How to reduce erroneous Emergency Department admissions for the frail elderly.

Background: Readmission after a first hospitalization is a common occurrence. It may be due to incomplete treatment, poor care for underlying problems or reflect bad coordination with health services at the time of discharge. The aim of this study was to identify the factors and classify the pathologies that expose elderly patients to erroneous access to the Emergency/Urgency Department (EUD). Study design: Retrospective observational study. Materials and methods: From January 2016 to December 2019 we studied patients who had at least one readmission to the EUD in the six months following discharge. All EUD accesses of the same patient that occurred for the problem treated during the previous hospitalization were identified. Data was provided by the University Hospital of Siena. Patients were stratified by age, gender, and municipality of residence. We used an ICD-9-CM coding system to describe health problems. Statistical analysis was carried out with Stata software. Results: We studied 1,230 patients (46.6% females) the mean age was 78.2 ± 14.3. Most of them, 721 (58.6%) were ≥80 years old, 334 (27.1%) were 65-79, 138 (11.2%) were 41-64, and only 37 (3.0%) were ≤40. Patients who lived in Municipality of Siena had a lower probability to return than to those living in other municipalities (OR 0.76; 95%CI: 0.62-0.93; p<0,05). The main causes of readmission for ≥65 years old were "symptoms, signs and ill-defined conditions" (18.3%), "respiratory diseases" (15.0%), "injury and poisoning" (14.1%), "cardiovascular diseases" (11.8%), "classification of factors influencing health status and contact with health services" (9.8%), "genitourinary diseases" (6.6%) and "digestive diseases (5.7%). Conclusions: We observed that patients residing a greater distance from the hospital facilitates the risk of readmission. The factors that were exposed could be used to identify frequent users and initiate measures to reduce their access.

Validation of the diagnosis of mesothelioma and BAP1 protein expression in a cohort of asbestos textile workers from Northern Italy.

Background: Diagnosis of mesothelioma based on death certificate is subject to misclassification, which may bias the results of epidemiology studies. A high proportion of mesothelioma harbor mutations in the BRCA1-associated protein 1 (BAP1) gene. Methods: We searched medical and pathology records and specimens for 127 workers from a textile-asbestos factory in Italy who died during 1963-2013 with a diagnosis of pleural or peritoneal neoplasm or mesothelioma on death certificate, to confirm the diagnosis with immunohistochemistry markers. We calculated the odds ratio of confirmation by selected characteristics and asbestos exposure variables. When sufficient pathology material was available, we analyzed BAP1 protein expression. Results: The diagnosis of mesothelioma was histologically confirmed for 35 cases (27.6%); 5 cases were classified as non-mesothelioma (3.9%), for 33 cases a mention of mesothelioma was found on record but no sufficient material was available for revision (26.0%); no records were available for 54 cases (death-certificate-only 42.5%). Diagnostic confirmation was not associated with sex, location of the neoplasm, age, or duration of employment; however, there was a significant association with time since first employment (P for linear trend 0.04). An association between duration of employment and time since first employment was observed for confirmed cases but not for death-certificate-only cases. BAP1 protein was lost in 18/35 cases (51.4%), without an association with sex, location, age, indices of asbestos exposure, or survival. Conclusions: We were able to confirm by immunohistochemistry a small proportion of mesothelioma diagnoses on certificates of deceased asbestos workers, and confirmation correlated with latency of asbestos exposure but not other characteristics. BAP1 protein loss is a frequent event in mesothelioma of asbestos-exposed workers, but does not correlate with exposure.

Monitoring antimicrobial resistance (AMR) using CUSUM control charts.

We evaluated the use of the Cumulative Summation (CUSUM) control chart methodology for detection of an excessive increase in antimicrobial-resistant (AMR) bacteria acquisition. We used administrative, clinical and bacteriological data from all 157,570 patients hospitalized for at least 48 h from January 1, 2010 to December 31, 2015 in a 654-bed university teaching hospital in Paris, France. Monthly computed CUSUM were evaluated for the detection of out-of-control situations, defined as incidence rates of acquired AMR bacterial colonization exceeding acceptable thresholds at the hospital and ward levels (based on six selected wards) for AMR bacteria overall and Extended-spectrum beta-lactamases Enterobacteriaceae (ESBL-E) and Methicillin-resistant Staphylococcus aureus (MRSA), specifically. During the study period, 1,403 samples of acquired AMR bacteria were identified including 1,129 ESBL-E and 151 MRSA. The incidence rate of acquired AMR bacteria was stable at the hospital and the wards level. When based on AMR bacteria overall, CUSUM alarms were triggered at the hospital level and at the ward level in four units. For ESBL-E, CUSUM tests generated alarms at the hospital level and for the same four wards, and for MRSA, CUSUM tests detected out-of-control situations in all the wards. The CUSUM approach appears complementary with hospital infection control strategies currently in practice and appears of interest in common practice as a simple tool for AMR surveillance.

Which factors are important for crossmodal attentional effect?

Some results in the literature suggest that crossmodal attention is very sensitive to the features of the experimental protocol. The current work examined the possible contribution of the asynchrony between the onset of the cue and the target (SOA) and the kind of task performed by the observer to the manifestation of crossmodal attentional effect. In a first experiment, a target (Gabor patch), whose spatial frequency had to be discriminated, was presented 133 or 159 ms after an auditory cue, in a close location on the same side or in a distant location on the opposite side. The crossmodal attentional effect was observed only for the 159 ms SOA. In a second experiment, the SOA was again 133 ms, but the location of the target had to be discriminated, instead of its spatial frequency. A crossmodal attentional effect was observed. The results of these two experiments indicate that crossmodal attentional effect depends on the SOA and the task. It takes longer to develop when the task requires the discrimination of the spatial frequency of the target than the discrimination of its location.

Trends in hospital acquired New Delhi metallo-beta-lactamase-producing Enterobacterales in Tuscany (Italy) from 2019 to 2021: impact of the COVID-19 pandemic.

OBJECTIVES: In Tuscany, Italy, New Delhi metallo-beta-lactamase-producing carbapenem-resistant Enterobacterales (NDM-CRE) in hospitalized patients has increasingly been observed since 2018, leading in 2019 to the implementation of enhanced control measures successfully reducing transmission. We describe the NDM-CRE epidemiology during the COVID-19 pandemic in Tuscany. METHODS: Data on NDM-CRE patients hospitalized in five Tuscan hospitals were collected from January 2019 to December 2021. Weekly rates of NDM-CRE cases on hospital days in medical and critical-care wards were calculated. In March-December 2020, NDM-CRE rates were stratified by COVID-19 diagnosis. Multi-variate regression analysis was performed to assess outcomes' differences among two periods analysed and between COVID-19 populations. RESULTS: Since March 2020, an increase in NDM-CRE cases was observed, associated with COVID-19 admissions. COVID-19 patients differed significantly from non-COVID-19 ones by several variables, including patient features (age, Charlson index) and clinical history and outcomes (NDM-CRE infection/colonization, intensive care unit stay, length of stay, mortality). During the pandemic, we observed a higher rate of NDM-CRE cases per hospital day in both non-COVID-19 patients (273/100,000) and COVID-19 patients (370/100,00) when compared with pre-pandemic period cases (187/100,00). CONCLUSIONS: Our data suggest a resurgence in NDM-CRE spread among hospitalized patients in Tuscany during the COVID-19 pandemic, as well as a change in patients' case-mix. The observed increase in hospital transmission of NDM-CRE could be related to changes in infection prevention and control procedures, aimed mainly at COVID-19 management, leading to new challenges in hospital preparedness and crisis management planning.

Consensus clustering methodology to improve molecular stratification of non-small cell lung cancer.

Recent advances in machine learning research, combined with the reduced sequencing costs enabled by modern next-generation sequencing, paved the way to the implementation of precision medicine through routine multi-omics molecular profiling of tumours. Thus, there is an emerging need of reliable models exploiting such data to retrieve clinically useful information. Here, we introduce an original consensus clustering approach, overcoming the intrinsic instability of common clustering methods based on molecular data. This approach is applied to the case of non-small cell lung cancer (NSCLC), integrating data of an ongoing clinical study (PROMOLE) with those made available by The Cancer Genome Atlas, to define a molecular-based stratification of the patients beyond, but still preserving, histological subtyping. The resulting subgroups are biologically characterized by well-defined mutational and gene-expression profiles and are significantly related to disease-free survival (DFS). Interestingly, it was observed that (1) cluster B, characterized by a short DFS, is enriched in KEAP1 and SKP2 mutations, that makes it an ideal candidate for further studies with inhibitors, and (2) over- and under-representation of inflammation and immune systems pathways in squamous-cell carcinomas subgroups could be potentially exploited to stratify patients treated with immunotherapy.

Automatic attention lateral asymmetry in visual discrimination tasks.

There is evidence that automatic visual attention favors the right side. This study investigated whether this lateral asymmetry interacts with the right hemisphere dominance for visual location processing and left hemisphere dominance for visual shape processing. Volunteers were tested in a location discrimination task and a shape discrimination task. The target stimuli (S2) could occur in the left or right hemifield. They were preceded by an ipsilateral, contralateral or bilateral prime stimulus (S1). The attentional effect produced by the right S1 was larger than that produced by the left S1. This lateral asymmetry was similar between the two tasks suggesting that the hemispheric asymmetries of visual mechanisms do not contribute to it. The finding that it was basically due to a longer reaction time to the left S2 than to the right S2 for the contralateral S1 condition suggests that the inhibitory component of attention is laterally asymmetric.

Somatostatin receptor tissue distribution in lung neuroendocrine tumours: a clinicopathologic and immunohistochemical study of 218 'clinically aggressive' cases.

BACKGROUND: The management of pulmonary neuroendocrine tumours (NETs), with special reference to clinically aggressive carcinoids and large-cell neuroendocrine carcinomas (LCNECs), is poorly standardised and data about somatostatin receptor (SSTR) expression or therapeutic guidelines for somatostatin analogue administration are still debated. MATERIALS AND METHODS: A series of 218 lung NETs [24 metastatic typical carcinoids (TCs), 73 atypical carcinoids (ACs), 60 LCNECs and 61 surgically resected small-cell lung carcinomas] were investigated for SSTR types 2A and 3 tissue distribution using immunohistochemistry, in correlation with clinicopathologic parameters, outcome, scintigraphy and treatment. RESULTS: SSTRs were heterogeneously distributed with a significant progressive decrease from low- to high-grade forms. SSTR type 2A was strikingly overexpressed in metastatic TCs as compared with ACs and clinically benign TCs. SSTR tissue immunolocalization correlated with octreotide scintigraphy in 20 of 28 cases. CONCLUSION: The immunohistochemical determination of SSTRs, with special reference to low-grade/intermediate-grade tumours, may assist the clinical approach with somatostatin analogue-based diagnostic and therapeutic procedures in clinically aggressive pulmonary NETs.

Lattice strain accommodation and absence of pre-transition phases in Ni50Mn25+xIn25-x.

The stoichiometric Ni50Mn25In25Heusler alloy transforms from a stable ferromagnetic austenitic ground state to an incommensurate modulated martensitic ground state with a progressive replacement of In with Mn without any pre-transition phases. The absence of pre-transition phases like strain glass in Ni50Mn25+xIn25-xalloys is explained to be the ability of the ferromagnetic cubic structure to accommodate the lattice strain caused by atomic size differences of In and Mn atoms. Beyond the critical value ofx= 8.75, the alloys undergo martensitic transformation despite the formation of ferromagnetic and antiferromagnetic clusters and the appearance of a super spin glass state.

Gastrointestinal stromal tumors (GIST): a proposal of a "CT-based predictive model of Miettinen index" in predicting the risk of malignancy.

PURPOSE: To identify the predictors of malignancy on CT for the evaluation of gastrointestinal stromal tumors (GIST) by correlating CT findings with the mitotic index in order to propose a "CT-based predictive model of Miettinen index." METHODS: One radiologist and one resident in radiology with 14- and 4-year experience in oncological field reviewed the CT findings of 42 patients by consensus, with respect to lesion site, size, contour, tumor growth pattern, enhancing pattern, degree of enhancement of tumor, percentage of tumor necrosis, mesenteric fat infiltration, ulceration, calcification, regional lymphadenopathy, direct invasion to adjacent organs, and distant metastasis. All parameters were correlated with the mitotic index evaluated at histopathological analysis following surgery. Normality of variables was evaluated using Shapiro-Wilk test. Pearson's correlation test was used to assess the interaction between variables. The diagnostic accuracy percentage of tumor necrosis was measured by receiver operating characteristic (ROC) analysis for detecting whether the number of mitosis per 50 high-power fields was > 5. RESULTS: A significant statistical correlation was found between percentage of tumor necrosis and the mitotic index (p < 0.005), dimension, and location of the tumor. CONCLUSION: CT could be an accurate technique in the prediction of malignancy of GIST in a CT risk assessment system, based on the location of the tumor, its size, and the percentage of tumor necrosis.

Singling out the effect of quenched disorder in the phase diagram of cuprates.

We investigate the specific influence of structural disorder on the suppression of antiferromagnetic order and on the emergence of cuprate superconductivity. We single out pure disorder, by focusing on a series of [Formula: see text] samples at fixed oxygen content y  = 0.35, in the range [Formula: see text]. The gradual Y/Eu isovalent substitution smoothly drives the system through the Mott-insulator to superconductor transition from a full antiferromagnet with Néel transition [Formula: see text] K at z = 0 to a bulk superconductor with superconducting critical temperature [Formula: see text] K at z = 1, [Formula: see text]. The electronic properties are finely tuned by gradual lattice deformations induced by the different cationic radii of the two lanthanides, inducing a continuous change of the basal Cu(1)-O chain length, as well as a controlled amount of disorder in the active Cu(2)O2 bilayers. We check that internal charge transfer from the basal to the active plane is entirely responsible for the doping of the latter and we show that superconductivity emerges with orthorhombicity. By comparing transition temperatures with those of the isoelectronic clean system we determine the influence of pure structural disorder connected with the Y/Eu alloy.

What's new in mesothelioma.

Malignant pleural mesothelioma is a neoplasm characterized by a very poor prognosis and medico-legal implications. Diagnosis, prognosis and therapy are often challenging and include several issues. Cytological diagnosis is frequently the first step of the diagnostic process, and although its sensitivity may be somewhat lower, diagnostic criteria should be taken into account. When effusion cytology is inconclusive for the diagnosis, tissue biopsies should be taken. Even if the morphologic criteria for deciding whether a mesothelial proliferation is a benign or a malignant process have been defined, the separation of benign from malignant mesothelial proliferation is often a difficult problem for the pathologist, particularly on small biopsies. Thirdly, when the diagnosis is made, despite many efforts have been made to identify possible new biomarkers for early diagnosis, prognostic stratification and also predictive tools should be defined. Nowadays, the main prognostic parameter is still represented by the histological subtype, having the epithelioid MPM a better outcome than the sarcomatoid or biphasic MPM. A nuclear grading system have been also proposed to stratify patient outcome. Reliable predictive biomarkers are still lacking in MPM and a personalized therapeutic concept is eagerly needed. Mesothelioma occurs mostly as sporadic cancer and the main risk factor is asbestos exposure, but it also occurs among blood relatives suggesting possible increased genetic susceptibility besides shared exposures. Recently the study of genetic predisposition syndrome raised new aspect in the occurrence of mesothelioma cases.This review summarize these most important issues.

Molecular and Histological Changes in Post-Treatment Biopsies of Non-Squamous Non-Small Cell Lung Cancer: A Retrospective Study.

BACKGROUND: Recently, in advanced non-small cell lung cancer (NSCLC), standard chemotherapy was flanked by biological agents directed against genomic abnormalities, including EGFR and ALK alterations, that significantly improved patient outcome. Despite these achievements, tumour progression almost always occurs and a reassessment of the tumour genetic profile may contribute to modulating the therapeutic regimen. Resampling may provide tissue for additional tests to detect acquired resistance and/or new genetic alterations, but the currently available information is limited. PATIENTS AND METHODS: Histological and genetic reassessments of biopsy or surgical tissue samples from 50 non-squamous NSCLC patients before and after at least one systemic treatment were performed. EGFR, KRAS, BRAF, PIK3CA and HER2 mutations were sequenced, p.T790M was identified with real-time PCR, and ALK and MET genomic alterations by fluorescence in situ hybridization. RESULTS: Overall in baseline biopsies, 37/50 (74 %) tumours had genetic alterations, either single (52 %) or multiple (22 %). Among them, 16 were EGFR mutations and 6 ALK rearrangements. In the second tissue sampling, 54 % of cases had additional genomic changes, including newly acquired alterations (81 %) or losses (18 %). The commonest changes were MET amplification and p.T790M mutation. One case had a histological shift from adenocarcinoma to small cell carcinoma. CONCLUSIONS: The remarkable number of molecular changes following systemic therapy and the genetic complexity of some cases underline the value of histological and molecular re-evaluation of lung cancer to tailor the most appropriate therapy during disease progression.

CDKN2A and BAP1 germline mutations predispose to melanoma and mesothelioma.

BAP1 germline mutations predispose to a cancer predisposition syndrome that includes mesothelioma, cutaneous melanoma, uveal melanoma and other cancers. This co-occurrence suggests that these tumors share a common carcinogenic pathway. To evaluate this hypothesis, we studied 40 Italian families with mesothelioma and/or melanoma. The probands were sequenced for BAP1 and for the most common melanoma predisposition genes (i.e. CDKN2A, CDK4, TERT, MITF and POT1) to investigate if these genes may also confer susceptibility to mesothelioma. In two out of six families with both mesothelioma and melanoma we identified either a germline nonsense mutation (c.1153C > T, p.Arg385*) in BAP1 or a recurrent pathogenic germline mutation (c.301G > T, p.Gly101Trp) in CDKN2A. Our study suggests that CDKN2A, in addition to BAP1, could be involved in the melanoma and mesothelioma susceptibility, leading to the rare familial cancer syndromes. It also suggests that these tumors share key steps that drive carcinogenesis and that other genes may be involved in inherited predisposition to malignant mesothelioma and melanoma.

Sperm washing and virus nucleic acid detection to reduce HIV and hepatitis C virus transmission in serodiscordant couples wishing to have children.

BACKGROUND: Use of a motile spermatozoa isolation process was assessed for reducing the transmission of HIV and hepatitis C virus (HCV) during artificial insemination in HIV-serodiscordant couples in which the man is infected. PATIENTS: Thirty-two HIV-1-infected clinically asymptomatic men, having a median CD4 cell count of 396 x 10(6)/l and a median blood plasma HIV-1 RNA content of 414 copies/ml. Of these, 16 were infected with both HIV and HCV. METHODS: Motile spermatozoa were isolated from 51 semen samples by density gradient and 'swim-up'. HIV-1 and HCV genomes were detected and quantified in the blood plasma and seminal plasma, and detected in seminal cell fractions obtained during spermatozoa isolation. RESULTS: HIV-1 RNA was detected in 30% of seminal plasma samples. HIV-1 genomes were found in 18% of seminal cell samples, but in none of the motile spermatozoa fractions after 'swim-up'. There was no correlation between the HIV-1 RNA concentrations in the blood and seminal plasma. HIV-1 genome was detected intermittently in patients who gave more than one sample. HCV RNA was detected in 20% of seminal plasma samples from HCV viraemic patients, but in no seminal cells or motile spermatozoa fractions. CONCLUSIONS: Purification of motile spermatozoa by density gradient plus 'swim-up' reduced the HIV-1 and HCV genomes in the semen of infected individuals to undetectable levels. This method, associated with a standardized virus assay, could be useful for serodiscordant couples (males infected) who wish to have children.

34betaE12 cytokeratin immunodetection in the differential diagnosis of neuroendocrine carcinomas of the breast.

Neuroendocrine (NE) carcinomas of the breast share morphologic and immunohistochemical features with NE tumors of other sites, either resembling typical carcinoids or the highly aggressive small cell carcinoma. In addition, some mucinous carcinomas or solid/papillary carcinomas may show a major NE component. This is generally recognized by specific immunodetection of pan-endocrine markers, although this approach may fail to recognize NE tumors lacking immunoreactivity for some NE products, because the antigen is produced but not retained in the cytoplasm. It has recently been reported that high molecular weight (HMW) cytokeratin (CK), recognized by clone 34betaE12, immunostaining selectively labels non-NE carcinomas (squamous-cell and adenocarcinomas) of the aerodigestive tract and lung. The role of such CK immunodetection in the differential diagnosis of NE carcinoma of the breast was evaluated. Twenty-four cases of breast carcinomas having NE differentiation were selected. Twenty-four cases of non-NE invasive breast carcinomas served as controls. HMW CK immunoreactivity was found in all but one case of non-NE carcinomas, but in only two NE tumors (having scattered positive cells only). The authors conclude that in breast carcinomas the presence of HMW CK immunoreactivity favors the diagnosis of non-NE carcinoma, whereas its absence supports that of a NE tumor (either a carcinoid or a small cell carcinoma or a mucinous carcinoma). HMW CK can be added to the list of markers useful in the differential diagnosis of NE from non-NE tumors.

Expression of the neuroendocrine phenotype in carcinomas of the breast.

Neuroendocrine (NE) features are detectable in carcinomas of the breast either as scattered cells immunoreactive for NE markers in carcinoma of the usual type (NOS), or as special type of tumors where the vast majority of the cells display NE characteristics. The former type of lesions, whose biological and diagnostic significance is not clear yet, might reproduce the same phenomenon known to occur in carcinomas of the gastrointestinal tract and pancreas. In the present review we focus on the latter type of lesions, a spectrum of breast tumors largely composed of NE cells. These carcinomas, that we consider the "NE differentiated carcinomas of the breast," are here distinguished from "breast carcinomas NOS with NE differentiation." The diagnostic and histogenetic features of the various types of "NE differentiated carcinomas of the breast," their histological and cytological features and the role and value of ancillary diagnostic techniques, are reviewed. Data of the literature are discussed and related to a relatively large personal series. In addition, divergent differentiation in NE carcinomas of the breast, which is a relatively frequent phenomenon of diagnostic interest but of unknown significance (mainly involving mucinous intra- and extracellular production) is discussed.