Neurodevelopmental Outcome after Culture-Proven or So-Called Culture-Negative Sepsis in Preterm Infants.

(1) Background: Prematurity is a serious condition associated with long-term neurological disability. This study aimed to compare the neurodevelopmental outcomes of preterm neonates with or without sepsis. (2) Methods: This single-center retrospective case-control study included infants with birth weight < 1500 g and/or gestational age ≤ 30 weeks. Short-term outcomes, brain MRI findings, and severe functional disability (SFD) at age 24 months were compared between infants with culture-proven or culture-negative sepsis or without sepsis. A chi-squared test or Mann-Whitney U test was used to compare the clinical and instrumental characteristics and the outcomes between cases and controls. (3) Results: Infants with sepsis (all sepsis n = 76; of which culture-proven n = 33 and culture-negative n = 43) were matched with infants without sepsis (n = 76). Compared with infants without sepsis, both all sepsis and culture-proven sepsis were associated with SFD. In multivariate logistic regression analysis, SFD was associated with intraventricular hemorrhage (OR 4.7, CI 1.7-13.1, p = 0.002) and all sepsis (OR 3.68, CI 1.2-11.2, p = 0.021). (4) Conclusions: All sepsis and culture-proven sepsis were associated with SFD. Compared with infants without sepsis, culture-negative sepsis was not associated with an increased risk of SFD. Given the association between poor outcomes and culture-proven sepsis, its prevention in the neonatal intensive care unit is a priority.

Machine learning-based prediction of hospital prolonged length of stay admission at emergency department: a Gradient Boosting algorithm analysis.

Objective: This study aims to develop and compare different models to predict the Length of Stay (LoS) and the Prolonged Length of Stay (PLoS) of inpatients admitted through the emergency department (ED) in general patient settings. This aim is not only to promote any specific model but rather to suggest a decision-supporting tool (i.e., a prediction framework). Methods: We analyzed a dataset of patients admitted through the ED to the "Sant"Orsola Malpighi University Hospital of Bologna, Italy, between January 1 and October 26, 2022. PLoS was defined as any hospitalization with LoS longer than 6 days. We deployed six classification algorithms for predicting PLoS: Random Forest (RF), Support Vector Machines (SVM), Gradient Boosting (GB), AdaBoost, K-Nearest Neighbors (KNN), and logistic regression (LoR). We evaluated the performance of these models with the Brier score, the area under the ROC curve (AUC), accuracy, sensitivity (recall), specificity, precision, and F1-score. We further developed eight regression models for LoS prediction: Linear Regression (LR), including the penalized linear models Least Absolute Shrinkage and Selection Operator (LASSO), Ridge and Elastic-net regression, Support vector regression, RF regression, KNN, and eXtreme Gradient Boosting (XGBoost) regression. The model performances were measured by their mean square error, mean absolute error, and mean relative error. The dataset was randomly split into a training set (70%) and a validation set (30%). Results: A total of 12,858 eligible patients were included in our study, of whom 60.88% had a PloS. The GB classifier best predicted PloS (accuracy 75%, AUC 75.4%, Brier score 0.181), followed by LoR classifier (accuracy 75%, AUC 75.2%, Brier score 0.182). These models also showed to be adequately calibrated. Ridge and XGBoost regressions best predicted LoS, with the smallest total prediction error. The overall prediction error is between 6 and 7 days, meaning there is a 6-7 day mean difference between actual and predicted LoS. Conclusion: Our results demonstrate the potential of machine learning-based methods to predict LoS and provide valuable insights into the risks behind prolonged hospitalizations. In addition to physicians' clinical expertise, the results of these models can be utilized as input to make informed decisions, such as predicting hospitalizations and enhancing the overall performance of a public healthcare system.

Spatiotemporal heterogeneity of SARS-CoV-2 diffusion at the city level using geographically weighted Poisson regression model: The case of Bologna, Italy.

This paper aimed to analyse the spatio-temporal patterns of the diffusion of SARS-CoV-2, the virus causing coronavirus 2019 (COVID-19, in the city of Bologna, the capital and largest city of the Emilia-Romagna Region in northern Italy. The study took place from February 1st, 2020 to November 20th, 2021 and accounted for space, sociodemographic characteristics and health conditions of the resident population. A second goal was to derive a model for the level of risk of being infected by SARS-CoV-2 and to identify and measure the place-specific factors associated with the disease and its determinants. Spatial heterogeneity was tested by comparing global Poisson regression (GPR) and local geographically weighted Poisson regression (GWPR) models. The key findings were that different city areas were impacted differently during the first three epidemic waves. The area-to-area influence was estimated to exert its effect over an area with 4.7 km radius. Spatio-temporal heterogeneity patterns were found to be independent of the sociodemographic and the clinical characteristics of the resident population. Significant single-individual risk factors for detected SARS-CoV-2 infection cases were old age, hypertension, diabetes and co-morbidities. More specifically, in the global model, the average SARS-CoV-2 infection rate decreased 0.93-fold in the 21-65 years age group compared to the >65 years age group, whereas hypertension, diabetes, and any other co-morbidities (present vs absent), increased 1.28-, 1.39- and 1.15-fold, respectively. The local GWPR model had a better fit better than GPR. Due to the global geographical distribution of the pandemic, local estimates are essential for mitigating or strengthening security measures.

Emergency Department Visits and Summer Temperatures in Bologna, Northern Italy, 2010-2019: A Case-Crossover Study and Geographically Weighted Regression Methods.

The aim of the study is to evaluate the association between summer temperatures and emergency department visits (EDVs) in Bologna (Italy) and assess whether this association varies across areas with different socioeconomic and microclimatic characteristics. We included all EDVs within Bologna residences during the summers of 2010-2019. Each subject is attributed a deprivation and a microclimatic discomfort index according to the residence. A time-stratified case-crossover design was conducted to estimate the risk of EDV associated with temperature and the effect modification of deprivation and microclimatic characteristics. In addition, a spatial analysis of data aggregated at the census block level was conducted by applying a Poisson and a geographically weighted Poisson regression model. For each unit increase in temperature above 26 °C, the risk of EDV increases by 0.4% (95%CI: 0.05-0.8). The temperature-EDV relationship is not modified by the microclimatic discomfort index but rather by the deprivation index. The spatial analysis shows that the EDV rate increases with deprivation homogeneously, while it diminishes with increases in median income and microclimatic discomfort, with differences across areas. In conclusion, in Bologna, the EDV risk associated with high temperatures is not very relevant overall, but it tends to increase in areas with a low socioeconomic level.

Length of Stay Analysis of COVID-19 Hospitalizations Using a Count Regression Model and Quantile Regression: A Study in Bologna, Italy.

This study aimed to identify and explore the hospital admission risk factors associated with the length of stay (LoS) by applying a relatively novel statistical method for count data using predictors among COVID-19 patients in Bologna, Italy. The second goal of this study was to model the LoS of COVID patients to understand which covariates significantly influenced it and identify the potential risk factors associated with LoS in Bolognese hospitals from 1 February 2020 to 10 May 2021. The clinical settings we focused on were the Intensive Care Unit (ICU) and ordinary hospitalization, including low-intensity stays. We used Poisson, negative binomial (NB), Hurdle-Poisson, and Hurdle-NB regression models to model the LoS. The fitted models were compared using the Akaike information criterion (AIC), Vuong's test criteria, and Rootograms. We also used quantile regression to model the effects of covariates on the quantile values of the response variable (LoS) using a Poisson distribution, and to explore a range of conditional quantile functions, thereby exposing various forms of conditional heterogeneity and controlling for unobserved individual characteristics. Based on the chosen performance criteria, Hurdle-NB provided the best fit. As an output from the model, we found significant changes in average LoS for each predictor. Compared with ordinary hospitalization and low-intensity stays, the ICU setting increased the average LoS by 1.84-fold. Being hospitalized in long-term hospitals was another contributing factor for LoS, increasing the average LoS by 1.58 compared with regular hospitals. When compared with the age group [50, 60) chosen as the reference, the average LoS decreased in the age groups [0, 10), [30, 40), and [40, 50), and increased in the oldest age group [80, 102). Compared with the second wave, which was chosen as the reference, the third wave did not significantly affect the average LoS, whereas it increased by 1.11-fold during the first wave and decreased by 0.77-fold during out-wave periods. The results of the quantile regression showed that covariates related to the ICU setting, hospitals with longer hospitalization, the first wave, and the out-waves were statistically significant for all the modeled quantiles. The results obtained from our study can help us to focus on the risk factors that lead to an increased LoS among COVID-19 patients and benchmark different models that can be adopted for these analyses.

The surname structure of Trentino (Italy) and its relationship with dialects and genes.

BACKGROUND: Thanks to the availability of rich surname, linguistic and genetic information, together with its geographic and cultural complexity, Trentino (North-Eastern Italy) is an ideal place to test the relationships between genetic and cultural traits. AIM: We provide a comprehensive study of population structures based on surname and dialect variability and evaluate their relationships with genetic diversity in Trentino. SUBJECTS AND METHODS: Surname data were collected for 363 parishes, linguistic data for 57 dialects and genetic data for different sets of molecular markers (Y-chromosome, mtDNA, autosomal) in 10 populations. Analyses relied on different multivariate methods and correlation tests. RESULTS: Besides the expected isolation-by-distance-like patterns (with few local exceptions, likely related to sociocultural instances), we detected a significant and geography-independent association between dialects and surnames. As for molecular markers, only Y-chromosomal STRs seem to be associated with the dialects, although no significant result was obtained. No evidence for correlation between molecular markers and surnames was observed. CONCLUSION: Surnames act as cultural markers as do other words, although in this context they cannot be used as reliable proxies for genetic variability at a local scale.

The impact of tocilizumab on respiratory support states transition and clinical outcomes in COVID-19 patients. A Markov model multi-state study.

BACKGROUND: The benefit of tocilizumab on mortality and time to recovery in people with severe COVID pneumonia may depend on appropriate timing. The objective was to estimate the impact of tocilizumab administration on switching respiratory support states, mortality and time to recovery. METHODS: In an observational study, a continuous-time Markov multi-state model was used to describe the sequence of respiratory support states including: no respiratory support (NRS), oxygen therapy (OT), non-invasive ventilation (NIV) or invasive mechanical ventilation (IMV), OT in recovery, NRS in recovery. RESULTS: Two hundred seventy-one consecutive adult patients were included in the analyses contributing to 695 transitions across states. The prevalence of patients in each respiratory support state was estimated with stack probability plots, comparing people treated with and without tocilizumab since the beginning of the OT state. A positive effect of tocilizumab on the probability of moving from the invasive and non-invasive mechanical NIV/IMV state to the OT in recovery state (HR = 2.6, 95% CI = 1.2-5.2) was observed. Furthermore, a reduced risk of death was observed in patients in NIV/IMV (HR = 0.3, 95% CI = 0.1-0.7) or in OT (HR = 0.1, 95% CI = 0.0-0.8) treated with tocilizumab. CONCLUSION: To conclude, we were able to show the positive impact of tocilizumab used in different disease stages depicted by respiratory support states. The use of the multi-state Markov model allowed to harmonize the heterogeneous mortality and recovery endpoints and summarize results with stack probability plots. This approach could inform randomized clinical trials regarding tocilizumab, support disease management and hospital decision making.

Relative Validity of an Italian EPIC Food Frequency Questionnaire for Dietary Factors in Children and Adolescents. A Rizzoli Orthopedic Institute Study.

Dietary factors play a major role in the development of non-communicable diseases, however little is known regarding the impact of nutrition on rare diseases like sarcomas. This Rizzoli Orthopedic Institute study aimed to evaluate the relative validity of a Food Frequency Questionnaire (FFQ) to measure the consumption of foods in comparison with a 3-days diary diet in a healthy Italian student population aged between 12 and 17 years. An extended version (including food groups for children) of the semi-quantitative FFQ used in the European Prospective Investigation into Cancer and Nutrition (EPIC) was administered. The validity of the FFQ was assessed by comparing the intakes from the FFQ against the 3-day diary method. 254 Italian subjects were included in the analyses: 128 females; 126 males; 116 from High Secondary School (14-17 years); 138 from Low Secondary School (12-13 years). Mean and median intakes are overall higher in the FFQs than in the food diaries. Spearman correlations adjusted for within-person variability were highest for legumes, vegetables and coffee/tea (>0.5), followed by potatoes, meat, fruits, breakfast cereals, biscuits and candies, and milk/yoghurts (>0.4). Moderate correlations were found for alcoholic drinks, soft drinks, juices, and grains (>0.3). For some food groups, such as fish, potatoes, and bread, correlations tend to become higher when stratifying the analyses for age group. These results demonstrate that the adapted EPIC COS FFQ validated in Italian adults is also appropriate and well understood by Italian children and adolescents.

Mental Health Disorders and Summer Temperature-Related Mortality: A Case Crossover Study.

Identifying the most vulnerable subjects is crucial for the effectiveness of health interventions aimed at limiting the adverse consequences of high temperatures. We conducted a case crossover study aimed at assessing whether suffering from mental health disorders modifies the effect of high temperatures on mortality. We included all deaths occurred in the area of Bologna Local Health Trust during the summers 2004-2017. Subjects with mental disorders were identified by using the local Mental Health Registry. A conditional logistic model was applied, and a z-test was used to study the effect modification. Several models were estimated stratifying by subjects' characteristics. For every 1 °C above 24 °C, mortality among people without mental disorders increased by 1.9% (95% CI 1.0-2.6, p < 0.0001), while among mental health service users, mortality increased by 5.5% (95% CI 2.4-8.6, p < 0.0001) (z-test equal to p = 0.0259). The effect modification varied according to gender, residency and cause of death. The highest probability of dying due to an increase in temperature was registered in patients with depression and cognitive decline. In order to reduce the effects of high temperatures on mortality, health intervention strategies should include mental health patients among the most vulnerable subjects taking account of their demographic and clinical characteristics.

Colorectal cancer screening: Assessment of CEACAM6, LGALS4, TSPAN8 and COL1A2 as blood markers in faecal immunochemical test negative subjects.

Prevention is essential to reduce Colorectal Cancer (CRC) mortality. We previously reported a panel of four genes: CEACAM6, LGALS4, TSPAN8, COL1A2 (CELTiC) able to discriminate patients with CRC. Here, we assessed the CELTiC panel by quantitative polymerase chain reaction, in the blood of 174 healthy subjects, who resulted negative to the faecal immunochemical test (FITN). Using non-parametric statistic and multinomial logistic models, the FITN were compared to previously analysed subjects: 36 false positive FIT (NFIT), who were negative at colonoscopy, 36 patients with low risk lesions (LR) and 92 patients with high risk lesions or CRC (HR/CRC). FITN showed a significantly lower expression of the four genes when compared to HR/CRC. Moreover, FITN showed a significantly lower expression of TSPAN8 and COL1A2 compared to NFIT and LR patients. The multinomial logistic model confirmed that TSPAN8 alone specifically discriminated FITN from NFIT, LR and HR/CRC, while LGALS4 was able to differentiate FITN from false positive FIT. Finally, ROC curves analysis of the comparisons between FITN and HR/CRC, LR or NFIT reported AUC greater than 0.87, with a sensitivity and specificity of 83% and 76%, respectively. The CELTiC panel was confirmed a useful tool to identify CRC patients and to discriminate false FIT positive subjects.

Pre-operative management of Pleomorphic and florid lobular carcinoma in situ of the breast: Report of a large multi-institutional series and review of the literature.

BACKGROUND: Pleomorphic and Florid Lobular carcinoma in situ (P/F LCIS) are rare variants of LCIS, the exact nature of which is still debated. AIM: To collect a large series of P/F LCIS diagnosed on preoperative biopsies and evaluate their association with invasive carcinoma and high grade duct carcinoma in situ (DCIS). Data obtained were compared with those reported in the literature. METHODS: A multi-institutional series of P/F LCIS was retrieved. All cases were diagnosed on pre-operative biopsies, which was followed by an open surgical excision. Data on post-operative histopathology were available. A literature review was performed. RESULTS: A total of 117 cases were collected; invasive carcinoma and/or DCIS was present in 78/117 cases (66.7%). Seventy cases of P/F LCIS were pure on biopsy and 31 of these showed pathological upgrade in post-surgical specimens. Pre-operative biopsy accuracy was 47/78 (60.3%); pre-operative biopsy underestimation of cancer was 31/78 (39,7.%). In the literature review papers, invasive carcinoma or DCIS was associated with 274 of 418 (65.5%) cases of P/F LCIS. Pre-operative biopsy accuracy was 66% (181/274) whereas pre-operative biopsy underestimation of cancer was 33.9% (93/274). CONCLUSIONS: The data presented here indicate that P/F LCIS is frequently associated with invasive carcinoma or high grade DCIS and that pre-operative biopsy is associated with an underestimation of malignancy. Open surgery is indicated when P/F LCIS is diagnosed pre-operatively.

The Ramazzini Institute 13-week pilot study glyphosate-based herbicides administered at human-equivalent dose to Sprague Dawley rats: effects on development and endocrine system.

BACKGROUND: Glyphosate-based herbicides (GBHs) are broad-spectrum herbicides that act on the shikimate pathway in bacteria, fungi, and plants. The possible effects of GBHs on human health are the subject of an intense public debate for both its potential carcinogenic and non-carcinogenic effects, including potential effects on the endocrine system The present pilot study examine whether exposure to GBHs at the dose of glyphosate considered to be "safe" (the US Acceptable Daily Intake - ADI - of 1.75 mg/kg bw/day), starting from in utero life, affect the development and endocrine system across different life stages in Sprague Dawley (SD) rats. METHODS: Glyphosate alone and Roundup Bioflow, a commercial brand of GBHs, were administered in drinking water at 1.75 mg/kg bw/day to F0 dams starting from the gestational day (GD) 6 (in utero) up to postnatal day (PND) 120. After weaning, offspring were randomly distributed in two cohorts: 8 M + 8F/group animals belonging to the 6-week cohort were sacrificed after puberty at PND 73 ± 2; 10 M + 10F/group animals belonging to the 13-week cohort were sacrificed at adulthood at PND 125 ± 2. Effects of glyphosate or Roundup exposure were assessed on developmental landmarks and sexual characteristics of pups. RESULTS: In pups, anogenital distance (AGD) at PND 4 was statistically significantly increased both in Roundup-treated males and females and in glyphosate-treated males. Age at first estrous (FE) was significantly delayed in the Roundup-exposed group and serum testosterone concentration significantly increased in Roundup-treated female offspring from the 13-week cohort compared to control animals. A statistically significant increase in plasma TSH concentration was observed in glyphosate-treated males compared with control animals as well as a statistically significant decrease in DHT and increase in BDNF in Roundup-treated males. Hormonal status imbalances were more pronounced in Roundup-treated rats after prolonged exposure. CONCLUSIONS: The present pilot study demonstrate that GBHs exposure, from prenatal period to adulthood, induced endocrine effects and altered reproductive developmental parameters in male and female SD rats. In particular, it was associated with androgen-like effects, including a statistically significant increase of AGDs in both males and females, delay of FE and increased testosterone in female.

Predicting return to work after acute myocardial infarction: Socio-occupational factors overcome clinical conditions.

OBJECTIVES: Return to work after acute myocardial infarction (AMI), a leading cause of death globally, is a multidimensional process influenced by clinical, psychological, social and occupational factors, the single impact of which, however, is still not well defined. The objective of this study was to investigate these 4 factors on return to work (RTW) within 365 days after AMI in a homogeneous cohort of patients who had undergone an urgent coronary angioplasty. PARTICIPANTS: We studied 102 patients, in employment at the time of AMI (88.24% of men), admitted to the Department of Cardiology of the University-Hospital of Ferrara between March 2015 to December 2016. Demographical and clinical characteristics were obtained from the cardiological records. After completing an interview on social and occupational variables and the Hospital Anxiety and Depression (HADS) questionnaire, patients underwent exercise capacity measurement and spirometry. RESULTS: Of the 102 patients, only 12 (12.76%) held a university degree, 68.63% were employees and 31.37% self-employed. The median number of sick-leave days was 44 (IQR 33-88). At day 30, 78.5% of all subjects had not returned to work, at day 60, 40.8% and at day 365 only 7.3% had not resumed working. At univariate analyses, educational degree (p = 0.026), self-employment status (p = 0.0005), white collar professional category (p = 0.020) and HADS depression score were significant for earlier return to work. The multivariate analysis confirms that having a university degree, being self-employed and presenting a lower value of HADS depression score increase the probability of a quicker return to work. CONCLUSIONS: These findings suggest that the strongest predictors of returning to work within 1 year after discharge for an acute myocardial infarction are related more to socio-occupational than to clinical parameters.

The Ramazzini Institute 13-week study on glyphosate-based herbicides at human-equivalent dose in Sprague Dawley rats: study design and first in-life endpoints evaluation.

BACKGROUND: Glyphosate-based herbicides (GBHs) are the most widely used pesticides worldwide, and glyphosate is the active ingredient of such herbicides, including the formulation known as Roundup. The massive and increasing use of GBHs results in not only the global burden of occupational exposures, but also increased exposure to the general population. The current pilot study represents the first phase of a long-term investigation of GBHs that we are conducting over the next 5 years. In this paper, we present the study design, the first evaluation of in vivo parameters and the determination of glyphosate and its major metabolite aminomethylphosphonic acid (AMPA) in urine. METHODS: We exposed Sprague-Dawley (SD) rats orally via drinking water to a dose of glyphosate equivalent to the United States Acceptable Daily Intake (US ADI) of 1.75 mg/kg bw/day, defined as the chronic Reference Dose (cRfD) determined by the US EPA, starting from prenatal life, i.e. gestational day (GD) 6 of their mothers. One cohort was continuously dosed until sexual maturity (6-week cohort) and another cohort was continuously dosed until adulthood (13-week cohort). Here we present data on general toxicity and urinary concentrations of glyphosate and its major metabolite AMPA. RESULTS: Survival, body weight, food and water consumption of the animals were not affected by the treatment with either glyphosate or Roundup. The concentration of both glyphosate and AMPA detected in the urine of SD rats treated with glyphosate were comparable to that observed in animals treated with Roundup, with an increase in relation to the duration of treatment. The majority of glyphosate was excreted unchanged. Urinary levels of the parent compound, glyphosate, were around 100-fold higher than the level of its metabolite, AMPA. CONCLUSIONS: Glyphosate concentrations in urine showed that most part of the administered dose was excreted as unchanged parent compound upon glyphosate and Roundup exposure, with an increasing pattern of glyphosate excreted in urine in relation to the duration of treatment. The adjuvants and the other substances present in Roundup did not seem to exert a major effect on the absorption and excretion of glyphosate. Our results demonstrate that urinary glyphosate is a more relevant marker of exposure than AMPA in the rodent model.

LGALS4, CEACAM6, TSPAN8, and COL1A2: Blood Markers for Colorectal Cancer-Validation in a Cohort of Subjects With Positive Fecal Immunochemical Test Result.

BACKGROUND: A noninvasive blood test for the early detection of colorectal cancer (CRC) is highly required. We evaluated a panel of 4 mRNAs as putative markers of CRC. MATERIALS AND METHODS: We tested LGALS4, CEACAM6, TSPAN8, and COL1A2, referred to as the CELTiC panel, using quantitative reverse transcription polymerase chain reaction, on subjects with positive fecal immunochemical test (FIT) results and undergoing colonoscopy. Using a nonparametric test and multinomial logistic model, FIT-positive subjects were compared with CRC patients and healthy individuals. RESULTS: All the genes of the CELTiC panel displayed statistically significant differences between the healthy subjects (n = 67), both low-risk (n = 36) and high-risk/CRC (n = 92) subjects, and those in the negative-colonoscopy, FIT-positive group (n = 36). The multinomial logistic model revealed LGALS4 was the most powerful marker discriminating the 4 groups. When assessing the diagnostic values by analysis of the areas under the receiver operating characteristic curves (AUCs), the CELTiC panel reached an AUC of 0.91 (sensitivity, 79%; specificity, 94%) comparing normal subjects to low-risk subjects, and 0.88 (sensitivity, 75%; specificity, 87%) comparing normal and high-risk/CRC subjects. The comparison between the normal subjects and the negative-colonoscopy, FIT-positive group revealed an AUC of 0.93 (sensitivity, 82%; specificity, 97%). CONCLUSION: The CELTiC panel could represent a useful tool for discriminating subjects with positive FIT findings and for the early detection of precancerous adenomatous lesions and CRC.

Unbiased pro-thrombotic features at diagnosis in 977 thrombocythemic patients with Philadelphia-negative chronic myeloproliferative neoplasms.

In patients with Philadelphia-negative chronic myeloproliferative neoplasms (MPNs), the anti-thrombotic and/or cytoreductive treatment in the follow-up may affect the evaluation of the pro-thrombotic weight of the clinical and biological characteristics at diagnosis. In order to avoid this potential confounding effect, we investigated the relationship between prior thrombosis (PrTh: thrombosis occurred before diagnosis and before treatment) and the characteristics at diagnosis in 977 thrombocythemic patients with MPN, reclassified according to the WHO 2008 criteria. PrTh occurred in 194 (19.9%) patients, with similar rates in the different MPNs. In multivariate analysis, PrTh rate was significantly related to minor thrombocytosis (platelets ≤700×10(9)/L), leukocytosis (leukocytes >10×10(9)/L), higher hematocrit (HCT >45%), JAK2 V617F mutation, older age, and cardiovascular risk factors (CVRFs). The highest PrTh rate (33.9%) was associated with the coexistence of minor thrombocytosis and leukocytosis. Of note, the inverse relationship between PrTh rate and platelet count is consistent with the hemostatic paradox of thrombocytosis. In conclusion, this analysis in MPN patients disclosed the unbiased characteristics at diagnosis with a pro-thrombotic effect. Moreover, it suggests that the optimal control of blood cells counts, and CVRFs might be of utmost importance in the prevention of thrombosis during the follow-up.

Clinical outcomes following stent placement in refractory benign esophageal stricture: a systematic review and meta-analysis.

BACKGROUND AND AIMS: The management of refractory benign esophageal strictures (RBESs) is challenging. Stent placement has been proposed as a possible rescue strategy. We performed a systematic review and meta-analysis to examine the efficacy of this strategy in the long-term resolution of dysphagia. METHODS: PubMed, SCOPUS, and Google Scholar were searched (up to January 2015). Studies recruiting adults with RBES treated with stent placement were eligible. The success, adverse event, and migration rates were pooled by means of a random-effect model to obtain odds with a 95 % confidence interval (CI). RESULTS: Eighteen studies (444 patients) were eligible for inclusion. The pooled clinical success rate was 40.5 % (95 %CI 31.5 % - 49.5 %), yielding odds of 0.68 (95 %CI 0.46 - 0.98) with high heterogeneity (I(2) = 65.0 %). The meta-regression analysis showed stricture etiology as the only influencing factor. Treatment with self-expanding plastic (SEPSs) and metal stents (SEMSs) did not result in significantly higher success rates than treatment with biodegradable stents (BDSs) (46.2 % vs. 40.1 % vs. 32.9 %, respectively). The migration rate was 28.6 % (95 %CI 21.9 % - 37.1 %), yielding odds of 0.40 (95 %CI 0.28 - 0.59), with migration rates for SEPSs and SEMSs reported as being not significantly higher than BDSs (33.3 % vs. 31.5 % vs. 15.3 %, respectively). The adverse event rate was 20.6 % (95 %CI 15.3 % - 28.1 %), yielding odds of 0.26 (95 %CI 0.18 - 0.39) with no significant difference between stent types (19.4 % vs. 21.9 % vs. 21.9 %, respectively). CONCLUSIONS: Stent placement in patients with RBES is effective in about 40 % of cases. Further studies should investigate whether the clinical success rate varies according to the stricture etiology.(PROSPERO registration number: CRD42015019017.).

Arm measurements as determinants of further survival in centenarians.

Being indicators of nutritional and functional status, anthropometric characters may have great prognostic significance for survival at extremely advanced ages. For ethical and practical reasons however it is advisable to use characters such as arm measurements easily measurable even in bedridden subjects. This study compares the influence of some upper arm measurements and of Body Mass Index (BMI) on survival of the 77 subjects aged 98 years and over (98+) recruited within the MALVA project, one of the first Italian population-based studies on extremely old people. Adopting methods for multiple imputation of missing values, Gompertz regression models adjusted for gender and age were estimated for each anthropometric character or combination of characters, i.e. BMI; mid-upper arm circumference (MUAC)+elbow breadth (EB)+triceps skinfold thickness (TSF); corrected arm muscle area (CAMA). Being underweight and having a low CAMA and a low MUAC/high EB were positively associated with an increased risk of death, while no significant association was found with the condition of being overweight/obese and the triceps skinfold thickness. When anthropometric variables were included in regression models along with covariates relating to nutritional and functional status, BMI and MUAC, but not CAMA, emerged as protective factors. It is suggested that MUAC can be recommended in evaluating the health status of extremely old people and that measuring EB may help to estimate the non-boney component of the arm.

Coronary revascularisation in stable patients after an acute coronary syndrome: a propensity analysis of early invasive versus conservative management in a register-based cohort study.

OBJECTIVES: To compare the effectiveness of in-hospital medical therapy versus coronary revascularisation added to medical therapy in patients who stabilised after an acute coronary syndrome (ACS). DESIGN: Propensity score-matched cohort study from the database of the Tampere ACS registry. SETTING: A single academic hospital in Finland. PARTICIPANTS: 1149 patients with a recent ACS, but no serious coexisting conditions: recurrent ischaemic episodes despite adequate medical therapy, haemodynamic instability, overt congestive heart failure and serious ventricular arrhythmias. PRIMARY AND SECONDARY OUTCOME MEASURES: The composite endpoint of major acute cardiovascular events (MACEs): unstable angina requiring rehospitalisation, stroke, myocardial infarction and all-cause mortality, at 6-month follow-up. RESULTS: Compared with standard medical treatment, revascularisation was associated with a lower rate of MACEs at 6 months in patients of the first quintile (HR 0.81; 95% CI 0.66 to 0.99), but a higher rate of MACEs in the fifth quintile (HR 4.74, CI 1.36 to 16.49; p=0.014). There were no significant differences in the rates of MACEs in the remaining three quintiles. Patients of the first quintile were the oldest (79.7±8.3 years) and had a more significant (p<0.001) history of prior myocardial infarction (37%) and poor renal function (creatine, µmol/l: 114.9±70.7). They also showed the highest C reactive protein (7.3±9.5 mg/l) levels. CONCLUSIONS: Our findings suggest that in-hospital coronary revascularisation did not lead to any advantage with signal of possible harm in the great majority of patients who stabilised after an ACS. An early invasive management strategy may be best reserved for elderly patients having high-risk clinical features and biochemical evidence of a strong inflammatory activity.

Attachment style and immunity: a 1-year longitudinal study.

Previous cross-sectional studies suggested an association between attachment-related avoidance and altered immune function. We aimed at testing this hypothesis with longitudinal data. A random sample of 65 female nurses provided a blood sample and completed measures of perceived stress, social support, alexithymia, and attachment style. Immune assays included lymphocyte proliferative response (LPR) to Phytohemagglutinin and NK cell cytotoxicity (NKCC). State measures (perceived stress and support) and immune measures were collected again after 4, 8, and 12 months. Linear mixed effects models were used to examine the relationship between attachment and immunity. While low to moderate levels of attachment-related avoidance were not associated with NKCC, there was a significant negative association (beta -.35; p=.005) between high levels of avoidance and NKCC. No association was observed between NKCC and attachment-related anxiety, and between LPR and both attachment dimensions. While our findings should be interpreted with caution due to study limitations such as the relatively small sample size and the inclusion of only female participants, they corroborate the notion that attachment is linked to physiology and health.