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Background and Aims: Hypoalbuminemia, as defined by serum albumin (SA) levels ≤35 g/L, is associated to venous and arterial thrombosis in general population and in patients at risk of cardiovascular disease. It is unknown if SA ≤35 g/L is also associated to portal vein thrombosis (PVT) in cirrhosis. Methods: Cirrhotic patients enrolled in the Portal vein thrombosis Relevance On Liver cirrhosis: Italian Venous thrombotic Events Registry (PRO-LIVER) study (n = 753), were followed-up for 2 years to assess the risk of PVT, that was diagnosed by Doppler ultrasonography. Child-Pugh classes, Model for End-Stage Liver Disease score, presence of hepatocellular carcinoma and laboratory variables including SA, D-dimer, and high-sensitivity C-reactive protein (hs-CRP) were measured at baseline. Results: SA ≤35 g/L was detected in 52% of patients. A logistic multivariate regression analysis showed that higher Child-Pugh class, hepatocellular carcinoma and thrombocytopenia were significantly associated to SA ≤35 g/L. In a subgroup of patients where data regarding hs-CRP and D-dimer were available, SA ≤35 g/L was inversely associated with hs-CRP and D-dimer. During the follow-up, a total of 61 patients experienced PVT. A Kaplan Meier survival analysis showed SA ≤35 g/L was associated to increased risk of PVT compared to SA >35 g/L (P = .005). A multivariate Cox proportional hazards regression analysis showed that male sex, lower platelet count, and SA ≤35 g/L remained associated to PVT after adjusting for confounding factors. Conclusion: Cirrhotic patients with SA ≤35 g/L are at higher risk of experiencing PVT compared to those with SA >35 g/L and could be considered as potential candidates to anticoagulant prophylaxis for PVT prevention.

Background: Four randomized controlled trials (RCTs) did not show a benefit of direct oral anticoagulant (DOAC) treatment compared with antiplatelet therapy for the prevention of recurrent strokes in patients with embolic stroke of undetermined source (ESUS). However, the balance between efficacy and safety in subgroups needs to be better defined. We aimed to assess the relative benefits of DOACs in key subgroups of adult patients with ESUS. Methods: We searched major databases (PubMed, Embase, CENTRAL, and Web of Science) for RCTs published from inception to 16 June 2024. The primary outcome was recurrent stroke, and the main safety outcomes were major bleeding and clinically relevant non-major bleeding (CRNB). We assessed the risk of bias using the Cochrane Risk of Bias tool 2. Results: We identified four RCTs, involving a total of 13,970 patients with ESUS. Compared to antiplatelet therapy, treatment with DOAC did not reduce the risk of recurrent stroke (RR 0.95, 95% CI 0.83–1.08, p = 0.45) or ischemic stroke (RR 0.92, 95% CI 0.80–1.05, p = 0.22) or increase major bleeding (RR 1.57, 95% CI 0.87–2.83; p = 0.14). DOAC treatment was associated with a significantly higher risk of CRNMB compared to aspirin (RR 1.52, 95% CI: 1.22–1.90; p = 0.0002). The subgroup analysis demonstrated that use of DOACs was associated with a significant protective effect in patients aged 75 or older (RR 0.76, 95% CI 0.60–0.97, p = 0.03) and when the time from index stroke to randomization was ≥8 days (RR 0.80, 95% CI 0.66–0.97, p = 0.02) in preventing recurrency of any type of stroke. Conclusions: Our meta-analysis showed lack of overall benefit of anticoagulation with DOAC compared to antiplatelet therapy for recurrent stroke prevention in adult patients with ESUS. However, the subgroup analyses suggest the possibility of interactions between age and timing of randomization since stroke and treatment with an DOAC in terms of recurrent stroke prevention. Further research toward tailoring the antithrombotic strategy according to patient characteristics is needed. [ABSTRACT FROM AUTHOR]

The impact of diabetic foot (DF) on the healthcare system represents a major public health problem, leading to a considerable clinical and economic burden. The factors contributing to DF's development and progression are strongly interconnected, including metabolic causes, neuropathy, arteriopathy, and inflammatory changes. Sodium–glucose cotransporter 2 inhibitors (SGLT2-i), novel oral hypoglycemic drugs used as an adjunct to standard treatment, have recently changed the pharmacological management of diabetes. Nevertheless, data about the risk of limb amputation, discordant and limited to canagliflozin, which is currently avoided in the case of peripheral artery disease, have potentially discouraged the design of specific studies targeting DF. There is good evidence for the single immunomodulatory, neuroprotective, and beneficial vascular effects of SGLT2-i. Still, there is no clinical evidence about the early use of SGLT2-i in diabetic foot due to the lack of longitudinal and prospective studies proving the effect of these drugs without confounders. This narrative review aims to discuss the main evidence about the impact of SGLT2-i on the three complications of diabetes implicated in the development of DF, the state of the art, and the potential future implications. [ABSTRACT FROM AUTHOR]

Introduction: Penile metastases (PMs) are a rare clinical presentation mainly related to advanced stages of disease. Considering the low incidence, an optimal treatment approach has not yet been defined; surgery, chemotherapy, and radiotherapy (RT) are different options used in the vast majority with palliative intent. The advances in modern RT can represent an innovative tool in PM management and a curative option. This paper aimed to report the case of a PM patient treated with stereotactic body radiotherapy (SBRT) and perform a systematic literature review of current evidence on the RT approach to PM. Case Presentation: We reported the case of an 80-year-old patient with PM from primary bladder cancer. Following the surgical approach for the primary tumor, evidence of PM was shown, and the patient was admitted to SBRT treatment on PM after an adjuvant RT course on the pelvis. A 25 Gy in 5-fraction SBRT treatment was performed, and a complete clinical response was shown at the first follow-up. A PubMed/MEDLINE and Embase systematic review was carried out. The search strategy terms were [("penile metastasis"/exp OR "penile metastasis" OR (penile AND ("metastasis"/exp OR metastasis))) AND ("radiotherapy"/exp OR radiotherapy)] and only original articles up to October 24, 2023 were considered. Conclusion: A total of 174 studies were obtained using the previously mentioned search strategy, and the analysis was performed on 15 papers obtained following the complete selection process. All reported evidence was focused on the palliative approach of PM, showing good results in terms of symptom control. The potential role of modern RT in the management of PM has yet to be defined. The reported case showed the feasibility and the clinical impact of SBRT in PM treatment. [ABSTRACT FROM AUTHOR]

Background/Objectives: The interpretation of evidence on the de-escalation of triple therapy with the withdrawal of inhaled corticosteroids (ICSs) to dual bronchodilator therapy with a long-acting muscarinic antagonist (LAMA) and a long-acting beta-agonist (LABA) in patients with chronic obstructive pulmonary disease (COPD) is conflicting. We evaluated the efficacy and safety of ICS discontinuation from LABA-LAMA-ICS triple therapy compared to its continuation. Methods: We searched PubMed, Embase, Scopus, Web Of Science, clinicaltrial.gov, and CENTRAL for RCTs and observational studies from inception to 22 March 2024, investigating the effect of triple therapy de-escalation with the withdrawal of ICSs to dual therapy on the risk of COPD exacerbation, pneumonia, and lung function. This study was registered with PROSPERO, CRD42024527942. Results: A total of 3335 studies was screened; 3 RCTs and 3 real-world non-interventional studies were identified as eligible. The analysis of the time to the first moderate or severe exacerbation showed a pooled HR of 0.96 (95% CI, 0.80–1.15; I2 = 77%) for ICS withdrawal compared to triple therapy continuation. The analysis according eosinophil levels showed that COPD subjects with ≥300 eosinophils/µL had a significant increase in the incidence of moderate or severe exacerbations when de-escalated to LABA/LAMA (pooled HR: 1.35, 95% CI: 1.00–1.82; I2: 56%). ICS withdrawal did not significantly affect the risk of mortality and pneumonia. Conclusions: The de-escalation of triple therapy with ICS withdrawal does not affect the main outcomes evaluated (moderate or severe exacerbations, change in trough FEV1). COPD patients with high blood eosinophils (≥2% or ≥300 cells/µL) are most likely to benefit from continuing triple therapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Gastric cancer (GC) represents a major global health challenge, ranking as the second leading cause of cancer-related deaths. The high mortality rate is primarily due to late-stage diagnoses, which limit effective treatment options. Recent research emphasizes the development of targeted therapies and radiation immunotherapy as promising alternatives to traditional approaches. The review authors summarize recent advancements in targeted therapies for gastric cancer, focusing on both laboratory and clinical studies. They explore targeted approaches that have shown potential for improving diagnostic accuracy and treatment effectiveness. The findings of this paper may significantly impact the research community by highlighting the importance of personalized medicine in gastric cancer treatment. By identifying specific molecular targets and utilizing nanotechnology for drug delivery, these advancements aim to enhance treatment efficacy while minimizing systemic toxicity. Overall, the review suggests the potential for improved prognosis and treatment strategies through targeted therapies and precision medicine. Gastric cancer (GC) is the second most common cause of cancer-related death worldwide and a serious public health concern. This high death rate is mostly caused by late-stage diagnoses, which lead to poor treatment outcomes. Radiation immunotherapy and targeted therapies are becoming increasingly popular in GC treatment, in addition to surgery and systemic chemotherapy. In this review, we have focused on both in vitro and in vivo research, which presents a summary of recent developments in targeted therapies for gastric cancer. We explore targeted therapy approaches, including integrin receptors, HER2, Claudin 18, and glutathione-responsive systems. For instance, therapies targeting the integrin receptors such as the αvβ3 and αvβ5 integrins have shown promise in enhancing diagnostic precision and treatment efficacy. Furthermore, nanotechnology provides novel approaches to targeted drug delivery and imaging. These include glutathione-responsive nanoplatforms and cyclic RGD peptide-conjugated nanoparticles. These novel strategies seek to reduce systemic toxicity while increasing specificity and efficacy. To sum up, the review addresses the significance of personalized medicine and advancements in gastric cancer-targeted therapies. It explores potential methods for enhancing gastric cancer prognosis and treatment in the future. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation is associated with several comorbidities, particularly cognitive impairment and dementia, especially in older patients. Non‐vitamin K oral anticoagulants (NOACs) or vitamin K antagonists (VKAs) were used to prevent thromboembolic events. However, data on the real benefit of these drugs on cognitive function decline remains controversial. In this study we evaluated the effect of NOACs compared to VKAs on the absolute and relative decline in cognitive function over time. Methods: Nine hundred and eighty‐three older patients with nonvalvular AF were enrolled (76 ± 6 years; 291 on VKAs and 692 on NOACs). The cognitive function was assessed with Mini Mental State examination (MMSE) score. The between‐arms difference of cognitive evolution over time was investigated by Linear Mixed Models and group‐based trajectory model analyses. Results: In the whole multicenter observational study, after a long follow‐up of 7.2 ± 3.4 years, the patients of the NOACs versus VKAs group had lowest absolute reduction of the MMSE score between baseline and follow‐up (−0.3 ± 0.03 vs.−1.7 ± 0.1, p < 0.001). After stratification into five subgroups according to trajectories of MMSE score over time, the probability to belong to trajectories with lower decline in cognitive functions was higher in patients on NOACs than in those on VKAs (3.93–13.88 times). Conclusion: In older patients with atrial fibrillation, the use of NOACs was associated with a smaller decline of cognitive function over time compared to the VKAs, regardless that patients in the NOACs group were older and with a higher burden of comorbidities. [ABSTRACT FROM AUTHOR]

Background: Current management of COPD is predominantly focused on respiratory aspects. A multidimensional assessment including nutritional assessment, quality of life and disability provides a more reliable perspective of the true complexity of COPD patients. Methods: This was a prospective observational study of 120 elderly COPD patients at high risk of acute exacerbations. The Mini Nutritional Assessment (MNA) was administered in addition to the usual respiratory assessment. The primary outcome was a composite of moderate or severe acute exacerbations during 52 weeks of follow-up. Results: The median MNA Short Form (SF) score was 11 (8–12), 39 participants (32.50%) had a normal nutritional status, 57 (47.5%) were at risk of malnutrition and 24 (20%) were malnourished. Our multivariate linear regression models showed that the MNA score was associated with dyspnea and respiratory symptom severity, assessed by the Modified British Medical Research Council (mMRC) scale and the COPD Assessment Test (CAT) score, with spirometric variables, in particular with the severity of airflow limitation based on the value of FEV1, and with poorer QoL, as assessed by the EQ-5D-3 questionnaire. Competing risk analysis according to nutritional status based on the MNA Total Score showed that COPD participants "at risk of malnutrition" and "malnourished" had a higher risk of moderate to severe acute exacerbations with sub-hazard ratios of 3.08 (1.40–6.80), p = 0.015, and 4.64 (1.71–12.55), p = 0.0002, respectively. Conclusion: Our study confirms the importance of assessing nutritional status in elderly COPD patients and its prognostic value. [ABSTRACT FROM AUTHOR]

Stroke represents one of the neurological diseases most responsible for death and permanent disability in the world. Different factors, such as thrombus, emboli and atherosclerosis, take part in the intricate pathophysiology of stroke. Comprehending the molecular processes involved in this mechanism is crucial to developing new, specific and efficient treatments. Some common mechanisms are excitotoxicity and calcium overload, oxidative stress and neuroinflammation. Furthermore, non-coding RNAs (ncRNAs) are critical in pathophysiology and recovery after cerebral ischemia. ncRNAs, particularly microRNAs, and long non-coding RNAs (lncRNAs) are essential for angiogenesis and neuroprotection, and they have been suggested to be therapeutic, diagnostic and prognostic tools in cerebrovascular diseases, including stroke. This review summarizes the intricate molecular mechanisms underlying ischemic and hemorrhagic stroke and delves into the function of miRNAs in the development of brain damage. Furthermore, we will analyze new perspectives on treatment based on molecular mechanisms in addition to traditional stroke therapies. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a systemic autoimmune disorder caused by inflammation of cartilaginous diarthrodial joints that destroys joints and cartilage, resulting in synovitis and pannus formation. Timely detection and effective management of RA are pivotal for mitigating inflammatory arthritis consequences, potentially influencing disease progression. Nuclear medicine using radiolabeled targeted vectors presents a promising avenue for RA diagnosis and response to treatment assessment. Radiopharmaceutical such as technetium-99m (99mTc), combined with single photon emission computed tomography (SPECT) combined with CT (SPECT/CT), introduces a more refined diagnostic approach, enhancing accuracy through precise anatomical localization, representing a notable advancement in hybrid molecular imaging for RA evaluation. This comprehensive review discusses existing research, encompassing in vitro, in vivo, and clinical studies to explore the application of 99mTc radiolabeled targeting vectors with SPECT imaging for RA diagnosis. The purpose of this review is to highlight the potential of this strategy to enhance patient outcomes by improving the early detection and management of RA. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the role of radiomics in preoperative outcome prediction in cirrhotic patients who underwent transjugular intrahepatic portosystemic shunt (TIPS) using "controlled expansion covered stents". Materials and Methods: This retrospective institutional review board-approved study included cirrhotic patients undergoing TIPS with controlled expansion covered stent placement. From preoperative CT images, the whole liver was segmented into Volumes of Interest (VOIs) at the unenhanced and portal venous phase. Radiomics features were extracted, collected, and analyzed. Subsequently, receiver operating characteristic (ROC) curves were drawn to assess which features could predict patients' outcomes. The endpoints studied were 6-month overall survival (OS), development of hepatic encephalopathy (HE), grade II or higher HE according to West Haven Criteria, and clinical response, defined as the absence of rebleeding or ascites. A radiomic model for outcome prediction was then designed. Results: A total of 76 consecutive cirrhotic patients undergoing TIPS creation were enrolled. The highest performances in terms of the area under the receiver operating characteristic curve (AUROC) were observed for the "clinical response" and "survival at 6 months" outcome with 0.755 and 0.767, at the unenhanced and portal venous phase, respectively. Specifically, on basal scans, accuracy, specificity, and sensitivity were 66.42%, 63.93%, and 73.75%, respectively. At the portal venous phase, an accuracy of 65.34%, a specificity of 62.38%, and a sensitivity of 74.00% were demonstrated. Conclusions: A pre-interventional machine learning-based CT radiomics algorithm could be useful in predicting survival and clinical response after TIPS creation in cirrhotic patients. [ABSTRACT FROM AUTHOR]

The Mediterranean diet (MD), rich in minimally processed plant foods and in monounsaturated fats but low in saturated fats, meat, and dairy products, represents one of the most studied diets for cardiovascular health. It has been shown, from both observational and randomized controlled trials, that MD reduces body weight, improves cardiovascular disease surrogates such as waist-to-hip ratios, lipids, and inflammation markers, and even prevents the development of fatal and nonfatal cardiovascular disease, diabetes, obesity, and other diseases. However, it is unclear whether it offers cardiovascular benefits from its individual components or as a whole. Furthermore, limitations in the methodology of studies and meta-analyses have raised some concerns over its potential cardiovascular benefits. MD is also associated with characteristic changes in the intestinal microbiota, mediated through its constituents. These include increased growth of species producing short-chain fatty acids, such as Clostridium leptum and Eubacterium rectale, increased growth of Bifidobacteria, Bacteroides, and Faecalibacterium prausnitzii species, and reduced growth of Firmicutes and Blautia species. Such changes are known to be favorably associated with inflammation, oxidative status, and overall metabolic health. This review will focus on the effects of MD on cardiovascular health through its action on gut microbiota. [ABSTRACT FROM AUTHOR]