IRIS UniSR (’Università Vita-Salute San Raffaele)
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Pathophysiology and evaluation of bone health in adrenal diseases
Adrenal diseases are associated with an increased risk of osteopenia/osteoporosis and fragility fractures. Although dual-energy X-ray absorptiometry remains the gold standard for assessing bone mineral density, its limitations in accurately predicting vertebral fractures underscore the need for complementary diagnostic tools, particularly in the context of adrenal disorders. Vertebral fractures, often asymptomatic, may go undetected without targeted assessments such as morphometric evaluation. Incorporating advanced diagnostic tools, such as the trabecular bone score, into the evaluation of adrenal disorder-related skeletal fragility may enhance the identification of high-risk patients and support tailored therapeutic strategies. This review explores skeletal fragility from pathophysiological, clinical, and diagnostic perspectives and provides guidance to physicians for the management of adrenal disorders to improve bone health outcomes
Artificial intelligence in antimicrobial stewardship: a systematic review and meta-analysis of predictive performance and diagnostic accuracy
The increasing threat of antimicrobial resistance has prompted a need for more effective antimicrobial stewardship programs (AMS). Artificial intelligence (AI) and machine learning (ML) tools have emerged as potential solutions to enhance decision-making and improve patient outcomes in AMS. This systematic review and meta-analysis aims to evaluate the impact of AI in AMS and to assess its predictive performance and diagnostic accuracy. We conducted a comprehensive literature search across PubMed/MEDLINE, Scopus, EMBASE, and Web of Science to identify studies published up to July 2024. Studies included were observational, cohort, or retrospective, focusing on the application of AI/ML in AMS. The outcomes assessed were the area under the curve (AUC), accuracy, sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV). We calculated the mean pooled effect size (ES) and its 95% confidence interval (CI) using a random-effects model. The risk of bias was assessed using the QUADAS-AI tool, and the protocol was registered in PROSPERO. Out of 3,458 retrieved articles, 80 studies met the inclusion criteria. Our meta-analysis demonstrated that ML models exhibited strong predictive performance and diagnostic accuracy, with the following results: AUC [ES: 72.28 (70.42-74.14)], accuracy [ES: 74.97 (73.35-76.58)], sensitivity [ES: 76.89; (71.90-81.89)], specificity [ES: 73.77; (67.87-79.67)], NPV [ES:79.92 (76.54-83.31)], and PPV [ES: 69.41 (60.19-78.63)] across various AMS settings. AI and ML tools offer promising enhancements due to their strong predictive performance. The integration of AI into AMS could lead to more precise antimicrobial prescribing, reduced antimicrobial resistance, and better resource utilization
Partial Detachment of the Gluteus Maximus Muscle to Expose the Proximal Third of the Sciatic Nerve in the Infragluteal Approach: An Alternative Technique to Minimize Iatrogenic Muscle Deafferentation Damage
Background: Exposing the proximal extrapelvic sciatic nerve usually requires a partial transsection of the gluteus maximus muscle. The authors describe a modified infragluteal technique for mobilizing the gluteus maximus muscle, with only partial detachment of the muscle aponeurosis attaching to the femur.An illustrative case is reported to demonstrate the surgical feasibility of the approach. The present technique offers good operability, with only a slight decrease in the angle of the surgical corridor compared with the standard infragluteal and transgluteal techniques, while preventing muscle damage resulting from muscle deafferentation
People with four-class drug-resistant HIV-1 may have low levels of intact DNA
We evaluated the HIV-1 reservoir in people with four-class drug-resistant (4DR) virus compared with those without drug resistance. Using the intact proviral DNA assay, we found that both groups had similar levels of intact HIV-1 DNA, suggesting that multidrug-resistant HIV does not significantly alter the size of the reservoir. These findings are a first step in studying the HIV-1 reservoir in the population with multidrug-resistant virus, and further studies are needed to confirm our results
Gender Influence on Bimekizumab Response in Patients with Psoriasis: Results of a Real-World Multicenter Retrospective Study—IL PSO (Italian Landscape PSOriasis)
Introduction: Several studies have demonstrated that psoriasis severity is generally greater in male patients, but it is unclear whether this gender difference may affect short-term therapeutic response. Notably, no studies have specifically investigated bimekizumab, a humanized, full-length IgG1 monoclonal antibody that acts as a dual inhibitor of interleukin (IL)-17A and IL-17F. Methods: This was a cross-sectional, observational, retrospective, multicenter analysis. A cohort of 318 patients with moderate to severe psoriasis, 229 male patients (median [IQR] age 35 [23–67] years) and 89 female patients (median [IQR] age 33 [20–68] years), were retrospectively evaluated for short-term response (16 weeks) to bimekizumab according to standard dosage (320 mg at weeks 0, 4, 8, 12, and 16, and every 8 weeks thereafter). Patients were assessed to evaluate whether gender differences in demographic and clinical characteristics can affect treatment response to standard dose of bimekizumab, during the first 16 weeks of treatment. Therapeutic outcomes were evaluated by analyzing Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI) scores recorded in each patient at three consecutive time points: baseline (T0), after 4 weeks (T4), and after 16 weeks of treatment (T16). Results: Male patients showed more severe disease at baseline, compared to female patients (p = 0.01). A significant reduction in disease severity was observed in both male and female patients after 16 weeks of treatment, but male patients showed a faster decrease in PASI score between baseline and week 4 of treatment compared to female patients (p < 0.001). Nevertheless, by week 16, difference in PASI response and DLQI reduction between genders became less pronounced. Conclusion: Although male patients exhibit greater disease severity at baseline compared to female patients, this does not result in a differential response to bimekizumab over the short term. Both male and female patients had equal probability of achieving complete or near-complete disease remission within the first 4 weeks of treatment, and both maintain this response status through week 16. The therapeutic benefit of bimekizumab may be due to the rapid dual inhibition of IL-17A and IL-17F, which may lead to consistent and robust clinical response across genders, regardless of baseline disease severity. Our results suggest a “gender severity-invariant effect” of bimekizumab, highlighting the treatment as rapidly effective in both genders, despite initial differences in disease severity
Transcatheter edge-to-edge repair in severe mitral regurgitation following acute myocardial infarction – aetiology-based analysis
Aims: To evaluate the association between transcatheter edge-to-edge repair (TEER) and outcomes in patients with significant mitral regurgitation (MR) following acute myocardial infarction (MI), focusing on the aetiology of acute post-MI MR in high-risk surgical patients. Methods and results: The International Registry of MitraClip in Acute Mitral Regurgitation following Acute Myocardial Infarction (IREMMI) includes 187 patients with severe MR post-MI managed with TEER. Of these, 176 were included in the analysis, 23 (13%) patients had acute papillary muscle rupture (PMR) and 153 (87%) acute secondary MR. The mean age was 70 ± 10 years and 41% were female. PMR patients had fewer cardiovascular risk factors: hypertension (52% vs. 73%, p = 0.04), diabetes (26% vs. 48%, p < 0.01) but a higher left ventricular ejection fraction (45± 15% vs.35± 10%, p < 0.01) compared secondary MR patients. PMR patients were more likely to present in cardiogenic shock (91% vs. 51%, p = 0.001), require mechanical circulatory support (74% vs. 34%, p = 0.01), and had a higher EuroSCORE II (23± 13% vs. 13± 11%, p = 0.011). The median time from MI to TEER was shorter in PMR (6 days) versus secondary MR (20 days) (p < 0.01). Procedural success was similar (87% vs. 92%, p = 0.49) with comparable MR grade reduction. However, PMR patients had significantly higher in-hospital mortality rates (adjusted odds ratio [OR] 3.05, 95% confidence interval [CI] 1.15–8.12, p = 0.02), 30-day mortality rates (unadjusted OR 3.99, 95% CI 1.42–11.26, p = 0.01) and a higher rate of conversion to surgical mitral valve replacement (22% vs. 3%, p < 0.01) (unadjusted OR 8.17, 95% CI 2.15–30.96, p < 0.001). Aetiology of MR, cardiogenic shock, and procedure timing significantly impacted in-hospital mortality. After adjusting for EuroSCORE II and cardiogenic shock, MR aetiology remained the strongest predictor (adjusted OR 6.71; 95% CI 2.06–21.86, p < 0.01). Conclusion: Transcatheter edge-to-edge repair may be considered a salvage or bridge procedure in decompensated post-MI MR patients of both aetiologies; however, patients with PMR have a higher risk of mortality and conversion to surgery
Validity and reliability of the Home Health Care Survey of the Consumer Assessment of Healthcare Providers and System (HHCAHPS) tool: a multicentre cross-sectional study
Introduction. This study aims to investigate the psychometric properties of the Home Health Care Survey of the Consumer Assessment of Healthcare Providers and System (HHCAHPS) in the Italian context. Methods. This is a secondary analysis of data from the AIDOMUS- IT study. A total of 9,780 patients cared for by home healthcare services completed the HHCAHPS along with a measure of satisfaction for the care received. Structural validity was assessed with a confirmatory analytical approach (CFA). Construct validity was ascertained via hypothesis testing (convergent validity) by correlating the HHCAHPS scores with the scores derived from the measure of patient satisfaction for care. Internal consistency was assessed with the Omega (ω) coefficient. Results. Structural validity was confirmed, with satisfactory fit indices of the CFA model specified according to the conceptualized three-factor structure (“care of patients”, “communication with the providers”, and “specific care issues”). Construct validity was confirmed with moderate correlations between the level of satisfaction for care and the factors “communication with the providers” (r = 0.39, p < 0.001), “care of patients” (r = 0.34, p < 0.001), and “specific care issues” (r = 0.19, p < 0.001). Internal consistency was satisfactory for the “specific care issues” factor (ω = 0.81), while it was at the threshold of acceptability for the other factors (ω = 0.60-0.62). Conclusions. This study shows that the HHCAHPS is valid and sufficiently reliable when tested on the Italian population. Therefore, this tool can be supportive for promoting research and designing interventions to promote patient-centered care within home healthcare settings
Therapeutical approach of tricuspid regurgitation and right heart failure
Significant tricuspid regurgitation (TR) is a relatively common condition, affecting approximately 4 % of the elderly population. However, there are currently no clear guidelines for its medical management due to a lack of sufficient data in the literature. This review examines the pathophysiology of TR, categorizes its etiologies, and evaluates therapeutic options, both pharmacological and non-pharmacological, to optimize intervention timing and hemodynamic management. Based on the etiology and severity of TR, we suggest a gradual, stage-based algorithm for diuretic therapy titration and a management approach derived from common clinical practices
Understanding the therapeutic toolkit for inflammatory bowel disease
Inflammatory bowel disease (IBD), encompassing ulcerative colitis and Crohn’s disease, is a group of chronic, immune-mediated disorders of the gastrointestinal tract that present substantial clinical challenges owing to their complex pathophysiology and tendency to relapse. A treat-to-target approach is recommended, involving iterative treatment adjustments to achieve clinical response, reduce inflammatory markers and achieve long-term goals such as mucosal healing. Lifelong medication is often necessary to manage the disease, maintain remission and prevent complications. The therapeutic landscape for IBD has evolved substantially; however, a ceiling on therapeutic efficacy remains and surgery is sometimes required (owing to uncontrolled disease activity or complications). Effective IBD management involves comprehensive care, including medication adherence and a collaborative clinician–patient relationship. This Review discusses current therapeutic options for IBD, detailing mechanisms of action, efficacy, safety profiles and guidelines for use of each drug class. We also explore emerging therapies and the role of surgery. Additionally, the importance of a multidisciplinary team and personalized care in managing IBD is emphasized, advocating for patient empowerment and involvement in treatment decisions. By synthesizing current knowledge and emerging trends, this Review aims to equip healthcare professionals with a thorough understanding of therapeutic options for IBD, enhancing informed, evidence-based decisions in clinical practice
Inflammation switches the chemoattractant requirements for naive lymphocyte entry into lymph nodes
Sustained lymphocyte migration from blood into lymph nodes (LNs) is important for immune responses. The CC-chemokine receptor-7 (CCR7) ligand CCL21 is required for LN entry but is downregulated during inflammation, and it has been unclear how recruitment is maintained. Here, we show that the oxysterol biosynthetic enzyme cholesterol-25-hydroxylase (Ch25h) is upregulated in LN high endothelial venules during viral infection. Lymphocytes become dependent on oxysterols, generated through a transcellular endothelial-fibroblast metabolic pathway, and the receptor EBI2 for inflamed LN entry. Additionally, Langerhans cells are an oxysterol source. Ch25h is also expressed in inflamed peripheral endothelium, and EBI2 mediates B cell recruitment in a tumor model. Finally, we demonstrate that LN CCL19 is critical in lymphocyte recruitment during inflammation. Thus, our work explains how naive precursor trafficking is sustained in responding LNs, identifies a role for oxysterols in cell recruitment into inflamed tissues, and establishes a logic for the CCR7 two-ligand system