Validity and reliability of the Structured Clinical Interview for Depersonalization-Derealization Spectrum (SCI-DER).

This study evaluates the validity and reliability of a new instrument developed to assess symptoms of depresonalization: the Structured Clinical Interview for the Depersonalization-Derealization Spectrum (SCI-DER). The instrument is based on a spectrum model that emphasizes soft-signs, sub-threshold syndromes as well as clinical and subsyndromal manifestations. Items of the interview include, in addition to DSM-IV criteria for depersonalization, a number of features derived from clinical experience and from a review of phenomenological descriptions. Study participants included 258 consecutive patients with mood and anxiety disorders, 16.7% bipolar I disorder, 18.6% bipolar II disorder, 32.9% major depression, 22.1% panic disorder, 4.7% obsessive compulsive disorder, and 1.5% generalized anxiety disorder; 2.7% patients were also diagnosed with depersonalization disorder. A comparison group of 42 unselected controls was enrolled at the same site. The SCI-DER showed excellent reliability and good concurrent validity with the Dissociative Experiences Scale. It significantly discriminated subjects with any diagnosis of mood and anxiety disorders from controls and subjects with depersonalization disorder from controls. The hypothesized structure of the instrument was confirmed empirically

Extracting Patient-Centered Outcomes from Clinical Notes in Electronic Health Records: Assessment of Urinary Incontinence After Radical Prostatectomy

Objective: To assess documentation of urinary incontinence (UI) in prostatectomy patients using unstructured clinical notes from Electronic Health Records (EHRs). Methods: We developed a weakly-supervised natural language processing tool to extract assessments, as recorded in unstructured text notes, of UI before and after radical prostatectomy in a single academic practice across multiple clinicians. Validation was carried out using a subset of patients who completed EPIC-26 surveys before and after surgery. The prevalence of UI as assessed by EHR and EPIC-26 was compared using repeated-measures ANOVA. The agreement of reported UI between EHR and EPIC-26 was evaluated using Cohen\u2019s Kappa coefficient. Results: A total of 4870 patients and 716 surveys were included. Preoperative prevalence of UI was 12.7 percent. Postoperative prevalence was 71.8 percent at 3 months, 50.2 percent at 6 months and 34.4 and 41.8 at 12 and 24 months, respectively. Similar rates were recorded by physicians in the EHR, particularly for early follow-up. For all time points, the agreement between EPIC-26 and the EHR was moderate (all p < 0.001) and ranged from 86.7 percent agreement at baseline (Kappa = 0.48) to 76.4 percent agreement at 24 months postoperative (Kappa = 0.047). Conclusions: We have developed a tool to assess documentation of UI after prostatectomy using EHR clinical notes. Our results suggest such a tool can facilitate unbiased measurement of important PCOs using real-word data, which are routinely recorded in EHR unstructured clinician notes. Integrating PCO information into clinical decision support can help guide shared treatment decisions and promote patient-valued care

Renal involvement in HCV related cirrhosis evidenced as glomerular and tubular derangement

Introduction and Aims: The relation between HCV infection and glomerular damage is well recognized, with evidences of negative impact on renal function. HCV replication in renal tubular cells on kidney biopsies has been reported but very limited data are available on HCV-mediated tubular damage. The aim of the study was to assess the presence of renal involvement (RI), glomerular or tubular, in patients with HCV cirrhosis. Methods: 98 patients with HCV cirrhosis Child Pugh-A were consecutively enrolled. Glomerular filtration rate (eGFR) was estimated with CKD-EPI 2009 equation. Urinary albumin/creatinine (ACR) and alpha1microglobulin/creatinine (a1MCR) ratios were calculated. Glomerular involvement was defined based on ACR>20μg/mg, tubular involvement based on a1MCR>14μg/mg plus fractional sodium excretion (FeNa)>1%. Urine concentration of Liver-type Fatty Acid-Binding Protein (L-FABP) and Kidney injury molecule-1 (KIM-1) were examined in morning midstream urine samples (ELISA) and the values normalized to urine creatinine concentration as expression of tubular derangement. Results: eGFR was ≥60 mL/min/1.73 m2 in 92 patients (93.8%) and between 45-59 mL/min/1.73 m2 in 6 patients (6.1%). Glomerular involvement was found in 19 patients (19.4%), tubular involvement in 31 patients (31.6%) and these co-occurred in 10 patients ( p=0.034). Patients with glomerular or tubular involvement, or both, considered as patients with RI, showed significantly lower eGFR values ( p=0.005) (Tab 1). A ROC curve was drafted and a cut point of 90 ml/min predicted RI (AUC: 0.700; sensitivity 63%, specificity 75%). Patients with RI were older, had higher ACR and a1MCR levels and exhibited a higher KDIGO stage (Tab 1). No association was found between RI and: HCV-RNA levels, liver stiffness and liver function tests. L-FABP and KIM-1 levels were significantly higher in patients with RI. Conclusions: Tubular and/or glomerular involvement is quite frequent in HCV cirrhotic patients, despite a normal eGFR. The evidence of tubular involvement suggests an alternative localization of HCV as renal disease

Gauge-invariant screening masses and static quark free energies in Nf=2+1 QCD at nonzero baryon density

We discuss the extension of gauge-invariant electric and magnetic screening masses in the quark-gluon plasma to the case of a finite baryon density, defining them in terms of a matrix of Polyakov loop correlators. We present lattice results for Nf=2+1 QCD with physical quark masses, obtained using the imaginary chemical potential approach, which indicate that the screening masses increase as a function of μB. A separate analysis is carried out for the theoretically interesting case μB/T=3iπ, where charge conjugation is not explicitly broken and the usual definition of the screening masses can be used for temperatures below the Roberge-Weiss transition. Finally, we investigate the dependence of the static quark free energy on the baryon chemical potential, showing that it is a decreasing function of μB, which displays a peculiar behavior as the pseudocritical transition temperature at μB=0 is approached

Secondary prevention medical therapy and outcomes in patients with myocardial infarction with non-obstructive coronary artery disease

Background: Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a heterogeneous entity with relevant long-term major cardiovascular events. Several trials have demonstrated that dual antiplatelet therapy (DAPT), b-blocker, renin-angiotensin-aldosterone system (RAAS) inhibitor and statin therapy improve the prognosis in patients with obstructive myocardial infarction (ob-MI). However, evidence on the best medical therapy for secondary prevention in MINOCA patients is lacking. Purpose: To investigate the effects of secondary prevention treatments at discharge on mid-term outcomes in MINOCA. Methods: Patients with acute myocardial infarction (MI) undergoing early coronary angiography between 2016 and 2018 were extracted from a clinical database. The diagnosis of MINOCA was made according to 2016 ESC MINOCA Position Paper criteria. Second-level diagnostic work-up including cardiac magnetic resonance was performed to exclude non-ischemic troponin elevation cause. The relationship between treatments and outcomes was evaluated by using Kaplan-Meier survival analysis and Cox regression models. All confirmed MINOCA were followed in our outpatient clinics. The primary endpoints were all-cause mortality, re-hospitalization for MI and a composite outcome including all-cause mortality, hospitalization for MI and ischemic stroke (MACE). Results: Out of 1,141 AMI who underwent coronary angiography, 134 were initially diagnosed as MINOCA. Patients with MINOCA were less likely to receive secondary prevention treatments than patients with obstructive coronary artery disease (CAD) MI (respectively, 42.1% vs 81.8% for DAPT; 75.5% vs 89.6% for b-blockers; 64.7% vs 80.3% for RAAS inhibitor and 63.9% vs 83% for statins). Based on the diagnostic work-up completed during the first month after discharge, a final sample of 88 patients had confirmed MINOCA. During an average follow-up of 19.35 \ub1 10.65 months, all-cause mortality occurred in 11 (12.5%) patients, recurrence of MI in 4 (4.5%), and MACE in 15 (17.0%) patients. Patients treated with RAAS inhibitors and statins had a significantly longer survival. On the contrary, no increase in survival was found in patients treated with b-blockers or DAPT. Cox multivariable analysis, including all secondary prevention drugs, showed that only RAAS inhibitors were associated with reduced all cause-mortality and MACE. Conclusion: This prospective study suggests that RAAS inhibitor therapy provides midterm beneficial effects on outcomes in MINOCA patients; in contrast, dual antiplatelet, b-blocker and statin therapy had no effects on mortality and MACE. These results should be considered preliminary and warrant confirmation from larger studies

Secondary prevention medical therapy and outcomes in patients with myocardial infarction with non-obstructive coronary artery disease

Background: Myocardial infarction with non-obstructive coronary arteries (MINOCA) is a heterogeneous entity with relevant long-term major cardiovascular events. Several trials have demonstrated that dual antiplatelet therapy (DAPT), b-blocker, renin-angiotensin-aldosterone system (RAAS) inhibitor and statin therapy improve the prognosis in patients with obstructive myocardial infarction (ob-MI). However, evidence on the best medical therapy for secondary prevention in MINOCA patients is lacking. Purpose: To investigate the effects of secondary prevention treatments at discharge on mid-term outcomes in MINOCA. Methods: Patients with acute myocardial infarction (MI) undergoing early coronary angiography between 2016 and 2018 were extracted from a clinical database. The diagnosis of MINOCA was made according to 2016 ESC MINOCA Position Paper criteria. Second-level diagnostic work-up including cardiac magnetic resonance was performed to exclude non-ischemic troponin elevation cause. The relationship between treatments and outcomes was evaluated by using Kaplan-Meier survival analysis and Cox regression models. All confirmed MINOCA were followed in our outpatient clinics. The primary endpoints were all-cause mortality, re-hospitalization for MI and a composite outcome including all-cause mortality, hospitalization for MI and ischemic stroke (MACE). Results: Out of 1,141 AMI who underwent coronary angiography, 134 were initially diagnosed as MINOCA. Patients with MINOCA were less likely to receive secondary prevention treatments than patients with obstructive coronary artery disease (CAD) MI (respectively, 42.1% vs 81.8% for DAPT; 75.5% vs 89.6% for b-blockers; 64.7% vs 80.3% for RAAS inhibitor and 63.9% vs 83% for statins). Based on the diagnostic work-up completed during the first month after discharge, a final sample of 88 patients had confirmed MINOCA. During an average follow-up of 19.35 ± 10.65 months, all-cause mortality occurred in 11 (12.5%) patients, recurrence of MI in 4 (4.5%), and MACE in 15 (17.0%) patients. Patients treated with RAAS inhibitors and statins had a significantly longer survival. On the contrary, no increase in survival was found in patients treated with b-blockers or DAPT. Cox multivariable analysis, including all secondary prevention drugs, showed that only RAAS inhibitors were associated with reduced all cause-mortality and MACE. Conclusion: This prospective study suggests that RAAS inhibitor therapy provides midterm beneficial effects on outcomes in MINOCA patients; in contrast, dual antiplatelet, b-blocker and statin therapy had no effects on mortality and MACE. These results should be considered preliminary and warrant confirmation from larger studies

Complex Alpine Extrication: Case Report of Mountain and Speleological Rescue Cooperation

AbstractMountain sporting activities are an increasingly popular practice that exposes mountaineers to a high risk of adverse events. This report describes a unique case of recovery in an austere environment that involved explosives. In June 2012, a 52-year-old man ascended a cliff tower in the Eastern Alps, Italy. A landslide occurred, and a boulder crushed the climber against a large stone located farther down the cliff, causing compression of the lower limbs and the pelvis with consequent severe musculoskeletal trauma. The National Alpine and Cave Rescue Unit (NACRU) arrived and proceeded with stabilization of the injured climber, which took 6 hours and involved a difficult extrication supported by the Cave Rescue division of NACRU. Unfortunately, during transport to the trauma center of Borgo Trento, Verona, the patient exhibited signs of progressive traumatic shock because of crush syndrome, hypovolemia, and acidosis, which led to cardiac arrest and death. Based on an extensive literature review, this report was determined to be the only one of a mountain rescue using explosives for the extrication of a victim in the Northeast Italian Alps. This case describes how a rescue in austere environments can represent a high-risk situation, and it shows how improvisation and cooperation between rescue teams are crucial for a successful recovery

Phosphorylated c-Src in the nucleus is associated with improved patient outcome in ER-positive breast cancer

Elevated c-Src protein expression has been shown in breast cancer and <i>in vitro</i> evidence suggests a role in endocrine resistance. To investigate whether c-Src is involved in endocrine resistance, we examined the expression of both total and activated c-Src in human breast cancer specimens from a cohort of oestrogen receptor (ER)-positive tamoxifen-treated breast cancer patients. Tissue microarray technology was employed to analyse 262 tumour specimens taken before tamoxifen treatment. Immunohistochemistry using total c-Src and activated c-Src antibodies was performed. Kaplan–Meier survival curves were constructed and log-rank test were performed. High level of nuclear activated Src was significantly associated with improved overall survival (<i>P</i>=0.047) and lower recurrence rates on tamoxifen (<i>P</i>=0.02). Improved patient outcome was only seen with activated Src in the nucleus. Nuclear activated Src expression was significantly associated with node-negative disease and a lower NPI (<i>P</i><0.05). On subgroup analysis, only ER-positive/progesterone receptor (PgR)-positive tumours were associated with improved survival (<i>P</i>=0.004). This shows that c-Src activity is increased in breast cancer and that activated Src within the nucleus of ER-positive tumours predicts an improved outcome. In ER/PgR-positive disease, activated Src kinase does not appear to be involved in <i>de novo</i> endocrine resistance. Further study is required in ER-negative breast cancer as this may represent a cohort in which it is associated with poor outcome

Tumour-derived alkaline phosphatase regulates tumour growth, epithelial plasticity and disease-free survival in metastatic prostate cancer

BACKGROUND: Recent evidence suggests that bone-related parameters are the main prognostic factors for overall survival in advanced prostate cancer (PCa), with elevated circulating levels of alkaline phosphatase (ALP) thought to reflect the dysregulated bone formation accompanying distant metastases. We have identified that PCa cells express ALPL, the gene that encodes for tissue nonspecific ALP, and hypothesised that tumour-derived ALPL may contribute to disease progression. METHODS: Functional effects of ALPL inhibition were investigated in metastatic PCa cell lines. ALPL gene expression was analysed from published PCa data sets, and correlated with disease-free survival and metastasis. RESULTS: ALPL expression was increased in PCa cells from metastatic sites. A reduction in tumour-derived ALPL expression or ALP activity increased cell death, mesenchymal-to-epithelial transition and reduced migration. Alkaline phosphatase activity was decreased by the EMT repressor Snail. In men with PCa, tumour-derived ALPL correlated with EMT markers, and high ALPL expression was associated with a significant reduction in disease-free survival. CONCLUSIONS: Our studies reveal the function of tumour-derived ALPL in regulating cell death and epithelial plasticity, and demonstrate a strong association between ALPL expression in PCa cells and metastasis or disease-free survival, thus identifying tumour-derived ALPL as a major contributor to the pathogenesis of PCa progression.British Journal of Cancer advance online publication, 22 December 2016; doi:10.1038/bjc.2016.402 www.bjcancer.com

New insights into the comorbid conditions of Turner syndrome: results from a long-term monocentric cohort study

Purpose Many questions concerning Turner syndrome (TS) remain unresolved, such as the long-term complications and, therefore, the optimal care setting for adults. The primary aim of this long-term cohort study was to estimate the incidence of comorbid conditions along the life course. Methods A total of 160 Italian patients with TS diagnosed from 1967 to 2010 were regularly and structurally monitored from the diagnosis to December 2019 at the University Hospital of Bologna using a structured multidisciplinary monitoring protocol. Results The study cohort was followed up for a median of 27 years (IQR 12-42). Autoimmune diseases were the comorbid condition with the highest incidence (61.2%), followed by osteoporosis and hypertension (23.8%), type 2 diabetes (16.2%) and tumours (15.1%). Median age of onset ranged from 22 years for autoimmune diseases to 39 years for type 2 diabetes. Malignant tumours were the most prominent type of neoplasm, with a cumulative incidence of 11.9%. Papillary thyroid carcinoma was the most common form of cancer, followed by skin cancer and cancer of the central nervous system. Only one major cardiovascular event (acute aortic dissection) was observed during follow-up. No cases of ischaemic heart disease, heart failure, stroke or death were recorded. Conclusions This cohort study confirms the need for continuous, structured and multidisciplinary lifelong monitoring of TS, thus ensuring the early diagnosis of important comorbid conditions, including cancer, and their appropriate and timely treatment. In addition, these data highlight the need for the increased surveillance of specific types of cancer in TS, including thyroid carcinoma