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Background: SARS-CoV-2's potential consequences on the developing brain are still unknown. The aim of this study was to describe cranial ultrasonographic (cUS) findings in a population of newborns exposed to SARS-CoV-2 born at San Marco Hospital in Catania., Methods: Two cohort of newborns, one exposed to SARS-CoV-2 both during gestation and at birth and one unexposed, were enrolled in this cross-sectional study conducted according to the STROBE guidelines (Strenghtening the Reporting of Observational Studies in Epidemiology) and underwent cUS. We performed a statistical analysis using the Fisher's exact test to assess whether significant differences among the two groups existed., Results: we enrolled 139 exposed newborns (62 females, 77 males with median gestational age 38.4 ± 1.9 W and median weight at birth 3142.8 ± 594.4 g) and 139 unexposed newborns (60 females, 79 males with median gestational age 38,9 ± 1.3 W and median weight at birth 3230 ± 336 g). cUS abnormalities were found in 32 exposed patients (23%) and in 23 (16.5%) unexposed patients. A statistically significant difference was found in the incidence of minor intracranial abnormalities (p 0.036) between exposed and unexposed patients and between newborns exposed during pregnancy and unexposed patients (p 0.016)., Conclusions: in our experience, the incidence of minor intracranial abnormalities was higher in SARS-COV-2-exposed newborns. Our results must be taken with caution and need further confirmation in larger studies but suggest to consider performing cUS at birth in newborns exposed to SARS-CoV-2 in research contexts., Competing Interests: Declarations. Ethics approvals and consent to participate: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee and with the Helsinki Declaration (as revised in 2013). The study was approved by the ethical committee of the Medical Faculty of the University of Catania (IRB n. 780). Written informed consent was obtained from the patient’s parents for publication of this case report and accompanying images. A copy of the written consent is available for review by the editorial office of this journal. Consent for publication: Written informed consent was obtained from the patient’s parents for publication of this case series and the accompanying images. Competing interests: Raffaele Falsaperla has an editorial role in this journal. Other authors have no competing interests to declare., (© 2024. The Author(s).)

Background: Walking speed, a key element of gait analysis, is essential for evaluating the biomechanics of the musculoskeletal system and is typically assessed on flat surfaces, such as walkways or treadmills. While many authors have compared the differences and similarities between treadmill and overground walking, no studies have yet investigated the differences between treadmill gait analysis at self-selected speed (SS) and overground simulated speed (OS). The hypothesis is that accurate kinematic measurements depend on selecting the correct gait speed; however, a mismatch between the perceived comfortable treadmill speed and actual overground speed may affect the accuracy of treadmill gait analyses. This study aimed to assess treadmill gait in healthy young adults by comparing the SS with the OS. The objectives were to determine whether participants could match SS with OS on a treadmill, examine sex differences in gait kinematics and spatiotemporal parameters (KSP) at different speeds, and identify which speed better reflects natural gait kinematics., Methods: A total of 60 healthy men and 70 healthy women, aged 22-35 years, participated in this cross-sectional study to investigate the gait kinematics and spatiotemporal differences between the SS and OS. Student's t-test, Bonferroni adjustment, Cohen's effect size, and quadratic regression were employed to analyse differences across walking speeds and groups., Results: A discrepancy between OS and SS was observed in 66.4% of the participants. Our findings revealed that the adjusted R² values for KSP at SS were consistently greater than those at OS, suggesting that SS offers a more robust and accurate representation of gait kinematics, whereas OS is less reliable., Conclusions: These findings underscore the importance of individualized speed selection in gait analysis, as it significantly impacts the accuracy of kinematic and spatiotemporal measurements. This insight is pivotal for clinicians and researchers to develop more effective rehabilitation strategies and comprehensively understand gait dynamics., (© 2024. The Author(s).)

Acute circulatory shock is a life-threatening emergency requiring an efficient and timely management plan, which varies according to shock etiology and pathophysiology. Specific guidelines have been developed for each type of shock; however, there is a need for a clear timeline to promptly implement initial life-saving interventions during the early phase of shock recognition and management. A simple, easily memorable bundle of interventions could facilitate standardized management with clear targets and specified timeline. The authors propose the "MINUTES" acronym which summarizes essential interventions which should be performed within the first 30 min following shock recognition. All the interventions in the MINUTES bundle are suitable for any patient with undifferentiated shock. In addition to the acronym, we suggest a timeline for each step, balancing the feasibility and urgency of each intervention. The MINUTES acronym includes seven sequential steps which should be performed in the first 30 min following shock recognition: Maintain "ABCs", INfuse vasopressors and/or fluids (to support hemodynamic/perfusion) and INvestigate with simple blood tests, Ultrasound to detect the type of shock, Treat the underlying Etiology, and Stabilize organ perfusion., (© 2024. The Author(s).)

Background: Point-of-care ultrasound (POCUS) is becoming increasingly crucial in the Pediatric Emergency Department for objective patient examination. However, despite its growing interest and wide-ranging applications, POCUS remains relatively unexplored in general pediatric training and education. Many physicians still find it challenging to comprehend and implement., Methods: A theoretical-practical POCUS course for pediatric residents was conducted at the University of Catania, Italy. The course's effectiveness and practical impact on residents was assessed through a pre-post training survey. The first part of the questionnaire focused on the self-perceived time needed to learn how to recognize the following conditions using POCUS: (i) Pleural effusion (ii) Lung consolidation (iii) Pneumothorax (PNX) (iv) Cardiac contractility (v) Pericardial effusion (vi) Perisplenic effusion (vii) Morison's pouch effusion (viii) Douglas' pouch effusion (ix) Filling and collapsibility of the inferior vena cava. In the second part, we compared the potential role of POCUS in (i) Reducing the use of ionizing radiation in children (ii) Increasing the sense of security in diagnosis and treatment decisions making and (iii) Increasing the residents' confidence level with POCUS after the course on a 1-to-10 rating scale., Results: Seventy-two residents participated in the study. The statistical analysis showed significant pre-post differences in almost all the items considered, except for "cardiac contractility" and "PNX". Furthermore, the perceived potential role of POCUS in reducing ionizing radiation usage and the sense of security in diagnosis and treatment decisions showed statistically significant differences (p < 0.05) before and after the course. Data analysis also revealed a consistently high confidence level with POCUS after the course., Conclusions: The results highlight the importance of including a POCUS track course in pediatric post-graduate programs due to its simplicity, rapid learning time, and clinical usefulness. Based on these findings, it would be recommended to increase the teaching hours dedicated to the recognition of pneumothorax and cardiology POCUS examination. Emphasizing POCUS training in pediatric education can enhance patient care and diagnostic accuracy while minimizing radiation exposure., (© 2024. The Author(s).)

Background: In the last decades, noninvasive ventilation (NIV) has been increasingly used to support patients with hypercapnic and hypoxemic acute respiratory failure. Pressure ulcers are a frequently observed NIV-related adverse effect, directly related to interface type and exposure time. Switching to a different interface has been proposed as a solution to improve patient comfort. However, large studies investigating the benefit of this strategy are not available. Thus, the aim of the ROTAtional-USE of interface STUDY (ROTA-USE STUDY) is to investigate whether a protocolized rotational use of interfaces during NIV is effective in reducing the incidence of pressure ulcers., Methods: The ROTA-USE STUDY is a pragmatic, parallel arm, open-label, multicenter, spontaneous, non-profit, randomized controlled trial requiring non-significant risk medical devices, with the aim to determine whether a rotational strategy of NIV interfaces is associated with a lower incidence of pressure ulcers compared to the standard of care. In the intervention group, NIV mask will be randomly chosen and rotated every 6 h. In the control group, mask will be chosen according to the standard of care of the participating centers and changed in case of discomfort or in the presence of new pressure sores. In both groups, the skin underneath the mask will be inspected every 12 h for any possible damage by blinded assessors. The primary outcome is the proportion of patients developing new pressure sores at 36 h from randomization. The secondary outcomes are (i) onset of pressure sores measured at different time points, i.e., 12, 24, 36, 48, 60, 72, 84, and 96 h; (ii) number and stage of pressure sores and comfort measured at 12, 24, 36, 48, 60, 72, 84, and 96 h; and (iii) the economic impact of the protocolized rotational use of interfaces. A sample size of 239 subjects per group (intervention and control) is estimated to detect a 10% absolute difference in the proportion of patients developing pressure sores at 36 h., Discussion: The development of pressure ulcers is a common side effect of NIV that negatively affects the patients' comfort and tolerance, often leading to NIV failure and adverse outcomes. The ROTA-USE STUDY will determine whether a protocolized rotational approach can reduce the incidence, number, and severity of pressure ulcers in NIV-treated patients., Trial Registration: ClinicalTrials.gov NCT05513508. Registered on August 24, 2022., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Endometrial scratching (ES) or injury is intentional damage to the endometrium performed to improve reproductive outcomes for infertile women desiring pregnancy. Moreover, recent systematic reviews with meta-analyses and randomized controlled trials demonstrated that ES is not effective, data on the safety are limited, and it should not be recommended in clinical practice. The aim of the current study was to assess the view and behavior towards ES among fertility specialists throughout infertility centers in Italy, and the relationship between these views and the attitudes towards the use of ES as an add-on in their commercial setting., Methods: Online survey among infertility centers, affiliated to Italian Society of Human Reproduction (SIRU), was performed using a detailed questionnaire including 45 questions with the possibility to give "closed" multi-choice answers for 41 items and "open" answers for 4 items. Online data from the websites of the infertility centers resulting in affiliation with the specialists were also recorded and analyzed. The quality of information about ES given on infertility centers websites was assessed using a scoring matrix including 10 specific questions (scored from 0 to 2 points), and the possible scores ranged from 0 to 13 points ('excellent' if the score was 9 points or more, 'moderate' if the score was between 5 and 8, and 'poor' if it was 4 points or less)., Results: The response rate was of 60.6% (43 questionnaires / 71 infertility SIRU-affiliated centers). All included questionnaires were completed in their entirety. Most physicians (~ 70%) reported to offer ES to less than 10% of their patients. The procedure is mainly performed in the secretory phase (69.2%) using pipelle (61.5%), and usually in medical ambulatory (56.4%) before IVF cycles to improve implantation (71.8%) without drugs administration (e.g., pain drugs, antibiotics, anti-hemorrhagics, or others) before (76.8%) or after (64.1%) the procedure. Only a little proportion of infertility centers included in the analysis proposes formally the ES as an add-on procedure (9.3%), even if, when proposed, the full description of the indications, efficacy, safety, and costs is never addressed. However, the overall information quality of the websites was generally "poor" ranging from 3 to 8 and having a low total score (4.7 ± 1.6; mean ± standard deviation)., Conclusions: In Italy, ES is a procedure still performed among fertility specialists for improving the implantation rate in IVF patients. Moreover, they have a poor attitude in proposing ES as an add-on in the commercial setting., (© 2023. The Author(s).)

Background: The incidence of the highly morbid and potentially lethal gangrenous cholecystitis was reportedly increased during the COVID-19 pandemic. The aim of the ChoCO-W study was to compare the clinical findings and outcomes of acute cholecystitis in patients who had COVID-19 disease with those who did not., Methods: Data were prospectively collected over 6 months (October 1, 2020, to April 30, 2021) with 1-month follow-up. In October 2020, Delta variant of SARS CoV-2 was isolated for the first time. Demographic and clinical data were analyzed and reported according to the STROBE guidelines. Baseline characteristics and clinical outcomes of patients who had COVID-19 were compared with those who did not., Results: A total of 2893 patients, from 42 countries, 218 centers, involved, with a median age of 61.3 (SD: 17.39) years were prospectively enrolled in this study; 1481 (51%) patients were males. One hundred and eighty (6.9%) patients were COVID-19 positive, while 2412 (93.1%) were negative. Concomitant preexisting diseases including cardiovascular diseases (p < 0.0001), diabetes (p < 0.0001), and severe chronic obstructive airway disease (p = 0.005) were significantly more frequent in the COVID-19 group. Markers of sepsis severity including ARDS (p < 0.0001), PIPAS score (p < 0.0001), WSES sepsis score (p < 0.0001), qSOFA (p < 0.0001), and Tokyo classification of severity of acute cholecystitis (p < 0.0001) were significantly higher in the COVID-19 group. The COVID-19 group had significantly higher postoperative complications (32.2% compared with 11.7%, p < 0.0001), longer mean hospital stay (13.21 compared with 6.51 days, p < 0.0001), and mortality rate (13.4% compared with 1.7%, p < 0.0001). The incidence of gangrenous cholecystitis was doubled in the COVID-19 group (40.7% compared with 22.3%). The mean wall thickness of the gallbladder was significantly higher in the COVID-19 group [6.32 (SD: 2.44) mm compared with 5.4 (SD: 3.45) mm; p < 0.0001]., Conclusions: The incidence of gangrenous cholecystitis is higher in COVID patients compared with non-COVID patients admitted to the emergency department with acute cholecystitis. Gangrenous cholecystitis in COVID patients is associated with high-grade Clavien-Dindo postoperative complications, longer hospital stay and higher mortality rate. The open cholecystectomy rate is higher in COVID compared with non -COVID patients. It is recommended to delay the surgical treatment in COVID patients, when it is possible, to decrease morbidity and mortality rates. COVID-19 infection and gangrenous cholecystistis are not absolute contraindications to perform laparoscopic cholecystectomy, in a case by case evaluation, in expert hands., (© 2022. The Author(s).)

Background: Although a general consensus that vaccines could be a complementary strategy against antimicrobial resistance (AMR), there is still the need for studies investigating the relationship between childhood vaccination coverage and AMR proportions in the overall population., Methods: We performed an ecological analysis of available Italian data (vaccination coverages, AMR proportions, number of isolates tested, and antibiotic use) to evaluate the relationships between vaccination coverages in children and AMR proportions in the last 2 decades., Results: After adjusting for covariates, we showed that AMR proportions decreased with increasing vaccination coverages, especially for some combinations of vaccines, pathogens, and antimicrobials. Vaccination coverages for pertussis, diphtheria, and tetanus were inversely related to proportions of E. coli resistant to fluoroquinolones and third generation cephalosporins, K. pneumoniae resistant to carbapenems and third generation cephalosporins, and P. aeruginosa resistant to piperacillin and tazobactam. Polio vaccination coverage was inversely related to proportions of E. coli and K. pneumoniae resistant to third generation cephalosporins., Conclusions: These results, however, should be interpreted cautiously due to the ecological nature of our analysis. For this reason, further studies designed ad hoc should be encouraged to measure the impact of increasing childhood vaccination coverage on AMR., (© 2022. The Author(s).)

Background: Natalizumab and fingolimod are used as high-efficacy treatments in relapsing-remitting multiple sclerosis. Several observational studies comparing these two drugs have shown variable results, using different methods to control treatment indication bias and manage censoring. The objective of this empirical study was to elucidate the impact of methods of causal inference on the results of comparative effectiveness studies., Methods: Data from three observational multiple sclerosis registries (MSBase, the Danish MS Registry and French OFSEP registry) were combined. Four clinical outcomes were studied. Propensity scores were used to match or weigh the compared groups, allowing for estimating average treatment effect for treated or average treatment effect for the entire population. Analyses were conducted both in intention-to-treat and per-protocol frameworks. The impact of the positivity assumption was also assessed., Results: Overall, 5,148 relapsing-remitting multiple sclerosis patients were included. In this well-powered sample, the 95% confidence intervals of the estimates overlapped widely. Propensity scores weighting and propensity scores matching procedures led to consistent results. Some differences were observed between average treatment effect for the entire population and average treatment effect for treated estimates. Intention-to-treat analyses were more conservative than per-protocol analyses. The most pronounced irregularities in outcomes and propensity scores were introduced by violation of the positivity assumption., Conclusions: This applied study elucidates the influence of methodological decisions on the results of comparative effectiveness studies of treatments for multiple sclerosis. According to our results, there are no material differences between conclusions obtained with propensity scores matching or propensity scores weighting given that a study is sufficiently powered, models are correctly specified and positivity assumption is fulfilled., (© 2022. The Author(s).)

Background: Alternating of Childhood (AHC) is an uncommon and complex disorder characterized by age of onset before 18 months with recurrent hemiplegia of one or either sides of the body or quadriplegia. The disorder is mainly caused by mutations in ATP1A3 gene, and to a lesser extent in ATP1A2 gene. In AHC neurological co-morbidities are various and frequently reported including developmental delay, epilepsy, tonic or dystonic spells, nystagmus,autonomic manifestations with intrafamilial variability., Case Presentation: Clinical and genetic findings of a couple of twins (Family 1: Case 1 and Case 2) and a couple of siblings (Family 2: Case 3 and Case 4) coming from two different Italian families affected by AHC were deeply examined. In twins of Family 1, a pathogenic variant in ATP1A3 gene (c.2318A>G) was detected. In siblings of Family 2, the younger brother showed a novel GRIN2A variant (c.3175 T > A), while the older carried the same GRIN2A variant, and two missense mutations in SCNIB (c.632 > A) and KCNQ2 (1870 G > A) genes. Clinical manifestations of the four affected children were reported along with cases of AHC drawn from the literature., Conclusions: Hemiplegic episode is only a sign even if the most remarkable of several and various neurological comorbidities in AHC affected individuals. Molecular analysis of the families here reported showed that clinical features of AHC may be also the result of an unexpected genetic heterogeneity., (© 2022. The Author(s).)

Background: In breast cancer (BC), recurrent fusion genes of estrogen receptor alpha (ESR1) and AKAP12, ARMT1 and CCDC170 have been reported. In these gene fusions the ligand binding domain of ESR1 has been replaced by the transactivation domain of the fusion partner constitutively activating the receptor. As a result, these gene fusions can drive tumor growth hormone independently as been shown in preclinical models, but the clinical value of these fusions have not been reported. Here, we studied the prognostic and predictive value of different frequently reported ESR1 fusion transcripts in primary BC., Methods: We evaluated 732 patients with primary BC (131 ESR1-negative and 601 ESR1-positive cases), including two ER-positive BC patient cohorts: one cohort of 322 patients with advanced disease who received first-line endocrine therapy (ET) (predictive cohort), and a second cohort of 279 patients with lymph node negative disease (LNN) who received no adjuvant systemic treatment (prognostic cohort). Fusion gene transcript levels were measured by reverse transcriptase quantitative PCR. The presence of the different fusion transcripts was associated, in uni- and multivariable Cox regression analysis taking along current clinico-pathological characteristics, to progression free survival (PFS) during first-line endocrine therapy in the predictive cohort, and disease- free survival (DFS) and overall survival (OS) in the prognostic cohort., Results: The ESR1-CCDC170 fusion transcript was present in 27.6% of the ESR1-positive BC subjects and in 2.3% of the ESR1-negative cases. In the predictive cohort, none of the fusion transcripts were associated with response to first-line ET. In the prognostic cohort, the median DFS and OS were respectively 37 and 93 months for patients with an ESR1-CCDC170 exon 8 gene fusion transcript and respectively 91 and 212 months for patients without this fusion transcript. In a multivariable analysis, this ESR1-CCDC170 fusion transcript was an independent prognostic factor for DFS (HR) (95% confidence interval (CI): 1.8 (1.2-2.8), P = 0.005) and OS (HR (95% CI: 1.7 (1.1-2.7), P = 0.023)., Conclusions: Our study shows that in primary BC only ESR1-CCDC170 exon 8 gene fusion transcript carries prognostic value. None of the ESR1 fusion transcripts, which are considered to have constitutive ER activity, was predictive for outcome in BC with advanced disease treated with endocrine treatment., (© 2022. The Author(s).)

Background: Identifying healthcare workers (HCW) who have less awareness and knowledge on antibiotic use and resistance represents a challenge for public health, since it might help the development of novel educational and training initiatives tailored on specific subgroups of professionals. This work aims to compare knowledge, attitudes and behaviors on antibiotic use and resistance across different groups of Italian HCW., Methods: We used data from the multi-country and multi-professional survey launched by the European Centre for Disease Prevention and Control between 28 January to 4 March 2019 to assess knowledge, attitude and behaviors of HCW on antibiotics, antibiotic use and resistance. We distinguished three clusters of HCW using the Two-Step Cluster analysis, based on their personal and professional characteristics (i.e. profession, role, activity as prescriber, setting, and activity as antibiotic use advisor)., Results: In general, cluster 1 consisted mostly of allied healthcare workers, while clusters 2 and 3 were made up almost completely of pharmacists and medical doctors, respectively. Interestingly, healthcare workers in cluster 3 had the highest knowledge on antibiotic use and resistance. Workers in cluster 1, instead, were those reporting the highest awareness of the importance and role of hand hygiene as an infection prevention and control measure. However, HCW in cluster 2 were those who recognized more their role of advisors on prudent antibiotic use., Conclusions: Italian HCW exhibited different knowledge, attitudes, and behaviors on antibiotic use and resistance. These findings raised the need for educational and training interventions targeting specific professional groups., (© 2021. The Author(s).)

Background: Spinal cord compression (SCC) is an uncommon, severe complication of Hodgkin lymphoma (HL), occurring in 0.2% of cases at the onset and in 6% during disease progression. We present a teenager with SCC with clinical onset of HL; her pre-existing neurological abnormalities covered the presence of an epidural mass, which could have misled us., Case Presentation: A 13-year-old girl presented with a three-month history of lower back pain and degrading ability to walk. She suffered from a chronic gait disorder due to her preterm birth. A magnetic resonance imaging of the spine revealed an epidural mass causing collapse of twelfth thoracic vertebra and thus compression and displacement of the spinal cord. Histological examination with immunohistochemical analysis of the epidural mass demonstrated a classic-type Hodgkin lymphoma. Early pathology-specific treatment allowed to avoid urgent surgery, achieve survival and restore of neurological function., Conclusions: Children and adolescents with back pain and neurological abnormalities should be prioritized to avoid diagnostic delay resulting in potential loss of neurological function. SCC requires a prompt radiological assessment and an expert multidisciplinary management., (© 2021. The Author(s).)

Background: This paper highlights the issues that one of the 90 Italian Research Ethics Committees (RECs) might encounter during the approval phase of a clinical trial to identify corrective and preventive actions for promoting a more efficient review process and ensuring review quality. Publications on the subject from Italy and the rest of Europe are limited; encouraging constructive debate can improve RECs' service to the subject of the clinical trial., Methods: We retrospectively reviewed a cohort of 822 clinical trial protocols, initially reviewed by REC, from June 2014 to December 2018. Data collected for each protocol were type of trial, sample size, use of placebo, number and kind of revisions requested by the REC before approval, and time taken for approval. Data for each protocol were collected by a trained clinical research assistant using the REC's files and electronic archives., Results: Almost 45% of the reviewed studies (374/822) required clarifications, significant changes to the documentation, or minor changes before final approval., Conclusions: Preventive measures are needed to reduce the number of requested corrections and thus also the time required for approval, while maintaining review quality. All critical points and proposals presented in this paper require harmonization through updates to European regulations, as regulatory harmonization produces better compliance with rules and reduces the number of changes required before the trials' final approval. Such updates include the development of standardized formats for informed consent, the verification of any evidence in favor of using off-label treatments over placebo as comparators, using multidisciplinary staff in clinical trials with children and adolescents, improving the legal definition of RECs to assign responsibilities and ensure independence, and providing guidance for RECs to engage clinical research assistants in internal audits.

Aim: The existing treatment options for neonatal seizures have expanded over the last few decades, but no consensus has been reached regarding the optimal therapeutic protocols. We systematically reviewed the available literature examining neonatal seizure treatments to clarify which drugs are the most effective for the treatment of specific neurologic disorders in newborns., Method: We reviewed all available, published, literature, identified using PubMed (published between August 1949 and November 2020), that focused on the pharmacological treatment of electroencephalogram (EEG)-confirmed neonatal seizures., Results: Our search identified 427 articles, of which 67 were included in this review. Current knowledge allowed us to highlight the good clinical and electrographic responses of genetic early-onset epilepsies to sodium channel blockers and the overall good response to levetiracetam, whose administration has also been demonstrated to be safe in both full-term and preterm newborns., Interpretation: Our work contributes by confirming the limited availability of evidence that can be used to guide the use of anticonvulsants to treat newborns in clinical practice and examining the efficacy and potentially harmful side effects of currently available drugs when used to treat the developing newborn brain; therefore, our work might also serve as a clinical reference for future studies.

Background: Portal vein thrombosis (PVT) occurs frequently in hepatocellular carcinoma (HCC) and is often diagnosed in the course of a routine patient evaluation and surveillance for liver cancer. The purpose of this study is to investigate the relationship between folate status and portal vein thrombosis., Methods: HCC with PVT patients were 78, HCC without PVT were 60 and control subjects were 70 randomly selected. We evaluate serum and red blood cellular folate, homocysteine, alpha fetal protein cholesterol, triglycerides, prothrombin time., Results: HCC patients with PVT showed lower levels of serum folate, respect HCC patients without PVT, with an average difference of 1.6 nmol/l p < 0.01 (95% CI - 2.54 to - 0.66), red cell folate 33.6 nmol/l p < 0.001 (95% CI - 43.64 to - 23.55) and albumin 0.29 g/dl p < 0.001 (95% CI - 0.42 to - 0.15); PVT patients displayed higher levels of bilirubin 0.53 mg/dl p < 0.001 (95% CI 0.23 to 0.78), INR 0.91 p < 0.001 (95% CI 0.72 to 1.09), γGT 7.9 IU/l (95% CI 4.14 to 11.65) and homocysteine 4.6 μmol/l p < 0.05 (95% CI 0.32 to 8.87) CONCLUSION: The low folate concentration and higher levels of homocysteine are associated with the loss of antithrombotic function, and with a more aggressive course of HCC and with a higher change of complications related to portal vein thrombosis.

Introduction: Depression is a highly prevalent condition in the elderly, with a vast impact on quality of life, life expectancy, and medical outcomes. Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed agents in this condition and, although generally safe, tolerability issues cannot be overlooked. Vortioxetine is an antidepressant with a novel mechanism of action. Based on studies to date, it may have a promising tolerability profile in the elderly, as it does not adversely affect psychomotor or cognitive performance and does not alter cardiovascular and endocrine parameters. The present study aims to assess the tolerability profile of vortioxetine in comparison with the SSRIs considered as a single group in elderly participants with depression. The rate of participants withdrawing from treatment due to adverse events after 6 months of follow up will be the primary outcome., Methods and Analysis: This is a pragmatic, multicentre, open-label, parallel-group, superiority, randomized trial funded by the Italian Medicines Agency (AIFA - Agenzia Italiana del Farmaco). Thirteen Italian Community Psychiatric Services will consecutively enrol elderly participants suffering from an episode of major depression over a period of 12 months. Participants will be assessed at baseline and after 1, 3 and 6 months of follow up. At each time point, the following validated rating scales will be administered: Montgomery-Åsberg Depression Rating Scale (MADRS), Antidepressant Side-Effect Checklist (ASEC), EuroQual 5 Dimensions (EQ-5D), Short Blessed Test (SBT), and Charlson Age-Comorbidity Index (CACI). Outcome assessors and the statistician will be masked to treatment allocation. A total of 358 participants (179 in each group) will be enrolled., Ethics and Dissemination: This study will fully adhere to the ICH E6 Guideline for Good Clinical Practice. Participants' data will be managed and safeguarded according to the European Data Protection Regulation 2016/679. An external Ethical Advisory Board will help guarantee high ethical standards., Trial Registration: Clinicaltrials.gov: NCT03779789 , Registered on 19 December 2018. Submitted on 19 December. EudraCT number: 2018-001444-66., Trial Status: Protocol version 1.5; 09/06/2018. Recruitment started In February 2019 and it is ongoing. It is expected to end approximately on 30 September 2021.

Background: Platinum/fluoropyrimidine regimens are the backbone of first-line chemotherapy for advanced gastric cancer (AGC). However response rates to first line chemotherapy range from 30 to 50% and disease progression occurs after 4-6 cycles. The optimal duration of first-line therapy is still unknown and its continuation until disease progression represents the standard. However this strategy is often associated with cumulative toxicity and rapid development of drug resistance. Moreover, only about 40% of AGC pts. are eligible for second-line treatment., Methods: This is a randomized, open-label, multicenter phase III trial. It aims at assessing whether switch maintenance to ramucirumab plus paclitaxel will extend the progression-free survival (PFS) of subjects with HER-2 negative AGC who have not progressed after 3 months of a first-line with a platinum/fluoropyrimidine regimen (either FOLFOX4, mFOLFOX6 or XELOX). The primary endpoint is to compare Progression-Free Survival (PFS) of patients in ARM A (switch maintenance to ramucirumab and placlitaxel) versus ARM B (continuation of the same first-line therapy with oxaliplatin/fluoropyrimidine). Secondary endpoints are: overall survival, time-to-treatment failure, overall response rate, duration of response, percentage of patients that will receive a second line therapy according to arm treatment, safety, quality of life. Exploratory studies including Next-Generation Sequencing (NGS) in archival tumor tissues are planned in order to identify potential biomarkers of primary resistance and prognosis., Discussion: The ARMANI study estimates if patients treated with early swich with ramucirumab plus paclitaxel received benefit when compared to those treated with continuation of first line therapy. The hypothesis is that the early administration of an active, non-cross resistant second-line regimen such as ramucirumab plus paclitaxel may prolong the time in which patients are progression-free, and consequently have a better quality of life. Moreover, this strategy may rescue all those subjects that become ineligible for second-line therapy due to the rapid deterioration of health status after the first disease progression., Trial Registration: ARMANI is registered at ClinicalTrials.gov ( NCT02934464 , October 17, 2016) and EudraCT(2016-001783-12, April 202,016).

This article is a review that addresses the following topics, divided by paragraphs. The first paragraph investigates the effects of physical activity on ovarian function, analyzing in particular the changes concerning the serum concentrations of follicle-stimulating hormone, luteinizing hormone, prolactin, growth hormone, thyroid hormones, leptin, ghrelin, neuropeptide Y. The second paragraph analyzes the effects of doping on the hypothalamic-pituitary-ovarian axis. Finally, the last paragraph analyzes the PCOS category, evaluating the effects of hyperandrogenism in relation to athletic performance.

Background: The evolution of technology in healthcare has increased the health care's costs and, the universal healthcare systems, in developed countries, need to ensure proper allocation of resources. Thus, the major issue is assessing the effectiveness of new medical technologies. The evaluation of quality of life in response to new treatments has become a key indicator in chronic conditions for which medical interventions are evaluated not only in terms of increasing the number of expected life years but also in terms of increasing quality of life. The aim of this observational study was to verify whether a simple instrument (EQ-5D-5 L) can capture variations in health-related quality of life (HRQoL) and allow us to evaluate the impact of different drug treatment protocols in patients with hepatitis C virus (HCV) on daily activities., Methods: Sixty six patients with HCV were consecutively enrolled in the Hepatology Unit at the University Hospital of Catania "G. Rodolico". Sixteen patients received new direct-acting-antiviral agents (DAAs) plus pegylated alpha interferon (Peg-α-IFN) protocol (Group A) and 50 DAAs IFN free protocol (Group B). The EQ-5D-5 L® questionnaire and visual analog scale (VAS) were given to both groups to calculate coefficient's utility. We used the EQ-5D-5 L Crosswalk Index Value Calculator to obtain the utility EQIndex and both parametric and non parametric tests for the statistical analysis., Results: The biopsy taken at the beginning of treatment showed comparable cell damage in both groups. The difference in the VAS results was negative for patients who received protocols containing IFN (indicating decreased quality of life),whereas it was positive in patients treated with IFN-free protocols. The baseline EQIndex did not reveal any differences between the two treatment groups. The post-treatment EQIndex was statistically better in the groups that received IFN-free therapy., Conclusions: When innovative treatments are introduced into clinical practice, assessing quality of life is mandatory to determine their benefits. The instruments used in the present study are effective in detecting the areas in which improvement has occurred. These instruments can be easily managed by general practitioners for follow up of progression of the disease and referred to the specialist.

Background: Although beneficial in clinical practice, the INtubate-SURfactant-Extubate (IN-SUR-E) method is not successful in all preterm neonates with respiratory distress syndrome, with a reported failure rate ranging from 19 to 69 %. One of the possible mechanisms responsible for the unsuccessful IN-SUR-E method, requiring subsequent re-intubation and mechanical ventilation, is the inability of the preterm lung to achieve and maintain an "optimal" functional residual capacity. The importance of lung recruitment before surfactant administration has been demonstrated in animal studies showing that recruitment leads to a more homogeneous surfactant distribution within the lungs. Therefore, the aim of this study is to compare the application of a recruitment maneuver using the high-frequency oscillatory ventilation (HFOV) modality just before the surfactant administration followed by rapid extubation (INtubate-RECruit-SURfactant-Extubate: IN-REC-SUR-E) with IN-SUR-E alone in spontaneously breathing preterm infants requiring nasal continuous positive airway pressure (nCPAP) as initial respiratory support and reaching pre-defined CPAP failure criteria., Methods/design: In this study, 206 spontaneously breathing infants born at 24(+0)-27(+6) weeks' gestation and failing nCPAP during the first 24 h of life, will be randomized to receive an HFOV recruitment maneuver (IN-REC-SUR-E) or no recruitment maneuver (IN-SUR-E) just prior to surfactant administration followed by prompt extubation. The primary outcome is the need for mechanical ventilation within the first 3 days of life. Infants in both groups will be considered to have reached the primary outcome when they are not extubated within 30 min after surfactant administration or when they meet the nCPAP failure criteria after extubation., Discussion: From all available data no definitive evidence exists about a positive effect of recruitment before surfactant instillation, but a rationale exists for testing the following hypothesis: a lung recruitment maneuver performed with a step-by-step Continuous Distending Pressure increase during High-Frequency Oscillatory Ventilation (and not with a sustained inflation) could have a positive effects in terms of improved surfactant distribution and consequent its major efficacy in preterm newborns with respiratory distress syndrome. This represents our challenge., Trial Registration: ClinicalTrials.gov identifier: NCT02482766 . Registered on 1 June 2015.

Smokers of any age can reap substantial health benefits by quitting. In fact, no other single public health effort is likely to achieve a benefit comparable to large-scale smoking cessation. Surveys document that most smokers would like to quit, and many have made repeated efforts to do so. However, conventional smoking cessation approaches require nicotine addicted smokers to abstain from tobacco and nicotine entirely. Many smokers are unable--or at least unwilling--to achieve this goal, and so they continue smoking in the face of impending adverse health consequences. In effect, the status quo in smoking cessation presents smokers with just two unpleasant alternatives: quit or suffer the harmful effects of continuing smoking. But, there is a third choice for smokers: tobacco harm reduction. It involves the use of alternative sources of nicotine, including modern smokeless tobacco products like snus and the electronic cigarette (E-cig), or even pharmaceutical nicotine products, as a replacement for smoking. E-cigs might be the most promising product for tobacco harm reduction to date, because, besides delivering nicotine vapour without the combustion products that are responsible for nearly all of smoking's damaging effect, they also replace some of the rituals associated with smoking behaviour. Thus it is likely that smokers who switch to E-cigs will achieve large health gains. The focus of this article is on the health effects of using an E-cig, with consideration given to the acceptability, safety and effectiveness of this product as a long-term substitute for smoking.

Background: The aim of the present study was to evaluate the survival, efficacy and safety of a modified RADPLAT-like protocol using carboplatin instead of cisplatin., Methods: Fifty-six patients with primary head and neck squamous cell carcinoma received 4 cycles of intra-arterial carboplatin (350 mg/m2 per cycle every 2 weeks), with concurrent three-dimensional conformal radiation therapy., Results: Two major and 4 minor complications were observed. Forty-five of the 56 patients (80%) completed the protocol, while 11 (20%) patients had to discontinue the intra-arterial infusions due to the occurrence of severe haematological toxicity, but were able to complete radiotherapy. Forty-four (98%) of the 45 patients who completed the protocol and 10 (91%) of the 11 who did not, were free of disease at the end of the treatment, for a comprehensive 96% of CR overall. After a median 23.55 months (range: 2 to 58 months) of follow-up, 40 patients (71%) are alive and disease-free, 1 (2%) is alive but affected by disease and 15 (27%) have died of the disease or other causes., Conclusion: Intra-arterial carboplatin administration with concurrent three-dimensional conformal radiation therapy seems to be a promising alternative to RADPLAT in the treatment of advanced head and neck tumours. Haematological and non-haematological toxicities are virtually similar, but carboplatin has the advantage in that it is not nephrotoxic and can be used at very high doses without any significant increase in the extent of side effects.