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Background: Sepsis is a critical condition characterized by severe immune dysregulation, ranking among the leading causes of morbidity and mortality in intensive care and internal medicine units. Nutritional status plays a pivotal role in modulating these responses, as when inadequate it can compromise immune defenses, the body’s ability to handle stress and inflammation, and the clinical course. Malnutrition is frequently observed in septic patients and is strongly associated with worse clinical outcomes, including increased mortality, prolonged hospital stays, and greater complication rates. In this context, nutritional scoring systems have emerged as valuable tools to evaluate patients’ nutritional status and predict clinical trajectories. Objectives: Given the absence of a direct comparison of their performance in an internal medicine setting, this study aimed to assess the effectiveness of various nutritional scores as predictive tools for clinical outcomes in septic patients, emphasizing their application within the field of internal medicine. Methods and Results: A retrospective analysis was conducted on 143 patients diagnosed with sepsis or septic shock who were admitted to an internal medicine unit. Key variables included clinical and laboratory parameters, comorbidities, and nutritional scores at the time of diagnosis. The modified Glasgow Prognostic Score (mGPS), the Prognostic Nutritional Index (PNI), the Controlling Nutritional Status (CONUT) score, the modified Nutrition Risk in Critically Ill (mNUTRIC) score, and the blood urea nitrogen-to-albumin ratio (BAR) were evaluated in forecasting mortality and clinical outcomes in patients with sepsis. Among them, the mNUTRIC score emerged as the strongest independent predictor of in-hospital mortality, with a good performance and a reasonable threshold for risk stratification. Conclusions: The study highlights the mNUTRIC score’s practicality and reliability in assessing nutritional and inflammatory risks in septic patients, particularly in non-ICU settings. These findings suggest its potential utility in guiding nutritional interventions and improving clinical outcomes, emphasizing the importance of integrating nutritional assessment into sepsis management.

HIV-infected patients show high risk of fracture. The aims of our study were to determine the prevalence of vertebral fractures (VFs) and their associations with vitamin D in HIV patients. 100 patients with HIV infection and 100 healthy age- and sex-matched controls were studied. Bone mineral density was measured by quantitative ultrasound at the non-dominant heel. Serum osteocalcin and C-terminal telopeptide of collagen type 1 served as bone turnover markers. Bone ultrasound measurements were significantly lower in patients compared with controls (Stiffness Index (SI): 80.58 ± 19.95% vs. 93.80 ± 7.10%, respectively, p < 0.001). VFs were found in 16 patients and in 2 controls. HIV patients with vertebral fractures showed lower stiffness index (SI) (70.75 ± 10.63 vs. 83.36 ± 16.19, respectively, p = 0.045) and lower vitamin D levels (16.20 ± 5.62 vs. 28.14 ± 11.94, respectively, p < 0.02). The majority of VFs (87.5%) were observed in HIV-infected patients with vitamin D insufficiency, and regression analysis showed that vitamin D insufficiency was significantly associated with vertebral fractures (OR 9.15; 95% CI 0.18–0.52, p < 0.04). VFs and are a frequent occurrence in HIV-infected patients and may be associated with vitamin D insufficiency.

Suboptimal vitamin D status was recently acknowledged as an independent predictor of cardiovascular diseases and all-cause mortality in several clinical settings, and its serum levels are commonly reduced in Rheumatoid Arthritis (RA). Patients affected by RA present accelerated atherosclerosis and increased cardiovascular morbidity and mortality with respect to the general population. In RA, it has been reported an impairment of the number and the activity of circulating proangiogenic haematopoietic cells (PHCs), including CD34+, that may play a role in endothelial homeostasis. The purpose of the study is to investigate the association between vitamin D levels and PHCs, inflammatory markers, and arterial stiffening in patients with RA. CD34+ cells were isolated from 27 RA patients and 41 controls. Vitamin D levels, C-reactive protein (CRP), fibrinogen, pulse wave velocity (PWV), and carotid intima-media thickness (cIMT) were also evaluated. CD34+ count and vitamin D levels were lower in RA patients as compared to controls, while fibrinogen, CRP, PWV and cIMT were higher in RA patients. CD34+ cell number appeared to be associated with vitamin D levels, and negatively correlated to fibrinogen and early atherosclerosis markers (PWV and cIMT); vitamin D levels appear also to be inversely associated to fibrinogen. RA patients with moderate disease activity presented with low vitamin D levels, low CD34+ cell count, increased PWV and cIMT; we found that vitamin D deficiency is associated to CD34+ cell reduction in peripheral blood, and with fibrinogen levels. This suggests that vitamin D might contribute to endothelial homeostasis in patients with RA.

Background and Objectives: Osteoporosis is a prevalent skeletal disorder characterized by decreased bone mass and compromised bone microarchitecture, leading to an elevated risk of fractures and significant morbidity, particularly among aging populations. Early diagnosis and personalized management are critical to reducing fracture incidence and associated healthcare burdens. Recent advances in artificial intelligence (AI) and machine learning (ML) have led to potential improvements in enhancing osteoporosis care by enabling accurate diagnostic imaging analysis, robust fracture risk prediction, and personalized therapeutic strategies. Materials and Methods: We performed a narrative review to summarize and critically evaluate the current literature on AI and ML applications in osteoporosis diagnosis and management. We searched relevant literature from inception to January 2025 to provide a comprehensive perspective, focusing on key themes, methodological approaches, and clinical implications. Results: Deep learning models, especially convolutional neural networks, facilitate rapid and accurate bone mineral density assessment from routine radiographs, expanding screening capabilities beyond conventional dual-energy X-ray absorptiometry (DXA). Machine learning algorithms harness clinical and demographic data to generate fracture risk models that often outperform traditional tools, enabling timely identification of high-risk individuals. Furthermore, AI-driven analyses of historical treatment responses coupled with real-time monitoring through wearable technologies and mobile applications allow for personalized therapeutic optimization and enhance patient engagement. Despite these promising advances, challenges remain regarding ethical considerations, data privacy, legal liability, incomplete model validation, lack of standardization, and the need for critical appraisal of real-world clinical efficacy for widespread clinical adoption. Conclusions: This narrative review indicates that AI and ML hold significant promise to revolutionize osteoporosis management by enabling early detection, precise risk stratification, and tailored interventions. However, the current evidence is heterogeneous, often lacking robust external validation and quantitative synthesis. Critical gaps include insufficient evaluation of model robustness across diverse populations, discussion of negative or conflicting results, and a comprehensive assessment of the limitations inherent in current AI evidence. Strategic efforts to validate, regulate, and critically integrate these technologies into routine clinical workflows are essential to realize their full potential and address the growing burden of osteoporosis worldwide.

Background: Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn’s disease (CD), are chronic and disabling diseases that affect patient health-related quality of life (HRQoL). IBD patients are frequently exposed to high levels of stress and psychological distress. Biological drugs have been proven to reduce inflammation, hospitalization, and most of the complications that characterize IBDs; their potential contribution to patients’ HRQoL remains to be explored. Aim: To evaluate and compare any change in the HRQoL and markers of inflammation in IBD patients undergoing biological drugs (infliximab or vedolizumab). Material and Methods: A prospective observational study was conducted on a cohort of IBD patients, aged >18 years, who were prescribed with infliximab or vedolizumab. Demographic and disease-related data at baseline were collected. Standard hematological and clinical biochemistry parameters, including C-reactive protein (CRP), white blood cells count (WBC), erythrocytes sedimentation rate (ESR), and α1 and α2 globulins were measured after a 12-h fast at baseline (T0), after 6 weeks (T1), and at 14 weeks (T2) of biological treatment. Steroid use, disease activity as measured by the Harvey–Bradshaw index (HBI) and partial Mayo score (pMS) for the CD and UC, respectively, were also recorded at each timepoint. The Short Form 36 Health Survey (SF-36), Functional Assessment of Chronic Illness Therapy (FACIT-F), and Work Productivity and Activity Impairment–General Health Questionnaire (WPAI:GH) were administered to each patient at baseline, T1, and T2 to address the study aims. Results: Fifty eligible consecutive patients (52% with CD and 48% with UC) were included in the study. Twenty-two patients received infliximab and twenty-eight received vedolizumab. We noted a significant reduction in the CRP, WBC, α1, and α2 globulins from T0 to T2 (p = 0.046, p = 0.002, p = 0.008, and p = 0.002, respectively). Participants showed a significant decrease in steroid administration during the observation period. A significant reduction in the HBI of CD patients at all three timepoints and a similarly significant decrease in the pMS of UC patients from baseline to T1 were recorded. Statistically significant changes were observed in all questionnaires during follow-up as well as an overall improvement in the HRQoL. The interdependence analysis carried out between the biomarkers and the scores of the individual subscales showed a significant correlation between the variation (Δ) of the CRP, Hb, MCH, and MCV with physical and emotional dimensions of the SF-36 and FACIT-F tools; work productivity loss expressed by some of the WPAI:GH items negatively correlated with the ΔWBC and positively with the ΔMCV, ΔMCH, and Δ α1 globulins. A sub-analysis according to the type of treatment showed that patients receiving infliximab experienced a more pronounced improvement in their HRQoL (according to both SF-36 and FACIT-F) compared with patients receiving vedolizumab. Conclusions: Both infliximab and vedolizumab played an important role in contributing to the improvement of the HRQoL in IBD patients by also reducing inflammation and, consequently, steroid use in patients with an active disease. HRQoL, being one of the treatment goals, should also be assessed when taking charge of IBD patients to assess their clinical response and remission. The specific correlation between the biomarkers of inflammation and life’s spheres, as well as their possible role as clinical markers of HRQoL, should be further investigated.

Proprotein convertase subtilisin/kexin type-9 (PCSK9) is a key regulator of low-density lipoprotein (LDL) metabolism involved in the degradation of the low-density lipoprotein receptor (LDLR) through complex mechanisms. The PCSK9 plasma levels change according to lipid lowering therapy (LLT). Few data exist regarding the role of PCSK9 in vascular damage. We aimed to evaluate the impact of PCSK9 plasma levels on pulse wave velocity (PWV) and the effect of PCSK9 inhibitors (PCSK9-i) on circulating PCSK9 and PWV in a cohort of heterozygous familial hypercholesterolemia (HeFH) subjects. In a previous step, HeFH patients were enrolled and LLT was prescribed according to guidelines. Biochemical analyses and PWV assessment were performed at baseline (T0), after 6 months of high-efficacy statin plus ezetimibe (T1) and after 6 months of PCSK9-i (T2). The PCSK9 levels were evaluated in 26 selected HeFH subjects at the three time points and 26 healthy subjects served as controls for the reference value for PCSK9 plasma levels. The PWV values decreased at each time point in HeFH subjects after LLT starting (8.61 ± 2.4 m/s, −8.7%; p < 0.001 vs. baseline at T1, and 7.9 ± 2.1 m/s, −9.3%; p < 0.001 vs. both T1 and baseline) and it was correlated to PCSK9 (r = 0.411, p = 0.03). The PCSK9 levels increased on statin/EZE therapy (+42.8% at T1) while it decreased after PCSK9-i was started (−34.4% at T2). We noted a significant relationship between PCSK9 levels and PWV changes at T1 and T2. In conclusion, PCSK9 levels were associated with baseline PWV values in HeFH subjects; moreover, we found that PCSK9 level variations seemed to be correlated with PWV changes on LLT. A longer observation time and wider sample size are needed to assess the potential role of PCSK9 plasma levels on the vascular function and remodelling, and to clarify the effects of PCSK9-i in these pathways.

Objective. To identify, evaluate, and synthesize evidence on the predictive power of circulating endothelial progenitor cells (EPCs) in cardiovascular disease, through a systematic review of quantitative studies. Data Sources. MEDLINE was searched using keywords related to “endothelial progenitor cells” and “endothelium” and, for the different categories, respectively, “smoking”; “blood pressure”; “diabetes mellitus” or “insulin resistance”; “dyslipidemia”; “aging” or “elderly”; “angina pectoris” or “myocardial infarction”; “stroke” or “cerebrovascular disease”; “homocysteine”; “C-reactive protein”; “vitamin D”. Study Selection. Database hits were evaluated against explicit inclusion criteria. From 927 database hits, 43 quantitative studies were included. Data Syntheses. EPC count has been suggested for cardiovascular risk estimation in the clinical practice, since it is currently accepted that EPCs can work as proangiogenic support cells, maintaining their importance as regenerative/reparative potential, and also as prognostic markers. Conclusions. EPCs showed an important role in identifying cardiovascular risk conditions, and to suggest their evaluation as predictor of outcomes appears to be reasonable in different defined clinical settings. Due to their capability of proliferation, circulation, and the development of functional progeny, great interest has been directed to therapeutic use of progenitor cells in atherosclerotic diseases. This trial is registered with registration number: Prospero CRD42015023717.

ObjectiveStill’s disease is more frequently observed in the paediatric context, but a delayed onset is not exceptional both in the adulthood and in the elderly. However, whether paediatric-onset, adult-onset and elderly-onset Still’s disease represent expressions of the same disease continuum or different clinical entities is still a matter of controversy. The aim of this study is to search for any differences in demographic, clinical features and response to treatment between pediatric-onset, adult-onset and elderly-onset Still’s disease.MethodsSubjects included in this study were drawn from the International AutoInflammatory Disease Alliance Network registry for patients with Still’s disease.ResultsA total of 411 patients suffering from Still’s disease were enrolled; the disease occurred in the childhood in 65 (15.8%) patients, in the adult 314 (76.4%) patients and in the elderly in 32 (7.8%) patients. No statistically significant differences at post-hoc analysis were observed in demographic features of the disease between pediatric-onset, adult-onset and elderly-onset Still’s disease. The salmon-coloured skin rash (p=0.004), arthritis (p=0.009) and abdominal pain (p=0.007) resulted significantly more frequent among paediatric patients than in adult cases, while pleuritis (p=0.015) and arthralgia (p<0.0001) were significantly more frequent among elderly-onset patients compared with paediatric-onset subjects. Regarding laboratory data, thrombocytosis was significantly more frequent among paediatric patients onset compared with adult-onset subjects (p<0.0001), while thrombocytopenia was more frequent among elderly-onset patients although statistical significance was only bordered. No substantial differences were observed in the response to treatments.ConclusionsDespite some minor difference between groups, overall, demographic, clinical, laboratory and treatments aspects of Still’s disease were similarly observed in patients at all ages. This supports that pediatric-onset, adult-onset and elderly-onset Still’s disease is the same clinical condition arising in different ages.

CD34+ circulating progenitor cells (CD34+CPCs) are a population of multipotent cells which can delay the development of atherosclerosis and cardiovascular disease (CVD) in conditions of increased CV risk. MicroRNAs (miRs) 221 and 222 modulate different genes regulating angiogenesis and inflammation; moreover, miR221/22 have beenshown to participate in differentiation and proliferation of CD34+CPCs, inhibiting cell migration and homing. miR221/222 in CD34+CPCs from hypertensive subjects are also increased and associated with CD34+cell number and reactive oxygen species (ROS). We evaluated CD34+CPC number, intracellular miR221/222 and ROS levels, arterial stiffness (AS)and echocardiography indices at baseline (T0).Then, after a six-month treatment with olmesartan, 20 mg/day (T1), in 57 hypertensive patients with left ventricular hypertrophy (LVH) and with no additional risk factor for CVD, and in 29 healthy controls (baseline),fibrinogen, C-reactive protein (CRP), glucose and lipid profiles were also evaluated.At T1, blood pressure values, CRP and fibrinogen levels, ROS and miR221/222 were significantly decreased (all p <0.001), as were AS indices and LV mass index (p<0.001), while cell number was increased (p<0.001). Olmesartan is effective in reducing miR and ROS levels in CD34+CPCs from hypertensive subjects, as well as in increasing CD34+CPC number, providing multilevel CV protection, in addition to its expected pharmacological effects.

Objectives The primary objective of this study was the translation and validation of the ANCA-associated vasculitis patient-reported outcome (AAV-PRO) questionnaire into Italian, denoted as AAV-PRO_ita. The secondary objective was to evaluate the impact of ANCA-associated vasculitis (AAV) on quality of life (QoL) and work impairment in a large cohort of Italian patients. Methods The study design took a prospective cohort study approach. First, the AAV-PRO was translated into Italian following the step guidelines for translations. The new AAV-PRO_ita questionnaire covered three disease domains: organ-specific and systemic symptoms and signs; physical function; and social and emotional impact. Second, Italian-speaking AAV patients were recruited from 17 Italian centres belonging to the Italian Vasculitis Study Group. Participants completed the AAV-PRO_ita questionnaire at three time points. Participants were also requested to complete the work productivity and activity impairment: general health questionnaire. Results A total of 276 AAV patients (56.5% women) completed the questionnaires. The AAV-PRO_ita questionnaire demonstrated a good internal consistency and test–retest reliability. Female AAV patients scored higher (i.e. worse) in all thee domains, especially in the social and emotional impact domain (P < 0.001). Patients on glucocorticoid therapy (n = 199) had higher scores in all domains, especially in the physical function domain (P < 0.001), compared with patients not on glucocorticoid therapy (n = 77). Furthermore, patients who had at least one relapse of disease (n = 114) had higher scores compared with those who had never had one (n = 161) in any domain (P < 0.05). Finally, nearly 30% of the patients reported work impairment. Conclusion The AAV-PRO_ita questionnaire is a new 29-item, disease-specific patient-reported outcome measuring tool that can be used in AAV research in the Italian language. Sex, glucocorticoids and relapsing disease showed the greatest impact on QoL. Lay Summary What does this mean for patients? Improved therapeutic strategies for ANCA-associated vasculitis (AAV) have transformed acute, life-threatening disease into more manageable, chronic disease. However, chronic disease still has an impact on AAV patients’ quality of life (QoL), employment and work disability. We translated the AAV-PRO questionnaire (which collects data on patient-reported outcomes) into Italian. Two hundred and seventy-six AAV patients in Italy then completed the questionnaire. We found that biological sex, steroid use and relapsing disease had the biggest impact on patients’ QoL. Research on treatment strategies based on a steroid-sparing regimen and an increased awareness of sex differences might improve the perceived QoL of AAV patients, reducing the psychosocial and work impact of this chronic disease. Our study emphasizes the usefulness of user-friendly, translated questionnaires in standardizing QoL and work disability data in different groups of AAV patients. Therefore, we advocate the widespread use of the AAV-PRO questionnaire globally. This approach would enable us to gather comprehensive data, ultimately facilitating a more tailored approach to care for AAV patients.