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Objectives Acute gastrointestinal graft-versus-host disease (GI-aGVHD) is a severe complication of allogeneic hematopoietic stem cell transplantation (HSCT). Diagnosis relies on clinical, endoscopic, and pathological investigations. Our purpose is to assess the value of magnetic resonance imaging (MRI) in the diagnosis, staging, and prediction of GI-aGVHD-related mortality. Methods Twenty-one hematological patients who underwent MRI for clinical suspicion of acute GI-GVHD were retrospectively selected. Three independent radiologists, blinded to the clinical findings, reanalyzed MRI images. The GI tract was evaluated from stomach to rectum by analyzing fifteen MRI signs suggestive of intestinal and peritoneal inflammation. All selected patients underwent colonoscopy with biopsies. Disease severity was determined on the basis of clinical criteria, identifying 4 stages of increasing severity. Disease-related mortality was also assessed. Results The diagnosis of GI-aGVHD was histologically confirmed with biopsy in 13 patients (61.9%). Using 6 major signs (diagnostic score), MRI showed 84.6% sensitivity and 100% specificity in identifying GI-aGVHD (AUC = 0.962; 95% confidence interval 0.891–1). The proximal, middle, and distal ileum were the segments most frequently affected by the disease (84.6%). Using all 15 signs of inflammation (severity score), MRI showed 100% sensitivity and 90% specificity for 1-month related mortality. No correlation with the clinical score was found. Conclusion MRI has proved to be an effective tool for diagnosing and scoring GI-aGVHD, with a high prognostic value. If larger studies will confirm these results, MRI could partly replace endoscopy, thus becoming the primary diagnostic tool for GI-aGVHD, being more complete, less invasive, and more easily repeatable. Key Points • We have developed a new promising MRI diagnostic score for GI-aGVHD with a sensitivity of 84.6% and specificity of 100%; results are to be confirmed by larger multicentric studies. • This MRI diagnostic score is based on the six MRI signs most frequently associated with GI-aGVHD: small-bowel inflammatory involvement, bowel wall stratification on T2-w images, wall stratification on post-contrast T1-w images, ascites, and edema of retroperitoneal fat and declivous soft tissues. • A broader MRI severity score based on 15 MRI signs showed no correlation with clinical staging but high prognostic value (100% sensitivity, 90% specificity for 1-month related mortality); these results also need to be confirmed by larger studies.

Background The multiorgan involvement of heart failure is similar to the spread observed in cancer. We proposed a new score, named HLM, analogous to TNM classification used in oncology. HLM refers to (i) H: heart damage, instead of “T” for tumor; (ii) L: lung involvement, instead of “N” for lymph nodes; (iii) M: systemic multiorgan involvement, instead of “M” for metastasis. Objectives to compare HLM score to NYHA class, ACC/AHA stages and left ventricular ejection fraction (LVEF) classification, to assess the most accurate prognostic tool for HF patients. Methods We performed a multicentric, observational, prospective study of consecutive patients admitted for HF, or at risk for HF. Parameters for heart, lungs and organs’ function were collected. Each patient was classified according to HLM, NYHA, ACC/AHA stages and LVEF classification. Patients were followed up for 12 months. The primary composite endpoint was all-cause death and rehospitalization due to HF. Results We enrolled 1720 patients who completed the 12-month follow-up. As shown by Kaplan Meier curves, HLM was the most accurate score to predict primary endpoint at 12- month. The area under the ROC curve (AUC) was greater for HLM score than NYHA, ACC/AHA stages and LVEF classification, regarding the composite endpoint (HLM=0.645; NYHA=0.580; ACC/AHA=0.589; LVEF=0.572) (Figure 1). HLM score related AUC showed statistically significant differences compared to LVEF (p=0.002), ACC/AHA (p=0.029) and NYHA (p=0.009). Conclusions HLM score has a greater prognostic power compared to other nosologies, in terms of the composite endpoint of all-cause death and rehospitalization due to HF, at 12-month follow-up. Key words: heart failure; HLM score; prognosis; mortality; rehospitalization. Figure 1.

Insomnia is a widespread sleep disorder associated with physical and mental health conditions. Although the heterogeneity of insomnia presentations has been acknowledged, research investigating clinically meaningful insomnia subtypes is still ongoing. This study aimed at exploring insomnia subtypes according to widely-used measures of symptoms severity and sleep quality among Italian university students using a latent profile analysis. Data were collected from 490 students reporting relevant insomnia symptoms through an online cross-sectional survey comprising the Insomnia Severity Index, the Pittsburgh Sleep Quality Index, the 21-item Depression Anxiety Stress Scale, and the Short Form-12. Latent profile analysis identified five insomnia subtypes. The severe insomnia (8.8%) group showed the highest insomnia severity, with diverse complaints concerning sleep quality and daytime functioning. Moderate insomnia with sleep duration complaints (8.4%) and moderate insomnia with medication use (15.9%) subgroups were characterized by middle range insomnia severity, with problems of sleep continuity and sleep medication use, respectively. Subthreshold insomnia with sleep latency complaints (20.4%) and subthreshold insomnia (46.5%) groups showed attenuated insomnia symptoms. Higher psychological complaints and worse quality of life were associated with greater sleep complaints. Overall, these findings highlight the relevance of sleep quality domains in identifying insomnia subtypes and might help optimize insomnia treatments.

Medical education is widely known to be demanding and stressful, with elevated levels of anxiety and depression among medical students. This study aims at examining well-being, perceived stress and quality of life in a sample of Italian first-year medical students in order to investigate the relations between these variables and individual characteristics and behaviours. An anonymous cross-sectional questionnaire was administered to a sample of 407 Italian first-year medical students. Psychological well-being, perceived stress and quality of life were assessed using standardised questionnaires PGWBI, PSS, SF-12. Data were analysed with multivariate statistical methods. Significant differences in PGWBI, PSS and SF-12 scores were found between males and females (with poorer scores for females), between smokers and non-smokers (with poorer scores for smokers) and between students who reported cannabis use in their lifetime and students who did not (with poorer scores for those who smoked cannabis). Logistic regression showed that gender (OR 0.38, 95% CI 0.24–0.61), reported cannabis use (OR 1.82, 95% CI 1.07–3.09) and regular physical exercise (OR 0.54, 95% CI 0.34–0.86) were significant predictors of distress. In summary, this study shows that female medical students and students who reported negative health behaviours and sporadic drug use reported lower psychological well-being and quality of life and higher stress, while positive health behaviours might prevent distress.

Patients with atrial fibrillation (AF) still experience a high mortality rate despite optimal antithrombotic treatment. We aimed to identify clinical phenotypes of patients to stratify mortality risk in AF. Cluster analysis was performed on 5171 AF patients from the nationwide START registry. The risk of all-cause mortality in each cluster was analyzed. We identified four clusters. Cluster 1 was composed of the youngest patients, with low comorbidities; Cluster 2 of patients with low cardiovascular risk factors and high prevalence of cancer; Cluster 3 of men with diabetes and coronary disease and peripheral artery disease; Cluster 4 included the oldest patients, mainly women, with previous cerebrovascular events. During 9857 person-years of observation, 386 deaths (3.92%/year) occurred. Mortality rates increased across clusters: 0.42%/year (cluster 1, reference group), 2.12%/year (cluster 2, adjusted hazard ratio (aHR) 3.306, 95% confidence interval (CI) 1.204–9.077, p = 0.020), 4.41%/year (cluster 3, aHR 6.702, 95%CI 2.433–18.461, p < 0.001), and 8.71%/year (cluster 4, aHR 8.927, 95%CI 3.238–24.605, p < 0.001). We identified four clusters of AF patients with progressive mortality risk. The use of clinical phenotypes may help identify patients at a higher risk of mortality.

Background Patients with atrial fibrillation (AF) experience a high mortality rate despite optimal antithrombotic treatment. Characteristics of AF patients at higher mortality risk have been barely described so far and no risk score has been specifically developed at this aim. Furthermore, a clinical approach based on risk scores present some limits such as to not consider some important risk factors for mortality, and many available scores have poor predictive value. Cluster analysis may play a role in overcoming limitations of risk scores, especially in the case of overlapping risk factors. Purpose To identify of clinical phenotypes by using an unbiased statistical approach, such as the cluster analysis. Methods Cluster analysis was used to identify clinical phenotypes of AF patients associated with all-cause mortality in 5,171 AF patients from the START registry. Clinical variables used for the analysis were age, sex, diabetes, previous cerebrovascular events, previous cardiovascular events, heart failure, peripheral artery disease, use of non-vitamin K oral anticoagulants, cancer, pulmonary disease, smoking habit, previous major bleeding. The risk of all-cause mortality in each cluster was analyzed. Results We identified 4 clusters (Figure 1). Cluster 1 was composed by youngest patients, with obesity and paroxysmal AF; Cluster 2 by patients with low cardiovascular risk factors and high proportion of cancer; Cluster 3 by men with diabetes and coronary and peripheral artery disease, a high proportion of thrombocytopenia, and a high use of aspirin, proton pump inhibitors, and statins; Cluster 4 included the oldest patients, mainly women, with previous cerebrovascular disease, persistent/ permanent AF, heart failure, kidney disease and anemia. In this cluster there was the highest use of digoxin and NOACs. During 9856,84 patient/years of observation, 386 deaths (3.92%/year) occurred. Mortality rates significantly increased across clusters: 0.42%/year (cluster 1, reference group), 2.12%/year (cluster 2, adjusted hazard ratio [aHR] 3.306, 95% confidence interval [CI] 1.204–9.077, p=0.020), 4.41%/year (cluster 3, aHR 6.702, 95% CI 2.433–18.461, p Conclusions We identified different clinical phenotypes of AF patients by cluster analysis which were specifically associated with mortality. This approach may help identify patients at higher risk of mortality. Figure 1 Funding Acknowledgement Type of funding source: None

Background Statins are guidelines recommended in patients with peripheral artery disease (PAD) for the prevention of cardiovascular (CV) events. Comprehensive meta-data on the impact of statins on major adverse limb events (MALE) in PAD patients are lacking. We examined the association of statin use with MALE in patients with PAD. Methods We performed a systematic review (registered at PROSPERO: number CRD42019137111) and metanalysis of studies retrieved from PubMed (via MEDLINE) and Cochrane (CENTRAL) databases addressing the impact of statin on MALE including amputation and graft occlusion/revascularization. Secondary endpoints were all-cause death, composite CV endpoints, CV death, and stroke. Results We included 51 studies with 138,060 PAD patients, of whom 48,459 (35.1%) were treated with statins. The analysis included 2 randomized controlled trials, 20 prospective, and 29 retrospective studies. Overall, 11,396 MALE events, 21,624 deaths, 4,852 composite CV endpoints, 4,609 CV deaths, and 860 strokes were used for the analysis. Statins reduced MALE incidence by 30% (pooled hazard ratio [HR]: 0.702; 95% confidence interval [CI]: 0.605–0.815) and amputations by 35% (HR: 0.654; 95% CI: 0.522–0.819), all-cause mortality by 39% (pooled HR: 0.608, 95% CI: 0.543–0.680), CV death by 41% (HR: 0.594; 95% CI: 0.455–0.777), composite CV endpoints by 34% (pooled HR: 0.662; 95% CI: 0.591–0.741) and ischemic stroke by 28% (pooled HR: 0.718; 95% CI: 0.620–0.831). Conclusion Statins reduce the incidence of MALE, all-cause, and CV mortality in patients with PAD. In PAD, a high proportion of MALE events and deaths could be prevented by implementing a statin prescription in this patient population.

In recent years, there has been a widespread cross-fertilization between Medical Statistics and Machine Learning (ML) techniques.

Unknown by-product in Simvastatin synthesis from Lovastatin was found. The elucidation of this molecular structure by means of (1)H and (13)C NMR spectroscopy, HPLC/MS, MS/MS and FT-IR was shown. The mentioned by-product, originated during Merck Sharp and Dhome synthesis scheme was isolated in the second-last step replacing butylamine with benzylamine. The spectroscopic results agreed with a molecular formula C(32)H(43)NO(3). The proposed structure of this compound, characterised by the presence of a conjugated dienic system in the heptanoic acid amide residue, was alpha,beta,gamma,delta unsaturated Simvastatin N-benzylamide.

6[3-(1-Adamantyl)-4-methoxyphenyl]-2-naphthoic acid (Adapalene®), a synthetic aromatic retinoid specific for RARβ and RARγ receptors, has been prepared utilizing a Pd/C-mediated Suzuki coupling between 6-bromo-2-naphthoic acid and 4-methoxyphenyl boronic acid, followed by introduction of an adamantyl group in the position 3 of the formed 6-(4-methoxyphenyl)-2-naphthoic acid. The interaction of 6-(4-methoxyphenyl)-2-naphthoic acid/ethyl ester and the 3-adamantyl analogs with DNA was studied in aqueous solution at physiological conditions by UV-vis spectroscopy. The calculated binding constants K(ligand-DNA) ranged between 1.1×10(4) M(-1) and 1.1×10(5) M(-1), the higher values corresponding to those of the adamantylated compounds. Molecular modeling studies have emphasized that the intercalative binding of adapalene and its derivatives to DNA is mainly stabilized by hydrophobic interactions related to the presence of the adamantyl group.