·9–35·1] in people aged 50–64 years); it was higher among people with a low educational level than among those with a high educational level, higher in those having economic difficulties than in those with no economic difficulties, and higher among Italian citizens than among non-citizens.InterpretationIn the past few years, prevalence of influenza vaccination in Italian adults with at least one chronic disease was well below the Ministry of Health's goal (75% minimum) and showed a downward trend. A major reason of this evolution is probably the changing public perception of the benefits and risks of vaccines. PASSI is a source of useful data not otherwise available for public health intervention.FundingItalian Ministry of Health.     

An area-based study on intrapartum antibiotic prophylaxis for preventing group B streptococcus early-onset disease: advances and limitations

Introduction: The prevalence of maternal group-B-streptococcus (GBS) colonization and risk factors (RFs) for neonatal early-onset disease (EOD) in Europe are poorly defined. Large-scale information concerning adherence to recommendations for preventing GBS-EOD are lacking.

Materials and methods: This was a 3-month retrospective area-based study including all regional deliveries ≥35 weeks' gestation (in 2012). The sensitivity, specificity, positive and negative predictive values, odds ratio and receiver operating characteristic (ROC) curve for intrapartum antibiotic prophylaxis (IAP) among full-term and preterm deliveries and prolonged membrane rupture (PROM) were calculated.

Results: Among 7133 women, 259 (3.6%) were preterm (35–36 weeks' gestation). Full-term women were 6874, and 876 (12.7%) had at least 1?RF. Most women (6495) had prenatal screening and 21.4% (1390) were GBS positive.

IAP was given to 2369 (33.2%) women (preterm, n?=?166; full term, n?=?2203). Compared to full-term, preterm women were less likely to receive IAP when indicated (73.2% versus 90.3%, p?Conclusions: Large-scale prenatal screening and IAP are feasible. Women delivering preterm are less likely to receive IAP when indicated. Most unnecessary antibiotics are given in cases of PROM.