Position Statement on Vascular Access Safety for Percutaneous Devices in AMI Complicated by Cardiogenic Shock.

In the United States, the frequency of using percutaneous mechanical circulatory support devices for acute myocardial infarction complicated by cardiogenic shock is increasing. These devices require large-bore vascular access to provide left, right, or biventricular cardiac support, frequently under urgent/emergent circumstances. Significant technical and logistical variability exists in device insertion, care, and removal in the cardiac catheterization laboratory and in the cardiac intensive care unit. This variability in practice may contribute to adverse outcomes observed in centers that receive patients with cardiogenic shock, who are at higher risk for circulatory insufficiency, venous stasis, bleeding, and arterial hypoperfusion. In this position statement, we aim to: 1) describe the public health impact of bleeding and vascular complications in cardiogenic shock; 2) highlight knowledge gaps for vascular safety and provide a roadmap for a regulatory perspective necessary for advancing the field; 3) propose a minimum core set of process elements, or "vascular safety bundle"; and 4) develop a possible study design for a pragmatic trial platform to evaluate which structured approach to vascular access drives most benefit and prevents vascular and bleeding complications in practice.

Heart Failure Population with Therapeutic Response to Sacubitril/Valsartan, Spironolactone and Candesartan: FDA Perspective.

Sacubitril/valsartan was approved by the Food and Drug Administration in 2015 to reduce the risk of cardiovascular death and hospitalization for heart failure (HHF) in patients with chronic heart failure with reduced ejection fraction defined as left ventricular ejection fraction (LVEF) ≤ 40%. This approval was based on PARADIGM-HF trial. Subsequently, PARAGON-HF was conducted to support a claim for sacubitril/valsartan in patients with heart failure with preserved ejection fraction (HFpEF), defined as LVEF ≥ 45%. PARAGON-HF failed to meet the pre-defined threshold for statistical significance for the primary composite endpoint. However, analysis of the primary endpoint by LVEF as a continuous variable demonstrated that sacubitril/valsartan was efficacious in patients with mildly abnormal LVEF similar to patients with LVEF ≤ 40% evaluated in PARADIGM-HF. This led to a broader indication for sacubitril/valsartan-"to reduce the risk of cardiovascular death and hospitalization for heart failure in adult patients with chronic heart failure. Benefits are most clearly evident in patients with left ventricular ejection fraction (LVEF) below normal. LVEF is a variable measure, so use clinical judgment in deciding whom to treat." This article describes the rationale for a revised indication for sacubitril/valsartan, emphasizes the need to go beyond a dichotomous classification of HF based on a traditional LVEF cut-off and clarifies that the product label for sacubitril/valsartan does not refer to HFpEF.

[Evaluation of a pulsed xenon ultraviolet light- emitting no-touch, portable device for disinfection of surfaces in operating rooms in the Policlinico University Hospital of Foggia, Italy, 2019. Preliminary results]. / Efficacia di un sistema di trattamento no-touch con unità mobile a luce UV pulsata allo Xeno per la disinfezione delle superfici nelle sale operatorie: risultati preliminari nel Policlinico Riuniti di Foggia, 2019.

OBJECTIVES: To evaluate the effectiveness and the frequency of use of a pulsed xenon ultraviolet light-emitting no-touch portable device (PX-UV), applied after perform current cleaning, in reducing environmental bacterial burden and the presence of pathogens on surfaces in the operating rooms at the Policlinico University Hospital of Foggia. DESIGN: Prospective before-and-after study with a follow up duration of four months, from May to August 2019. SETTING AND PARTICIPANTS: Two operating rooms of an Orthopaedic and a Neurosurgical ward in a 780-bed university hospital in the District of Foggia, Italy (about 600,000 inhabitants). MAIN OUTCOME MEASURES: According to the hygienic standards proposed by the Italian Workers Compensation Authority (ISPESL), the total and the average bacterial load and the presence of six pathogens were evaluated between pre- and post- PX-UV use combined with routine manual cleaning. RESULTS: The PX-UV system was applied at five distinct time points: t1: start of the experiment, t2: after 28 days, t3: after 13 days, t4: after 7 days, and t5: after 8 days (t2-t5: 28 days in total). About 16-min of PX-UV cycle showed significant reduction in the level of environmental contamination by decreasing the mean colony count by 87.5%, compliant with the standard (5< X ≤15 CFU per plat). Staphylococcus aureus and Acinetobacter baumannii that had been isolated in some of the samplings before PX-UV were no longer detected after t1, t2 and t5 treatments. Before PX-UV, the mean colony count was similar between t1 and t2 (p>0.05); after t3 and t4 treatments, it was lower before t5 in both the Orthopaedic and Neurosurgical operating rooms (= -97% and -75%, respectively; p<0,01). CONCLUSIONS: Implication for practice: PX-UV could supplement the standard cleaning process in reducing the microbial burden in the operating rooms and potentially achieving lower healthcare-associated surgical site infections rates.

Varicella zoster immunity loss in multiple sclerosis patient treated with ocrelizumab.

Ocrelizumab is a novel humanized anti-CD20 antibody used for treatment of relapsing remitting and primary progressive multiple sclerosis with evidence of inflammatory activity. Guidelines suggest assessing vaccination status and eventually vaccinate patients with multiple sclerosis before new disease modifying therapy initiation. However, there are not any specific recommendations about vaccinal immunity reassessment after ocrelizumab injection. We describe the case of a patient who loss varicella zoster vaccinal immunity after the first ocrelizumab infusion. It is advisable to reassess vaccinal immunity to isolate non-immune patients and to adopt suitable preventive measures, including close contacts vaccination and avoidance of contacts with active infection.

Impaired autophagy increases susceptibility to endotoxin-induced chronic pancreatitis.

Chronic pancreatitis (CP) is associated with elevated plasma levels of bacterial lipopolysaccharide (LPS) and we have demonstrated reduced acinar cell autophagy in human CP tissue. Therefore, we investigated the role of autophagy in experimental endotoxin-induced pancreatic injury and aimed to identify LPS in human CP tissue. Pancreatic Atg7-deficient mice were injected with a single sub-lethal dose of LPS. Expression of autophagy, apoptosis, necroptosis, and inflammatory markers was determined 3 and 24 h later utilizing immunoblotting and immunofluorescence. The presence of LPS in pancreatic tissue from mice and from patients and healthy controls was determined using immunohistochemistry, immunoblots, and chromogenic assay. Mice lacking pancreatic autophagy exhibited local signs of inflammation and were particularly sensitive to the toxic effect of LPS injection as compared to control mice. In response to LPS, Atg7Δpan mice exhibited enhanced vacuolization of pancreatic acinar cells, increase in TLR4 expression coupled to enhanced expression of NF-κΒ, JNK, and pro-inflammatory cytokines by acinar cells and enhanced infiltration by myeloid cells (but not Atg7F/F controls). Cell death was enhanced in Atg7Δpan pancreata, but only necroptosis and trypsin activation was further amplified following LPS injection along with elevated pancreatic LPS. The presence of LPS was identified in the pancreata from all 14 CP patients examined but was absent in the pancreata from all 10 normal controls. Altogether, these results support a potential role for metabolic endotoxemia in the pathogenesis of CP. Moreover, the evidence also supports the notion that autophagy plays a major cytoprotective and anti-inflammatory role in the pancreas, and blunting metabolic endotoxemia-induced CP.

COVID-19: Effects of lockdown on adenotonsillar hypertrophy and related diseases in children.

BACKGROUND: In response to the coronavirus pandemic 2019 (COVID-19), Italy established the national school closings from March 5, 2020. It has been shown that during school closures, there are significant decreases in the diagnoses of the respiratory infections. This has brought as well to a reduction in all those symptoms related to adenotonsillar hypertrophy. METHODS: The study included 162 children, aged between 3 and 13 years, waiting for adenoidectomy and/or tonsillectomy, eventually combined with tympanocentesis or tube insertion. Parents have been called to answer a telephone interview aimed at detecting how the symptoms related to adenotonsillar hypertrophy were changing during lockdown. RESULTS: There was an improvement in the overall symptomatology of children during the lockdown period. The value attributed by parents to the children's general assessment during the lockdown period decreased significatively during the quarantine (p = 0,0000). CONCLUSIONS: The present study demonstrates that lockdown can have a positive impact on those specific diseases derived from precocious socialization and that it results to be particularly effective for the most vulnerable children. Indeed, lockdown has resulted to be so efficient that it has caused a modification in a medical and surgical therapeutic indication.

The impact of age on intravesical instillation of Bacille Calmette-Guerin treatment in patients with high-grade T1 bladder cancer.

Intravesical instillation of Bacille Calmette-Guèrin (BCG) is the standard adjuvant treatment for high-risk non muscle invasive bladder cancer (NMIBC). Since its mechanism of action is supposed to be linked to the immune system efficiency and senescence could negatively affect this efficiency, BCG efficacy in the elderly has been questioned. This study aimed to assess the impact of age on BCG efficacy and safety in patients with high-grade T1 bladder cancer (BC).Among 123 patients with high-grade T1 BCG scheduled for BCG treatment, 82 were <75 year-old (group A) and 41 were ≥75 year-old (group B). Follow-up: urine cytology and cystoscopy every 3 months for the first 2 years, every 6 months for the third year, and then yearly. Tumor recurrence was defined as pathological evidence of disease at the bladder biopsy; tumor progression was defined as pathological shift to muscle invasive disease at the bladder biopsy or the imaging techniques showing recurrent BC and distant metastasis likely related to it.The median follow-up was 65 months (range 11-152). Recurrence occurred in 35 patients, 19 (23.2%) in the group A and 16 (39%) in the group B. Progression occurred in 18 patients, 12 (14.6%) in the group A and 6 (14.6%) in the group B. Recurrence free rate was similar in both groups up to 2 years. The 5 years progression rate was almost the same in both groups A and B (85.9% vs 84.7%), whereas the 5 years cancer-specific survival (CSS) was 92.6% in the group A and 85.4% in the group B. Of the 18 patients with progression, 11 underwent cystectomy; 12 patients died because of their BC. Kaplan-Meier plots pointed out no difference in recurrence-free, progression-free, and CSS between the 2 groups. Adverse events were similar in the 2 groups. Only 4 (3.3%) patients, 2 (2.4%) in the group A and 2 (4.8%) in the group B, experienced mild adverse reactions compatible with treatment.Elderly patients with high-grade T1 BC are not poorer candidates to BCG treatment, as they had similar benefit and adverse reactions than those aging ≥75 years.

Food-borne botulism in Apulia region, Italy: an expert witness testimony.

We report the epidemiology of food-borne botulism in Puglia, Italy, between 1977-2017, using surveillance data and Experts' personal observations. As the disease is rare, the diagnosis is often missed or delayed, and cases are initially misdiagnosed. This was the case of a family outbreak of botulism in the 1970s.

The role of lipofilling in reconstructions with dermal regeneration template: clinical and histological assessment.

Skin and soft tissue reconstruction represents one of the most debated issues of plastic surgery. The advent of regenerative medicine has shown new pathways with the use of lipofilling and dermal regeneration templates. The aim of this study was to investigate the histological and clinical modifications occurring after lipofilling in the areas previously reconstructed with Integra® and an autologous thin dermal-epidermal graft. Histological and immunohistochemical analysis were performed on nine patients to compare skin before and after lipofilling. Pre- and post-operative examinations (POSAS, VAS scale) were carried out as well as taking clinical photographs. The authors detected an overall clinical and histological improvement in all cases. Data obtained from POSAS and VAS scale showed a statistically significant (p less than 0.05) improvement concerning all variables investigated before surgery. The biopsies revealed qualitative modifications with hematoxylin-eosin and Masson trichrome stain. Immunohistochemistry with CD31 antibody also demonstrated quantitative changes with an increased number of vessels. The photographs enabled to compare the clinical situation before and after lipofilling with better aesthetic outcomes. Lipofilling gave good functional and aesthetic results in the areas treated with Integra® and autologous thin dermal-epidermal grafts.

Evaluation of measles and rubella integrated surveillance system in Apulia region, Italy, 3 years after its introduction.

This study aimed at evaluating the integrated measles and rubella surveillance system (IMRSS) in Apulia region, Italy, from its introduction in 2013 to 30 June 2016. Measles and rubella case reports were extracted from IMRSS. We estimated system sensitivity at the level of case reporting, using the capture-recapture method for three data sources. Data quality was described as the completeness of variables and timeliness of notification as the median-time interval from symptoms onset to initial alert. The proportion of suspected cases with laboratory investigation, the rate of discarded cases and the origin of infection were also computed. A total of 127 measles and four rubella suspected cases were reported to IMRSS and 82 were laboratory confirmed. Focusing our analysis on measles, IMRSS sensitivity was 82% (95% CI: 75-87). Completeness was >98% for mandatory variables and 57% for 'genotyping'. The median-time interval from symptoms onset to initial alert was 4.5 days, with a timeliness of notification of 33% (41 cases reported ⩽48 h). The proportion of laboratory investigation was 87%. The rate of discarded cases was 0.1 per 100 000 inhabitants per year. The origin of infection was identified for 85% of cases. It is concluded that IMRSS provides good quality data and has good sensitivity; still efforts should be made to improve the completeness of laboratory-related variables, timeliness and to increase the rate of discarded cases.

Brand-to-generic levetiracetam switching: a 4-year prospective observational real-life study.

BACKGROUND AND PURPOSE: The purpose of this study was to determine whether switching from branded levetiracetam (Keppra® ) to a levetiracetam generic equivalent product (Matever® ) in an epilepsy cohort could provide adequate results in terms of seizure control and tolerability. METHODS: To be eligible for the study, patients had to have been taking Keppra® as monotherapy or polytherapy for at least 6 months. Between March 2013 and April 2017, patients were invited to switch to Matever® as part of their follow-up. We evaluated the number of seizures per month, drug-related adverse events and electroencephalography before the switch (T0, baseline) and 6 months after switching (T1). Furthermore, we reported the long-term follow-up of patients who continued to use Matever® after the end of the study, considering the most recent visit for each patient (T2). RESULTS: A total of 55 patients refused the switch. Among the remaining 125 patients, 59 (47%) were treated using Keppra® as monotherapy and 66 (53%) were on Keppra® as polytherapy. All 125 patients were subjected to switching from Keppra® to Matever® . Comparing patients before (T0) and after (T1) switching, we found no statistically significant differences in terms of seizure frequency and occurrence of adverse effects. There were no significant differences (number of seizures/month and drug-related adverse events) between patients treated with Matever® as monotherapy and patients who refused the switch and continued to use Keppra® as monotherapy for a long-term follow-up of 48 months. Electroencephalography findings were also unchanged. CONCLUSION: In our sample, brand-to-generic levetiracetam switching was effective and safe in both monotherapy and polytherapy regardless of the epilepsy syndrome.

Effects of short-to-long term enzyme replacement therapy (ERT) on skeletal muscle tissue in late onset Pompe disease (LOPD).

AIMS: Pompe disease is an autosomal recessive lysosomal storage disorder resulting from deficiency of acid α-glucosidase (GAA) enzyme. Histopathological hallmarks in skeletal muscle tissue are fibre vacuolization and autophagy. Since 2006, enzyme replacement therapy (ERT) is the only approved treatment with human recombinant GAA alglucosidase alfa. We designed a study to examine ERT-related skeletal muscle changes in 18 modestly to moderately affected late onset Pompe disease (LOPD) patients along with the relationship between morphological/biochemical changes and clinical outcomes. Treatment duration was short-to-long term. METHODS: We examined muscle biopsies from 18 LOPD patients at both histopathological and biochemical level. All patients underwent two muscle biopsies, before and after ERT administration respectively. The study is partially retrospective because the first biopsies were taken before the study was designed, whereas the second biopsy was always performed after at least 6 months of ERT administration. RESULTS: After ERT, 15 out of 18 patients showed improved 6-min walking test (6MWT; P = 0.0007) and most of them achieved respiratory stabilization. Pretreatment muscle biopsies disclosed marked histopathological variability, ranging from an almost normal pattern to a severe vacuolar myopathy. After treatment, we detected morphological improvement in 15 patients and worsening in three patients. Post-ERT GAA enzymatic activity was mildly increased compared with pretreatment levels in all patients. Protein levels of the mature enzyme increased in 14 of the 18 patients (mean increase = +35%; P < 0.05). Additional studies demonstrated an improved autophagic flux after ERT in some patients. CONCLUSIONS: ERT positively modified skeletal muscle pathology as well as motor and respiratory outcomes in the majority of LOPD patients.

Epidemiology and cost of cervical cancer care and prevention in Apulia (Italy), 2007/2016.

BACKGROUND: According to recent estimates, cervical cancer is worldwide the second most common cancer in females and the fourth overall. The number of deaths for cervical cancer is around 7.5% of all female cancer deaths. Cervical cancer is the only tumour with a known necessary cause, the HPV infection and, globally, HPV is the most common sexually transmitted infection. Two major approaches for cervical cancer prevention have been designed: primary prevention by HPV vaccination and secondary prevention by screening. The aim of our study is to design an overview of epidemiology, cost of the therapies and cost of prevention measures (screening and vaccines) 9 years after the introduction of anti-HPV vaccination in the Apulia Regional Immunization Program. STUDY DESIGN: Retrospective observational study. METHODS: To describe the epidemiology of cervical cancer, we analysed data from the Apulia regional archive of hospital discharge forms (SDO). We considered all records referred to cervical cancer using the ICD 9 code 180.xxx both in primary and secondary diagnosis, for the years 2007-2016. Subjects living in Apulia have been considered. Costs of hospitalization were computed considering generated Diagnosis Related Groups (DRG). To describe the Apulian screening program, we analysed data from Regional Screening Data warehouse; the cost of the single test was established according to the Tariff List from the Ministry of Health. Finally, vaccination data were extracted by Regional Immunization Database and official ex-factory price has been used to calculate the costs of immunization program. RESULTS: From 2007 to 2016, an important decrease in the incidence rate of cervical cancer in Apulia has been noted, ranging from 43.7 per 100,000 residents in 2007 to 21.0 per 100,000 residents in 2016. From an economic point of view, a clear reduction (39%) is observed in hospitalization costs over time. Total costs of prevention programs increased over time and globally exceed € 54,000,000, with a decreasing trend for vaccine prophylaxis and an increasing trend for screening. CONCLUSIONS: The incidence and costs of cervical cancer in Apulia, although already significantly decreasing, likely will be further reduced since 2027-2032, when we can observe the effects of vaccine prophylaxis on the burden of disease; on this occasion it will be also possible to quantify the actual cost-effectiveness of the vaccine. In our opinion, in the future the Apulia healthcare executives should enhance and improve the active screening test offer, without underestimating the importance of sexual education in young people, especially in those who have not had sexual debut yet.

Local deprivation status and seasonal influenza vaccination coverage in adults ≥ 65 years residing in the Foggia municipality, Italy, 2009-2016.

INTRODUCTION: In Italy, vaccination against seasonal influenza has been recommended for the elderly since 1980, but coverage is still far below the WHO minimum target level of 75%. Effective interventions to improve influenza vaccination should take into account socioeconomic determinants of inequalities in vaccine uptake. This study aimed to assess differences in vaccination coverage, by socioeconomic status, among people ≥ 65 years of age residing in the Foggia municipality, Italy. METHODS: A Socio-Economic-Health Deprivation Index (SEHDI) was constructed by using a multivariate analysis model. The resident population, for census block, was classified in 5 deprivation groups. Differences in demographic and socioeconomic indicators, the standardized mortality ratios (SMRs), and the average vaccination coverage among deprivation groups were evaluated with the linear F-test. The association between census variables and influenza vaccination coverage, in each deprivation group, was assessed using the Pearson bivariate correlation. RESULTS: The SEHDI allowed to identify factors related to ageing, housing, household size and composition, and education. Forty percent of people residing in the Foggia municipality lived in conditions of socioeconomic and health deprivation. Belonging to families with 3 or 4 members was associated with increased coverage rates. In the most deprived group, vaccination uptake was positively associated with the dependency ratio. CONCLUSIONS: The results of this study have shown that there is still large room for improving influenza vaccination coverage among subjects belonging to the most deprived areas. Surveillance of trends in influenza vaccine uptake by socioeconomic groups is a feasible contribution to implementing effective, tailored to the frail older persons, vaccine utilization programs.

Incidence of Type 1 Diabetes among Children and Adolescents in Italy between 2009 and 2013: The Role of a Regional Childhood Diabetes Registry.

BACKGROUND: Surveillance represents a key strategy to control type 1 diabetes mellitus (T1DM). In Italy, national data are missing. This study aimed at evaluating the incidence of T1DM in subjects <18 year olds in Apulia (a large southeastern region, about 4,000,000 inhabitants) and assessing the sensitivity of the regional Registry of Childhood-Onset Diabetes (RCOD) in the 2009-2013 period. METHODS: We performed a retrospective study matching records from regional Hospital Discharge Registry (HDR), User Fee Exempt Registry (UFER), and Drugs Prescription Registry (DPR) and calculated T1DM incidence; completeness of each data source was also estimated. In order to assess the RCOD sensitivity we compared cases from the registry to those extracted from HDR-UFER-DPR matching. RESULTS: During 2009-2013, a total of 917 cases (about 184/year) in at least one of the three sources and an annual incidence of 25.2 per 100,000 were recorded, lower in infant, increasing with age and peaked in 5- to 9-year-olds. The completeness of DPR was 78.7%, higher than that of UFER (64.3%) and of HDR (59.6%). The RCOD's sensitivity was 39.05% (360/922; 95% CI: 34.01%-44.09%). CONCLUSIONS: Apulia appeared as a high-incidence region. A full, active involvement of physicians working in paediatric diabetes clinics would be desirable to improve the RCOD performance.

Proceedings of the Consensus Day Meeting: Implications for Rotavirus Vaccination in the 2014 Apulian Lifetime Immunization Schedule. Foggia, 17 April 2015.

Recommendations for vaccination against rotavirus (RV) were issued in Apulia in 2006; the vaccine was free of charge to children who entered day care or nursery school by 1 year of age or those affected by chronic diseases for which diarrhea caused by rotavirus can increase the risk of complications and hospitalization. In 2014, vaccination became available to all healthy children with only a copayment. However, there has not been a significant increase in vaccination coverage. On April 17, 2015, Apulian public health physicians and paediatricians met to share strategies to promote the RV vaccine indications provided in the regional immunization schedule. During the meeting, presentation of data reports were interspersed with discussions that were led with a "bottom-up" approach. The discussants responded to pre-planned questions raised by the participants and encouraged by the discussion.

Estimates of the burden of meningococcal disease in Italy: implications for prevention and control.

Meningococcal disease is an acute, severe bacterial infection caused by Neisseria meningitidis. The most common presentations of invasive meningococcal infection (IMD) are meningitis and sepsis, less common pathologic presentations include focal infections. IMD can develop from initial symptoms to death within 24 hours. As many as 20% of survivors have permanent sequelae. Infants < 1 year of age have the highest incidence and adolescents the highest carriage prevalence. In Italy, the incidence of IMD was 0.25 confirmed cases per 100,000 in 2011, but this may have been considerably underestimated due to under-detection and under-reporting. Recently, we estimated the impact of the MenC universal vaccination on the burden of meningococcal meningitis in Puglia by assessing the completeness of three registration sources (notifications, hospitalizations, and laboratory surveillance). The sensitivity of the three systems was 36.7% (95% CI: 17.5%-57.9%) and registrations lost nearly 28 cases/year in the period 2001- 2013. In the National Surveillance of Invasive Bacterial Diseases, serogroup B accounted for 64.9% of samples serotyped in 2011. Applying this percentage to the total number of hospitalizations for IMD registered in the same year (n = 256), we obtained an estimated 166 episodes attributable to serogroup B. Our work highlights the importance of enhancing surveillance for meningococcal disease and strengthening vaccinations against all preventable serogroups.