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BackgroundPublished risk tools do not provide possible management options for syncope in the emergency department (ED). Using the 30-day observed risk estimates based on the Canadian Syncope Risk Score (CSRS), we developed personalised risk prediction to guide management decisions.MethodsWe pooled previously reported data from two large cohort studies, the CSRS derivation and validation cohorts, that prospectively enrolled adults (≥16 years) with syncope at 11 Canadian EDs between 2010 and 2018. Using this larger cohort, we calculated the CSRS calibration and discrimination, and determined with greater precision than in previous studies the 30-day risk of adjudicated serious outcomes not identified during the index ED evaluation depending on the CSRS and the risk category. Based on these findings, we developed an on-line calculator and pictorial decision aids.Results8233 patients were included of whom 295 (3.6%, 95% CI 3.2% to 4.0%) experienced 30-day serious outcomes. The calibration slope was 1.0, and the area under the curve was 0.88 (95% CI 0.87 to 0.91). The observed risk increased from 0.3% (95% CI 0.2% to 0.5%) in the very-low-risk group (CSRS −3 to –2) to 42.7% (95% CI 35.0% to 50.7%), in the very-high-risk (CSRS≥+6) group (Cochrane-Armitage trend test p20% of high/very-high-risk patients (score +4 to+11) including 4%–6% deaths. The online calculator and the pictorial aids can be found at: https://teamvenk.com/csrsConclusions30-day observed risk estimates from a large cohort of patients can be obtained for management decision-making. Our work suggests very-low-risk and low-risk patients may be discharged, discussion with patients regarding investigations and disposition are needed for medium-risk patients, and high-risk patients should be hospitalised. The online calculator, accompanied by pictorial decision aids for the CSRS, may assist in discussion with patients.

Background Coronavirus disease 2019 is revolutionizing healthcare delivery. The aim of this study was to reach a consensus among experts as to the possible applications of telemedicine in the proctologic field. Methods A group of 55 clinical practice recommendations was developed by a clinical guidance group based on coalescence of evidence and expert opinion. The Telemedicine in Proctology Italian Working Group included 47 Italian Society of Colorectal Surgery nominated experts evaluating the appropriateness of each clinical practice recommendations based on published RAND/UCLA methodology in 2 rounds. Results Stakeholder median age was 53 years (interquartile range limits 40–60), and 38 (81%) were men. Nine (19%) panelists reported no experience with telemedicine before the pandemic. Agreement was obtained on a minimum of 3 to 5 years of practice in the proctologic field before starting teleconsultations, which should be regularly paid, with advice and prescriptions incorporated into a formal report sent to the patient by e-mail along with a receipt. Of the panelists, 35 of 47 (74%) agreed that teleconsultation carries the risk of misdiagnosis of cancer, thus recommending an in-person assessment before scheduling any surgery. Fifteen additional clinical practice recommendations were re-elaborated in the second round and assessed by 44 of 47 (93.6%) panelists. The application of telemedicine for the diagnosis of common proctologic conditions (eg, hemorrhoidal disease, anal abscess and fistula, anal condylomas, and anal fissure) and functional pelvic floor disorders was generally considered inappropriate. Teleconsultation was instead deemed appropriate for the diagnosis and management of pilonidal disease. Conclusion This e-consensus revealed the boundaries of telemedicine in Italy. Standardization of infrastructures, logistics, and legality remain to be better elucidated.

Introduction Prolonged labor increases the risk of maternal and fetal complications. The active management of labor has been proven effective in lowering neonatal and maternal morbidity by shortening the duration of labor. Several pharmaceutical and non-pharmaceutical approaches are currently being used in the active management of labor. Hyoscine Butyl-bromide (HBB) is an antispasmodic and anticholinergic drug that acts as a cervical spasmolytic agent. It has been widely used in everyday practice for shortening the active phase of labor. Nonetheless, only a few trials have been conducted on the topic. Objective This review aimed to evaluate whether HBB is effective in decreasing the mean duration of the active phase of labor. Study design An electronic search was conducted on Medline (through PubMed), Scopus, ClinicalTrials.gov, EMBASE, PROSPERO, and Cochrane Library from the beginning of all databases to December 2019. Results were limited to randomized trials. Restriction for English language was applied. Inclusion criteria were: randomized clinical trials regarding primiparae or multiparae women with a singleton vertex pregnancy at term who were randomized to HBB versus placebo or other drugs. Primary outcome evaluated was the mean reduction of the active phase of labor. Data collection and analysis Eight randomized clinical trials, including 1159 pregnant women, were analyzed. Significant heterogeneity (I2 = 99 %) between studies was noted for the primary outcome. The active phase of labor duration was significantly reduced in the treatment arm compared to controls [mean difference (MD) −83.93 min (95 % confidence interval (CI) −163.61, −4.25)]. Achieved reduction in primiparae women was −55.09 min [95 % CI −68.83, −41.35; I2 = 37 %]. Conclusion HBB is an effective treatment to shorten the duration of the active phase of labor in primiparae and multiparae women.

Summary: Background/Objective: A preoperative reliable classification system between clinical and computed tomography (CT) findings to better plan surgery in acute complicated diverticulitis (ACD) is lacking. We studied the inter-observer agreement of CT scan data and their concordance with the preoperative clinical findings and the adherence with the intraoperative status using a new classification of diverticular disease (CDD). Methods: 152 patients operated on for acute complicated diverticulitis (ACD) were retrospectively enrolled. All patients were studied with CT scan within 24 h before surgery and CT images were blinded reanalyzed by 2 couples of radiologists (A/B). Kappa value evaluated the inter-observer agreement between radiologists and the concordance between CDD, preoperative clinical findings and findings at operation. Univariate and multivariate analysis were used to evaluate the predicting values of CT classification and CDD stage at surgery on postoperative outcomes. Results: Overall inter-observer agreement for the CDD was high, with a kappa value of 0.905 (95% CI = 0.850–0.960) for observers A and B, while the concordance between radiological and surgical findings was weak (kappa values = 0.213 and 0,248, respectively and 95% CI = 0.106 to 0.319 and 95% CI = 0.142 to 0.355, respectively). When overall morbidity, mortality and the need of a terminal colostomy were considered as main endpoints no concordance was observed between surgical and radiological findings and the CDD (P=NS). Conclusions: The need for a more accurate classification of ACD, able to better stage this emergency, and to provide surgeons with reliable information for the best treatment is advocated. Keywords: Acute complicated diverticulitis, Inter-observer agreement, CDD, CT scanning, Operative findings, Predicting value

Objectives: The main goal of our research was to explore correlations between a history of uterine myomectomy and maternal-fetal outcomes, throughout a comparison between vaginal deliveries in patients with or without a history of uterine myoma excision. Materials and methods: A prospective study was carried out at two tertiary care hospitals between January 2019 and January 2020. Women were assigned into two groups according to the history of laparoscopic or laparotomic myomectomy (Group 1) or without myomectomy (Group 2). Results: 80 women successfully delivered after myomectomy. Pregnancies with previous laparoscopic or laparotomic myomectomy were associated with a minor rate of spontaneous labor onset (RR 1.17; 95% CI 1.04 − 1.31) and with an increased rate of emergency cesarean section (RR 1.22; 95% CI 1.09 − 1.36). Moreover, myomectomy group had a significant number of indications to emergency cesarean section correlated to suspected uterine rupture (RR 1.19; 95% CI 1.02–1.39). There were no uterine ruptures or neonatal deaths recorded. First stage of labor was longer in the myomectomy group (316 vs 204 mins, p = 0.01). No differences in the rates of the prolonged first and second stage of labor, postpartum hemorrhage and vaginal laceration, and no neonatal adverse outcomes were found between groups. Conclusions: Pregnancies after myomectomy might be associated with an elevated rate of emergency cesarean section only due to a higher percentage of suspected uterine rupture, without a real hazard of adverse obstetric or neonatal outcomes.

Purpose We investigated the safety of primary hip and knee replacements with same day discharge (SDD) and their effect on length of stay (LOS) of traditional inpatient arthroplasties at our elective orthopaedic ward. Methods 200 patients underwent elective, unilateral primary day case total hip (THA, n = 94), total knee (TKA, n = 60) and unicondylar knee replacements (UKA, n = 46). SDD rates, reasons for failure to discharge, readmission, complication and satisfaction rates were recorded at 6-week follow up. Changes in LOS of inpatient arthroplasties (n = 6518) and rate of patients discharged with only one night stay treated at the same ward were tracked from 1 year prior to introduction of day case arthroplasty (DCA) program to the end of observation period. Results 166 patients (83%) had SDD while 34 (17%) needed overnight stay. Main reasons for failure to discharge were lack of confidence (4%) fainting due to single vasovagal episode (3.5%), urine retention (3%) and late resolution of spinal anaesthesia (3%). 5 patients (3%) had readmission within 6 weeks, including 1 (0.6%) with a partial and treated pulmonary embolism. 163 patients were satisfied with SDD (98%). After launching the DCA program, average LOS of inpatients was reduced from 2.3 days to 1.8 days and rate of discharge with only 1-night stay increased from 12% to around 60%. Conclusion Introduction of routine SDD hip and knee arthroplasty programme at an elective orthopaedic centre is safe and also may confer wider benefits leading to shorter inpatient hospital stays.

Degenerative lumbar spine disease is one of the leading causes of disability worldwide. Lumbar interbody fusion (LIF) is a valid approach in the treatment of several segmental spine pathologies, including degenerative disc disease. LIF may be performed through open and minimally invasive procedures. This review aims to assess the state of the art in the field of minimally invasive spine surgery in the treatment of degenerative disc disease.

Background: The aims of the present study are to: (1) assess the frequency of maternity blues (MB); (2) identify the clinical and social characteristics more frequently associated with the onset of depressive symptoms after delivery; and (3) verify the hypothesis that the presence of maternity blues is a risk factor for the onset of a full-blown depressive episode in the 12 months after delivery.Methods: This is a longitudinal observational study. All pregnant women who gave birth at the inpatient unit of Gynecology and Obstetrics of the University of Campania “Luigi Vanvitelli” from December 2019 to February 2021 have been invited to participate in the study. Upon acceptance, women were asked to complete the Italian version of the Edinburgh Postnatal Depression Scale along with an ad-hoc questionnaire on the women's sociodemographic, gynecological and peripartum characteristics as well as their psychiatric history. Women have been reassessed after one, 3, 6 and 12 months.Results: A total of 359 women were recruited within 3 days from delivery, with a mean EPDS total score of 5.51 (±4.20). Eighty-three women (23.1%) reported the presence of maternity blues. Mean EPDS total scores were 12.8 (±0.2) in the MB group vs. 4.26 (±0.2) in the group without MB (p p p < 0.000), almost three times higher after 3 months (OR: 2.98; CI: 0.50–5.46, p < 0.01) and almost six times higher after 12 months (OR: 5.88; CI: 3.20–8.54, p < 0.000).Conclusions: Although MB was a self-limiting condition in the majority of cases, depressive symptoms arose quite often immediately after the childbirth. Professionals should be trained to monitor symptoms of MB and its transition toward a depressive episode.

Background: COVID-19 is an emerging infectious disease, that is heavily challenging health systems worldwide. Admission Arterial Blood Gas (ABG) and Lung Ultrasound (LUS) can be of great help in clinical decision making, especially during the current pandemic and the consequent overcrowding of the Emergency Department (ED). The aim of the study was to demonstrate the capability of alveolar-to-arterial oxygen difference (AaDO2) in predicting the need for subsequent oxygen support and survival in patients with COVID-19 infection, especially in the presence of baseline normal PaO2 / FiO2 ratio (P/F) values. Methods: A cohort of 223 swab-confirmed COVID-19 patients underwent clinical evaluation, blood tests, ABG and LUS in the ED. LUS score was derived from 12 ultrasound lung windows. AaDO2 was derived as AaDO2 = ((FiO2) (Atmospheric pressure − H2O pressure) − (PaCO2/R)) − PaO2. Endpoints were subsequent oxygen support need and survival. Results: A close relationship between AaDO2 and P/F and between AaDO2 and LUS score was observed (R2 = 0.88 and R2 = 0.67, respectively; p < 0.001 for both). In the subgroup of patients with P/F between 300 and 400, 94.7% (n = 107) had high AaDO2 values, and 51.4% (n = 55) received oxygen support, with 2 ICU admissions and 10 deaths. According to ROC analysis, AaDO2 > 39.4 had 83.6% sensitivity and 90.5% specificity (AUC 0.936; p < 0.001) in predicting subsequent oxygen support, whereas a LUS score > 6 showed 89.7% sensitivity and 75.0% specificity (AUC 0.896; p < 0.001). Kaplan–Meier curves showed different mortality in the AaDO2 subgroups (p = 0.0025). Conclusions: LUS and AaDO2 are easy and effective tools, which allow bedside risk stratification in patients with COVID-19, especially when P/F values, signs, and symptoms are not indicative of severe lung dysfunction.

Background This paper describes the clinical practice and performance of cell-free DNA sequencing-based non-invasive prenatal testing (NIPT) as a screening method for fetal trisomy 21, 18, and 13 (T21, T18, and T13) and sex chromosome aneuploidies (SCA) in a general Italian pregnancy population. Methods The AMES-accredited laboratory offers NIPT in maternal blood as a screening test for fetal T21, T18, T13 and SCA. Samples were sequenced on a NextSeq 550 (Illumina) using the VeriSeq NIPT Solution v1 assay. Results A retrospective analysis was performed on 36,456 consecutive maternal blood samples, including 35,650 singleton pregnancies, 800 twin pregnancies, and 6 triplet pregnancies. Samples were tested between April 2017 and September 2019. The cohort included 46% elevated-risk and 54% low-risk patients. A result indicative of a classic trisomy was found in 356 (1%) of singleton or twin samples: 254 T21, 69 T18, and 33 T13. In addition, 145 results (0.4%) were indicative of a SCA. Of the combined 501 screen-positive cases, 484 had confirmatory diagnostic testing. NIPT results were confirmed in 99.2% (247/249) of T21 cases, 91.2% (62/68) of T18 cases, 84.4% (27/32) of T13 cases, and 86.7% (117/135) of SCA cases. In the 35,955 cases reported as unaffected by a classic trisomy or SCA, no false negative cases were reported. Assuming that false negative results would be reported, the sensitivity of NIPT was 100.00% for T21 (95% Cl 98.47–100.0), T18 (95% Cl 94.17–100.0), and T13 (95% Cl 87.54–100.0). The specificities were 99.99% (95% Cl 99.98–100.0), 99.98% (95% Cl 99.96–100.0), 99.99% (95% Cl 99.97–100.0), and 99.95% (95% Cl 99.92–99.97) for T21, T18, T13, and SCA, respectively. Conclusion This retrospective analysis of a large cohort of consecutive patients who had whole-genome sequencing-based NIPT for classic trisomies and SCA shows excellent detection rates and low false positive rates.

Background. Diabetes in pregnancy is associated with an increased risk to the woman and to the developing fetus. Currently, there is no consensus on the optimal management strategies for the follow-up and the timing of delivery of pregnancies affected by gestational and pregestational diabetes, with different international guidelines suggesting different management options. Materials and Methods. We conducted a retrospective cohort study from January 2017 to January 2021, to compare maternal and neonatal outcomes of pregnancies complicated by gestational and pregestational diabetes, followed-up and delivered in a third level referral center before and after the introduction of a standardized multidisciplinary management protocol including diagnostic, screening, and management criteria. Results. Of the 131 women included, 55 were managed before the introduction of the multidisciplinary management protocol and included in group 1 (preprotocol), while 76 were managed according to the newly introduced multidisciplinary protocol and included in group 2 (after protocol). We observed an increase in the rates of vaginal delivery, rising from 32.7% to 64.5% ( P < 0.001 ). No differences were found in neonatal outcomes, and the only significant difference was demonstrated for the rates of fetal macrosomia (20% versus 5.3%, P : 0.012). Therefore, the improvements observed in the maternal outcomes did not impact negatively on fetal and neonatal outcomes. Conclusion. The introduction of a standardized multidisciplinary management protocol led to an improvement in the rates of vaginal delivery and in the rate of successful induction of labor in our center. A strong cooperation between obstetricians, diabetologists, and neonatologists is crucial to obtain a successful outcome in women with diabetes in pregnancy.

To estimate the correlation between the maternal perception of Braxton-Hicks contractions (BHC) and foetal wellbeing throughout antepartum computerised cardiotocography (cCTG) parameters, we performed a prospective observational study between April 2019 and March 2020. Non-labouring women with a term pregnancy were recruited. We collected data regarding maternal perception of BHC in the last two weeks before delivery. For each patient, an external computerised cardiotocography (cCTG) was registered. Women were subdivided in accordance with perception or non-perception of BHC. Fifty women were recruited. Women who felt BHC showed higher foetal heart rate (135 bpm vs 128 bpm, p = .008), lower long-term variability (47.2 ms vs 57.7 ms, p = .02) and reduced number of accelerations (7.8 vs 11.4, p = .04). In conclusion, the absence of mother's perception of BHC showed lower baseline foetal heart rate, increased number of accelerations and higher long-term variability related to mothers who perceived BHC.IMPACT STATEMENTWhat is already known on this subject? BHC are common painful contractions that start in the third trimester. They are random spots of uterine action that happen in the absence of sufficient gap-junction connectivity. BHC have a significant impact on foetal wellbeing.What do the results of this study add? BHC are associated with reduced long-term variability during cCTG examination. Moreover, baseline foetal heart rate seems lower, and accelerations are less frequent when BHC are felt by pregnant women.What are the implications of these findings for clinical practice and/or further research? These findings could be related to a cumulative effect on the uterine flow mediated by BHC. Further researches are needed to state the impact of BHC on the foetal wellbeing. What is already known on this subject? BHC are common painful contractions that start in the third trimester. They are random spots of uterine action that happen in the absence of sufficient gap-junction connectivity. BHC have a significant impact on foetal wellbeing. What do the results of this study add? BHC are associated with reduced long-term variability during cCTG examination. Moreover, baseline foetal heart rate seems lower, and accelerations are less frequent when BHC are felt by pregnant women. What are the implications of these findings for clinical practice and/or further research? These findings could be related to a cumulative effect on the uterine flow mediated by BHC. Further researches are needed to state the impact of BHC on the foetal wellbeing.

Background: Besides reducing the quality of obstetric care, the direct impact of COVID-19 on pregnancy and postpartum is uncertain. Objective: To evaluate the characteristics of pregnant women who died due to COVID-19. Search strategy: Cochrane Library, Embase, MEDLINE, Scopus, and Google Scholar were searched from inception to February 2021. Selection criteria: Studies that compared deceased and survived pregnant women with COVID-19. Data collection and analysis: Relevant data were extracted and tabulated. The primary outcome was maternal co-morbidity. Main results: Thirteen studies with 154 deceased patients were included. Obesity doubled the risk of death (relative risk [RR] 2.48, 95% confidence interval [CI] 1.41–4.36, I2=0%). No differences were found for gestational diabetes (RR 5.71; 95% CI 0.77–42.44, I2=94%) or asthma (RR 2.05, 95% CI 0.81–5.15, I2=0%). Overall, at least one severe co-morbidity showed a twofold increased risk of death (RR 2.26, 95% CI 1.77–2.89, I2=76%). Admission to intensive care was related to a fivefold increased risk of death (RR 5.09, 95% CI 2.00–12.98, I2=56%), with no difference in need for respiratory support (RR 0.53, 95% CI 0.23–1.48, I2=95%) or mechanical ventilation (RR 4.34, 95% CI 0.96–19.60, I2=58%). Conclusion: COVID-19 with at least one co-morbidity increases risk of intensive care and mortality.

Introduction: Cesarean section affects subsequent spontaneous pregnancies because of implantation issues. However, its impact on post-embryo transfer pregnancies is still debated. This review aimed to evaluate the impact of a previous cesarean section on fertility and pregnancy outcomes of women undergoing fresh or frozen embryo transfer. Material and methods: MEDLINE, Scopus, ClinicalTrials.gov, Scielo, EMBASE, Cochrane Library at the CENTRAL, and LILACS were searched from inception to February 2021. Studies were included if they evaluated reproductive or pregnancy outcomes after fresh or frozen embryo transfer in infertile women with a previous cesarean section relative to women with a previous vaginal delivery. Random-effect meta-analyses to calculate risk ratio (RR) or mean differences with 95% confidence intervals (CI) followed by subgroup analysis for fresh and frozen embryo transfer were performed. Risk of bias and quality assessment were conducted using Newcastle–Ottawa scale and GRADE criteria. The review was registered in the International Prospective Register of Systematic Reviews (CRD42021226297). Results: Ten studies, with data provided for 13696 participants, were eligible. For embryo transfers after cesarean section, compared with vaginal delivery, there was a significant reduction of the live birth rate (RR 0.88, 95% CI 0.79–0.99) and biochemical pregnancy rate (RR 0.89, 95% CI 0.82–0.96). No statistically significant differences were found for clinical pregnancy rate (RR 0.92, 95% CI 0.84–1.02), ectopic pregnancies (RR 1.00, 95% CI 0.68–1.46), pregnancy loss (RR 1.05, 95% CI 0.94–1.18), multiple pregnancies (RR 0.80, 95% CI 0.63–1.02), stillbirths (RR 0.86, 95% CI 0.27–2.69), birth defects (RR 1.71, 95% CI 0.49–5.96) or birthweight (mean difference 46.82, 95% CI −40.16 to 133.80). Subgroup analysis revealed an increased risk for preterm birth in post-cesarean section fresh embryo transfer pregnancies (RR 1.59, 95% CI 1.16–2.19). Conclusions: Low-grade evidence shows that post-embryo transfer pregnancies in infertile women who had a previous cesarean delivery result in reduced biochemical pregnancy and live birth rates relative to women with a previous vaginal delivery. An increased risk for preterm birth is notable in post-fresh embryo transfer pregnancies.

It is widely acknowledged that obesity is a growing public clinical issue involving both physical and psychological well-being. Nevertheless, the relationship between psychological features and weight gain is still unclear. Although emotional eating (EE) and personality traits are considered significant predictors of eating disorders, their role in obesity without eating disorders (OB-wed) is far from proven. The present study aimed at investigating the cumulative effect of EE and personality traits on overeating behavior in a sample of 266 university students (169 female, mean age = 21.85, SD = 2.39) stratified based on their body mass index (BMI, normal weight, overweight, obese). They were enrolled during free screening days promoted by the Human Dietetic and Sport Service of a Southern Italian university. The results show a psychological pattern of increasing overeating behavior and lower Self-Directedness combined with higher Sadness and Anger. However, OB-wed subjects overate regardless of this emotional/personological configuration.

Background: Surgical treatment of anal fistulas is still a challenge. The aims of this study were to evaluate the adoption and healing rates for the different surgical techniques used in Italy over the past 15 years. Methods: This was a multicenter retrospective observational study of patients affected by simple and complex anal fistulas of cryptoglandular origin who were surgically treated in the period 2003–2017. Surgical techniques were grouped as sphincter-cutting or sphincter-sparing and as technology-assisted or techno-free. All patients included in the study were followed for at least 12 months. Results: A total of 9,536 patients (5,520 simple; 4,016 complex fistulas) entered the study. For simple fistulas, fistulotomy was the most frequently used procedure, although its adoption significantly decreased over the years (P < .0005), with an increase in sphincter-sparing approaches; the overall healing rate in simple fistulas was 81.1%, with a significant difference between sphincter-cutting (91.9%) and sphincter-sparing (65.1%) techniques (P = .001). For complex fistulas, the adoption of sphincter-cutting approaches decreased, while sphincter-sparing techniques were mildly preferred (P < .0005). Moreover, there was a significant trend toward the use of technology-assisted procedures. The overall healing rate for complex fistulas was 69.0%, with a measurable difference between sphincter-cutting (81.1%) and sphincter-sparing (61.4%; P = .001) techniques and between techno-free and technology-assisted techniques (72.5% and 55.0%, respectively; P = .001). Conclusion: Surgical treatment of anal fistulas has changed, with a trend toward the use of sphincter-sparing techniques. The overall cure rate has remained stable, even if the most innovative procedures have achieved a lower success rate.

Recent literature highlights that the use of smartphones during meals increases the number of calories ingested in young people. Although the distraction interferes with physiological signals of hunger and satiety, a social facilitation effect has also been suggested. Cognition is a pivotal component in regulating food intake, and activities requiring high perceptual demands should be discouraged during meals.

BACKGROUND: Ovarian cancer is the first cause of death among gynecological malignancies with a high incidence of recurrence. Different treatment options are suitable to prolong the survival rate of these patients. Over the last years, one of the most intriguing methods, adopted in different oncologic centers worldwide, is the hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: A meta-analysis was performed to value the role of HIPEC for ovarian cancer recurrence. Search strategy was conducted with a combination of the following keywords: “ovarian recurrence, ovarian cancer recurrence, peritoneal cancer recurrence, ovarian recurrence AND HIPEC, secondary cytoreduction HIPEC”. Seven studies were selected for analysis. RESULTS: In women with recurrent ovarian cancer (ROC), the use of HIPEC in addition to cytoreductive surgery and chemotherapy significantly improved 1-year overall survival (OS) when compared to protocols without HIPEC (OR 2.42; 95% CI, 1.06–5.56; P=0.04; I(2)=4%). The improvement in OS was maintained significant also after 2, 3 and 5 years respectively (OR 3.33; 95% CI, 1.81–6.10; P

The early detection of skin cancer is of crucial importance to plan an effective therapy to treat the lesion. In routine medical practice, the diagnosis is based on the visual inspection of the lesion and it relies on the dermatologists&rsquo, expertise. After a first examination, the dermatologist may require a biopsy to confirm if the lesion is malignant or not. This methodology suffers from false positives and negatives issues, leading to unnecessary surgical procedures. Hyperspectral imaging is gaining relevance in this medical field since it is a non-invasive and non-ionizing technique, capable of providing higher accuracy than traditional imaging methods. Therefore, the development of an automatic classification system based on hyperspectral images could improve the medical practice to distinguish pigmented skin lesions from malignant, benign, and atypical lesions. Additionally, the system can assist general practitioners in first aid care to prevent noncritical lesions from reaching dermatologists, thereby alleviating the workload of medical specialists. In this paper is presented a parallel pipeline for skin cancer detection that exploits hyperspectral imaging. The computational times of the serial processing have been reduced by adopting multicore and many-core technologies, such as OpenMP and CUDA paradigms. Different parallel approaches have been combined, leading to the development of fifteen classification pipeline versions. Experimental results using in-vivo hyperspectral images show that a hybrid parallel approach is capable of classifying an image of 50 &times, 50 pixels with 125 bands in less than 1 s.

The aim of this systematic literature review and meta-analysis is to assess the impact of hysteroscopic metroplasty for dysmorphic uteri on reproductive outcomes in women with recurrent miscarriages. Available studies were identified through a PubMed, Scopus, and Cochrane search until June 2019. Live-birth rate, clinical pregnancy and miscarriage rate after hysteroscopic metroplasty was evaluated. DerSimonian and Laird’s random-effect model was used for relative risks, Freeman-Tukey Double Arcsine for pooled estimates and exact method to stabilize variances and CIs. Heterogeneity was quantified using I2-statistics. Six out of 164 published studies met the inclusion criteria. All (n = 221) women underwent metroplasty, using 5Fr-hysteroscope with bipolar electrodes or 26Fr/28Fr-resectoscope in outpatient or inpatient settings. After 6 to 60-month follow-up, reported live-birth rate was 50% (0.37-0.63 95% CI) from a clinical pregnancy rate of 73% (0.51-0.91 95% CI) and miscarriage rate was 23% (0.15-0.30 95% CI). Hysteroscopic metroplasty for dysmorphic uteri led half of the women who experienced recurrent miscarriages at least one live birth and is correlated to few surgical and obstetric complications. However, randomized clinical trials and case-control studies are unavailable due to ethical constrains; inhomogenity of follow-up durations and standardized protocols regarding preoperative diagnosis and post-surgical management resrict our conclusions.

Background: Ion channels play a crucial role in many physiological processes. Several subtypes are expressed in the endometrium. Endometriosis is strictly correlated to estrogens and it is evident that expression and functionality of different ion channels are estrogen-dependent, fluctuating between the menstrual phases. However, their relationship with endometriosis is still unclear. Objective: To summarize the available literature data about the role of ion channels in the etiopathogenesis of endometriosis. Methods: A search on PubMed and Medline databases was performed from inception to November 2019. Results: Cystic fibrosis transmembrane conductance regulator (CFTR), transient receptor potentials (TRPs), aquaporins (AQPs), and chloride channel (ClC)-3 expression and activity were analyzed. CFTR expression changed during the menstrual phases and was enhanced in endometriosis samples; its overexpression promoted endometrial cell proliferation, migration, and invasion throughout nuclear factor kappa-light-chain-enhancer of activated B cells-urokinase plasminogen activator receptor (NFκB-uPAR) signaling pathway. No connection between TRPs and the pathogenesis of endometriosis was found. AQP5 activity was estrogen-increased and, through phosphatidylinositol-3-kinase and protein kinase B (PI3K/AKT), helped in vivo implantation of ectopic endometrium. In vitro, AQP9 participated in extracellular signal-regulated kinases/p38 mitogen-activated protein kinase (ERK/p38 MAPK) pathway and helped migration and invasion stimulating matrix metalloproteinase (MMP)2 and MMP9. ClC-3 was also overexpressed in ectopic endometrium and upregulated MMP9. Conclusion: Available evidence suggests a pivotal role of CFTR, AQPs, and ClC-3 in endometriosis etiopathogenesis. However, data obtained are not sufficient to establish a direct role of ion channels in the etiology of the disease. Further studies are needed to clarify this relationship.

Abnormal hippocampal neural plasticity has been implicated in behavioural abnormalities and complex neuropsychiatric conditions, including bipolar disorder (BD). However, the determinants of this neural alteration remain unknown. This work tests the hypothesis that the neurotransmitter serotonin (5-HT) is a key determinant of hippocampal neuroplasticity, and its absence leads to maladaptive behaviour relevant for BD. Depletion of brain 5-HT in Tph2 mutant mice resulted in reduced behavioural despair, reduced anxiety, marked aggression and lower habituation in novel environments, reminiscent of bipolar-associated manic behaviour. Treatment with valproate produced a substantial improvement of the mania-like behavioural phenotypes displayed by Tph2 mutants. Brain-wide fMRI mapping in mutants revealed functional hippocampal hyperactivity in which we also observed dramatically increased neuroplasticity. Importantly, remarkable correspondence between the transcriptomic profile of the Tph2 mutant hippocampus and neurons from bipolar disorder patients was observed. Chronic stress reversed the emotional phenotype and the hippocampal transcriptional landscape of Tph2 mutants. These changes were associated with inappropriate activation of transcriptional adaptive response to stress as assessed by gene set enrichment analyses in the hippocampus of Tph2 mutant mice. These findings delineate 5-HT as a critical determinant in BD associated maladaptive emotional responses and aberrant hippocampal neuroplasticity, and support the use of Tph2−/− mice as a new research tool for mechanistic and therapeutic research in bipolar disorder.

// Sara Franceschi 1 , Francesca Lessi 1 , Paolo Aretini 1 , Valerio Ortenzi 2 , Cristian Scatena 2 , Michele Menicagli 1 , Marco La Ferla 1 , Prospero Civita 1 , Katia Zavaglia 3 , Claudia Scopelliti 1 , Alessandro Apollo 4 , Francesco Giovanni Carbone 2 , Riccardo Vannozzi 5 , Generoso Bevilacqua 6 , Francesco Pasqualetti 7 , Antonio Giuseppe Naccarato 2 and Chiara Maria Mazzanti 1 1 Fondazione Pisana per la Scienza, Onlus, Pisa, Italy 2 Department of Translational Research and New Technologies in Medicine, University Hospital of Pisa, Pisa, Italy 3 SOD Molecular Genetics, University Hospital of Pisa, Pisa, Italy 4 Tumor Cell Biology Unit, Istituto Tumori Toscana, Florence, Italy 5 Neurosurgery Department, University Hospital of Pisa, Pisa, Italy 6 Pathological Anatomy Section, San Rossore Clinic, Pisa, Italy 7 Radiotherapy Department, University Hospital of Pisa, Pisa, Italy Correspondence to: Chiara Maria Mazzanti, email: c.mazzanti@fpscience.it Keywords: glioblastoma; next generation sequencing (NGS); recurrence free survival (RFS); onco-drivers; tumor suppressors Received: November 17, 2017 Accepted: April 02, 2018 Published: May 08, 2018 ABSTRACT Glioblastoma is a devastating disease that despite all the information gathered so far, its optimal management remains elusive due to the absence of validated targets from clinical studies. A better clarification of the molecular mechanisms is needed. In this study, having access to IDH1 wild-type glioblastoma of patients with exceptionally long recurrence free survival (RFS), we decided to compare their mutational and gene expression profile to groups of IDH1 wild-type glioblastoma of patients with shorter RFS, by using NGS technology. The exome analysis revealed that Long-RFS tumors have a lower mutational rate compared to the other groups. A total of 158 genes were found differentially expressed among the groups, 112 of which distinguished the two RFS extreme groups. Overall, the exome data suggests that shorter RFS tumors could be, chronologically, in a more advanced state in the muli-step tumor process of sequential accumulation of mutations. New players in this kind of cancer emerge from the analysis, confirmed at the RNA/DNA level, identifying, therefore, possible oncodrivers or tumor suppressor genes.

The Covid-19 European outbreak in February 2020 has challenged the world's health systems, eliciting an urgent need for effective and highly reliable diagnostic instruments to help medical personnel. Deep learning (DL) has been demonstrated to be useful for diagnosis using both computed tomography (CT) scans and chest X-rays (CXR), whereby the former typically yields more accurate results. However, the pivoting function of a CT scan during the pandemic presents several drawbacks, including high cost and cross-contamination problems. Radiation-free lung ultrasound (LUS) imaging, which requires high expertise and is thus being underutilised, has demonstrated a strong correlation with CT scan results and a high reliability in pneumonia detection even in the early stages. In this study, we developed a system based on modern DL methodologies in close collaboration with Fondazione IRCCS Policlinico San Matteo's Emergency Department (ED) of Pavia. Using a reliable dataset comprising ultrasound clips originating from linear and convex probes in 2908 frames from 450 hospitalised patients, we conducted an investigation into detecting Covid-19 patterns and ranking them considering two severity scales. This study differs from other research projects by its novel approach involving four and seven classes. Patients admitted to the ED underwent 12 LUS examinations in different chest parts, each evaluated according to standardised severity scales. We adopted residual convolutional neural networks (CNNs), transfer learning, and data augmentation techniques. Hence, employing methodological hyperparameter tuning, we produced state-of-the-art results meeting F1 score levels, averaged over the number of classes considered, exceeding 98%, and thereby manifesting stable measurements over precision and recall., Graphical abstract Image 1

VincenzoMonda,1,* MarcoLa Marra,1,* RaffaellaPerrella,2 GiorgioCaviglia,2 AlessandroIavarone,3 SergioChieffi,1 GiovanniMessina,4 MarcoCarotenuto,5 MarcellinoMonda,1 AntoniettaMessina1 1Department of Experimental Medicine, Section of Human Physiology, University of Campania Luigi Vanvitelli, Naples, Italy; 2Neurological and Stroke Unit, CTO Hospital, AORN ‘‘Ospedali dei Colli’’, Naples, Italy; 3Department of Psychology, University of Campania Luigi Vanvitelli, Naples, Italy; 4Department of Clinical and Experimental Medicine, University of Foggia, Foggia, Italy; 5Clinic of Child and Adolescent Neuropsychiatry, Department of Mental Health, Physical and Preventive Medicine, University of Campania Luigi Vanvitelli, Naples, Italy *These authors contributed equally to this work Abstract: Recent findings showed that obesity represents an additional risk factor to developing brain illness such as cognitive impairments and psychopathological disorders. However, some benefits of overweight in the elderly have been identified and an “obesity paradox” has been shown. Currently, it is still unknown how obesity and brain functioning could be linked, and the process by which body fat independently injures cognitive abilities and psychological well-being remains unclear. To establish the independent role of obesity on cognitive abilities and mental health, clarifying the role played by several factors and understanding their interaction is essential. In this review, we discuss the relationship between obesity and brain illness and underline the role played by confounders and other covariates to determine this link. Keywords: obesity, cognitive decline, mood disorders, obesity paradox

INTRODUCTION Preservation of kidney and renal function is the goal of nonoperative management (NOM) of renal trauma (RT). The advantages of NOM for minor blunt RT have already been clearly described, but its value for major blunt and penetrating RT is still under debate. We present a systematic review and meta-analysis on NOM for RT, which was compared with the operative management (OM) with respect to mortality, morbidity, and length of hospital stay (LOS). METHODS The Preferred Reporting Items for Systematic Reviews and Meta-analyses statement was followed for this study. A systematic search was performed on Embase, Medline, Cochrane, and PubMed for studies published up to December 2015, without language restrictions, which compared NOM versus OM for renal injuries. RESULTS Twenty nonrandomized retrospective cohort studies comprising 13,824 patients with blunt (2,998) or penetrating (10,826) RT were identified. When all RT were considered (American Association for the Surgery of Trauma grades 1-5), NOM was associated with lower mortality and morbidity rates compared to OM (8.3% vs 17.1%, odds ratio [OR] 0.471; 95% confidence interval [CI] 0.404-0.548; P

5-Fluorouracil is commonly used for gastrointestinal cancer treatment in an adjuvant setting; however, the toxicity can lead to a reduction, delay, or discontinuation of treatment. We retrospectively investigated the association between the 5-fluorouracil degradation rate (5-FUDR) and genetic polymorphisms of TSER, DPYD, and MHTFR with toxicity in colorectal cancer patients treated with adjuvant FOLFOX. Pretreatment 5-FUDR and MTHFR A1298T or C677T, TSER, and DPYD gene polymorphisms were characterized in stages II-III colorectal cancer patients. Patients were classified into three metabolic classes according to the 5-FUDR value. Association with toxicities was evaluated retrospectively using logistic regression analysis. Overall, 126 patients were selected (35 women, 91 men). Seven patients were poor metabolizers, 116 patients were normal metabolizers and three patients were ultra-rapid metabolizers. The median 5-FUDR was 1.53 ng/ml/10 cells/min (range: 0.42-2.57 ng/ml/10 cells/min). Severe, rate-limiting toxicities (grades 3-4) were encountered in 22.2% of patients. No associations between MTHFR or TSER polymorphisms and toxicity were detected, whereas 5-FUDR showed a statistically significant association with toxicity (P=0.0047). The DPYD heterozygous mutation was detected in only one patient, who showed grade 4 hematological toxicity and a lower 5-FUDR value. The 5-FUDR value seems not to be affected by MTHFR and TSER polymorphisms. Compared with the available pharmacogenomics tests, the pretreatment evaluation of 5-FUDR increases the proportion of identified colorectal patients at high risk for severe toxicity. Thus, it appears to be a suitable pretreatment toxicity biomarker in a subgroup of patients in whom dose-intensity maintenance is the key factor.

Disease-independent sources of biomarker variability include pre-analytical, analytical and biological variance. The aim of the present study was to evaluate whether the pre-analytical phase has any impact on the emerging heart disease TWEAK and HMGB1 protein markers and miRNA biomarkers, and whether peptidome profiling allows the identification of pre-analytical quality markers.An assessment was made of sample type (serum, EDTA-Plasma, Citrate-Plasma, ACD-plasma, Heparin-plasma), temperature of sample storage (room temperature or refrigerated), time of sample storage (0.5, 3, 6 and 9h) and centrifugation (one or two-step). Aliquots of all processed samples were immediately frozen (-80°C) before analysis. Proteins were assayed by ELISAs, miRNA expression profile by microarray and peptidome profiling by MALDI-TOF/MS.Temperature, time and centrifugation had no impact on TWEAK and HMGB1 results, which were significantly influenced by matrix type, TWEAK levels being significantly higher (F=194.7, p0.0001), and HMGB1 levels significantly lower (F=36.32, p0.0001) in serum than in any other plasma type. Unsuitable miRNA results were obtained using Heparin-plasma. Serum miRNA expression profiles depended mainly on temperature, while EDTA-plasma miRNA expression profiles were strongly affected by the centrifugation method used. MALDI-TOF/MS allowed the identification of seven features as indices of pre-analytical serum (m/z at 1206, 1350, 1865 and 2021) or EDTA-plasma (m/z 1897, 2740 and 2917) degradation.Serum and EDTA-plasma allow the analysis of both proteins and miRNA emerging biomarkers of heart diseases. Refrigerated storage prevents an altered miRNA expression profile also in cases of a prolonged time-interval between blood drawing and processing.

© 2020 Elsevier Ltd Background: Observational studies have suggested that accelerated surgery is associated with improved outcomes in patients with a hip fracture. The HIP ATTACK trial assessed whether accelerated surgery could reduce mortality and major complications. Methods: HIP ATTACK was an international, randomised, controlled trial done at 69 hospitals in 17 countries. Patients with a hip fracture that required surgery and were aged 45 years or older were eligible. Research personnel randomly assigned patients (1:1) through a central computerised randomisation system using randomly varying block sizes to either accelerated surgery (goal of surgery within 6 h of diagnosis) or standard care. The coprimary outcomes were mortality and a composite of major complications (ie, mortality and non-fatal myocardial infarction, stroke, venous thromboembolism, sepsis, pneumonia, life-threatening bleeding, and major bleeding) at 90 days after randomisation. Patients, health-care providers, and study staff were aware of treatment assignment, but outcome adjudicators were masked to treatment allocation. Patients were analysed according to the intention-to-treat principle. This study is registered at ClinicalTrials.gov (NCT02027896). Findings: Between March 14, 2014, and May 24, 2019, 27 701 patients were screened, of whom 7780 were eligible. 2970 of these were enrolled and randomly assigned to receive accelerated surgery (n=1487) or standard care (n=1483). The median time from hip fracture diagnosis to surgery was 6 h (IQR 4–9) in the accelerated-surgery group and 24 h (10–42) in the standard-care group (p

Background and Objectives: Hot flushes and sleep disturbances are the most common vasomotor symptoms (VMS) reported by postmenopausal women. Hormonal treatment is to date referred to as the gold standard approach but not suitable for all the patients. Alternative treatments are needed in case of a contraindication to menopausal hormone therapy (MHT), adverse side effects, and poor compliance. Paroxetine salt is the only nonhormonal medication approved by the US Food and Drug Administration for the management of VMS. Nonetheless, few trials with low consensus are available about this topic. In this review, we aimed to evaluate the efficacy of low-dose paroxetine therapy in the treatment of vasomotor hot flushes and night sleep disturbances in postmenopausal women. Materials and Methods: We performed an electronic search from the beginning of all databases to July 2019. All results were then limited to a randomized trial. Restrictions for language or geographic location were not utilized. Inclusion criteria were randomized clinical trials of physiological or surgical postmenopausal women experiencing hot flushes and sleep disturbances who were randomized to either low-dose paroxetine or placebo (i.e., formulations without active ingredients). The primary outcome evaluated was the mean weekly reduction of hot flushes. Results: Five randomized clinical trials, including 1482 postmenopausal women, were analyzed. Significant heterogeneity (I2 = 90%) between studies was noted. Hot flushes episodes were significantly reduced in the treatment arm compared to placebo (mean difference (MD) −7.97 [−10.51, −5.92] episodes/week). Results on the improvement on sleep were limited by being reported in only two studies; however, no significant reduction of night-time awakenings was observed (MD, −0.40 awakenings/night [−1.38, 0.58 CI]). Conclusions: Low-dose paroxetine is an effective treatment for vasomotor menopause symptoms, including hot flushes.

Simone Vigneri,1,2 Gianfranco Sindaco,2 Marco La Grua,2 Matteo Zanella,2 Laura Ravaioli,2 Valentina Paci,2 Gilberto Pari2 1Department of Experimental Biomedicine and Clinical Neurosciences, University of Palermo, Palermo, 2Advanced Algology Research and Pain Medicine Unit, Santa Maria Maddalena Hospital, Occhiobello, RO, Italy Objective: The aim of this study was to investigate the therapeutic effectiveness of epidural morphine and bupivacaine in patients with chronic lumbosacral radicular neuropathic pain after the cessation of treatment.Methods: Twenty-two patients with chronic lumbosacral pain with neuropathic features were enrolled. An indwelling catheter was placed into the epidural space, and each patient received an epidural injection of morphine chlorhydrate and bupivacaine up to three times a day. The medication was administered for 4 weeks. The pain intensity score on a 0–10 numeric rating scale (NRS), the total pain rating index rank (PRIr-T), and its coefficients were evaluated before treatment and 1 month after catheter removal. P-value 30% in NRS) was reached and maintained in half of the patients at follow-up.Conclusion: Combined epidural morphine and bupivacaine seems to be effective in the treatment of neuropathic pain. Keywords: epidural, opioids, bupivacaine, neuropathic pain, chronic pain

Pilonidal disease (PD) is a common disease of the natal cleft, which can lead to complications including infection and abscess formation. Various operative management options are available, but the ideal technique is still debatable. Recurrent PD after surgical treatment is frequent event for the 25–30% of cases. The present study evaluated endoscopic pilonidal sinus treatment (EPSiT) in recurrent and multi-recurrent PD. Of the consecutive prospective patients with recurrent PD, 122 were enrolled in a prospective international multicenter study conducted at a secondary and tertiary colorectal surgery centers. Primary endpoint was to evaluate short- and long-term outcomes: healing rate/time, morbidity rate, re-recurrence rate, and patient’s quality of life (QoL). Complete wound healing rate was occurred in 95% of the patient, with a mean complete wound healing time of 29 ± 12 days. The incomplete healing rate (5%) was significantly related to the number of external openings (p = 0.008), and recurrence was reported in six cases (5.1%). Normal daily activity was established on the first postoperative day, and the mean duration before patients returned to work was 3 days. QoL significantly increased between the preoperative stage and 30 days after the EPSiT procedure (45.3 vs. 7.9; p

Trastuzumab is an effective therapeutic treatment for Her2-like breast cancer; despite this most of these tumors develop resistance to therapy due to specific gene mutations or alterations in gene expression. Understanding the mechanisms of resistance to Trastuzumab could be a useful tool in order to identify combinations of drugs that elude resistance and allow a better response for the treated patients. Twelve primary biopsies of Her2+/hormone receptor negative (ER-/PgR-) breast cancer patients were selected based on the specific response to neoadjuvant therapy with Trastuzumab and their whole exome was sequenced leading to the identification of 18 informative gene mutations that discriminate patients selectively based on response to treatment. Among these genes, we focused on the study of the ANKRD44 gene to understand its role in the mechanism of resistance to Trastuzumab. The ANKRD44 gene was silenced in Her2-like breast cancer cell line (BT474), obtaining a partially Trastuzumab-resistant breast cancer cell line that constitutively activates the NF-kb protein via the TAK1/AKT pathway. Following this activation an increase in the level of glycolysis in resistant cells is promoted, also confirmed by the up-regulation of the LDHB protein and by an increased TROP2 protein expression, found generally associated with aggressive tumors. These results allow us to consider the ANKRD44 gene as a potential gene involved in Trastuzumab resistance.

Glioblastoma (GB) is the most aggressive type of primary brain tumor. Despite the progress in recent years regarding the diagnosis and treatment of GB, the recurrence rate remains high, due to the infiltrative and dispersive nature of the tumor, which typically results in poor patient prognosis. In the present study, 19 formalin-fixed, paraffin-embedded GB samples were selected from patients with GB tumors. The samples were classified into a short or long recurrence-free survival (RFS) group, based on the time of first recurrence of the disease in the patients. The 19 samples were molecularly characterized for mutations in the isocitrate dehydrogenase 1 (IDH1) gene, amplification of the epidermal growth factor receptor (EGFR) gene, presence of the EGFR variant III, and methylation of the promoter region of the O6-methylguanine-DNA methyltransferase (MGMT) gene. Then, the expression of 84 genes involved in cell-cell and cell-matrix interactions, and that of 84 microRNAs (miRNAs) associated with brain cancer, was profiled. In addition, a copy number variation analysis of 23 genes reported to undergo frequent genomic alterations in human glioma was also performed. Differences in the expression levels of a number of genes were detected across the short and long RFS groups. Among these genes, 5 in particular were selected, and a 5-genes combination approach was developed, which was able to differentiate between patients with short and long RFS outcome. The high levels of sensitivity and precision displayed by this 5-genes combination approach, which were confirmed with a cross-validation method, provide a strong foundation for further validation of the involvement of the aforementioned genes in GB in a larger patient population. In conclusion, the present study has demonstrated how the expression pattern of miRNAs and mRNAs in patients with GB defines a particular molecular hallmark that may increase or reduce the aggressive behavior of GB tumors, thus influencing the survival rates of patients with GB, their response to therapy and their tendency to suffer a relapse.

BACKGROUND Catalase gene (CAT) polymorphisms were analyzed as responsible for the deficiency of catalase enzyme activity and concomitant accumulation of excessive hydrogen peroxide in vitiligo patients. Catalase is a well-known oxidative stress regulator that could play an important role in the pathogenesis of vitiligo. This study was conducted to evaluate three CAT gene polymorphisms (-89A/T, 389C/T, 419C/T) and their association with vitiligo susceptibility in Sicilian population. METHODS Sixty out of 73 Sicilian patients with vitiligo were enrolled and submitted to CAT gene analysis. RESULTS Contrary to the Northern part of Europe but likewise to the Mediterranean area, the frequency of the CAT genotypes in Sicily is equally distributed. Out of all CAT genotypes, only CAT-89 T/T frequency was found to be significantly higher amongst vitiligo patients than controls. CONCLUSIONS Despite the involvement of the CAT enzyme in the pathogenesis of vitiligo, the biological significance of CAT gene polymorphisms is still controversial. With the only exception for CAT variant -89A/T, the other studied CAT gene polymorphisms (389C/T and 419C/T) might not to be associated with vitiligo in Sicilian population.

Adaptation to environmental insults is an evolutionary mechanism essential for survival. The hippocampus participates in controlling adaptive responses to stress and emotional state through the modulation of neuroplasticity events, which are dysregulated in stress-related neuropsychiatric disorders. The neurotransmitter serotonin (5-HT) has been proposed as a pivotal player in hippocampal neuroplasticity in both normal and neuropsychiatric conditions though its role remains still poorly understood. Here, we investigated the impact of 5-HT deficiency on hippocampal activity combining RNA-seq, in vivo neuroimaging, neuroanatomical, biochemical and behavioral experiments on 5-HT depleted mice. We unveil that serotonin is required for appropriate activation of neuroplasticity adaptive mechanisms to environmental insults. Bidirectional deregulation of these programs in serotonin depleted mice is associated with opposite behavioral traits that model core symptoms of bipolar disorder. These findings delineate a previously unreported buffering role of 5-HT in instructing hippocampal activity and emotional responses to environmental demands.

Background/Aims The prognosis of pancreatic adenocarcinoma (PAC) is poor. The serum carbohydrate antigen 19-9 (CA 19-9) level has been identified as a prognostic indicator of recurrence and reduced overall survival. The aim of this study was to identify preoperative prognostic factors and to create a prognostic model able to assess the early recurrence risk for patients with resectable PAC. Methods A series of 177 patients with PAC treated surgically at the St. Andrea Hospital of Rome between January 2003 and December 2011 were reviewed retrospectively. Univariate and multivariate analyses were utilized to identify preoperative prognostic indicators. Results A preoperative CA 19-9 level >228 U/mL, tumor size >3.1 cm, and the presence of pathological preoperative lymph nodes statistically correlated with early recurrence. Together, these three factors predicted the possibility of an early recurrence with 90.4% accuracy. The combination of these three preoperative conditions was identified as an independent parameter for early recurrence based on multivariate analysis (p=0.0314; hazard ratio, 3.9811; 95% confidence interval, 1.1745 to 15.3245). Conclusions PAC patient candidates for surgical resection should undergo an assessment of early recurrence risk to avoid unnecessary and ineffective resection and to identify patients for whom palliative or alternative treatment may be the treatment of choice.

Background: During the last few years, the gastric cancer nodal staging has been extensively revised. Lately, a new system emerged in this field with the purpose of implementing the prognostic stratification: the lymph-node ratio (LNR). The aim of this study was to investigate the prognostic value of the LNR in relation to cancer survivors undergoing resection for gastric adenocarcinoma. Methods: Off 227 patients undergoing surgical resection for gastric cancer at our Department, 129 curative gastric resections with more than 15 nodes harvested were selected. The LNR was calculated and patients were stratified into 6 subgroups based on the ratio values. The subgroups were compared for data analysis. Survivals were calculated by the Kaplan-Meier method, and the mean follow-up period was 40 months. ROC curves were calculated in order to analyze the performance of the LNR system. Results: LNR stratification correlated with the stage of the disease, with the rate of patients undergoing chemotherapy and patients presenting with a relapse of disease at follow-up. Moreover, an increased ratio correlated with a worse overall, a disease-free and a disease-specific survival of the patients. The ROC curves documented a significant performance of the stratification system with the endpoints of disease-free and disease-specific survivals. Conclusion: LNR stratification correlated with cancer-related survivals in our case series. It is a reliable system that might improve current nodal staging and thereby the identification of patients with a higher risk of recurrence or cancer-related mortality.

Background/aim Grade C postoperative pancreatic fistula (POPF) is a life-threatening complication of pancreaticoduodenectomy (PD), with its surgical management remaining under debate. Occasionally, POPF is associated with a compromised anastomotic Roux-limb. Our series focused to this sort of grade C mixed fistula. Patients and methods Between April 2004 and March 2014, 5 out of 12 patients with grade C POPF were classified as grade C mixed POPFs. Surgery consisted of associating resection of the anastomotic jejunal segment with resection and closure of the pancreatic stump. Results Four patients suffered from a grade C mixed POPF discharging into a single dehiscent site; 1 patient was found with two dehiscent points in all (pancreatic anastomosis and jejunal rim). For all of them, the described surgical procedure resulted in complete recovery. Conclusion For grade C pancreatico-digestive POPF, resecting anastomotic jejunal segment during dismantling of the pancreatico-digestive anastomosis appears a very promising surgical technique.

Acid ceramidase (AC) is a lysosomal cysteine hydrolase that catalyzes the conversion of ceramide into fatty acid and sphingosine. This reaction lowers intracellular ceramide levels and concomitantly generates sphingosine used for sphingosine-1-phosphate (S1P) production. Since increases in ceramide and consequent decreases of S1P reduce proliferation of various cancers, AC might offer a new target for anti-tumor therapy. Here we used CrispR-Cas9-mediated gene editing to delete the gene encoding for AC, ASAH1, in human A375 melanoma cells. ASAH1-null clones show significantly greater accumulation of long-chain saturated ceramides that are substrate for AC. As seen with administration of exogenous ceramide, AC ablation blocks cell cycle progression and accelerates senescence. Importantly, ASAH1-null cells also lose the ability to form cancer-initiating cells and to undergo self-renewal, which is suggestive of a key role for AC in maintaining malignancy and self-renewal of invasive melanoma cells. The results suggest that AC inhibitors might find therapeutic use as adjuvant therapy for advanced melanoma.

Leiomyosarcomas of the inferior vena cava (IVCLMS) are a very rare tumor accounting for fewer than 700 cases reported in the literature. A systematic overview and analysis of IVCLMS is here presented with the intent to produce a complete analytical study of epidemiology, histopathology, radiological diagnosis, surgical treatment, palliation, and survival outcomes of this tumor.

Papillary thyroid carcinoma is the most frequent histologic type of thyroid tumor. Few studies investigated the role of c-KIT expression in thyroid tumors, suggesting a role for this receptor and its ligand in differentiation and growth control of thyroid epithelium and a receptor loss following malignant transformation. We investigated and correlated c-KIT expression levels and two known markers of thyrocytes differentiation, PAX8 and TTF-1, in malignant and benign cytological thyroid samples. Moreover, we performed functional studies on human papillary thyroid carcinoma cell line to associated c-KIT expression to thyrocytes differentiation and tumor proliferation. c-KIT and PAX8 expression resulted higher in benign samples compared to the malignant ones, and the expression levels of these two genes were significantly correlated to each other. We also observed that c-KIT overexpression led to an increase of PAX8 expression level together with a decrease of proliferation. Furthermore, c-KIT overexpressing cells showed a regression of typical morphological features of malignancy. Taken together these results suggest that c-KIT could be involved in the differentiation of thyroid cells and in tumor progression.

Background Survival after resection of pancreatic adenocarcinoma is poor. Several prognostic factors such as the status of the resection margin, lymph node status, or tumor grading have been identified. Aim of the study was to evaluate the prognostic significance of the lymph node ratio (LNR) for resected pancreatic ductal adenocarcinoma. Materials and Methods Data were collected from 101 patients who had undergone pancreatoduodenectomy for pancreatic ductal adenocarcinoma. Patients were divided into four groups according to the absolute LNR (0, 0–0.199, 0.2–0.399, >0.4). Kaplan–Meier and Cox proportional hazard models were used to evaluate the prognostic effect. Results The actuarial 3- and 5-year survival rates were 32 and 17%, respectively. The median survival was 19 months. Patients with LNR 0/0–0.199/0.2–0.399/>0.4 survived 40.2/30.5/18.1, and 13.6 months, respectively (P = 0.001). At the multivariate analysis, lymph node status was not found to be a significant prognostic factor; on the contrary LNR >0.2 (P = 0.007), positive resection margin (P = 0.001), and grading (P = 0.05) were significantly related to survival. Conclusion LNR is a more powerful predictor of survival than the lymph node status in patients undergoing pancreaticoduodenectomy for ductal adenocarcinoma. J. Surg. Oncol. 2011; 104:629–633. © 2011 Wiley Periodicals, Inc.

Purpose To present a case of partially thrombosed 5 cm wide aneurysm of the origin of common hepatic artery with occlusion of common hepatic artery distal to the aneurysm and proper hepatic artery revascularized by gastroduodenal and superior mesenteric arteries. Case report After a preliminary 3D rotational angiography evaluation a stent graft was deployed in the celiac axis to exclude the common hepatic artery and the aneurysm taking the advantage of developed complete collateral liver blood supply. Two year CT follow up showed stent patency without clinical and radiological evidence of visceral ischemic damage. Clinical and technical considerations are discussed. Conclusions The positive mid-term outcome confirms the efficacy of endovascular exclusion with stent graft, in the treatment of hepatic artery aneurysm in selected cases.

Background and aims Stress is hypothesized to facilitate the development of obesity, whose the foundations are already set during childhood and adolescence. We investigated the relationship between the stress-system, selected mechanisms of energy homeostasis and insulin resistance (IR) in a sample of European adolescents. Methods and results Within HELENA-CSS, 723 adolescents (12.5–17.5 years) from 10 European cities provided all the necessary data for this study. Fasting blood samples were collected for cortisol, leptin, insulin and glucose analysis. HOMA-IR was calculated from insulin and glucose concentrations. Adolescents' body fat (BF) %, age and duration of exclusive breastfeeding were assessed. For boys and girls separately, the relationship of cortisol with leptin, insulin, glucose and HOMA-IR was examined by computing Pearson correlation coefficients and Hierarchical Linear Models (HLMs), with ‘city' as cluster unit, adjusting for age, BF% and duration of exclusive breastfeeding. In boys, Pearson correlation coefficients illustrated positive correlations of cortisol with insulin ( r = 0.144; p = 0.013), glucose ( r = 0.315; p r = 0.180; p = 0.002), whilst in girls, this positive relationship was observed for leptin ( r = 0.147; p = 0.002), insulin ( r = 0.095; p = 0.050) and HOMA-IR ( r = 0.099; p = 0.041), but not for glucose ( r = 0.054; p = 0.265). Observed associations were independent of adolescents' age, BF% and duration of exclusive breastfeeding after computing HLMs. Conclusion This study suggests that the stress-system is positively related to mechanisms of energy homeostasis and IR in European adolescents, and reveals a potential small gender difference in this relationship. The hypothesis that stress might facilitate the development of obesity during adolescence is supported.

Third-generation aromatase inhibitors (AI) are potent suppressors of aromatase activity. The aim of this study was to measure the incidence of adverse effects in breast cancer patients treated with AI-based adjuvant therapy and the relationship with the CYP19A1 genotypes.Forty-five postmenopausal breast cancer patients (46-85 yrs) in AI adjuvant treatment were genotyped for the rs4646 polymorphisms of CYP19A1 gene and three variations were identified. Toxicities were registered at each follow-up medical examination, and classified in accord with the Common Terminology Criteria for Adverse Events.Twenty-four (53.3%) patients presented the GG genotype; 19 (42.2%) the GT, and 2 (4.4%) the TT. The AI treatment was Anastrazole for 35 patients (77.8%) and Letrozole for the others (n=10; 22.2%). Osteoporosis was significantly associated with the GG genotype (p=0.001). Treatment discontinuation (TD) was observed in 6 cases (13.3%). The only parameter able to predict TD was the appearance of severe arthralgia/myalgia (Odds Ratio, OR=23.75; p=0.009), when adjusted for age and AI treatment.Our results suggest that CYP19A1 polymorphic variants may influence susceptibility to develop AI-related side effects. Further prospective studies are needed to confirm the role of the aromatase gene (CYP19A1) polymorphisms in predicting adverse effects to AI-based therapy.Üçüncü jenerasyon aromataz inhibitörleri (Aİ) aromataz aktivitesinin potent supresörleridir. Bu çalışmanın amacı Aİ bazlı adjuvan terapi ile tedavi edilen meme kanserli hastalarda advers etkilerin insidansını ve CYP19A1 genotipleri ile ilişkisini belirlemekti.Aİ adjuvan tedavisindeki 45 postmenopozal meme kanserli hasta (46–85 yaş) CYP19A1 geninin RS4646 polimorfizmleri için genotiplendirildi ve üç varyasyon tanımlandı. Toksisiteler her takipteki tıbbi muayenede kaydedildi ve Advers Olaylar için Ortak Terminoloji Kriterleri ile uyumlu olarak sınıflandırıldı.Yirmi dört (%53,3) hasta GG, 19’u (%42,2) GT ve 2’si (%4,4) TT genotipi gösterdi. Aİ tedavisi 35 hasta (%77,8) için Anastrozol ve diğerleri (n=10; %22,2) için Letrozol idi. Osteoporoz, GG genotipi ile anlamlı olarak ilişkiliydi (p=0,001). Tedaviye devam etmeme (TD) 6 olguda (%13,3) görüldü. Yaşa ve Aİ tedavisine göre düzeltildiğinde, TD’yi öngörebilecek tek parametre şiddetli artralji/miyalji oluşumu idi (Odds Oranı, OR=23,75; p=0,009).Bulgularımız CYP19A1 polimorfik varyantların Aİ ile ilişkili yan etkiler geliştirme duyarlılığını etkileyebileceğini düşündürmektedir. Aİ bazlı terapilerin advers etkilerini öngörmede aromataz gen (CYP19A1) polimorfizminin rolünü doğrulamak için ileri prospektif çalışmalara ihtiyaç vardır.

Mouse Mammary Tumor Virus (MMTV) causes mammary carcinoma or lymphoma in mice. An increasing body of evidence in recent years supports its involvement also in human sporadic breast cancer. It is thus of importance to develop new strategies to impair the development, growth and metastasis of MMTV-associated cancers. The signal peptide of the envelope precursor protein of this virus: MMTV-p14 (p14) is an excellent target for such strategies, due to unique characteristics distinct from its regular endoplasmic reticulum targeting function. These include cell surface expression in: murine cancer cells that harbor the virus, human breast cancer (MCF-7) cells that ectopically express p14, as well as cultured human cells derived from an invasive ductal breast carcinoma positive for MMTV sequences. These findings support its use in signal peptide-based immune targeting. Indeed, priming and boosting mice with p14 elicits a specific anti-signal peptide immune response sufficient for protective vaccination against MMTV-associated tumors. Furthermore, passive immunization using a combination of anti-p14 monoclonal antibodies or the transfer of T-cells from immunized mice (Adoptive Cell Transfer) is also therapeutically effective. With reports demonstrating involvement of MMTV in human breast cancer, we propose the immune-mediated targeting of p14 as a strategy for prevention, treatment and diagnosis of MMTV-associated cancers.