Complement inhibition for prevention of antibody-mediated rejection in immunologically high-risk heart allograft recipients

Allosensitization represents a major barrier to heart transplantation (HTx). We assessed the efficacy and safety of complement inhibition at transplant in highly sensitized heart transplant recipients. We performed a single-center, single-arm, open-label trial (NCT02013037). Patients with panel reactive antibodies (PRA) ≥70% and pre–formed donor-specific antibodies (DSA) were eligible. In addition to standard of care, patients received nine infusions of eculizumab during the first 2 months posttransplant. The primary composite endpoint was antibody-mediated rejection (AMR) ≥pAMR2 and/or left ventricular dysfunction during the first year. Secondary endpoints included hemodynamic compromise, allograft rejection, and patient survival. Twenty patients were included. Median cPRA and mean fluorescence intensity of immunodominant DSA were 95% (90%–97%) and 6250 (5000–10 000), respectively. Retrospective B cell and T cell flow crossmatches were positive in 14 and 11 patients, respectively. The primary endpoint occurred in four patients (20%). Survival at 1 year was 90% with no deaths resulting from AMR. In a prespecified analysis comparing treated patients to matched control patients, we observed a dramatic reduction in the risk of biopsy-proven AMR in patients treated with eculizumab (HR = 0.36, 95% CI = 0.14–0.95, p = .032). Our findings support the prophylactic use of complement inhibition for heart transplantation at high immunological risk. ClinincalTrials.gov, NCT02013037.     

New anatomical reference systems for the bones of the foot and ankle complex: definitions and exploitation on clinical conditions

Medial tibial stress syndrome (MTSS) is one of the most common lower leg injuries in sporting populations. It accounts for between 6 and 16% of all running injuries, and up to 53% of lower leg injuries in military recruits. Various treatment modalities are available with varying degrees of success. In recalcitrant cases, surgery is often the only option. To evaluate whether ultrasound-guided injection of 15% dextrose for treatment of recalcitrant MTSS decreases pain and facilitates a return to desired activity levels for those who may otherwise be considering surgery or giving up the sport. The study design was a prospective consecutive case series involving eighteen patients: fifteen male and three female; (mean age = 31.2 years) with recalcitrant MTSS. They were referred from sports injury clinics across the UK, having failed all available conservative treatment. An ultrasound-guided sub-periosteal injection of 15% dextrose was administered by the same clinician (NP) along the length of the symptomatic area. Typically, 1 mL of solution was injected per cm of the symptomatic area. Pain was assessed using a 10-cm visual analog scale (VAS) at baseline, short-term, medium-term (mean 18 weeks), and long-term (mean 52 weeks) follow-up. Symptom resolution and return to activity were measured using a Likert scale at medium and long-term follow-up. Statistical analyses were performed using SPSS for Mac version 19.0.0 (IBM, New York, NY, US). The Shapiro-Wilk test was used to evaluate the normality of the distribution of data. Friedman’s non-parametric test was used to compare the within-patient treatment response over time. Post-hoc Wilcoxon signed-rank tests with Bonferroni corrections were performed to determine VAS average pain response to treatment over five paired periods. Patients reported a significant (p < 0.01) reduction in median VAS pain score at medium and long-term follow-up compared to baseline. Median improvement per patient was 4.5/10. Patients rated their condition as ‘much improved’ at medium-term follow-up and the median return to sports score was ‘returned to desired but not pre-injury level’ at medium-term and long-term follow-up. No adverse events were reported. Ultrasound-guided 15% dextrose prolotherapy injection has a significant medium-term effect on pain in MTSS. This benefit may be maintained long-term; however, more robust trials are required to validate these findings in the absence of controls. Clinicians should consider the use of ultrasound-guided injection of 15% dextrose as a viable treatment option to reduce pain and aid return to activity for patients with recalcitrant MTSS.     

Thermal discomfort in healthcare workers during the COVID-19 pandemic

Introduction:Due to the COVID-19 pandemic, healthcare workers are now required to use additional personal protective equipment (PPEs) to protect themselves against the virus. That led to an increased clothing insulation which is negatively affecting the perceived healthcare workers’ thermal sensation.Objectives:While demonstrating through software simulations the potential level of thermal discomfort healthcare workers involved in the COVID-19 emergency can be subjected to, this work aims at identifying measures to improve thermal sensation perception and acceptable thermal conditions for medical personnel.Methods:After having obtained the insulation values of individual clothing used by staff during COVID-19 emergency through the use of a thermal well-being evaluation software, the Fanger indexes (PMV - Predicted Mean Vote and PPD - Predicted Percentage of Dissatisfied) were calculated in order to estimate staff satisfaction to microclimatic conditions.Results:The use of COVID-19 additional PPEs with an air temperature equal to 22 °C (normally considered optimal) brings the PMV index equal to 0.6, which corresponds to 11.8 % being unsatisfied (PPD) due to perceived heat.Discussion:The use of additional protective devices significantly increases the clothing insulation level, facilitating the onset of conditions of thermal discomfort in the health workers. Workers engaged in the execution of nasopharyngeal swabs were most affected by the summer weather conditions and certainly represent the most critical category, for which it would be recommended to implement a higher turnover of service to reduce individual exposure time and consequent discomfort.     

Incentives for voluntary health insurance in a national health system: Evidence from Italy

ObjectivesThe paper evaluates the extent to which the government's policy to encourage the purchase of voluntary health insurance (VHI) may have led to income-related horizontal inequity in access to health care in a universal health care system (NHS).MethodsAd hoc tax return data for the universe of Italian taxpayers for years 2009-2016 are used to estimate the tax benefits granted to taxpayers who hold VHI, the redistributive impact, and the public budget effect. The income elasticity of tax benefits is estimated using tax return data and considering some taxpayers’ characteristics (income class, gender, age, and geographic area). Standard inequality indices are computed to assess income-related horizontal inequity in access to health care.ResultsTax incentives, especially those granted to employer-paid health insurance, have a sizeable impact on tax revenue and introduce into the Italian NHS significant income-related horizontal and vertical inequity in access to health care. The results suggest a distributional profile of tax incentives that is highly concentrated in favor of wealthier taxpayers.ConclusionOur analysis adds novel evidence that may contribute to the current debate on whether and to what extent countries in which all citizens have access to free healthcare and equal standards of healthcare services should subsidize VHI, especially when the coverage doubles the healthcare services provided by universal public insurance. We show that VHI reduces tax revenues and introduces disparities among citizens in terms of access to healthcare services.     

Healthcare Workers’ (HCWs) attitudes towards mandatory influenza vaccination: A systematic review and meta-analysis

Influenza is a disease responsible for thousands of deaths every year. Although healthcare workers (HCWs) represent a way of contagion for patients, vaccination coverage among them is low. Mandatory vaccination has been proposed, but controversies remain. This systematic review and meta-analysis aimed to assess the acceptance of mandatory vaccination by HCWs, and to investigate associated characteristics. MEDLINE, Scopus, Embase, PsycInfo, CINAHL and Web of Science were used to search for studies assessing the topic. PRISMA statements were followed. Of the 13,457 univocal records found, 52 studies were included in the systematic review and 40 in the meta-analysis. The pooled proportion of HCWs accepting the policy was of 61% (95% CI: 53%- 68%) but with great heterogeneity between continents (from 54% in Europe to 69% in Asia) and in different professionals (from 40% in nurses to 80% in students). Vaccinated HCWs agreed more frequently with mandatory vaccination than non-vaccinated ones. More studies that consider mandatory vaccination acceptance as the main outcome are needed, but the results of this study confirm that in some settings the majority of HCWs favour mandatory vaccination. This, combined with effects that a flu epidemic could have if overlapped to pandemics with similar symptoms, requires renewed considerations on mandatory vaccination.     

Zoledronic acid-related angiogenesis modifications and survival in advanced breast cancer patients.

The proven antiangiogenic activity of zoledronic acid, a third-generation bisphosphonate widely used in bone metastatic cancer patients, led us to investigate if the vascular endothelial growth factor (VEGF)-related zoledronic acid modifications are correlated with survival advantages in advanced breast cancer patients. Forty-two consecutive breast cancer patients with scintigraphic and radiographic evidence of bone metastases were treated with a single infusion of 4 mg zoledronic acid before anticancer chemotherapy. The patients were prospectively evaluated for circulating levels of VEGF and interferon-gamma (IFN-gamma) just before and at 1, 2, 7, and 21 days after zoledronic acid infusion. Afterward, clinical outcome was prospectively monitored. The basal serum VEGF median levels were significantly decreased at each time point, but the major reduction was recorded 21 days after the infusion. In particular, 25 patients of 42 (59.5%) experienced a reduction of at least 25% in the VEGF circulating levels. In contrast, no statistically significant modifications of the IFN-gamma serum levels were recorded. We stratified patients on the basis of this VEGF reduction 21 days after the infusion. No differences in patient features were recorded between those with or without the VEGF reduction. The analysis of survival showed that patients with a reduction in the VEGF circulating levels had a longer time to first skeletal-related event (p = 0.0002), time to bone progression disease (p = 0.0024), and time to performance status worsening (p = 0.0352) than those without the VEGF reduction. No statistically significant differences were recorded in terms of overall survival and time to visceral progression. This study confirms that zoledronic acid could have an in vivo antiangiogenic property and that the VEGF modifications may represent a surrogate marker able to predict time to first skeletal-related event, time to bone progression disease, and time to worsening of performance status.     

Non-traumatic brain abscess

Between 1953 and 1989 eighty cases of non-traumatic brain abscess were treated in our department. We have re-examined the clinical and neuroradiological features of this pathological process and present our therapeutic approach and results. We believe that the optimal treatment for brain abscess consists of surgical removal.The prognosis for these lesions has undergone a marked improvement over the last two decades in response to neuroradiological, microbiological and surgical advances. The most influential prognostic factor seems to be preoperative clinical status.     

Prospective Recruitment of Women Receiving Prenatal Care from Diverse Provider Arrangements: A Potential Strategy

Objectives: This study describes the use of a Medicaid managed care list to prospectively recruit into a research project pregnant women receiving care from a variety of providers. Method: A list of women enrolled in Medicaid managed care was used to recruit pregnant African-American and Latina women into a study of prenatal care satisfaction. Due to privacy concerns, the researchers were not able to directly access names from the list. Instead, a managed care contract agency sent recruitment letters to 1009 pregnant African-American and Latina Medicaid recipients. Response rates by ethnicity and several other key variables are calculated. The biases associated with this method of recruiting pregnant women from a variety of providers are discussed. Results: Thirty-five percent of the women contacted returned consent forms and agreed to have researchers approach them; the response rate for African-American women was 43% and for Latinas was 29% (p < 0.0001). Respondents were younger and later in their pregnancies than nonrespondents, but did not differ from them by zip code of residence. The women recruited into the study obtained prenatal care from a diverse group of providers. Conclusions: While the use of a prospectively generated list of pregnant Medicaid recipients to recruit low-income pregnant women into a research study may be associated with some selection bias, the potential cost savings, decreased effort, and diminished recall bias may make their use a feasible sampling alternative, particularly when the researcher desires to recruit women seeking care from a variety of provider arrangements.     

Prevalence of hepatitis C virus genotypes in southern Italy

HCV is ubiquitous. In 50% of all cases it causes chronic hepatitis that often evolves into liver cirrhosis and hepatocellular carcinoma. Recently HCV has been classified in 5 genotypes by Okamoto. The purpose of this study is to evaluate the prevalence of 5 genotypes in Campania, a region of Southern Italy, where the prevalence of anti-HCV antibodies ranges from 0.87 to 4%, and to evaluate the correlation between the HCV genotypes and the severity of histological damage. One hundred and thirty-five anti-HCV positive patients were enrolled and tested by PCR to identify HCV-RNA. One hundred and twenty-four patients resulted HCV-RNA positive. Genotyping was performed as described by Okamoto et al. with minor modifications of the specific primer to type III proposed by Silini et al. Eight patients were negative for all genotypes. Eight patients were positive for type I(1a), 61 for type II(1b), 39 for type III(2a), 11 for type IV(2b) and 1 for type V(3a). In 4 cases two different genotypes were present in the same sample [II(1b)-IV(2b), III(2a)-II(1b) twice, III(2a)-IV(2b)]. Histological evaluation of liver damage showed: CPH (22 cases), minimal CAH (56), severe CAH (31) and liver cirrhosis (15). There was no statistically significant correlation between the 5 genotypes and the severity of histological damage. Data on the prevalence of genotype II(1b) in Italy are similar to those reported for other European countries. The prevalence of genotypes in Southern Italy is similar to that reported in the population of Northern Italy.     

Molecular approach to the nucleo-melanosomal interaction in human melanoma cells

This paper presents evidence that L-tyrosine oxidation products and 5,6-dihydroxyindole, an intermediate of melanin synthesis bind to and modify DNA structure, as tested by extracting cell DNA, using topoisomerase I and denaturation assays. When supercoiled plasmid pCU18 or pBR322 DNAs are treated with 5,6-dihydroxyindole the supercoiled species disappear and are converted to species less mobile in a gel retardation test with respect to relaxed DNA. 5,6-Dihydroxyindole causes an easier acid denaturation of the double helix. The results, that are dose dependent,would point to both intercalation and cross-linking of DNA by 5,6-dihydroxyindole and its oxidation product(s). ³H-L-tyrosine deriving radioactivity, bound to nuclear DNA, is higher at low pH, (5.6) if compared to pH 6.8. The highest radioactivity bound to cell DNA is found during the transition from the amelanotic to the melanotic phenotype in human melanoma cell lines. As a control, the binding of ³H-L-tyrosine radioactivity to human prostate fibroblast DNA was investigated.