The Italian Servizio Sanitario Nazionale (SSN) and other universal healthcare systems face increasing pressure from aging, multimorbidity, malnutrition, obesity and the widespread consumption of ultra-processed foods (UPFS). Hospitals struggle not only with resources but with managing complexity. Medicine (IM) wards absorb most acute admissions and represent the hidden backbone of hospital functioning. Delayed discharges, hospital malnutrition, and obesity-related meta-inflammation illustrate systemic inefficiency and escalating costs. Evidence shows that internist-led interventions, including systematic nutritional screening, integrated obesity care, and the use of point-of-care ultrasound (POCUS), improve patient outcomes and hospital efficiency. The evolving role of IM requires combining holistic oversight with subspecialty competence (cardio-pulmonary, neuro-internal medicine, onco-internal medicine, gastro-metabolism, geriatrics, immunology, an infectious diseases). As guardians of health, internists must extend their role beyond acute care to prevention regulation of UPFs, and sustainable patient transitions. In conclusion, strengthening Internal Medicine is essential for preserving universal healthcare. Internists—generalist in vision, subspecialist in competence, ultrasonographer in practice—are both the economic and ethical backbone of hospitals and the guardians of public health.

Peripheral arterial disease (PAD) is a systemic atherosclerotic condition associated with substantial morbidity and mortality. Although excessive alcohol consumption has been implicated in cardiovascular disease, the prevalence of harmful drinking patterns and their association with PAD severity at clinical presentation remain poorly defined. In this observational cohort study, 103 consecutive patients with symptomatic lower‑extremity PAD were enrolled. Alcohol exposure was assessed using the Alcohol Use Disorders Identification Test - Consumption (AUDIT-C) questionnaire and Lifetime Drinking History (LDH); AUD was diagnosed according to Diagnostic and Statistical Manual of Mental Disorders (DSM)‑5 criteria. PAD severity was classified by Rutherford categories. Associations between alcohol consumption patterns and PAD severity were evaluated using logistic and ordered logistic regression models. Overall, 24.3% of patients were non-drinkers, 40.8% reported moderate alcohol consumption, 13.5% met criteria for at-risk drinking, and 21.4% were diagnosed with AUD. Patients with AUD were younger, had longer smoking exposure, and higher gamma-glutamyl transferase levels compared with those without AUD. Severe PAD at presentation (Rutherford category 6) was more frequent among patients with AUD than among those without AUD (36.4% vs. 12.3%). In multivariable analyses, AUD remained associated with severe PAD, although with borderline statistical significance. In contrast, at-risk alcohol consumption was not independently associated with PAD severity. Higher daily alcohol intake was associated with increased odds of advanced PAD in univariate analysis. Ordered logistic regression suggested a trend toward a more severe Rutherford category among patients with AUD, although this association did not reach statistical significance. These findings indicate that AUD is common among patients with symptomatic PAD and may be associated with greater disease severity at presentation, supporting the clinical relevance of systematic AUD screening in vascular care settings.

Background/Objectives: Cardiovascular (CV) and cerebrovascular diseases, primarily attributed to atherosclerosis, stand as leading global causes of morbidity and mortality. This study aims to evaluate the impact of preclinical atherosclerosis parameters, including intima-media thickness (IMT) and arterial stiffness, in a seven-year follow-up of 100 patients with CV risk factors but no known history of CV or cerebrovascular diseases. Methods: Between April 2014 and December 2015, 100 patients presenting with suspected ischemic heart disease were enrolled. The study integrates the color Doppler examination of the supra-aortic trunks with the evaluation of preclinical parameters of atherosclerosis, such as intima-media thickness (IMT), βeta index, and pulse wave velocity (PWV), as well as echocardiographic evaluations, including global longitudinal strain (GLS). CV risk factors, metabolic syndrome, and insulin resistance were assessed and measured for each patient using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR). Two- and seven-year follow-ups assessed various CV events. Results: The study population comprised 67% males and 33% females. Metabolic syndrome, impaired fasting glycemia and hypertension were prevalent. The mean value of IMT was 1.21 ± 0.26 mm, and PWV was 8.47 ± 2.14 m/s. The 7-year follow-up identified IMT, PWV, and HOMA-IR as strong positive predictors of cardiovascular events, with PWV emerging as a particularly sensitive indicator of early events. Conclusions: Insulin resistance and cardiovascular risk factors may contribute to early alterations in myocardial and vascular function, even in the absence of overt disease. PWV, as a recognized surrogate marker of arterial stiffness, may serve as a sensitive tool for the early prediction of cardiovascular events. A comprehensive screening, including the assessment of markers indicating subclinical vascular alterations, along with the implementation of preventive interventions, is crucial for populations at risk.

Patients with type 2 diabetes mellitus (T2DM) and chronic limb-threatening ischemia (CLTI) undergoing lower extremity revascularization (LER) face high risks of major adverse cardiovascular events (MACE) and major adverse limb events (MALE), despite guideline-directed lipid-lowering therapy. Apolipoprotein B100 (ApoB100), reflecting total atherogenic particle number, may identify residual risk beyond LDL-cholesterol (LDL-C). Therefore, we investigated whether baseline ApoB100 levels independently predict MACE and MALE beyond conventional risk factors in this high-risk population. In this prospective cohort study, 167 T2DM patients with CLTI undergoing LER were followed for 12 months with visits at 1, 3, 6, and 12 months post-procedure. We measured baseline ApoB100 and assessed its ability to predict MACE, MALE, and composite endpoints, adjusting for clinical covariates. Composite events occurred in 49.1

Background and Aims:Proprotein convertase subtilisin/kexin type-9 (PCSK9) plays a crucial role in pathophysiologic processes leading to limb and cardiovascular complications in diabetes, including cholesterol homeostasis, inflammation, and endothelial oxidative stress. This study examined the association between PCSK9 levels and major adverse limb events (MALEs) in patients with type 2 diabetes mellitus (T2DM) and chronic limb-threatening ischemia (CLTI) after endovascular revascularization. Methods:This prospective cohort study included 147 T2DM patients with peripheral artery disease undergoing endovascular revascularization for CLTI. Clinical assessments, including PCSK9 blood levels, were performed, and patients were followed for 12 months to monitor MALEs. Logistic regression and ROC curve analyses assessed the relationship between PCSK9 and MALEs. Results:During follow-up, 53 patients experienced MALEs. These patients were younger and had more severe peripheral artery disease. PCSK9 levels were significantly higher in those with MALEs (410.5 ng/mL) versus those without (360.6 ng/mL). ROC analysis showed that adding PCSK9 to cardiovascular risk factors improved MALE prediction. PCSK9 levels and Rutherford 4 category were independent risk factors for MALEs. Conclusion:Elevated PCSK9 levels are strongly associated with increased MALE risk in T2DM patients and may influence age of presentation and disease severity in CLTI. These findings highlight PCSK9 as a potential predictive biomarker and therapeutic target for vascular complications.

Chronic limb-threatening ischemia (CLTI) presents a major clinical challenge in patients with Type 2 Diabetes Mellitus (T2DM), requiring lower extremity revascularization (LER) to mitigate adverse cardiovascular and limb outcomes. Lipoprotein(a) (Lp(a)) has been implicated in cardiovascular risk, but its role in patients with T2DM and CLTI undergoing revascularization remains unclear. Thus, this study aimed to investigate the prognostic value of Lp(a) levels in diabetic CLTI patients for major adverse cardiovascular events (MACE), major adverse limb events (MALE), or both after LER. In this prospective cohort study of 158 individuals with T2DM and CLTI undergoing LER, baseline clinical data were collected, including Lp(a) levels. Patients were followed for occurrence of MACE, MALE, or both over a 12-month period. During follow-up, 74 patients (46.8

Individuals with chronic inflammatory and immune disorders are at an increased risk of atherosclerotic events and premature cardiovascular (CV) disease. Despite extensive literature exploring the relationship between “non-traditional” atherosclerotic conditions and CV risk, many aspects remain unresolved, including the underlying mechanisms promoting the “non-traditional CV risk”, the development of an innovative and comprehensive CV risk assessment tool, and recommendations for tailored interventions. This review aims to evaluate the available evidence on key “non-traditional” CV risk-enhancer conditions, with a focus on assessing and managing CV risk factors. We conducted a comprehensive review of 412 original articles, narrative and systematic reviews, and meta-analyses addressing the CV risk associated with “non-traditional” atherosclerotic conditions. The analysis examined the underlying mechanisms of these relationships and identified strategies for assessing and mitigating elevated risk. A major challenge highlighted is the difficulty in quantifying the contribution of individual risk factors and disease-specific elements to CV risk. While evidence supports the cardiovascular benefits of statins beyond lipid lowering, such as pleiotropic and endothelial effects, current guidelines lack specific recommendations for the use of statins or other therapies targeting non-traditional CV risk factors. Additionally, the absence of validated cardiovascular risk scores that incorporate non-traditional risk factors hinders accurate CV risk evaluation and management. The growing prevalence of “non-traditional CV risk-enhancer conditions” underscores the need for improved awareness of CV risk assessment and management. A thorough understanding of all contributing factors, including disease-specific elements, is crucial for accurate prediction of cardiovascular disease (CVD) risk. This represents an essential foundation for informed decision-making in primary and secondary prevention. We advocate for future research to focus on developing innovative, disease-specific CV risk assessment tools that incorporate non-traditional risk factors, recognizing this as a promising avenue for translational and clinical outcome research.

Peripheral arterial disease (PAD) is more prevalent in individuals with type 2 diabetes mellitus (T2DM). The most severe complication of PAD is chronic limb-threatening ischemia (CLTI), which is associated with major adverse cardiovascular events (MACE) and major adverse limb events (MALE) following lower limb revascularization (LER). This study investigates the relationship between baseline levels of Klotho and FGF23 and the risk of cardiovascular and limb-related outcomes after LER in a selected cohort of older adults. The study enrolled 109 older patients with PAD and CLTI requiring LER. Baseline levels of Klotho and FGF23 were measured, and their associations with subsequent MACE and MALE were analyzed over a 12-month follow-up period. Using stepwise multivariable logistic regression and Cox proportional hazards models, we found that among 109 older patients with PAD and CLTI undergoing LER, independent predictors of MACE included age (p = 0.016), male sex (p = 0.006), BMI (p = 0.004), diabetes duration (p = 0.031), hypertension (p = 0.013), and smoking status (p < 0.001), with higher FGF23 (p < 0.001) and lower Klotho levels (p = 0.002) significantly associated with increased risk; in the Cox model, increased Klotho was linked to a reduced risk of MACE (95

Aim of this study is to evaluate any differences in VWF antigen, VWF activity and ADAMTS-13 activity before and after successful and non-successful Percutaneous Transluminal Angioplasty (PTA) in subjects with type 2 diabetes (T2DM) complicated by Chronic limb-threatening ischemia (CLTI) in diabetic foot vasculopathy.Methods: In this prospective observational pilot study, we enrolled 35 T2DM subjects who underwent lower limb PTA. Transcutaneous oximetry was performed in all patients before and 6 weeks after PTA. The change in oxygen partial pressure (TcpO2) before and after PTA was expressed as TcpO2-delta (aTcpO2). VWF antigen, VWF activity and ADAMTS-13 activity were measured before and 6 weeks after PTA; changes were expressed as delta and ratio from baseline. Results: Subjects with aTcpO2 < 15 mmHg presented higher aVWF activity (p = 0.050) and lower ADAMTS-13 activity ratio (p = 0.080). Subjects with aTcpO2 < 30 mmHg showed lower ADAMTS-13 activity a and ratio (p = 0.028).Conclusions: VWF antigen levels and VWF activity may potentially affect PTA outcome. Higher levels of VWF could derive from VWF release as consequence of PTA-induced mechanical endothelial damage and/or oxidative stress-induced modifications of VWF structure with impairment of VWF-ADAMTS13 interactions.

Context Coronary collateral (CC) vessel development appears to be protective with regard to adverse cardiovascular events and survival in patients with coronary chronic total occlusion (CTO). The influence of type 2 diabetes mellitus (T2DM) on CC growth has been controversial. In particular, the role of diabetic microvascular complications (DMC) in determining coronary collateralization has not been elucidated. Objective To investigate whether patients with DMC presented differences in CC vessel presence and grading as compared with patients without DMC. Methods We conducted a single-center observational study, including consecutive T2DM patients, without previous cardiovascular history, undergoing a clinically indicated coronary angiography for chronic coronary syndrome (CCS) and angiographic evidence of at least one CTO. Patients were subdivided into 2 study groups according to the presence/absence of at least one DMC (neuropathy, nephropathy, or retinopathy). The presence and grading of angiographically visible CC development from the patent vessels to the occluded artery were assessed using the Rentrop classification. Results We enrolled 157 patients (mean age 68.6 & PLUSMN; 9.8 years; 120 [76.4%] men). Patients with DMC (75 [47.8%]) had a higher prevalence of CC (69 [92.0%] vs 62 [75.6%], P = .006) and high-grade CC (55 [73.3%] vs 39 [47.6%], P = .001) compared with those without, and we found a positive association between the number of DMC in each patient and the prevalence of high-grade CC. Conclusion Among T2DM patients with coronary CTO, the presence of DMC was associated with a high CC development.

Objective: Li-Fraumeni Syndrome (LFS) is a rare autosomal-dominant syndrome caused by aheterozygous germline mutation of the TP53 gene.It is characterized by early-onset malignancies and high penetrance.Non-bacterial thrombotic endocarditis (NBTE) is an uncommon condition for which cancer is a significant risk factor.Here we present a complex case of LFS unveiled by a NBTE-related ischemic stroke.Case presentation: A 41-year-old woman was admitted following a syncopal episode, preceded by a history of ischemic stroke.She had a notable family history of cancers.Imaging studies revealed ischemic damage and hemorrhagic infarcts, indicating a possible embolic origin or neoplastic involvement.Subsequent examinations revealed a NBTE on the aortic valve as well as multiple primary malignancies including high-grade invasive ductal carcinoma in the breast and primary lung adenocarcinoma.Genetic testing confirmed the presence of a pathogenic variant in TP53.Conclusion: This case underscores the intricate interplay between LFS, oncological manifestations, and thrombotic complications leading to ischemic stroke through NBTE embolization.

Chronic limb-threatening ischemia (CLTI) significantly increases the risk of major adverse limb events (MALE) and major adverse cardiac events (MACE) after lower extremity revascularization (LER). This study aims to identify novel biomarkers that help to further reduce the risk of postoperative cardiovascular complications. In this prospective, nonrandomized, observational study, baseline serum levels of sirtuin 1 (SIRT1) were assessed in 147 diabetic patients scheduled for LER due to CLTI, and participants were followed for the occurrence of MALE and MACE over 12 months. Fifty-three patients experienced MALE, and 33 experienced MACE within the follow-up period. Lower baseline SIRT1 levels were significantly associated with an increased risk of MALE and MACE, independent of other risk factors. The ROC curve analysis identified a SIRT1 cutoff of 3.79 ng/mL for predicting the risk of MALE. Moreover, incorporating SIRT1 into predictive models significantly enhanced the accuracy of predicting adverse outcomes. Results suggest serum SIRT1 is a potential independent marker for predicting MALE and MACE in diabetic patients with CLTI undergoing LER. Further research is needed to clarify the mechanistic pathways in which SIRT1 may influence cardiovascular outcomes, and the role of this novel biomarker in the management of PAD and CLTI among patients with diabetes.

AIMS:Despite general agreement on the benefits of the Heart Team approach for patients with cardiac diseases, few data are available on its real impact on the decision-making process. The aim of the study is to define the evolution over time of the level of agreement with the systematic discussion of patients in the Heart Team and to evaluate the adherence to the Heart Team recommendations and the impact of the Heart Team on the clinical outcome of the patients. METHODS:In 2015--2016, an experienced cardiac surgeon and a cardiologist independently reviewed clinical data of a series of 100 patients (Group 1, G1) and subsequently for each patient recommended treatment (surgical, percutaneous, hybrid or medical therapy) or further diagnostic investigations. The next day, each case was discussed by the Hospital Heart Team. The Heart Team recommendation, the subsequent treatment received by the patient and the in-hospital outcome were recorded. The same study procedure was repeated in 2017 in a second (G2) and in 2018 in a third (G3) group, both of them including 100 patients. RESULTS:Complete agreement in treatment selection by the cardiac surgeon, cardiologist and the Heart Team was observed in 43% of cases in G1 and in 70% and 68% in G2 and G3, respectively (G1 vs. G2: P  < 0.001, G1 vs. G3: P  = 0.01, G2 vs. G3: P  = 0.30). Agreement was less frequent in patients with a higher risk profile and in patients with aortic valve stenosis. The Heart Team decision was implemented in 95% of cases with a 30-day mortality of 0.67%. CONCLUSION:Agreement in treatment selection among the cardiac surgeon, cardiologist and Heart Team appears to be low in the initial experience. Subsequently, it seems to steadily increase over time up to a limit, when it reaches a plateau of stable results. Heart Team clinical cases discussion, based on both guidelines and multidisciplinary experience, represents a key step in defining the best patient treatment pathway, potentially improving the decision-making process and clinical results.

Peripheral arterial disease (PAD) afflicts millions of people across the globe, with the severe form often culminating in chronic limb-threatening ischemia (CLTI) [...]

Cardiovascular complications after lower extremity revascularization (LER) are common in diabetic patients with peripheral arterial disease (PAD) and chronic limb threatening ischemia (CLTI). The Klotho-fibroblast growth factor 23 (FGF23) axis is associated with endothelial injury and cardiovascular risk. We aimed to analyze the relationship between Klotho and FGF23 serum levels and the incidence of major adverse cardiovascular events (MACE) and major adverse limb events (MALE) after LER in diabetic patients with PAD and CLTI. Baseline levels of Klotho and FGF23, and their association with subsequent incidence of MACE and MALE were analyzed in a prospective, non-randomized study in a population of diabetic patients with PAD and CLTI requiring LER. A total of 220 patients were followed for 12 months after LER. Sixty-three MACE and 122 MALE were recorded during follow-up period. Baseline lower Klotho serum levels (295.3 ± 151.3 pg/mL vs. 446.4 ± 171.7 pg/mL, p < 0.01), whereas increased serum levels FGF23 (75.0 ± 11.8 pg/mL vs. 53.2 ± 15.4 pg/mL, p < 0.01) were significantly associated with the development of MACE. Receiver operating characteristic (ROC) analysis confirmed the predictive power of Klotho and FGF23 baseline levels. Furthermore, decreased Klotho levels were associated with the occurrence of MALE after LER (329.1 ± 136.8 pg/mL vs 495.4 ± 183.9 pg/mL, p < 0.01). We found that Klotho and FGF23 baseline levels are a potential biomarker for increased cardiovascular risk after LER in diabetic patients with PAD and CLTI.

BackgroundInfective endocarditis (IE) could be suspected in any febrile patients admitted to the emergency department (ED). This study was aimed at assessing clinical criteria predictive of IE and identifying and prospectively validating a sensible and easy-to-use clinical prediction score for the diagnosis of IE in the ED. Methods and ResultsWe conducted a retrospective observational study, enrolling consecutive patients with fever admitted to the ED between January 2015 and December 2019 and subsequently hospitalized. Several clinical and anamnestic standardized variables were collected and evaluated for the association with IE diagnosis. We derived a multivariate prediction model by logistic regression analysis. The identified predictors were assigned a score point value to obtain the Clinical Rule for Infective Endocarditis in the Emergency Department (CREED) score. To validate the CREED score we conducted a prospective observational study between January 2020 and December 2021, enrolling consecutive febrile patients hospitalized after the ED visit, and evaluating the association between the CREED score values and the IE diagnosis. A total of 15 689 patients (median age, 71 [56-81] years; 54.1% men) were enrolled in the retrospective cohort, and IE was diagnosed in 267 (1.7%). The CREED score included 12 variables: male sex, anemia, dialysis, pacemaker, recent hospitalization, recent stroke, chest pain, specific infective diagnosis, valvular heart disease, valvular prosthesis, previous endocarditis, and clinical signs of suspect endocarditis. The CREED score identified 4 risk groups for IE diagnosis, with an area under the receiver operating characteristic curve of 0.874 (0.849-0.899). The prospective cohort included 13 163 patients, with 130 (1.0%) IE diagnoses. The CREED score had an area under the receiver operating characteristic curve of 0.881 (0.848-0.913) in the validation cohort, not significantly different from the one calculated in the retrospective cohort (P=0.578). ConclusionsIn this study, we propose and prospectively validate the CREED score, a clinical prediction rule for the diagnosis of IE in patients with fever admitted to the ED. Our data reflect the difficulty of creating a meaningful tool able to identify patients with IE among this general and heterogeneous population because of the complexity of the disease and its low prevalence in the ED setting.

OBJECTIVE: SARS-CoV-2 disease (COVID-19) has become a pandemic disease, determining a public health emergency. The use of artificial intelligence in identifying easily available biomarkers capable of predicting the risk for severe disease may be helpful in guiding clinical decisions. The aim of the study was to investigate the ability of interleukin (IL)-6, troponin I, and D-dimer to identify patients with COVID-19 at risk for intensive care unit (ICU)-admission and death by using a machine-learning predictive model. PATIENTS AND METHODS: Data on demographic characteristics, underlying comorbidities, symptoms, physical and radiological findings, and laboratory tests have been retrospectively collected from electronic medical records of patients admitted to Policlinico A. Gemelli Foundation from March 1, 2020, to September 15, 2020, by using artificial intelligence techniques. RESULTS: From an initial cohort of 425 patients, 146 met the inclusion criteria and were enrolled in the study. The in-hospital mortality rate was 15%, and the ICU admission rate was 41%. Patients who died had higher troponin I (p-value<0.01) and IL-6 values (p-value=0.04), compared to those who survived. Patients admitted to ICU had higher levels of troponin I (p-value<0.01) and IL-6 (p-value<0.01), compared to those not admitted to ICU. Threshold values to predict in-hospital mortality and ICU admission have been identified. IL-6 levels higher than 15.133 ng/L have been associated with a 22.91% risk of in-hospital mortality, and IL-6 levels higher than 25.65 ng/L have been associated with a 56.16% risk of ICU admission. Troponin I levels higher than 12 ng/L have been associated with a 26.76% risk of in-hospital mortality and troponin I levels higher than 12 ng/L have been associated with a 52.11% risk of ICU admission. CONCLUSIONS: Levels of IL-6 and troponin I are associated with poor COVID-19 outcomes. Cut-off values capable of predicting in-hospital mortality and ICU admission have been identified. Building a predictive model using a machine-learning approach may be helpful in supporting clinical decisions in a more precise and personalized way.