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As the primary screening test, E6/E7 mRNA has shown similar sensitivity for CIN3+ and lower positivity rate than the HPV DNA test. Nevertheless, the overall mRNA positivity is too high for immediate colposcopy, making a triage test necessary. The aim was to estimate the mRNA performance as a primary test with different triage strategies. All HPV DNA-positives were tested for mRNA, cytology and p16/ki67. A sample of HPV DNA-negatives was also tested for mRNA to estimate test specificity. We included all CIN3+ histologically diagnosed within 24 months since recruitment. Of the 41 127 participants, 7.7% were HPV DNA-positive, of which 66.4% were mRNA-positive. Among the HPV DNA-negatives, 10/1108 (0.9%) were mRNA-positive. Overall, 97 CIN3+ were found. If mRNA was used as the primary test, it would miss about 3% of all CIN3+ with a 22% reduction of positivity compared with HPV DNA. The weighted specificity estimate forCIN2 was 94.5% (95% CI = 93.9%-94.9%) and sensitivity for CIN3+ was 96.9% (95% CI = 91.3%-99.1%). If all the weighted estimated 6.0% mRNA-positive women had been referred to colposcopy, PPV for CIN3+ would have been 4.2%. Cytology or p16/ki67 triage would decrease immediate referral to 1.7% and 2.0%, increasing PPV to 11.2% and 11.7%, respectively; total colposcopy referral would be 4.0% and 3.9%, respectively. As the primary screening test, the mRNA assay showed a positivity rate lower than that of HPV DNA, with a small number of CIN3+ missed. Triage with cytology or p16/ki67 would only marginally decrease overall colposcopy referral.

International audience; Background - Infective endocarditis (IE) is a common and serious complication in patients receiving chronic hemodialysis (HD). Objectives - This study sought to investigate whether there are significant differences in complications, cardiac surgery, relapses, and mortality between IE cases in HD and non-HD patients. Methods - Prospective cohort study (International Collaboration on Endocarditis databases, encompassing 7,715 IE episodes from 2000 to 2006 and from 2008 to 2012). Descriptive analysis of baseline characteristics, epidemiological and etiological features, complications and outcomes, and their comparison between HD and non-HD patients was performed. Risk factors for major embolic events, cardiac surgery, relapses, and in-hospital and 6-month mortality were investigated in HD-patients using multivariable logistic regression. Results - A total of 6,691 patients were included and 553 (8.3%) received HD. North America had a higher HD-IE proportion than the other regions. The predominant microorganism was Staphylococcus aureus (47.8%), followed by enterococci (15.4%). Both in-hospital and 6-month mortality were significantly higher in HD versus non-HD-IE patients (30.4% vs. 17% and 39.8% vs. 20.7%, respectively; p

This retrospective multicenter cohort study aimed to evaluate the clinical outcomes (mortality rate, operative time, complications) of elective laparoscopic cholecystectomy (LC) when performed by a surgical resident in comparison to experienced consultant in the backdrop of Italian academic centers.Retrospective review of all patients undergoing elective LC between January 2016 and January 2022 at six teaching hospitals across Italy was performed. Cases were identified using the Current Procedural Terminology (CPT) code 5123 (LC without cholangiogram). All cases of emergency surgery, ASA score 3, or when cholecystectomy was performed with another surgical procedure, were excluded. All suitable cases were divided into 2 groups based on primary surgeon: consultant or senior resident. Main outcome was complication rates (intraoperative and peri/postoperative); secondary outcomes included operative time, the length of stay, and the rate of conversion to open.A total of 2331 cases (1425 females) were included, of which, consultants performed 1683 LCs (72%), while the residents performed 648 (28%) surgeries. The groups were statistically comparable regarding demographics, history of previous abdominal surgery, operative time, or intraoperative complications. The rate of conversion to open cholecystectomy was 1.42% for consultant and none for resident (p = 0.02). A statistically significant difference was observed between groups regarding the average length of stay (2.2 ± 3 vs 1.6 ± 1.3 days p = 0.03). Similarly, postoperative complications (1.7% vs 0.5%) resulted in statistically significant (p = 0.02) favoring resident group.Our study demonstrates that in selected patients, senior residents can safely perform LC when supervised by senior staff surgeons.

Objective To evaluate the accuracy and reproducibility of hiatal surface area (HSA) measurement on dedicated multidetector computed tomography (MDCT) acquisition, in patients, previously subjected to laparoscopic sleeve gastrectomy (LSG), and affected by gastroesophageal reflux disease (GERD). Intraoperative HSA measurement was considered the reference standard. Methods Fifty-two candidates for laparoscopic hiatal hernia repair were prospectively included in the study. MDCT images were acquired during swallowing of oral iodinated contrast media and during strain. Measurements were performed by nine readers divided into three groups according to their experience. Results were compared with intraoperative measurements by means of Spearman correlation coefficient. Reproducibility was evaluated with intra- and interreader agreement by means of weighted Cohen’s kappa and intraclass correlation coefficient (ICC). Results Significant differences between MDCT and intraoperative HSA measurements were observed for swallowing imaging for less experienced readers (p = 0.037, 0.025, 0.028 and 0.019). No other statistically significant differences were observed (p > 0.05). The correlation between HSA measured intraoperatively and on MDCT was higher for strain imaging compared to swallowing (r = 0.94—0.92 vs 0.94—0.89). The overall reproducibility of MDCT HSA measurement was excellent (ICC of 0.95; 95% CI 0,8993 to 0,9840) independently of reader’s experience Conclusion HSA can be accurately measured on MDCT images. This method is reproducible and minimally influenced by reader experience. The preoperative measurement of HSA has potential advantages for surgeons in terms of correct approach to hiatal defects in obese patient.

Objective To evaluate performance of the first round of HPV-based screening in Tuscany region and compare it with the prior round of Pap-based screening Setting Tuscany region of Italy, where HPV-based cervical cancer screening started in 2013, with a strong level of centralization screening tests at the Regional Laboratory for Cancer Prevention (ISPRO). Methods The transition from Pap- to HPV-based screening was initiated for older women and at 3 out of 12 Tuscany Local Health Units (LHUs). Data from the Florence and Grosseto LHUs (about 300,000 women) were analysed and performance screening indicators estimated. Results HPV-based indicators recorded good performance, with increased compliance vs. the Pap-based programme. We registered a substantial decrease in waiting times from sampling to test reporting, probably related to the centralization strategy. Since the screening protocol was the same and conducted at a single laboratory, we could hypothesize that the difference in HPV positivity (6.8% in Florence vs. 8.4% in Grosseto) was due to a real difference in HPV prevalence among women of the two LHUs. The transition to HPV-based screening led to a significant increase both in colposcopy referral rate (4.3% vs. 1.2%) and CIN2+ detection rate (8.3‰ vs. 3.4‰). Conclusions HPV-based is more effective in detecting high-grade precancerous and cancerous lesions than Pap-based screening and is characterized by an “anticipatory effect” in the detection of CIN2+ lesions. The transition from Pap-based to HPV-based screening programme should include increased resources dedicated to colposcopy services. Centralization in a laboratory with long experience in this field promotes efficiency of the screening process.

Background: It has been suggested that patients with a Body Mass Index (BMI) of > 60 kg/m2 should be offered expedited Bariatric Surgery (BS) during the Coronavirus Disease-2019 (COVID-19) pandemic. The main objective of this study was to assess the safety of this approach. Methods: We conducted a global study of patients who underwent BS between 1/05/2020 and 31/10/2020. Patients were divided into three groups according to their preoperative BMI - Group I (BMI60 kg/m2). The effect of preoperative BMI on 30-day morbidity and mortality, procedure choice, COVID-19 specific safety protocols, and comorbidities was assessed. Results: This study included 7084 patients (5197;73.4 % females). The mean preoperative weight and BMI were 119.49 ± 24.4 Kgs and 43.03 ± 6.9 Kg/m2, respectively. Group I included 6024 (85 %) patients, whereas Groups II and III included 905 (13 %) and 155 (2 %) patients, respectively. The 30-day mortality rate was higher in Group III (p = 0.001). The complication rate and COVID-19 infection were not different. Comorbidities were significantly more likely in Group III (p = 70 kg/m2 had a 30-day mortality of 7.7 % (2/26). None of these patients underwent a Roux-en-Y Gastric Bypass. Conclusion: The 30-day mortality rate was significantly higher in patients with BMI > 60 kg/m2. There was, however, no significant difference in complications rates in different BMI groups, probably due to differences in procedure selection.

As the world population is aging rapidly, emergency abdominal surgery for acute abdomen in the elderly represents a global issue, both in developed and developing countries. Data regarding all the elderly patients who underwent emergency abdominal surgery from January 2017 to December 2017 at 36 Italian surgical departments were analyzed with the aim to appraise the contemporary reality regarding the use of emergency laparoscopy for acute abdomen in the elderly. 1993 patients were enrolled. 1369 (68.7%) patients were operated with an open technique; whereas, 624 (31.3%) underwent a laparoscopic operation. The postoperative morbidity rate was 32.6%, with a statically significant difference between the open and the laparoscopic groups (36.2% versus 22.1%, p < 0.001). The reported mortality rate was 8.8%, with a statistically significant difference between the open and the laparoscopic groups (11.2% versus 2.2%, p < 0.001). Our results demonstrated that patients in the ASA II (58.1%), ASA III (68.7%) and ASA IV (88.5%) groups were operated with the traditional open technique in most of the cases. Only a small percentage of patients underwent laparoscopy for perforated gastro-duodenal ulcer repair (18.9%), adhesiolyses with/without small bowel resection (12.2%), and large bowel resection (10.7%). Conversion to open technique was associated with a higher mortality rate (11.1% versus 2.2%, p < 0.001) and overall morbidity (38.9% versus 22.1%, p = 0.001) compared with patients who did not undergo conversion. High creatinine (p < 0.001) and glycaemia (p = 0.006) levels, low hemoglobin levels (p < 0.001), oral anticoagulation therapy (p = 0.001), acute respiratory failure (p < 0.001), presence of malignancy (p = 0.001), SIRS (p < 0.001) and open surgical approach (p < 0.001) were associated with an increased risk of postoperative morbidity. Regardless of technical progress, elderly patients undergoing emergency surgery are at very high risk for in-hospital complications. A detailed analysis of complications and mortality in the present study showed that almost 9% of elderly patients died after surgery for acute abdomen, and over 32% developed complications.

Background: Metabolic and bariatric surgery (MBS) is an effective treatment for adolescents with severe obesity. Objectives: This study examined the safety of MBS in adolescents during the coronavirus disease 2019 (COVID-19) pandemic. Methods: This was a global, multicentre and observational cohort study of MBS performed between May 01, 2020, and October 10,2020, in 68 centres from 24 countries. Data collection included in-hospital and 30-day COVID-19 and surgery-specific morbidity/mortality. Results: One hundred and seventy adolescent patients (mean age: 17.75 ± 1.30 years), mostly females (n=122, 71.8%), underwent MBS during the study period. The mean pre-operative weight and body mass index were 122.16 ± 15.92 kg and 43.7± 7.11 kg/m2, respectively. Although majority of patients had pre-operative testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (n=146; 85.9%), only 42.4% (n=72) of the patients were asked to self-isolate pre-operatively. Two patients developed symptomatic SARS-CoV-2 infection post-operatively (1.2%). The overall complication rate was 5.3% (n=9). There was no mortality in this cohort. Conclusions: MBS in adolescents with obesity is safe during the COVID-19 pandemic when performed within the context of local precautionary procedures (such as pre-operative testing). The 30-day morbidity rates were similar to those reported pre-pandemic. These data will help facilitate the safe re-introduction of MBS services for this group of patients.

Background Infective endocarditis (IE) is a life-threatening disease whose prognosis is often difficult to predict based on clinical data. Biomarkers have been shown to favorably affect disease management in a number of cardiac disorders. Aims of this retrospective study were to assess the prognostic role of procalcitonin (PCT), pro-adrenomedullin (pro-ADM) and copeptin in IE and their relation with disease characteristics and the traditional biomarker C-reactive protein (CRP). Methods We studied 196 patients with definite IE. Clinical, laboratory and echocardiography parameters were analyzed, with a focus on co-morbidities. PCT, pro-ADM and copeptin were measured on stored plasma samples obtained on admission during the acute phase of the disease. Results Pro-ADM and copeptin were significantly higher in older patients and associated with prior chronic kidney disease. Pro-ADM was an independent predictor of hospital mortality (OR 3.29 [95%C.I. 1.04–11.5]; p = 0.042) whilst copeptin independently predicted 1-year mortality (OR 2.55 [95%C.I. 1.18–5.54]; p = 0.017). A high PCT value was strictly tied with S. aureus etiology (p = 0.001). CRP was the only biomarker associated with embolic events (p = 0.003). Conclusions Different biomarkers correlate with distinct IE outcomes. Pro-ADM and copeptin may signal a worse prognosis of IE on admission to the hospital and could be used to identify patients who need more aggressive treatment. CRP remains a low-cost marker of embolic risk. A high PCT value should suggest S. aureus etiology.

The aim of this original research is to evaluate the effect of SG on alcohol intake symptoms, blood alcohol content (BAC), and alcohol metabolite levels. At 0–6–12 months after SG, BAC of patients was measured at 0, 15, 30, and 60 min, and then every 30 min, and urinary metabolite (ethanol and acetaldehyde) levels were measured 2 h after consuming a standard red wine drink. Symptoms perceived by patients were evaluated using symptom alcoholization post-obesity surgery scores. Thirty obese patients (12 men/18 women; mean body mass index, 44 ± 4 kg/m2) who underwent SG were enrolled in this study. At 12 months after SG, no alcohol use disorder was observed and BAC tended to peak after 15 min, with alcohol intoxication symptoms (nausea/vomiting, flushing, and diaphoresis), and return to zero after 90 min of wine intake. Ethanol and acetaldehyde levels were significantly different at 12 months compared with the levels at time 0 (p

BACKGROUND: Obesity represents a risk factor for COVID-19 infection. Therefore, in order to reduce COVID-19 related comorbidities in obese population a continuation of obesity treatment is needed. However, bariatric procedures were postponed because of COVID-19 restrictions, delaying treatment for obese patients seeking for surgery. This study aimed to test the feasibility of a telematics pre-operative psychological and nutritional assessment as an alternative tool during COVID-19 outbreak. METHODS: Twenty-six patients were contacted. The pre-operative assessment consisted in 3-weekly one-to-one online sessions and a final in-person multidisciplinary session. The protocol feasibility has been evaluated on the following outcome: rejection rate (%), dropout rate (%), compliance and satisfaction's degree. RESULTS: Eighteen participants completed the whole protocol and 10% dropped-out. Seventy-two percent of participants obtained an excess weight loss ≥5%. All participants were satisfied of the telematics assessment. CONCLUSIONS: COVID-19 emergency has changed standard hospital procedures and this study could represent a landmark for an online pre-operative assessment method to adopt in case of new restrictions.

Background Occult hepatitis B infection consists of persistence of HBV genomes in hepatocytes,absence of serum HBsAg, low/undetectable serum HBVDNA. Reactivation of HBV infection may occur during immunosuppression, but few data are available in heart transplant. Objectives We followed-up heart recipients with or without markers of previous HBV infection,evaluating prevalence of HBV markers, incidence of HBV reactivation and its virological and clinical features. Study design Heart failure patients listed for heart transplant (2007–2013) were screened for current or past HBV infection. Transplanted patients with past HBV infection (anti-HBc+/±anti-HBs+/HBVDNA−) were followed up as cases, and an equal number of HBV negative patients as controls. Virological reactivation was detected by standard real-time and home-made highly sensitive PCR (surface/core HBVDNA regions). Clinical status and progression were assessed by liver histology, ultrasound or elastography. Results 67 patients underwent heart transplant, including 4 (5.9%) HBsAg+ subjects. Cases were 11/67 (16.4%). During a median follow-up of 30 months, only one of these 11 patients presented viral reactivation (HBVDNA 209 IU/mL) at month 22, and started antiviral treatment. Four other recipients showed virological events of uncertain significance (sensitive PCR-only intermittently positive). Clinical signs of liver disease were observed in only one case at the last follow-up. A nonsignificant difference in survival was observed between cases and all other heart recipients without prior HBV contact (death rate 5/11 vs 15/52, respectively; p = 0.097). Conclusions HBV genotypic reactivation in HBsAg−/anti-HBc+/HBVDNA− heart recipients is uncommon. Virological events of uncertain significance occur more frequently; their clinical impact seems to be negligible.

Bjornstad syndrome is a rare condition characterized by pili torti and sensorineural hearing loss associated with pathological variations in BCS1L. Mutations in this gene are also associated with the more severe complex III deficiency and GRACILE syndrome. We report the first Italian patients with Bjornstad syndrome, two siblings with pili torti and sensorineural hearing loss, in whom we detected two novel compound heterozygous mutations in BCS1L. A thorough clinical evaluation did not reveal any features consistent with complex III deficiency or GRACILE syndrome.

Objectives In vitro models showing synergism between polymyxins and carbapenems support combination treatment for carbapenem-resistant Gram-negative (CRGN) infections. We tested the association between the presence of in vitro synergism and clinical outcomes in patients treated with colistin plus meropenem. Methods This was a secondary analysis of AIDA, a randomized controlled trial comparing colistin with colistin–meropenem for severe CRGN infections. We tested in vitro synergism using a checkerboard assay. Based on the fractional inhibitory concentration (ΣFIC) index for each colistin–meropenem combination, we categorized results as synergistic, antagonistic or additive/indifferent. The primary outcome was clinical failure at 14 days. Secondary outcomes were 14- and 28-day mortality and microbiological failure. Results The sample included 171 patients with infections caused by carbapenem-resistant Acinetobacter baumannii (n = 131), Enterobacteriaceae (n = 37) and Pseudomonas aeuruginosa (n = 3). In vitro testing showed synergism for 73 isolates, antagonism for 20 and additivism/indifference for 78. In patients who received any colistin plus meropenem, clinical failure at 14 days was 59/78 (75.6%) in the additivism/indifference group (reference category), 54/73 (74.0%) in the synergism group (adjusted odds ratio (aOR) 0.76, 95% CI 0.31–1.83), and 11/20 (55%) in the antagonism group (aOR 0.77, 95% CI 0.22–2.73). There was no significant difference between groups for any secondary outcome. Comparing the synergism group to patients treated with colistin monotherapy, synergism was not protective against 14-day clinical failure (aOR 0.52, 95% CI 0.26–1.04) or 14-day mortality (aOR1.09, 95% CI 0.60–1.96). Discussion In vitro synergism between colistin and meropenem via checkerboard method did not translate into clinical benefit.

BACKGROUND The objective of this study was to describe the determinants of adequacy and positivity of the p16/Ki-67 assay in a human papillomavirus (HPV)-positive screening population enrolled within the New Technologies for Cervical Cancer 2 (NTCC2) study. METHODS ThinPrep slides were immunostained for p16/Ki-67; each slide had 3 reports from different laboratories. The authors included population-related, sampling-related/staining-related, and interpretation-related variables in the analyses. Adequacy and positivity proportions were stratified by variables of interest. Univariate and multivariate logistic models were used to identify determinants of adequacy and positivity. RESULTS In total, 3100 consecutive HPV-positive cases were analyzed. Because every slide was interpreted by 3 centers, 9300 reports were obtained, including 905 (9.7%) that were inadequate and 2632 (28.3%) that were positive. The percentage of cases in which all 3 reports were inadequate increased with increasing age of the women and with inadequate cytology. The highest percentage of adequacy in all 3 reports and of cases with all 3 reports positive was observed in specimens from women who had grade ≥2 cervical intraepithelial neoplasia (CIN2+), atypical squamous cells of undetermined significance or more severe (ASC-US+) cytology, or mRNA positivity. The number of inadequate reports was significantly associated with increasing age, inadequate cytology, mRNA negativity, and scant cellularity. A positive p16/Ki-67 report was associated with an ASC-US+ result and with a positive mRNA result in cases both with and without CIN2+ but was associated with an HPV type 16 and/or 18 infection only in CIN2+ cases. The presence of CIN2+ was strongly associated with dual staining positivity. CONCLUSIONS The interpretation of p16/Ki-67 results may be influenced by several different variables, all of which are part of the steps in the procedure, and by the characteristics of the screened population.

Many subjects with somatic pathologies or traumas in their recent anamnesis tend to experience symptoms and changes to their daily life parameters after technically successful treatment. Hence, this study aims to validate an investigation tool inspired by the prosthetic–bionic paradigm—namely, the PBP-Q—which allows for the evaluation of variation in questions relating to identity, psychosociality, and psychopathology in relation to the use of a prosthesis or device. We gathered 118 participants (68 females and 50 males) aged between 27 and 94 years (Mean = 58.42 ± 15.17). We performed both exploratory (EFA) and confirmatory (CFA) factor analyses on this sample. Moreover, we calculated the internal consistency for the PBP-Q scales and the total score for the questionnaire’s final 26-item and 5-factor versions. The five scales are psychological well-being; interpersonal relationships; professional relationships; autonomy and safety; addictions, compulsions, and obsessions. The internal consistency is good for both the total score and the subscales. In conclusion, overall, the PBP-Q has satisfactory psychometric properties, especially considering the measure’s complexity. It provides a quick and effective way to evaluate the changes that might arise after the use of a prosthesis or device and, subsequently, has implications for clinical practice.

Background: Treatment of chronic hepatitis B (CHB) with polymerase inhibitors is key to prevent disease flares and progression toward advanced liver disease. Efficacy and tolerability of newer agents has been reported anecdotally in transplant recipients. Methods: In this prospective, observational study, we assessed outcomes of therapy with tenofovir (TDF), entecavir (ETV), and telbivudine (LdT) in 13 heart transplant recipients (HTR) with CHB. Results: Most patients were hepatitis B e antigen negative, had low baseline hepatitis B virus (HBV) DNA, and normal aminotransferases. Liver biopsy showed a median fibrosis score of 1.5 (range 0–4). Glomerular filtration rate (GFR) was

Diagnosing a complex genetic syndrome and correctly assigning the concomitant phenotypic traits to a well-defined clinical form is often a medical challenge. In this work, we report the analysis of a family with complex phenotypes, including microcephaly, intellectual disability, dysmorphic features, and polydactyly in the proband, with the aim of adding new aspects for obtaining a clear diagnosis. We performed array-comparative genomic hybridization and quantitative reverse transcriptase PCR (qRT-PCR) analyses. We identified a deletion of chromosome 20p12.1 involving the macrodomain containing 2/mono-ADP ribosylhydrolase 2 gene (MACROD2) in several members of the family. This gene is actually not associated with a specific syndrome but with congenital anomalies of multiple organs. qRT-PCR showed higher levels of a MACROD2 mRNA isoform in the individuals carrying the deletion. Our results, together with other data reported in the literature, support the hypothesis that the deletion in MACROD2 can affect correct embryonic development and that the presence of another associated event, such as epigenetic modifications at the MACROD2 locus, can influence the level of severity of the pathology.

Laparoscopic sleeve gastrectomy (LSG) has gained popularity in the last 10 years for its good results in weight loss and comorbidity control. However, guidelines on the pathological examination of the specimen are lacking. The aim of this retrospective study was to determine the usefulness of the routine specimen examination when presurgery endoscopy (upper gastrointestinal endoscopy, UGIE) and multiple gastric biopsies are part of the preoperative work-up. A retrospective review of records of the patients submitted to LSG between January 2012 and August 2017 was carried out. Sex, age, histopathology findings in the presurgery endoscopy biopsies and surgical specimen, and the prevalence of Helicobacter pylori infection were analyzed. A total of 925 patients entered the study group (mean age = 44.1 years, Females = 80.3%, BMI = 44.58 kg/m2). The most common histopathology pattern in the endoscopy biopsies and in the surgical specimens was inactive chronic gastritis (64.4 and 55.6%, respectively). Helicobacter pylori infection was 24.6 and 2.48%, respectively. Ninety-nine percent (n 796) of patients with non-significant endoscopy biopsy findings showed the same patterns in specimen analysis. Only three patients (0.3%) who had intestinal presurgery metaplasia were positive in the specimen analysis, and two cases of gastric stromal neoplasms (gastrointestinal stromal tumor and gastric leiomyoma) were found intraoperatively. Most of the findings are non-significant and can be predicted if UGIE plus multiple biopsies is routinely included in the bariatric work-up with significant cost reduction. In those patients who had a significant finding prior to the surgery or intraoperatively, the pathological examination of the specimen is recommended.

In Italy, the cohorts of women who were offered Human papillomavirus (HPV) vaccination in 2007/08 will reach the age (25years) for cervical cancer (CC) screening from 2017. The simultaneous shift from cytology-based screening to HPV test-based screening gives the opportunity for unprecedented reorganisation of CC prevention. The ONS (National Screening Monitoring Centre) Directive and the GISCi (Italian Group for Cervical Screening) identified the consensus conference as the most suitable method for addressing this topic. A summary of consensus recommendations is reported here. The main objective was to define the best screening methods in girls vaccinated against HPV and the knowledge required for defining evidence-based screening strategies. A Jury made recommendations about questions and proposals formulated by a panel of experts representative of Italian scientific societies involved in CC prevention and based on systematic reviews of literature and evidence. The Jury considered changing the screening protocols for girls vaccinated in their twelfth year as appropriate. Tailored screening protocols based on vaccination status could be replaced by "one size fits all" protocols only when a herd immunity effect has been reached. Vaccinated women should start screening at age 30, instead of 25, with HPV test. Furthermore, there is a strong rationale for applying longer intervals for re-screening HPV negative women than the currently recommended 5years, but research is needed to determine the optimal screening time points. For non-vaccinated women and for women vaccinated in their fifteenth year or later, the current protocol should be kept.

Background The study presents cross-sectional accuracy of E6 and E7 (E6/E7) mRNA detection and p16/ki67 dual staining, alone or in combination with cytology and human papillomavirus (HPV)16/18 genotyping, as a triage test in HPV DNA-positive women and their impact on cervical intraepithelial neoplasia (CIN2+) overdiagnosis. Methods Women aged 25-64 years were recruited. HPV DNA-positive women were triaged with cytology and tested for E6/E7 mRNA and p16/ki67. Cytology positive women were referred to colposcopy, and negatives were randomly assigned to immediate colposcopy or to 1-year HPV retesting. Lesions found within 24 months since recruitment were included. All P values were 2-sided. Results 40 509 women were recruited, and 3147 (7.8%) tested HPV DNA positive; 174 CIN2+ were found: sensitivity was 61.0% (95% confidence interval [CI] = 53.6 to 68.0), 94.4% (95% CI = 89.1 to 97.3), and 75.2% (95% CI = 68.1 to 81.6) for cytology, E6/E7 mRNA, and p16/ki67, respectively. Immediate referral was 25.6%, 66.8%, and 28.3%, respectively. Overall referral was 65.3%, 78.3%, and 63.3%, respectively. Cytology or p16/ki67, when combined with HPV16/18 typing, reached higher sensitivity with a small impact on referral. Among the 2306 HPV DNA-positive and cytology-negative women, relative CIN2+ detection in those randomly assigned at 1-year retesting vs immediate colposcopy suggests a -28% CIN2+ regression (95% CI = -57% to +20%); regression was higher in E6/E7 mRNA-negatives (Pinteraction = .29). HPV clearance at 1 year in E6/E7 mRNA and in p16/ki67 negative women was about 2 times higher than in positive women (Pinteraction < .001 for both). Conclusions p16/ki67 showed good performance as a triage test. E6/E7 mRNA showed the highest sensitivity, at the price of too high a positivity rate to be efficient for triage. However, when negative, it showed a good prognostic value for clearance and CIN2+ regression.

Background and objectives A randomized trial was conducted in Tuscany, Italy, to evaluate the effectiveness of HPV vaccination for 25 year old (yo) women who attend at the first time cervical cancer screening. The trial also evaluated immune response after vaccination, reductions of cytological abnormalities and the impact of vaccination on screening activity. Study design During 2010–2011, all 25 yo women who were invited to the Florence cervical cancer screening programme were also asked to participate in the trial. Enrolled women were randomized into study and control groups. Those in the study group were offered HPV vaccination after the usual Pap test. The cytology distribution and prevalence for any high risk (hr) HPV type were compared at the subsequent screening round in an intention-to-treat analysis. The impact of HPV vaccination was evaluated per protocol comparing vaccinated women with the control group. Results Our results showed a reduction in HPV prevalence at recall for any hr-HPV type but it was not statistically significant, being 17.1% vs 21.4%, p = 0.20 in the study and control groups, respectively. If we restricted the analysis to vaccinated women, strong reductions of the HPV 16,18,31,33,45 and HPV 31,33,45 infections were observed, being 5.3% vs 12.8%, p < 0.01 and 2.1% vs 6.5%, p = 0.02, respectively. Significant reductions for any hr-HPV infection and for HPV 16 infection were also observed in women HPV 16/18 negative at enrolment, being 12% vs 21.4%, p < 0.01 and 0.6% vs 6.7%, p-value < 0.01, respectively. In women hr-HPV negative at enrolment no infections due to HPV 16 or HPV 18 were observed and there was a big reduction for any hr-HPV infection (7.1% vs 21.4% p < 0.01). A strong antibody response was observed not only for HPV 16 & 18 but also for their related types. Conclusions Our findings suggest that HPV vaccination at the age 25 is beneficial if it is offered to hr-HPV negative women. Our data will assist in developing a cost effectiveness model for choosing the best strategy to integrate screening and vaccination for the coming years. Clinical trial registration number is NCT02296255. (Less)

Cervical cancer screening programmes in Italy actively invite all 25-64-year-old resident women for the Pap test every 3 years irrespective of their citizenship. Immigrant women come from countries where screening is absent or poorly implemented and the prevalence of human papillomavirus is often high. These women therefore have significant risk factors for cervical cancer. The Italian Group for Cervical Cancer Screening promoted a survey of all the screening programmes on the participation and the positivity and detection rates in Italian and foreign women in 2009-2011. Aggregated data for participation, cytology results, compliance with colposcopy and histology results were collected, distinguishing between women born in Italy and abroad. All comparisons were age adjusted. Forty-eight programmes out of 120 participated in the immigrant survey, with 3 147 428 invited and 1 427 412 screened Italian women and 516 291 invited and 205 948 screened foreign women. Foreign women had a slightly lower participation rate compared with Italians (39.9 vs. 45.4%), whereas compliance with colposcopy was similar (90%). Foreigners showed a higher risk of pathological findings than Italians: cytology positivity [relative risk (RR)=1.25, 95% confidence interval (CI) 1.24-1.27] and detection rate for cervical intraepithelial neoplasia grade 2 (CIN2) (RR=1.39, 95% CI 1.31-1.47), CIN3 (RR=2.07, 95% CI 1.96-2.18) and cancer (RR=2.68, 95% CI 2.24-3.22). The ratio between cancer and CIN was higher in immigrants (0.06 vs. 0.04, P0.01). Foreign women had a higher risk of cervical precancer and cancer. Because of their high risk and because opportunistic screening does not cover this often disadvantaged group, achieving high participation in screening programmes for foreigners is critical to further reducing the cervical cancer burden in Italy.

Laparoscopic sleeve gastrectomy (SG) represents, at present, the most performed bariatric procedure worldwide with excellent long-term results on weight loss and comorbidities control. After the gastrectomy procedure, together with hormonal modification, several changes in taste and habits occur, including the potential modification in alcohol consumption. The aim of this prospective study was to determine the frequency and the amount of alcohol use before and after SG using a modified version of the Alcohol Use Disorder Identification Test (AUDIT) at 1-year follow-up and eventually to evaluate relationships between different ages and sexes. A total of 142 patients were prospectively enrolled and evaluated before and 1 year after SG with a modified AUDIT. The exclusion criteria were as follows: history of alcohol abuse, presence of psychopathology or cognitive impairments, diabetes mellitus type II decompensated, or previous gastrointestinal, liver, and pancreatic resective surgery. Subgroup analyses were performed between male and female and between under and over 40 years old. The median AUDIT score decreased from 2.70 (range 1–18) before surgery to 1.38 (range 1–7) after 1 year of SG, indicating a marked reduction in alcohol use. The most consumed alcoholic drink was beer (36.6%/n = 52) while after surgery the consumption of beer decreased considerably (21.1%/n = 30). The frequency of alcohol consumption also decreased: at baseline 45% of patients consumed alcoholic drinks “from 2 to 4 times per month”, whereas 26 and 39.4% consumed alcohol “never” and “less than once a month,” respectively. After surgery, nobody consumed more then six alcoholic drinks. No differences were found between the subgroups in terms of alcohol consumption and social behavior. The alcohol preference is modified and decreased 1 year after SG and this could be related to the strict nutritional follow-up and to the hormonal changes. Studies with large samples and long-term follow-up are needed to confirm our data. IV.

The aim of the present paper is to report the results of a single institution series of hiatal hernia repair (HHR) with augmented mesh hiatoplasty focusing on safety and efficacy profile of Bio-A absorbable synthetic mesh. A retrospective evaluation of prospectively maintained database showed 120 consecutive patients submitted to HHR reinforced with bio-absorbable synthetic mesh. The study populations included two groups: (A) 92 obese patients—reinforced hiatoplasty concurrent with bariatric procedure; (B) 28 non-obese patients—reinforced hiatoplasty concurrent with antireflux surgery. Symptoms assessment was made with GERD-HRQL and Rome III. The X-ray with barium swallow, the CT scan, in selected cases, and the endoscopy were used as recurrence evaluation and as endoscopic complications assessment. Only patients with a mean follow-up of 12 months were included in this study. A Cox hazard was made to evaluate factors affecting the recurrence. No case of intra-peri and post-operative (mean follow-up of 41 months) complications mesh related were registered. The dysphagia-rate was 8.7% for Group A and 11% for Group B. 74% of Group A and 61% of Group B patients are actually PPIs free with median GERD-HRQL score of 4 (from 16) and 6 (from 23), respectively (difference pre-post-operative

Diagnosing a complex genetic syndrome and correctly assigning the concomitant phenotypic traits to a well-defined clinical form is often a medical challenge. In this work, we report the analysis of a family with complex phenotypes, including microcephaly, intellectual disability, dysmorphic features, and polydactyly in the proband, with the aim of adding new aspects for obtaining a clear diagnosis. We performed array-comparative genomic hybridization and quantitative reverse transcriptase PCR (qRT-PCR) analyses. We identified a deletion of chromosome 20p12.1 involving the macrodomain containing 2/mono-ADP ribosylhydrolase 2 gene (MACROD2) in several members of the family. This gene is actually not associated with a specific syndrome but with congenital anomalies of multiple organs. qRT-PCR showed higher levels of a MACROD2 mRNA isoform in the individuals carrying the deletion. Our results, together with other data reported in the literature, support the hypothesis that the deletion in MACROD2 can affect correct embryonic development and that the presence of another associated event, such as epigenetic modifications at the MACROD2 locus, can influence the level of severity of the pathology.

In both plants and animals, male gametogenesis is particularly sensitive to heat stress, to the extent that a single hot or cold day can compromise crop productivity or population persistence. In animals, heat stress during development can impact a male’s ability to secure copulations and/or his post-copulatory fertility. Despite such observations, relatively few studies have examined the consequences of developmental temperature on the reproductive behaviour and physiology of males and females. Here we report for the first time the effects of developmental temperature on the phenotypic expression of both apyrene and eupyrene sperm and the copulatory behaviour of the Indian meal moth, Plodia interpunctella. We show that the length of both apyrene and eupyrene sperm decrease with increasing developmental temperature and that males are less likely to engage in copulation when reared at the highest and lowest temperatures. Where copulation occurred, the duration of copula decreased as male developmental temperature increased. We argue that identification of the mechanisms and consequences of reproductive failure in animals facing heat stress will help understand how wild and domesticated populations will respond to global climate change. We also contend that such studies will help elucidate long-standing evolutionary questions around the maintenance of genetic variation in traits highly relevant to fitness and the role of phenotypic plasticity in driving the evolution of novel traits.

Chronic hepatitis B is prevalent in the transplant setting and may cause significant complications. Effective control of viral replication is needed. Besides lamivudine, very little data are available on safety and efficacy of other drugs. We describe our experience with adefovir dipivoxil (ADV) in eight heart transplant recipients. Studies included a baseline liver biopsy, thrice-monthly clinical, biochemical, and virological evaluations, including genotyping and viral load, polymerase gene sequencing for resistance mutations, liver and kidney function tests, and liver ultrasound. Of eight patients, six had fibrosis score ≤2 and negative HBeAg and seven had hepatitis B virus (HBV) genotype D. Upon ADV start, median HBV-DNA was 5.8 logs IU/mL and alanine aminotransferase (ALT) levels were mostly normal. All patients had prior mild-to-moderate renal functional impairment. Seven of eight patients started ADV after a previous course of lamivudine. Five of these seven patients became HBV-DNA undetectable within eight months. One patient with low baseline viremia started ADV de novo and suppressed HBV-DNA. Median treatment duration was 66 months. ADV daily dose was halved in one patient due to renal function worsening. No ALT flares, hypophosphatemia, liver decompensation, liver cancer, or emergence of resistance was observed. Our data suggest that ADV may be a safe and effective rescue treatment for heart transplant recipients with lamivudine-resistant chronic hepatitis B.

The classical pegylated interferon α (peg-IFNα) and ribavirin (RBV) treatment of chronic hepatitis C (CHC) is progressively being replaced by new direct acting antivirals, whose costs remain a major barrier to widespread use. Using baseline data and viral kinetics, we developed a predictive algorithm to allocate to DAA patients who are not going to respond to peg-IFNα/RBV. This prospective study evaluated 205 CHC patients treated with peg-IFNα/RBV. HCVRNA kinetics during the initial 3 days of therapy and baseline variables including age, genotype, fibrosis and ALTs were used to construct a prediction rule in terms of sustained virological response (SVR). One hundred and twenty-one patients achieved an SVR (59%). Variables independently associated with SVR were HCVRNA, ALT, glycaemia, viral genotype, and fibrosis. The decline of viremia from baseline to 48/72 h was significantly different in SVR compared to non-SVR patients (2.2 vs. 0.65 log10 IU/mL; p 1.2 logs had a positive predictive value of 92%. A combination of HCVRNA kinetics and a score based on pre-treatment parameters was highly accurate in predicting SVR in most patients. Outcome of peg-IFNα/RBV treatment may be predicted combining evaluation of baseline variables and HCVRNA kinetics. This allows to individualize treatment, reserving newer and more expensive DAAs to CHC patients who are in most need of them.

Objectives: Left-sided methicillin-susceptible Staphylococcus aureus (MSSA) endocarditis treated with cloxacillin has a poorer prognosis when the vancomycin minimum inhibitory concentration (MIC) is >= 1.5 mg/L. We aimed to validate this using the International Collaboration on Endocarditis cohort and to analyse whether specific genetic characteristics were associated with a high vancomycin MIC (> 1.5mg/L) phenotype.Methods: All patients with left-sided MSSA infective endocarditis treated with antistaphylococcal beta-lactam antibiotics between 2000 and 2006 with available isolates were included. Vancomycin MIC was determined by Etest as either high (>= 1.5 mg/L) or low (

Otosclerosis, the single most common cause of hearing impairment in white adults, is characterised by bone dystrophy localized to the otic capsule and isolated endochondral bone sclerosis with alternating phases of bone resorption and formation. Conductive hearing loss develops when otosclerotic foci invade the stapedio-vestibular joint (oval window) and interfere with free motion of the stapes, but affected subjects frequently develop profound sensorineural hearing loss. The aetiology of otosclerosis is unknown. In the last years, several association studies have been performed and have suggested that single nucleotide polymorphisms in some genes may be implicated in development of otosclerosis. The strongest association has been demonstrated for the reelin gene, located on chromosome 7q22.1, which encodes an extracellular matrix protein. The involvement of reelin in the pathogenesis of otosclerosis is controversial; it was identified in European and North African populations, but was excluded in an Indian population. To analyze the role of reelin in otosclerosis, it has been studied in a case-control analysis for the polymorphism rs39335 in a southern Italy population. In this population, the pathogenic link between the rs39335 variant and otosclerosis was excluded.L'otosclerosi, la causa più comune di perdita uditiva tra gli adulti bianchi, è caratterizzata da distrofia ossea localizzata alla capsula otica e sclerosi ossea encondrale isolata con alternanza di fasi di riassorbimento e formazione dell'osso. L'ipoacusia trasmissiva si sviluppa quando i focolai otosclerotici invadono l'articolazione stapedio-ovalare (finestra ovale) ed interferiscono con il libero movimento della staffa, ma spesso i soggetti affetti sviluppano un'ipoacusia neurosensoriale profonda. Ad oggi, l'eziologia dell'otosclerosi non è ancora nota. Negli ultimi anni, studi di associazione di diversi polimorfismi sono stati eseguiti e hanno suggerito il coinvolgimento di alcuni di essi nell'insorgenza dell'otosclerosi. L'associazione più forte è stata dimostrata per il gene relina, localizzato sul cromosoma 7q22.1 codificante una proteina della matrice extracellulare. Il coinvolgimento di relina nella patogenesi dell'otosclerosi è controverso in quanto è stato identificato in alcune popolazioni Europee e del Nord Africa, ma è stato escluso nella popolazione Indiana. Per analizzare l'importanza di relina nell'otosclerosi è stato realizzato uno studio di associazione caso-controllo per il polimorfismo rs39335 in una popolazione del Sud Italia. In questa popolazione l'associazione del polimorfismo rs9335 nello sviluppo dell'otosclerosi è stata esclusa.

Childhood obesity is an emerging health problem. Surgical treatment of obese adolescents, particularly those affected by congenital syndrome, represents a controversial issue. The aim of this multicenter study was to retrospectively assess the results of laparoscopic sleeve gastrectomy (LSG) in a cohort of adolescents affected by morbid obesity, with or without congenital syndromes.Forty-one obese (BMI 49 ± 6 kg/mAll the operations were completed laparoscopically and no intra-operative complications were recorded. No mortality was recorded while peri- or post-operative complications only occurred in two patients (4.9%). The EWL% at 6, 12, and 24 months were 42.3, 58.3, and 59.4, respectively. %EWL was comparable (p = 0.7) between non-syndromic and syndromic obese adolescents at 24 months. Conversely patients with previous intragastric balloon surgery had a significant lower EWL (%) at 24 month (p 0.01). Moreover, at the same time point, co-morbidity resolution rate was 78.2% while improvement rate was 57.6%. Specifically, remission rate of type 2 diabetes (T2DM), hypertension and obstructive sleep apnea (OSA) were 71, 75 and 61%, respectively.LSG is advantageous in the treatment of morbidly obese juveniles concerning safety, weight loss and co-morbidity control and at same time presenting, a possible effective therapeutic option for patients affected by congenital syndrome.

Cervical cancer screening by human papillomavirus (HPV) DNA testing with cytology triage is more effective than cytology testing. Compared to cytology, the HPV DNA test's higher sensitivity, which allows better protection with longer intervals, makes it necessary to triage the women with a positive result to compensate its lower specificity. We are conducting a large randomized clinical trial (New Technologies for Cervical Cancer 2 [NTCC2]) within organized population-based screening programs in Italy using HPV DNA as the primary screening test to evaluate, by the Aptima HPV assay (Hologic), the use of HPV E6-E7 mRNA in a triage test in comparison to cytology. By the end of June 2016, data were available for 35,877 of 38,535 enrolled women, 2,651 (7.4%) of whom were HPV DNA positive. Among the samples obtained, 2,453 samples were tested also by Aptima, and 1,649 (67.2%) gave a positive result. The proportion of mRNA positivity was slightly higher among samples tested for HPV DNA by the Cobas 4800 HPV assay (Roche) than by the Hybrid Capture 2 (HC2) assay (Qiagen). In our setting, the observed E6-E7 mRNA positivity rate, if used as a triage test, would bring a rate of immediate referral to colposcopy of about 4 to 5%. This value is higher than that observed with cytology triage for both immediate and delayed referrals to colposcopy. By showing only a very high sensitivity and thus allowing a longer interval for HPV DNA-positive/HPV mRNA-negative women, a triage by this test might be more efficient than by cytology.

The evaluation of academic education has become crucial in the European Union since the Bologna Process encouraged all European universities to reach high quality standards in education. Although several studies have been conducted on the quality of undergraduate nursing education, few studies have explored this topic from the students' perspective. The purpose of this study was to describe the experience of educational quality in undergraduate nursing students.The phenomenological method was used to study 55 students (mean age 24 years; 73% female) pursuing a baccalaureate degree in nursing in three universities in central Italy.The following five themes emerged from the phenomenological analysis: 1) quality of faculties: teaching skills, preparation, sensitivity to students, self-discipline; 2) theory-practice integration and communication between teaching and clinical area; 3) general management and organization of the programme; 4) quality of infrastructures: libraries, classrooms, information technology, services, administration, and communication; and 5) clinical tutorship: humanity, relationships and ability of the clinical tutor to guide and support.This study's novel finding was a deeper understanding of the educational quality's meanings among undergraduate nursing students. Students thought educational quality consisted of the faculty members' sensitivity towards their problems and the clinical tutors' humanity, interpersonal skills, guidance and support.Scopo. La valutazione della formazione accademica è diventata fondamentale nell'Unione Europea da quando il Processo di Bologna ha incoraggiato tutte le università europee a raggiungere elevati standard di qualità nella formazione. Anche se diversi studi sono stati condotti sulla qualità della formazione negli studenti di infermieristica, pochi hanno esplorato questa tematica dalla prospettiva degli studenti. Lo scopo di questo studio è stato di descrivere l'esperienza della qualità formativa negli studenti del corso di laurea in infermieristica. Metodo. E’ stato utilizzato il metodo fenomenologico per studiare 55 studenti (età media 24 anni; 73% donne) che frequentavano il corso di laurea in infermieristica in tre università del centro Italia. Risultati. Dall'analisi fenomenologica sono emersi i seguenti cinque temi: 1) Qualità dei docenti: capacità di insegnamento, preparazione, sensibilità per gli studenti, autodisciplina; 2) Integrazione teoria-pratica e comunicazione tra l'insegnamento e l'area clinica; 3) gestione generale e organizzazione del corso; 4) la qualità delle infrastrutture: biblioteche, aule, tecnologie dell'informazione, servizi, amministrazione, comunicazione; e 5) tutorato clinico: umanità, relazioni e capacità del tutor clinico di guidare e supportare lo studente. Conclusione. I risultati di questo studio forniscono una comprensione nuova e più approfondita sul significato della qualità della formazione negli studenti di infermieristica. Gli studenti ritenevano che la qualità della formazione consistesse nella sensibilità dei docenti verso i loro problemi e nell’umanità, capacità interpersonali, guida e supporto dei tutor cli.

Background Infective endocarditis (IE) due to gram-negative (GN) bacilli is uncommon. Although multi- and extensively-drug resistant (MDR/XDR) GN infections are emerging, very few data are available on IE due to these microrganisms. Methods In this study, we describe the clinical characteristics, course and outcome of five contemporary, definite, MDR/XDR GNIE cases seen at our centre. Results All patients had been admitted to a hospital during the 6 months before IE onset, 2 were on hemodialysis and 3 on intravenous medications. Three of the 5 cases were hospital-acquired. Intracardiac prosthetic devices were present in all cases (3 central venous lines, 2 prosthetic heart valves, 2 pacemakers). Mean Charlson comorbidity index was 5.8. Causative pathogens were XDR Pseudomonas aeruginosa (2 cases), XDR Acinetobacter baumannii, MDR Burkolderia cepacia and MDR Escherichia coli (1 case each). Concomitant pathogens with a MDR/XDR phenotype were isolated in 4 patients. Both valves and intracardiac devices and left and right sides of the heart were involved. The rate of complications was high. Antibiotic treatment hinged on the use of colistin, a carbapenem or both. Cardiovascular surgical procedures were performed in 3 patients. Despite aggressive therapeutic regimens, outcomes were poor. Clearance of bacteremia was obtained in 3 patients, in-hospital death occurred in 3 patients, only 1 patient survived during follow up. Conclusions MDR/XDR GN are emerging as a cause of IE in carriers of intracardiac prostheses with extensive healthcare contacts and multiple comorbidities. Resistant GNIE has a complicated course and shows a dismal prognosis.

Few studies analyzed the risk for high-grade squamous intraepithelial lesions or worse (HSIL+) among immigrants and natives attending organized cervical cancer (CC) screening programs (SP). We evaluated participation and diagnosis of HSIL+ by country of birth with logistic models. Overall 540,779 invitation letters were delivered to target women of Florence SP in three screening rounds (years 2000–2002, 2003–2005, 2006–2008). The probability of attending screening was lower for immigrants than natives, but the difference decreased from 35 % (1st round) to 20 % (2nd–3rd round) for women born in high migration pressure (HMP) countries. The risk of HSIL+ was double than natives for HMP-born women from countries with high prevalence of human papillomavirus, even adjusting for age and previous history of Pap test. This is an important public health problem due to an increasing proportion over time of immigrant women with a lower attendance and greater risk for CC.

The GJB2 gene located on chromosome 13q12 and encoding the connexin 26 (Cx26) protein, a transmembrane protein involved in cell-cell attachment of almost all tissues, including the skin, causes autosomal recessive and sometimes dominant nonsyndromic sensorineural hearing loss. GJB2 mutations have also been identified in syndromic disorders exhibiting hearing loss associated with skin problems. Recently, a new mutation, p.G130V in the GJB2 gene has been reported as causative for Vohwinkel syndrome. In this case the p.G130V mutation was found in two patients (son and father) with palmoplantar keratoderma. The father also showed also skin constrictions of the 2nd and 3rd toes of the right foot. Here, we report on another family with palmoplantar keratoderma associated with a dominant form of hearing loss confirming the genotype-phenotype correlation between the mutation p.G130V and the skin abnormalities observed in syndromic disorders with hearing loss as described by [Snoeckx et al. (2005) Hum Mutat 26:60-65].

Background Cytomegalovirus (CMV) infection is a major complication of immunosuppression after heart transplant. Recent studies suggest the actual immunosuppressive regimen may affect the risk of CMV infection. Objectives To evaluate incidence, risk factors and clinical consequences of CMV infection and assess the possible differential effect of distinct immunosuppressive protocols. Study design Single centre, prospective cohort study of 378 consecutive heart transplant recipients undergoing CMV monitoring. Preemptive treatment was the standard of care. Patients were grouped as follows: group A, without any CMV infection; group B, with CMV infection not requiring pre-emptive treatment; group C, treated for CMV infection or disease. Results Most recipients never required antiviral therapy because of no CMV infection/disease (group A, 31%) or CMV levels below the cut-off for pre-emptive treatment (group B, 28%). Group C recipients (41%) were significantly older than group A patients (49.1 ± 13.2 vs. 44.8 ± 15.1 years; p = 0.028). Most cases occurred within the second month post-transplant. CMV viremia was detected in 77% and 62% of patients primed with thymoglobulin or ATG Fresenius, respectively, (OR 2.06, 95% C.I. 1.27–3.34; p = 0.0034). Use of everolimus was associated with a significantly lower rate of CMV infection compared to azathioprine or mycophenolate (OR 0.19, 95% C.I. 0.09–0.39; p Conclusion In a large and homogeneous cohort of heart transplant recipients, we observed a strong relationship between the immune suppressive regimen and CMV infection, as well as an increased incidence of other opportunistic infections in recipients with CMV infection/disease.

In the majority of insects, sperm fertilize the egg via a narrow canal through the outer chorion called the micropyle. Despite having this one primary function, there is considerable unexplained variation in the location, arrangement and number of micropyles within and between species. Here, we examined the relationship between micropyle number and female mating pattern through a comparative analysis across Lepidoptera. Three functional hypotheses could explain profound micropylar variation: (i) increasing micropyle number reduces the risk of infertility through sperm limitation in species that mate infrequently; (ii) decreasing micropyle number reduces the risk of pathological polyspermy in species that mate more frequently; and (iii) increasing micropyle number allows females to exert greater control over fertilization within the context of post-copulatory sexual selection, which will be more intense in promiscuous species. Micropyle number was positively related to the degree of female promiscuity as measured by spermatophore count, regardless of phylogenetic signal, supporting the hypothesis that micropyle number is shaped by post-copulatory sexual selection. We discuss this finding in the context of cryptic female choice, sperm limitation and physiological polyspermy.

Blood coagulation plays a key role in the pathogenesis of infective endocarditis (IE). Conditions associated with thrombophilia could enhance IE vegetation formation and promote embolic complications. In this study, we assessed prevalence, correlates, and clinical consequences of hyper-homocysteinemia (h-Hcy) in IE. Homocysteine (Hcy) plasma levels were studied in 246 IE patients and 258 valvular heart disease (VHD) patients, as well as in 106 healthy controls. IE patients showed Hcy levels comparable to VHD patients (14.9 [3–81] vs 16 [5–50] μmol/L, respectively; P = 0.08). H-Hcy was observed in 48.8% of IE patients and 55.8% of VHD (P = 0.13). Vegetation size and major embolic complications were not related to Hcy levels. IE patients with h-Hcy had a higher prevalence of chronic kidney disease and a higher 1-year mortality (19.6% vs 9.9% in those without h-Hcy; OR 2.21 [1.00–4.89], P = 0.05). However, at logistic regression analysis, h-Hcy was not an independent predictor of 1-year mortality (OR 1.87 [95% CI 0.8–4.2]; P = 0.13). Our data suggest h-Hcy in IE is common, is related to a worse renal function, and may be a marker of cardiac dysfunction rather than infection. H-Hcy does not appear to favor IE vegetation formation or its symptomatic embolic complications.

Background: In Italy, cervical cancer screening programmes actively invite women aged 25–64 years. Programmes are hindered by low participation. Methods: A sample of non-responder women aged 35–64 years, belonging to three different programmes (in Rome, Florence and Teramo), was randomly split into four arms: two control groups received standard recall letters to perform either Pap-test (first group) or human papillomavirus (HPV) test (second group) at the clinic. A third arm was sent letters offering a self-sampler for HPV testing, to be requested by phone, whereas a fourth group was directly sent the self-samplers home. Results: Compliance with standard recall was 13.9% (N619). Offering HPV test at the clinic had a nonsignificant effect on compliance (N616, relative risk (RR)=1.08; 95% CI=0.82–1.41). Self-sampler at request had the poorest performance, 8.7% (N622, RR=0.62; 95% CI=0.45–0.86), whereas direct mailing of the self-sampler registered the highest compliance: 19.6% (N616, RR=1.41; 95% CI=1.10–1.82). This effect on compliance was observed only in urban areas, Florence and Rome (N438, RR=1.69; 95% CI=1.24–2.30), but not in Abruzzo (N178, RR=0.95; 95% CI=0.61–1.50), a prevalently rural area. Conclusions: Mailing self-samplers to non-responders may increase compliance as compared with delivering standard recall letters. Nevertheless, effectiveness is context specific and the strategy costs should be carefully considered.

Amid growing concern about keeping exotic species as companion animals, nonhuman primates have been highlighted as inappropriate for private ownership. However, there has been no comprehensive review of the suitability of primates as pets, using a framework such as Schuppli and Fraser's (2000). Schuppli and Fraser incorporate welfare of the individual, of others, and of the environment. This article (a) examines the numbers, origins, ages, and ownership trends of primates kept as pets in the United Kingdom and (b) identifies a number of welfare, health, and environmental concerns. Overall, strong evidence supports the argument that primates are not suitable pets; it is unlikely that the welfare of pet primates can be adequately addressed in normal households. Finally, using unpublished data on complaints and inquiries received by the Royal Society for the Prevention of Cruelty to Animals, the study assesses the degree of public concern about the welfare of primates kept as pets in England and Wales. The article identifies a wide range of concerns about keeping pet primates and concludes that this practice should end.

Laparoscopic revisional bariatric surgery (RBS) is increasingly common. A tailored decision-making process is advocated. In this retrospective study, we reviewed the RBS experience of a single center, analyzing perioperative complications to provide insight into management options and midterm outcomes. Records from November 2011 to March 2015 were reviewed from prospectively maintained database. Six hundred eighteen patients underwent laparoscopic bariatric procedures; of these, 81 (13.1 %) underwent RBS. Patients with a minimum follow-up of 6 months (n = 77) were evaluated. Fifty-nine underwent revised laparoscopic sleeve gastrectomy, and 18 underwent revised Roux-en-Y gastric bypass. Indications for RBS were inadequate weight loss or weight regain in 42 cases (54.5 %) and gastroesophageal reflux disease (GERD), procedure-related complications, or technical failure in 35 cases (45.5 %). There were no deaths or conversions to open surgery. After a mean follow-up of 22 months, body mass index (BMI) decreased from 40.9 ± 6.7 to 31.9 ± 4.8 kg/m2, mean % excess weight loss (%EWL) was 58 ± 24.3 %, and 55.3 % of patients had resolution of comorbidities. Eight major complications (10.4 %) occurred: five leaks and three intra-abdominal hematomas. Non-surgical management succeeded in 50 % of complications. This study confirms that RBS is challenging; a complication rate of 10 % is expected. Major surgery can be avoided when devoted endoscopists and radiologists are available. Intensive follow-up after complications allows early diagnosis and treatment of unfavorable sequelae. RBS induced a mean %EWL of 58 % at 2 years and resolution of comorbidities in 50 % of cases. However, the durability of these effects remains questionable.

Ophthalmic emergency (OE) triage is essential for prompt recognition of urgent cases. To date, no formal eye-dedicated triaging system has been widely accepted. The purpose of the present study is to propose a fast, accurate, and reproducible coding scale called the Rome Eye System for Scoring Urgency and Emergency (Rescue).Phase 1 of the study is a retrospective analysis of electronic medical records (EMR); phase 2 is a prospective consecutive series. Phase 1 included 160,936 patients. Phase 2 included 1000 consecutive patients referred to the emergency department (ED) of our institution. In phase 1, the authors retrospectively analyzed EMRs of patients presenting to the ED, listing signs and symptoms most frequently associated with hospitalization. Redness, pain, loss of vision, and the risk for an open eye were identified and assigned a score ranging from 0 to 12. Color coding was assigned based on increasing scoring: 0-3 white, 4-7 green, 8-12 yellow code. In phase 2, 1000 consecutive ED patients were enrolled and prospectively coded according to RESCUE. After diagnosis and proper treatment, EMRs were retrospectively reviewed by a masked physician and patients recoded (Retro coding) according to clinical course. Correlation between Rescue and Retro coding was calculated.Prospective and retrospective ED color coding correlation.A total of 160,936 EMR were retrospectively analyzed; 2407 (1.4%) patients required hospitalization. Loss of vision (90%), redness (76%), and pain (47%) were the most frequent complaints. Rescue significantly correlated to Retro coding (p0.01): 841/1000 patients coded exactly the same color, 45/1000 were overestimated by one color class, none by two, 107/1000 underestimated by one, and 6/1000 by two classes. The 32/1000 hospitalized patients in the prospective cohort had a Rescue score significantly higher than non-admitted patients (p0.01) and color coding among admitted and dismissed patients was significantly different as well (p0.01).The Rescue system seems promising in terms of usefulness and ease of implementation. The high correlation between Rescue code assigned prospectively and the post-diagnosis coding, as well as the prompt discrimination of cases that eventually required hospitalization, may lead to a wider use of the Rescue system. Further testing on larger samples and different institutions is warranted.

Compared to spontaneous screening, an organized screening programme is characterized by the presence of protocols and recommendations for all stages including follow-up. Despite the availability of well-functioning screening programmes throughout the country, the follow-up protocol after an abnormal Pap test and negative colposcopy is not clearly defined in Italy, and there is no uniformity of indications. HPV testing for oncogenic human papillomavirus (hr-HPV) has a high negative predictive value (NPV) and high positive predictive value (PPV) for CIN2+ and its employment can reduce follow-up assessments. In order to provide indications about the management of women with ASC-US+ and the follow-up of women with cytological abnormalities and negative colposcopy, a literature analysis was carried out, taking into consideration European and American guidelines and good practice recommendations from the most important scientific associations and regulatory agencies. GISCi (Italian Group for Cervical Screening) drafted recommendations for the management of women with ASC-US, L-SIL, ASC-H, AGC, and H-SIL until their return to the routine screening interval. This protocol can be applied not only in the management of abnormal Pap smears in cytology-based programmes, but also in the management of abnormal Pap test triage after HPV positive test when HPV is the primary screening test. The protocols approved within the screening programmes must have an extensive consensus among all involved professionals, including any that women might meet outside the programme.

Parathyroid autotransplantation plays an important role in preventing hypoparathyroidism following thyroidectomy. The preferred reimplantation site is still the sternocleidomastoid muscle, but this approach does not permit to check graft vitality postoperatively. The authors report the first prospective evaluation of normal parathyroid gland reimplantation in forearm subcutaneous tissue (using the same technique proposed during parathyroidectomy for hyperplasia) in case of devascularized or inadvertently removed glands during thyroid surgery. From January 2013 to August 2014, we performed 348 consecutive thyroidectomies for various disease, both benign and malignant. In 25 cases, due to inadvertent parathyroid removal or evidence of insufficient blood supply, we removed and fragmented the gland into 0.5–1 mm slices (one for frozen section) and reimplanted it into two subcutaneous pockets on the non-dominant forearm. After surgery we checked grafted gland function by evaluation of serum parathormone gradient between reimplanted versus non-reimplanted arm (considering significant a ratio of 1.5 or more), at 1 week, 1 and 3 months after surgery. We observed recovery of reimplanted graft function in 48, 88 and 96 % of patients respectively at 1 week, 1 and 3 months after surgery. All patients showed normal parathormone levels in peripheral blood (non-reimplanted arm). In one case we observed post-operative wound hematoma on graft-site. This patient showed no graft functionality in post-operative period (even at 3 months follow-up). Parathyroid gland reimplantation in forearm subcutaneous tissue during thyroid surgery is a safe, easy and effective procedure; furthermore, it allows a good control of graft functionality and would allow an easy grafted gland removal if needed.

Blood coagulation plays a key role in the pathogenesis of infective endocarditis (IE). Conditions associated with thrombophilia could enhance IE vegetation formation and promote embolic complications.In this study, we assessed prevalence, correlates, and clinical consequences of hyper-homocysteinemia (h-Hcy) in IE.Homocysteine (Hcy) plasma levels were studied in 246 IE patients and 258 valvular heart disease (VHD) patients, as well as in 106 healthy controls.IE patients showed Hcy levels comparable to VHD patients (14.9 [3-81] vs 16 [5-50] μmol/L, respectively; P = 0.08). H-Hcy was observed in 48.8% of IE patients and 55.8% of VHD (P = 0.13). Vegetation size and major embolic complications were not related to Hcy levels. IE patients with h-Hcy had a higher prevalence of chronic kidney disease and a higher 1-year mortality (19.6% vs 9.9% in those without h-Hcy; OR 2.21 [1.00-4.89], P = 0.05). However, at logistic regression analysis, h-Hcy was not an independent predictor of 1-year mortality (OR 1.87 [95% CI 0.8-4.2]; P = 0.13).Our data suggest h-Hcy in IE is common, is related to a worse renal function, and may be a marker of cardiac dysfunction rather than infection. H-Hcy does not appear to favor IE vegetation formation or its symptomatic embolic complications.

Background Chronic hepatitis C patients with coexisting heart disease are often denied antiviral treatment due to safety concerns. However, this is not evidence-based. Aims To evaluate safety and efficacy of pegylated interferon and ribavirin in chronic hepatitis C patients with heart disease. Methods Patients with overt heart disease (ischaemic heart disease, prior mechanical heart valve replacement, chronic arrhythmias and cardiomyopathy) and chronic hepatitis C were treated with standard pegylated interferon/ribavirin doses for standard duration. Cardiovascular safety was monitored by electrocardiography, echocardiography and measurement of troponin and B-type natriuretic peptide. Results Twenty-three patients (65.2% male, median age 57 years, 47.8% genotype 1) were treated. Three patients (13%) suspended treatment prematurely; 52% obtained sustained virological response, 39% relapsed, 9% were non-responders. No serious adverse event was observed. Post-treatment clinical examination, electrocardiography and echocardiography did not show any sign of progression of the pre-existing heart disease. Conclusions Treatment with pegylated interferon/ribavirin may be safely offered to carefully selected chronic hepatitis C patients with coexisting, clinically significant heart disease. In these patients, the outcome of antiviral treatment overlaps that observed in other patient subgroups.

Background Totally implantable venous access devices can be implanted both by percutaneous approaches and by surgical approaches with cephalic vein or external jugular vein cut-down techniques that are related to low intraoperative complication rates. The authors report a prospective evaluation of 83 consecutive external jugular vein cut-down approaches for totally implantable venous access devices implantation. Methods Eighty three consecutive patients (28 M, 55 F, mean age 54.2) suffering from solid tumors (58) or hematologic diseases (25) were consecutively submitted to totally implantable venous access devices insertion through external jugular vein cut-down approach (75 on right side, 8 on left side). Results All devices were surgically implanted; no instances of intraoperative complications were detected. After a minimum follow-up of 150 days, only one case of wound hematoma and one case of device malfunction due to incorrect catheter angulation were noted. Postoperative patient satisfaction was evaluated by the use of specific questionnaire that demonstrated a good satisfaction and compliance (92.8 %) of patients with implanted devices. Conclusions Despite the lack of controlled studies comparing external jugular vein cut-down approach vs other approaches, this approach should be considered as a tool for long-term central vein catheters positioning, both as an alternative and for primary approach.