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BACKGROUND MXPyV, like MWPyV, was identified in stool samples from children suffering diarrhea in Mexico. In this study, we used a home-made real time PCR to investigate the presence of this novel viruses in stool specimen collected from under-Five- Year-Old Children with gastroenteritis. METHODS A total of 192 fecal specimens previously screened for RV, ADV, NoV, HPeV and SaV, were tested for MWPyV with Taqman real time PCR. RESULTS The most commonly detected virus was NoV GII (33.8%), followed by RV (21.3%), SaV (10.9%), HPeV(8%), NoV GI (6.7%) and AdV (1%). Real time PCR detected MWPyV in 1/192 (0.5%) patients. CONCLUSIONS We detected MWPyV in 0.5% of fecal specimens collected from pediatric patients suffering gastroenteritis which is smaller than the previously reported in literature (4.4% in Australia and 12% Mexico).

We have clarified the role of Universal Neonatal Hearing Screening (UNHS) for both early diagnosis and rapid treatment in order to improve the prognosis of the deaf child and reduce patient management costs. Although in Sicily UNHS has been progressively implemented, there is scarce data in the literature on this matter. Therefore, the main objective was to collect in the year 2018 the following data: number of newborns screened for hearing loss, number of infants "referred" to transiently evoked otoacoustic emissions (TEOAE), number of infants with pathologic auditory brainstem response (ABR) and number of infants affected by permanent hearing loss.UNHS monitoring was conducted through the collection of data through a questionnaire, which was analysed evaluating the effectiveness and adherence to the screening program prepared by the Department for Health Activities and the Epidemiological Observatory (DASOE).In 2018, there were 40,243 newborns in Sicily. A total of 37,562 newborns were screened (93.3%). There were 1,328 "referred" infants with TEOAE (3.5%). On the 2The monitoring of the UNHS in Sicily has allowed obtaining the data of individual centres, absent in the literature to date, to verify the effectiveness of the screening, according to JCIH criteria, to highlight some criticalities and, finally, to propose possible solutions.Screening uditivo neonatale universale nella regione Sicilia nel 2018.Abbiamo chiarito il ruolo dello screening uditivo neonatale universale (UNHS) sia come diagnosi precoce che come trattamento rapido al fine di migliorare la prognosi del bambino sordo e ridurre i costi di gestione del paziente. Anche se in Sicilia l’UNHS è stato progressivamente attuato, vi sono scarsi dati nella letteratura in materia. Pertanto, l’obiettivo principale è stato quello di raccogliere nell’anno 2018 i seguenti dati: numero di neonati sottoposti a screening per la perdita dell’udito, numero di neonati risultati “refer” alle TEOAE, numero di lattanti con ABR patologico e numero di lattanti affetti da perdita permanente dell’udito.Il monitoraggio del UNHS è stato condotto attraverso la raccolta dei dati forniti dal questionario, che valuta l’efficacia dello screening e l’aderenza alle fasi successive.Nel 2018, i nati in Sicilia sono stati 40.243. Sono stati sottoposti a screening 37.562 neonati, pari al 93,3%. Sono risultati “refer” con le TEOAE 1.328 neonati (pari al 3,5%). Al 2° livello, i neonati “refer” esaminati sono stati 1.080 su 1.328 attesi (dispersi 248 neonati refer, pari al 18,6%). I neonati “refer” confermati con le TEOAE sono stati 113 su 1.080, mentre i neonati “refer” confermati con ABR sono stati 71. Al 3° livello, i bambini esaminati sono stati 67 su 71 previsti: ventotto bambini soffrivano di perdita monolaterale dell’udito (13 lieve, 13 moderata, 1 grave e 1 profonda) e trentanove soffrivano di perdita bilaterale dell’udito (1 lieve, 19 moderata, 13 grave e 7 profonda). Escludendo 7 bambini provenienti dalla NICU, i bambini con perdita dell’udito sono stati 60 su 37.562 (pari all’1,5‰).Il monitoraggio dell’UNHS in Sicilia ha permesso di ottenere i dati dei singoli centri, dati assenti nella letteratura, di verificare l’efficacia dello screening, secondo criteri JCIH, di evidenziare alcune criticità e, infine, di proporre possibili soluzioni.

Healthcare utilisation databases, and other secondary data sources, have been used with growing frequency to assess health outcomes and healthcare interventions worldwide. Their increased popularity as a research tool is due to their timely availability, the large patient populations covered, low cost, and applicability for studying real-world clinical practice. Despite the need to measure Italian National Health Service performance both at regional and national levels, the wealth of good quality electronic data and the high standards of scientific research in this field, healthcare research and public health policies seem to progress along orthogonal dimensions in Italy. The main barriers to the development of evidence-based public health include the lack of understanding of evidence-based methodologies by policy makers, and of involvement of researchers in the policy process. The CRACK programme was launched by some academics from the Lombardy Region. By extensively using electronically stored data, epidemiologists, biostatisticians, pharmacologists and clinicians applied methods and evidence to several issues of healthcare research. The CRACK programme was based on their intention to remove barriers that thwart the process of bridging methods and findings from scientific journals to public health practice. This paper briefly describes aim, articulation and management of the CRACK programme, and discusses why it might find articulated application in Italy.

Interest in performing dosimetry for clinical radiopharmaceutical therapy procedures has grown in recent years. Several approved therapies include dosimetry in the Food and Drug Administration-approved label instructions, and other therapies are best used under a patient-tailored paradigm. This paper, which is a product of the Society of Nuclear Medicine and Molecular Imaging Dosimetry Task Force, presents motivations and general workflows for radiopharmaceutical therapy dosimetry, as well as existing strategies for obtaining reimbursement for clinical activities related to dosimetry. Several specific patient examples are provided, including suggested codes for reimbursement. In addition to current reimbursement approaches, key dosimetry services that are not supported under the current coding structure are presented and suggested as areas of focus in the coming years.

Parenteral nutrition (PN) is essential to support premature infants' growth and varies with enteral nutrition (EN) advancement rates. Data on PN duration's impact on premature infants' growth are limited. The aim of this multicenter observational study was to determine the effect of early PN duration on body composition at term corrected gestational age (CGA) in very low-birth-weight (VLBW) premature infants.VLBW infants exposed to PN in the first week of life and exposed to significantly different EN regimens were divided into two groups on the basis of early PN duration. Infants with a birth weight (BW)1000 g and PN duration28 days and infants with a BW 1000-1500 g and PN duration14 days were assigned to the "short-PN" group. Infants receiving PN for longer durations were assigned to the "long-PN" group. Body composition was assessed via air displacement plethysmography at term CGA or before discharge.Sixty-two and 53 infants were assigned to the short-PN and long-PN groups, respectively. The two groups were significantly different in BW and GA, so a nested case-control study was conducted after matching 36 infant pairs. Infants in the long-PN group had significantly lower fat-free mass (FFM) z-scores, but both groups had comparable fat mass (FM) z-scores. Long PN was a significant negative predictor of FFM z-score in the multivariate regression analysis.In VLBW premature infants, PN duration is negatively associated with FFM z-scores at term CGA without affecting FM z-scores.

BACKGROUND Observational studies showed that exposure to exogenous insulin increases fracture risk. However, it remains unclear whether the observed association is a function of the severity of underlying type 2 diabetes mellitus, complications, therapies, comorbidities, or all these factors combined. That being so, and because of the relative infrequency of these events, it is important to study this further in a large-database setting. QUESTION/PURPOSES: (1) Is switching from oral antidiabetic agents to insulin associated with an increased fracture risk? (2) How soon after switching does the increased risk appear, and for how long does this increased risk persist? METHODS Data from healthcare utilization databases of the Italian region of Lombardy were used. These healthcare utilization databases report accurate, complete, and interconnectable information of inpatient and outpatient diagnoses, therapies, and services provided to the almost 10 million residents in the region. The 216,624 patients on treatment with oral antidiabetic therapy from 2005 to 2009 were followed until 2010 to identify those who modified their antidiabetic therapy (step 1 cohort). Among the 63% (136,307 patients) who experienced a therapy modification, 21% (28,420 patients) switched to insulin (active exposure), and the remaining 79% (107,887 patients) changed to another oral medication (referent exposure). A 1:1 high-dimension propensity score matching design was adopted for balancing patients on active and referent exposure. Matching failed for 3% of patients (926 patients), so the cohort of interest was formed by 27,494 insulin-referent couples. The latter were followed until 2012 to identify those who experienced hospital admission for fracture (outcome). A Cox proportional hazard model was fitted to estimate the hazard ratio (HR) for the outcome risk associated with active-exposure (first research question). Between-exposure comparison of daily fracture hazard rates from switching until the 24 successive months was explored through the Kernel-smoothed estimator (second research question). RESULTS Compared with patients on referent exposure, those who switched to insulin had an increased risk of experiencing any fracture (HR = 1.5 [95% CI 1.3 to 1.6]; p < 0.001). The same risk was observed for hip and vertebral fractures, with HRs of 1.6 (95% CI 1.4 to 1.8; p < 0.001) and 1.8 (95% 1.5 to 2.3; p < 0.001), respectively. Differences in the daily pattern of outcome rates mainly appeared the first 2 months after switching, when the hazard rate of patients on active exposure (9 cases for every 100,000 person-days) was higher than that of patients on referent exposure (4 cases for every 100,000 person-days). These differences persisted during the remaining follow-up, though with reduced intensity. CONCLUSIONS We found quantitative evidence that switching from oral antidiabetic therapy to insulin is associated with an increased fracture risk, mainly in the period immediately after the start of insulin therapy. The observed association may result from higher hypoglycemia risk among patients on insulin, which leads to a greater number of falls and resulting fractures. However, although our study was based on a large sample size and highly accurate data, its observational design and the lack of clinical data suggest that future research will need to replicate or refute our findings and address the issue of causality, if any. Until then, though, prescribers and patients should be aware of this risk. Careful control of insulin dosage should be maintained and measures taken to reduce fall risk in these patients. LEVEL OF EVIDENCE Level III, therapeutic study.

OBJECTIVES Although it has been postulated that patients might benefit from the centralization of high-volume specialized centres, conflicting results have been reported on the relationship between the number of lung resections performed and the long-term, all-cause mortality rates among patients who underwent surgery for lung cancer. A population-based observational study was performed to contribute to the ongoing debate. METHODS The 2613 patients, all residents of the Lombardy region (Italy), who underwent lung resection for lung cancer from 2012 to 2014 were entered into the cohort and were followed until 2018. The hospitals were classified according to the annual number of pulmonary resections performed. Three categories of lung resection cases were identified: low (≤30), intermediate (31–95) and high (>95). The outcome of interest was all-cause death. A frailty model was used to estimate the death risk associated with the categories of numbers of lung resections performed, taking into account the multilevel structure of the data. A set of sensitivity analyses was performed to account for sources of systematic uncertainty. RESULTS The 1-year and 5-year survival rates of cohort members were 90% and 63%. Patients operated on in high-volume centres were on average younger and more often women. Compared to patients operated on in a low-volume centre, the mortality risk exhibited a significant, progressive reduction as the numbers of lung resections performed increased to intermediate (−13%; 95% confidence interval +10% to −31%) and high (−26%; 0% to −45%). Sensitivity analyses revealed that the association was consistent. CONCLUSIONS Further evidence that the volume of lung resection cases performed strongly affects the long-term survival of lung cancer patients has been supplied.

Auoxo3 is a gold(iii) compound endowed with cytotoxic activity towards a variety of malignant cells. Encapsulation of Auoxo3 within horse spleen ferritin (Ft) improves the selectivity of the gold compound towards cancer cells over normal cells. In the current work, the changes in protein expression are presented in response to MCF-7 stimulation with Auoxo3-encapsulated Ft versus the free Au(iii) compound by a label-free proteomics approach. A 159-protein dataset showed significant changes between the stimulations with Auoxo3 and Auoxo3-encapsulated Ft, suggesting that this cellular perturbation caused the alteration of different cellular processes. In detail, roughly 30% of proteins were downregulated mainly in the spliceosome complex (U2AF1, SF3B2, PRPF4, SNSRP200, EFTUD2, PRPF6, and PRPF8) in agreement with the cytostatic effect observed during cellular growth. Another 30% of proteins were upregulated primarily in glutathione biosynthesis, suggesting an alteration of the redox potential, as validated by Western blot analyses. To the best of our knowledge, this work represents the first large scale proteomics study on the effects of a gold-based drug encapsulated within the Ft nanocage on cancer cells.

Objective Several factors affect adherence to antihypertensive drug treatment, but whether these factors include a sex difference is unclear. Aim of the study was to compare persistence with antihypertensive drug therapy between men and women in a large cohort of patients. Methods The 60 526 residents of the Italian Lombardy Region aged 40-80 years newly treated with antihypertensive drugs during 2010 were identified and followed for 1 year after the first prescription. Discontinuation of treatment was defined as lack of prescription renewal for at least 90 days. Log-binomial regression models were fitted to estimate the risk ratio of treatment discontinuation in relation to sex. Other than for the whole population, analyses were stratified according to age, comorbidity status and the initial antihypertensive treatment strategy. Results Thirty-seven percent of the patients discontinued the drug treatment during follow-up. Compared with women, men had a 10% lower risk of discontinuation of drug treatment (95% confidence interval: 8-12). Persistence on antihypertensive treatment was better in men than in women, this being the case in both younger (40-64 years) and older patients (65-80 years), in patients starting treatment with any major antihypertensive drug and in patients who had a low comorbidity status. There was no evidence that men and women had a different risk of treatment discontinuation when their comorbidity status was worse, or initial antihypertensive treatment was based on drug combinations. Conclusion Our data show that in a real-life setting, men are more persistent to antihypertensive drug therapy than women.

Angiogenin (Ang) is a potent angiogenic protein that is overexpressed in many types of cancer at concentration values correlated to the tumor aggressiveness. Here, by means of an integrated multi-technique approach based on crystallographic, spectrometric and spectroscopic analyses, we demonstrate that the anti-cancer drug oxaliplatin efficiently binds angiogenin. Microscopy cellular studies, carried out on the prostate cancer cell (PC-3) line , show that oxaliplatin inhibits the angiogenin prompting effect on cell proliferation and migration, which are typical features of angiogenesis process. Overall, our findings point to angiogenin as a possible target of oxaliplatin, thus suggesting a potential novel mechanism for the antineoplastic activity of this platinum drug and opening the avenue to novel approaches in the combined anti-cancer anti-angiogenic therapy.

Accidente cerebrovascular isquémico; Tratamiento de reperfusión; Factores de riesgo Ischemic Stroke; Reperfusion treatment; Risk factors Accident cerebrovascular isquèmic; Tractament de reperfusió; Factor de risc Objective The purpose of this study was to identify risk factors for acute symptomatic seizures and post-stroke epilepsy after acute ischemic stroke and evaluate the effects of reperfusion treatment. Methods We assessed the risk factors for post-stroke seizures using logistic or Cox regression in a multicenter study, including adults from 8 European referral centers with neuroimaging-confirmed ischemic stroke. We compared the risk of post-stroke seizures between participants with or without reperfusion treatment following propensity score matching to reduce confounding due to treatment selection. Results In the overall cohort of 4,229 participants (mean age 71 years, 57% men), a higher risk of acute symptomatic seizures was observed in those with more severe strokes, infarcts located in the posterior cerebral artery territory, and strokes caused by large-artery atherosclerosis. Strokes caused by small-vessel occlusion carried a small risk of acute symptomatic seizures. 6% developed post-stroke epilepsy. Risk factors for post-stroke epilepsy were acute symptomatic seizures, more severe strokes, infarcts involving the cerebral cortex, and strokes caused by large-artery atherosclerosis. Electroencephalography findings within 7 days of stroke onset were not independently associated with the risk of post-stroke epilepsy. There was no association between reperfusion treatments in general or only intravenous thrombolysis or mechanical thrombectomy with the time to post-stroke epilepsy or the risk of acute symptomatic seizures. Interpretation Post-stroke seizures are related to stroke severity, etiology, and location, whereas an early electroencephalogram was not predictive of epilepsy. We did not find an association of reperfusion treatment with risks of acute symptomatic seizures or post-stroke epilepsy.

Genome-wide association studies (GWASs) have identified a melanoma-associated locus on chromosome band 7p21.1 with rs117132860 as the lead SNP and a secondary independent signal marked by rs73069846. rs117132860 is also associated with tanning ability and cutaneous squamous cell carcinoma (cSCC). Because ultraviolet radiation (UVR) is a key environmental exposure for all three traits, we investigated the mechanisms by which this locus contributes to melanoma risk, focusing on cellular response to UVR. Fine-mapping of melanoma GWASs identified four independent sets of candidate causal variants. A GWAS region-focused Capture-C study of primary melanocytes identified physical interactions between two causal sets and the promoter of the aryl hydrocarbon receptor (AHR). Subsequent chromatin state annotation, eQTL, and luciferase assays identified rs117132860 as a functional variant and reinforced AHR as a likely causal gene. Because AHR plays critical roles in cellular response to dioxin and UVR, we explored links between this SNP and AHR expression after both 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and ultraviolet B (UVB) exposure. Allele-specific AHR binding to rs117132860-G was enhanced following both, consistent with predicted weakened AHR binding to the risk/poor-tanning rs117132860-A allele, and allele-preferential AHR expression driven from the protective rs117132860-G allele was observed following UVB exposure. Small deletions surrounding rs117132860 introduced via CRISPR abrogates AHR binding, reduces melanocyte cell growth, and prolongs growth arrest following UVB exposure. These data suggest AHR is a melanoma susceptibility gene at the 7p21.1 risk locus and rs117132860 is a functional variant within a UVB-responsive element, leading to allelic AHR expression and altering melanocyte growth phenotypes upon exposure.

Hepatocyte growth factor-overexpressing mice that harbor a deletion of the Ink4a/p16 locus (HP mice) form melanomas with low metastatic potential in response to UV irradiation. Here we report that these tumors become highly metastatic following hemizygous deletion of the Nme1 and Nme2 metastasis suppressor genes (HPN mice). Whole-genome sequencing of melanomas from HPN mice revealed a striking increase in lung metastatic activity that is associated with missense mutations in eight signature genes (Arhgap35, Atp8b4, Brca1, Ift172, Kif21b, Nckap5, Pcdha2, and Zfp869). RNA-seq analysis of transcriptomes from HP and HPN primary melanomas identified a 32-gene signature (HPN lung metastasis signature) for which decreased expression is strongly associated with lung metastatic potential. Analysis of transcriptome data from The Cancer Genome Atlas revealed expression profiles of these genes that predict improved survival of patients with cutaneous or uveal melanoma. Silencing of three representative HPN lung metastasis signature genes (ARRDC3, NYNRIN, RND3) in human melanoma cells resulted in increased invasive activity, consistent with roles for these genes as mediators of the metastasis suppressor function of NME1 and NME2. In conclusion, our studies have identified a family of genes that mediate suppression of melanoma lung metastasis, and which may serve as prognostic markers and/or therapeutic targets for clinical management of metastatic melanoma.

Advanced interventional pulmonary procedures of the airways, pleural space, and mediastinum continue to evolve and be refined. Health care, finance, and clinical professionals are challenged by both the indications and related coding complexities. As the scope of interventional pulmonary procedures expands with advanced technique and medical innovation, program planning and ongoing collaboration among clinicians, finance executives, and reimbursement experts are key elements for success. We describe advanced bronchoscopic procedures, appropriate Current Procedural Terminology coding, valuations, and necessary modifiers to fill the knowledge gap between basic and advanced procedural coding. Our approach is to balance the description of procedures with the associated coding in a way that is of use to the proceduralist, the coding specialist, and other nonclinical professionals.

Acute and transient psychotic disorders (ATPDs) include short-lived psychotic episodes with a high probability of developing psychotic recurrences. Clinical care for ATPD is currently limited by the inability to predict outcomes. Real-world electronic health record (EHR)-based retrospective cohort study STROBE/RECORD compliant included all individuals accessing the South London and Maudsley NHS Trust between 2006 and 2017 and receiving a first diagnosis of ATPD (F23, ICD-10). After imputing missing data, stepwise and LASSO Cox regression methods employing a priori predictors (n = 23) were compared to develop and internally validate an individualized risk prediction model to forecast the risk of psychotic recurrences following TRIPOD guidelines. The primary outcome was prognostic accuracy (area under the curve [AUC]). 3018 ATPD individuals were included (average age = 33.75 years, 52.7% females). Over follow-up (average 1042 ± 1011 days, up to 8 years) there were 1160 psychotic recurrences (events). Stepwise (n = 12 predictors) and LASSO (n = 17 predictors) regression methods yielded comparable prognostic accuracy, with an events per variable ratio >100 for both models. Both models showed an internally validated adequate prognostic accuracy from 4 years follow-up (AUC 0.70 for both models) and good calibration. A refined model was adapted in view of the new ICD-11 criteria on 307 subjects with polymorphic ATPD, showing fair prognostic accuracy at 4 years (AUC: stepwise 0.68; LASSO 0.70). This study presents the first clinically based prediction model internally validated to adequately predict long-term psychotic recurrence in individuals with ATPD. The model can be automatable in EHRs, supporting further external validations and refinements to improve its prognostic accuracy.

Extracellular vesicles (EVs) and their cargo represent an intriguing source of cancer biomarkers for developing robust and sensitive molecular tests by liquid biopsy. Prostate cancer (PCa) is still one of the most frequent and deadly tumor in men and analysis of EVs from biological fluids of PCa patients has proven the feasibility and the unprecedented potential of such an approach. Here, we exploited an antibody-based proteomic technology, i.e. the Reverse-Phase Protein microArrays (RPPA), to measure key antigens and activated signaling in EVs isolated from sera of PCa patients. Notably, we found tumor-specific protein profiles associated with clinical settings as well as candidate markers for EV-based tumor diagnosis. Among others, PD-L1, ERG, Integrin-β5, Survivin, TGF-β, phosphorylated-TSC2 as well as partners of the MAP-kinase and mTOR pathways emerged as differentially expressed endpoints in tumor-derived EVs. In addition, the retrospective analysis of EVs from a 15-year follow-up cohort generated a protein signature with prognostic significance. Our results confirm that serum-derived EV cargo may be exploited to improve the current diagnostic procedures while providing potential prognostic and predictive information. The approach proposed here has been already applied to tumor entities other than PCa, thus proving its value in translational medicine and paving the way to innovative, clinically meaningful tools.

To date, very few studies focused their attention on efficacy and safety of recanalisation therapy in acute ischemic stroke (AIS) patients with cancer, reporting conflicting results. We retrospectively analysed data from our database of consecutive patients admitted to the Udine University Hospital with AIS that were treated with recanalisation therapy, i.e. intravenous thrombolysis (IVT), mechanical thrombectomy (MT), and bridging therapy, from January 2015 to December 2019. We compared 3-month dependency, 3-month mortality, and symptomatic intracranial haemorrhage (SICH) occurrence of patients with active cancer (AC) and remote cancer (RC) with that of patients without cancer (WC) undergoing recanalisation therapy for AIS. Patients were followed up for 3 months. Among the 613 AIS patients included in the study, 79 patients (12.9%) had either AC (n = 46; 7.5%) or RC (n = 33; 5.4%). Although AC patients, when treated with IVT, had a significantly increased risk of 3-month mortality [odds ratio (OR) 6.97, 95% confidence interval (CI) 2.42–20.07, p = 0.001] than WC patients, stroke-related deaths did not differ between AC and WC patients (30% vs. 28.8%, p = 0.939). There were no significant differences between AC and WC patients, when treated with MT ± IVT, regarding 3-month dependency, 3-month mortality and SICH. Functional independence, mortality, and SICH were similar between RC and WC patients. In conclusion, recanalisation therapy might be used in AIS patients with nonmetastatic AC and with RC. Further studies are needed to explore the outcome of AIS patients with metastatic cancer undergoing recanalisation therapy.

Summary There is a lack of appropriate melanoma models that can be used to evaluate the efficacy of novel therapeutic modalities. Here, we discuss the current state of the art of melanoma models including genetically engineered mouse, patient-derived xenograft, zebrafish, and ex vivo and in vitro models. We also identify five major challenges that can be addressed using such models, including metastasis and tumor dormancy, drug resistance, the melanoma immune response, and the impact of aging and environmental exposures on melanoma progression and drug resistance. Additionally, we discuss the opportunity for building models for rare subtypes of melanomas, which represent an unmet critical need. Finally, we identify key recommendations for melanoma models that may improve accuracy of preclinical testing and predict efficacy in clinical trials, to help usher in the next generation of melanoma therapies.

Summary Background The most frequent abdominal surgery performed for benign disease in females of fertile age is appendectomy, which remains among the most common surgeries and is a possible cause of peritoneal adhesions. The fact that appendectomy can cause adhesions may lead one to think that this may be a relevant risk factor for infertility; however, there is no universal agreement regarding the association between appendectomy and fertility. The aim of this review is to evaluate weather appendectomy may have a relevant impact on female fertility. Methods The search was conducted in PubMed and there was no limitation set on the date of publication. All studies regarding populations of female patients who had undergone appendectomy for inflamed appendix, perforated appendix, or negative appendix between childhood and the end of the reproductive period were included. Results Some authors believe that pelvic surgery can cause adhesions which can potentially lead to tubal infertility by causing tubal obstruction or by altering motility of fimbriae, tubal fluid secretion, and embryo transport. On the other hand, the most recent evidence reported that removal of the appendix seems to be associated with an increased pregnancy rate in large population studies. Conclusion Despite the existence of contrasting opinions concerning fertility after appendectomy, the most recent evidence suggests that appendectomy may actually lead to improved fertility and decreased time to pregnancy. Appendectomy seems to be correlated with improved fertility and higher pregnancy rates.

PURPOSE To evaluate the prescription of preventive medications with questionable usefulness in community dwelling elderly adults with cancer or chronic progressive diseases during the last year of life. METHODS Through the utilization of the healthcare databases of the Lombardy region, Italy, we identified two retrospective cohorts of patients aged 65 years or more, who died in 2018 and had a diagnosis of either a solid cancer (N = 19 367) or a chronic progressive disease (N = 27 819). We estimated prescription of eight major classes of preventive drugs 1 year and 1 month before death; continuation or initiation of preventive drug use during the last month of life was also investigated. RESULTS Over the last year of life, in both oncologic and non-oncologic patients, we observed a modest decrease in the prescription of blood glucose-lowering drugs, anti-hypertensives, lipid-modifying agents, and bisphosphonates, and a slight increase in the prescription of vitamins, minerals, antianemic drugs, and antithrombotic agents (among oncologic patients only). One month before death, the prescription of preventive drugs was still common, particularly for anti-hypertensives, antithrombotics, and antianemics, with more than 60% of patients continuing to be prescribed most preventive drugs and an over 10% starting a therapy with an antithrombotic, an antianemic, or a vitamin or mineral supplement. CONCLUSION These findings support the need for an appropriate drug review and improvement in the quality of drug prescription for vulnerable populations at the end-of-life.

Purpose This meta-analysis study was designed to analyze endoscopic surgery’s role in treating rhinogenic contact point headache. Methods We performed a comprehensive review of the last 20 years’ English language regarding Rhinogenic contact point headache and endoscopic surgery. We included the analysis papers reporting post-operative outcomes through the Visual Analogue Scale or the Migraine Disability Assessment scale. Results We provided 18 articles for a total of 978 RCPH patients. While 777 (81.1%) subjects underwent functional nasal surgery for RCPH, 201 patients (20.9%) were medically treated. A significant decrease from the VAS score of 7.3 ± 1.5 to 2.7 ± 1.8 was recorded (p p Conclusion At comparison, surgical treatment in patients with rhinogenic contact points exhibited significantly better values at short-term, medium-term, and long term follow up. Endoscopic surgery should be proposed as the choice method in approaching the symptomatic patient.

Purpose:Uveal melanoma is the most common eye cancer in adults. Approximately 50% of patients with uveal melanoma develop metastatic uveal melanoma (mUM) in the liver, even after successful treatment of the primary lesions. mUM is refractory to current chemo- and immune-therapies, and most mUM patients die within a year. Uveal melanoma is characterized by gain-of-function mutations in GNAQ/GNA11, encoding Gαq proteins. We have recently shown that the Gαq–oncogenic signaling circuitry involves a noncanonical pathway distinct from the classical activation of PLCβ and MEK–ERK. GNAQ promotes the activation of YAP1, a key oncogenic driver, through focal adhesion kinase (FAK), thereby identifying FAK as a druggable signaling hub downstream from GNAQ. However, targeted therapies often activate compensatory resistance mechanisms leading to cancer relapse and treatment failure.Experimental Design:We performed a kinome-wide CRISPR-Cas9 sgRNA screen to identify synthetic lethal gene interactions that can be exploited therapeutically. Candidate adaptive resistance mechanisms were investigated by cotargeting strategies in uveal melanoma and mUM in vitro and in vivo experimental systems.Results:sgRNAs targeting the PKC and MEK–ERK signaling pathways were significantly depleted after FAK inhibition, with ERK activation representing a predominant resistance mechanism. Pharmacologic inhibition of MEK and FAK showed remarkable synergistic growth-inhibitory effects in uveal melanoma cells and exerted cytotoxic effects, leading to tumor collapse in uveal melanoma xenograft and liver mUM models in vivo.Conclusions:Coupling the unique genetic landscape of uveal melanoma with the power of unbiased genetic screens, our studies reveal that FAK and MEK–ERK cotargeting may provide a new network-based precision therapeutic strategy for mUM treatment.See related commentary by Harbour, p. 2967

IntroductionDespite overlaying an irreplaceable role as a key diagnostic tool in modern medicine, the role of radiologist still appears to be unclear to patients.Methods We conducted a survey in outpatient clinic of Radiological Sciences Department of the University Hospital “A. Gemelli” in Rome, aiming to assess how correct patients identify the figure of the radiologist. The patients were interviewed by the trained physician using structured questionnaire.Results We included the number of 259 patients. Majority were female 63.3%, most were 60-69 years old (24.3%), have finished second grade secondary school (35.1%) and were subjected to magnetic resonance (28.6%) while the least were subjected to chest X-ray (8.1%). Only 38.7% answered correctly to question No 1 “Who performed your examination?”, and only 30.9% correctly identified the radiologist as a person interpreting the exam (question No 2 “Who is going to interpret your radiological examination?”). Overall, 16.8% responded correctly to the both questions. Significantly less patients with primary school (OR: 0.18, CI 95% 0.06-0.49) and first grade secondary school (OR: 0.37, CI 95% 0.18-0.75) correctly addressed the question No 1 in compare to those with second grade secondary school. The first grade secondary education (OR: 0.43, CI 95% 0.20-0.92) was inversely associated with correct answer to question No 2. Patients with primary education were significantly less prone to give both correct answers (OR: 0.12, CI 95% 0.02-0.60).Conclusion We report insufficient knowledge among patients on radiologist’s role in healthcare system. The level of knowledge is associated with level of education.

Three novel platinum(II) complexes bearing N-heterocyclic ligands, i.e., Pt2c, Pt-IV and Pt-VIII, were previously prepared and characterized. They manifested promising in vitro anticancer properties associated with non-conventional modes of action. To gain further mechanistic insight, we have explored here the reactions of these Pt compounds with a few model proteins, i.e., hen egg white lysozyme (HEWL), bovine pancreatic ribonuclease (RNase A), horse heart cytochrome c (Cyt-c) and human serum albumin (HSA), primarily through ESI MS analysis. Characteristic and variegate patterns of reactivity were highlighted in the various cases that appear to depend both on the nature of the Pt complex and of the interacting protein. The protein-bound Pt fragments were identified. In the case of the complex Pt2c, the adducts formed upon reaction with HEWL and RNase A were further characterized by solving the respective crystal structures: this allowed us to determine the exact location of the various Pt binding sites. The implications of the obtained results are discussed in relation to the possible mechanisms of action of these innovative anticancer Pt complexes.

In this paper, I analyse video recordings of speech-language therapy sessions for people diagnosed with aphasia. I particularly explore the way in which the speech-language therapists instruct the patients to correctly pronounce speech sounds (e.g. phonemes, syllables) by deploying not only audible but also visible forms of cues. By using their bodies – face and gestures – as an instructional tool, the therapists make visual perceptual access to articulatory features of pronunciation relevant and salient. They can also make these sensory practices accountable through the use of other senses, such as touch. Data was collected in a hospital and in a rehabilitation clinic, tracking each patient’s recovery, and is part of a longitudinal multisite corpus. The paper considers the way in which participants in the therapeutic process use and coordinate forms of sensory access to language that are based on hearing and seeing. It highlights the importance of audio and video recordings to make accessible the auditory and visual details of these sensorial experiences – particularly, proper framings and the complementary use of fixed and mobile cameras.