BACKGROUND: Alcohol is a major modifiable cause of morbidity, premature mortality and health inequalities, yet evidence informing "low-risk" thresholds and prevention strategies is fragmented. METHODS: Umbrella systemati...BACKGROUND: Alcohol is a major modifiable cause of morbidity, premature mortality and health inequalities, yet evidence informing "low-risk" thresholds and prevention strategies is fragmented. METHODS: Umbrella systematic review conducted according to PRISMA 2020 (protocol on OSF). PubMed/MEDLINE and Scopus were searched (Jan 2015-Mar 2026). An overlap-management approach selected an anchor synthesis per research question (Q1-Q37); supporting records were retained for triangulation. Quality appraisal used design-appropriate tools. Synthesis was narrative. RESULTS: Of 14,991 records, 49 were included (46 systematic reviews/meta-analyses, 2 WHO documents, 1 cross-sectional study) covering 37 pre-specified questions. Across most outcomes, higher intake and riskier patterns were associated with higher risk, with harms evident at levels often labelled 'moderate'. Any drinking increased injury odds (OR 2.80). Dose-response evidence showed steep gradients for cirrhosis (RR 9.35 in women and 2.82 in men at 40 g/day) and small but measurable increases in selected cancers at light drinking (e.g., breast cancer RR 1.05). In primary care, brief interventions reduced consumption at 12 months by -20 g/week. Pricing measures and some availability restrictions were directionally associated with lower consumption and harms, whereas evidence for other policy levers was more heterogeneous. CONCLUSIONS: Overall evidence favoured lower alcohol intake and avoidance of heavy episodic drinking, although confidence varied by endpoint and was limited for several questions by the quality of the available syntheses. Apparent low-dose benefits were not robust to bias-aware analyses. These findings support a pragmatic counselling and policy message of "less is better" rather than a universal safe threshold.
Bertola R, Maranini B, Garaffoni C
… +6 more, Pozzuto M, Riva Cambrino AL, Spinelli A, Govoni M, Bortoluzzi A, Silvagni E
Eur J Intern Med
· 2026 Mar · PMID 41887988
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OBJECTIVES: To evaluate the clinical-demographic drivers of treatment choice among targeted synthetic (ts-) and biologic (b-) disease-modifying anti-rheumatic drugs (DMARDs) and therapeutic outcomes in a cohort of patien...OBJECTIVES: To evaluate the clinical-demographic drivers of treatment choice among targeted synthetic (ts-) and biologic (b-) disease-modifying anti-rheumatic drugs (DMARDs) and therapeutic outcomes in a cohort of patients with rheumatoid arthritis (RA) before and after the European Medicines Agency (EMA) pronouncement on Janus Kinase Inhibitors (JAKis) in January 2023. METHODS: This single-center, ambidirectional study enrolled patients with RA who were initiating a new course of b/tsDMARDs. Retrospective (2019-2022) and prospective cohorts (2023-2024) were compared, and disease activity and treatment response (achievement of remission or low disease activity) were evaluated at 3 and 6-month follow-up. RESULTS: The study analyzed 539 treatment courses (300 retrospective, 239 prospective) in 380 patients. Following the EMA guidelines, tumor necrosis factor-α inhibitors (TNFis) became the predominant bDMARD (from 32% to 41.4%), whilst JAKis prescriptions declined, particularly in the first-line settings (from 18% to 4.1%). The risk factors proposed by the EMA did not significantly prevent treatment with JAKis. However, we observed that a benefit associated with the first-line treatment in terms of target achievement (adjusted OR for non-response retrospective cohort 0.30, 95%CI 0.14-0.62) was mitigated in the prospective phase (OR 0.82, 95%CI 0.33-2.07). CONCLUSION: The 2023 EMA pronouncement on JAKis led to a shift in prescription patterns, promoting TNFis versus JAKis. The decline in JAKis prescription did not appear to be driven by EMA-identified baseline risk factors, suggesting a generalized, categorical change. This channeling may have compromised the appropriateness of treatment choices, diminishing effectiveness in the prospective cohort, particularly for first-line therapies.
Eur J Intern Med
· 2026 Jun · PMID 41876327
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Point-of-care ultrasound (POCUS) is widely used in Internal Medicine for rapid bedside assessment, but conventional modalities such as B-mode and Doppler provide limited information on tissue microvascular perfusion. Con...Point-of-care ultrasound (POCUS) is widely used in Internal Medicine for rapid bedside assessment, but conventional modalities such as B-mode and Doppler provide limited information on tissue microvascular perfusion. Contrast-enhanced ultrasound (CEUS) can address this limitation by enabling real-time visualization of parenchymal and vascular microcirculation through intravenous administration of microbubble contrast agents. The present work will summarize the technical principles, clinical applications, and practical considerations of bedside CEUS in common Internal Medicine scenarios. When performed using contrast-specific imaging, CEUS can be safely administered at the bedside, including patients with renal dysfunction or hemodynamic instability. In selected clinical settings, CEUS may complement conventional POCUS by refining diagnostic interpretation, such as identifying pancreatic necrosis, characterizing abscesses and complicated cholecystitis, differentiating infarction from infection in solid organs, and assessing vascular abnormalities including thrombi or endoleaks. In postoperative or traumatic contexts, CEUS may assist in distinguishing hematomas from abscesses and in detecting active bleeding, supporting timely referral for interventional management. In chronic liver disease, CEUS can help differentiate bland from malignant portal vein thrombosis, with relevant implications for clinical decision-making. Despite these potential advantages, bedside CEUS should not be considered a routine extension of standard POCUS. Its application is limited by operator dependency, acoustic window constraints, and heterogeneous levels of supporting evidence across indications. When applied to focused clinical questions by appropriately trained clinicians and integrated within established diagnostic pathways, CEUS represents a valuable adjunct to bedside ultrasound. Further prospective studies are needed to better define its role in Internal Medicine practice.
Tolosa-Ridao C, Villalobos T, Gómez L
… +18 more, Boix-Palop L, Xercavins M, Sangil A, Canet M, Mesa A, López M, Muntañola A, Vall-Llovera F, Martí JM, Julià M, Santiago R, Bustamante G, Viladot E, Dietl B, Jaén A, Rodríguez-Carballeira M, Pérez P, Calbo E
Eur J Intern Med
· 2026 Mar · PMID 41876326
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BACKGROUND: Antibiotic treatment for asymptomatic bacteriuria (AB) is not recommended in the general population, and its significance in oncohematological patients remains unclear. OBJECTIVES: This study aimed to determi...BACKGROUND: Antibiotic treatment for asymptomatic bacteriuria (AB) is not recommended in the general population, and its significance in oncohematological patients remains unclear. OBJECTIVES: This study aimed to determine the prevalence of AB in hematologic patients and assess the frequency of bacteremia caused by the same microorganism isolated in untreated baseline asymptomatic bacteriuria (Baseline-AB) during myelosuppression. METHODS: A prospective, observational study was conducted from 2012-2017 in adult patients admitted for chemotherapy. Urine cultures (UCs) were performed, and no prophylactic antibiotics were administered. Blood and UC samples were collected during episodes of febrile neutropenia (FN) before antibiotic administration and compared with baseline UC results. RESULTS: Among 121 patients, 167 FN episodes were recorded, with 19 (11.3%) having Baseline-AB. A urinary focus was found in 1/19 (5.2%) of the Baseline-AB episodes, compared to 9/148 (6%) of the non baseline-AB (No-Baseline-AB) episodes (OR: 0.86; 95% CI:0.10-7.17;p = 0.88). Bacteremia occurred in 4/19 (21%) of the Baseline-AB episodes and in 38/148 (25.6%) of the No-Baseline-AB episodes. Only 1/19 patients in the Baseline-AB group (5.2%) had bacteremia caused by the same microorganism identified in the baseline UC. OUTCOME: FN resolved in all Baseline-ABs and in 96.6% of No-Baseline-ABs. Overall mortality occurred in 9/121 (7.4%) patients. CONCLUSION: Baseline-ABs were present in more than 10% of episodes, but no correlation was found between Baseline-ABs and bacteremia during FN. Only one case showed the same pathogen in both the baseline UC and the blood culture, suggesting that routine antibiotic treatment for Baseline-AB may not be necessary in this population.
Tambaro F, Imbimbo G, Pace V
… +8 more, Orlando S, Belloni E, Nigri G, Rizzo V, Picconi O, Amabile MI, Muscaritoli M, Molfino A
Eur J Intern Med
· 2026 Mar · PMID 41866269
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BACKGROUND: MicroRNAs regulate adipose tissue function, but their depot-specific expression in cancer remains poorly understood. This study analyzed the expression of selected microRNAs in subcutaneous (SAT) and visceral...BACKGROUND: MicroRNAs regulate adipose tissue function, but their depot-specific expression in cancer remains poorly understood. This study analyzed the expression of selected microRNAs in subcutaneous (SAT) and visceral adipose tissue (VAT) of gastrointestinal cancer patients versus controls to elucidate their roles in adipose tissue remodeling. METHODS: We conducted a cross-sectional study including gastrointestinal cancer patients and controls undergoing surgery for malignant or benign conditions. SAT and VAT biopsies were collected intraoperatively for miRNA expression analysis by RT-qPCR. Adiposity was evaluated by CT-scan to quantify total adipose tissue and categorize participants according to median adiposity level. RESULTS: Gastrointestinal cancer patients vs. controls showed higher relative expression of miR-128 in both SAT and VAT (p = 0.006 and p = 0.040), miR-155 in VAT (p = 0.018), and lower miR-181a in VAT (p = 0.004). Within cancer group, miR-26a and miR-128 were lower in VAT vs SAT (p < 0.001), while miR-155 levels were higher in VAT vs SAT (p < 0.001). MiR-26a was higher in SAT regardless of adiposity level, while miR-128 and miR-144 showed depot- and adiposity-dependent variations, with downregulation of miR-128 in VAT from low-adiposity patients and lower miR-144 in SAT from high-adiposity. MiR-155 was elevated in VAT from low-adiposity patients, whereas miR-181a expression remained unchanged across depots and adiposity levels. CONCLUSIONS: This is the first study comparing both SAT and VAT microRNA from the same cancer patients, stratified by adiposity assessed via CT-scan, showing depot-specific miRNA regulation. Our findings indicate that VAT is prone to metabolic dysregulation, with miR-155 emerging as a potential indicator of visceral fat remodeling.
BACKGROUND: Pulmonary embolism (PE) is associated with high mortality and morbidity. However, data on the long-term mortality risk in cancer-free PE patients compared to the general population remains limited. AIM: To st...BACKGROUND: Pulmonary embolism (PE) is associated with high mortality and morbidity. However, data on the long-term mortality risk in cancer-free PE patients compared to the general population remains limited. AIM: To study long-term all-cause mortality (one year and longer) in cancer-free PE patients versus matched population controls, stratified by the presence or absence of comorbidities. To assess the impact of comorbidities on life expectancy and to identify predictors of long-term mortality. METHODS: A nationwide Swedish register study including cancer-free patients diagnosed with a first-time PE from 2006 to 2023 and matched population controls. All-cause mortality was analyzed using Cox proportional hazard regression models, expressed as adjusted hazard ratios (aHRs). RESULTS: A total of 49,596 PE cases (mean age 67.3 years, 52.1% women) and 196,039 matched controls were included. One-year mortality was higher in PE cases (7.5%) compared to controls (1.6%). Among the PE cases, 53.6% had no comorbidities at baseline. Yet, the excess mortality risk remained elevated: one-year aHR 3.72 (95% CI, 3.36 - 4.12); beyond three years, aHR 1.54 (95% CI, 1.46 - 1.63). During follow-up, 18.5% of cases developed ischemic heart disease, and 22.7% heart failure. Cases without baseline comorbidities reached the 75th percentile of the survival distribution 8.1 years later (95% CI, 7.09-9.10) compared to PE patients with one or more comorbidities. Predictors of long-term mortality included heart failure (aHR 1.97, 95% CI, 1.88-2.06) and liver disease (aHR 2.17, 95% CI 1.88-2.51) CONCLUSION: PE increased long-term mortality risk even in the absence of baseline comorbidities. However, a substantial proportion of cases developed important conditions during follow-up, particularly cardiovascular diseases.
Vikse J, Lanzillotta M, Goni E
… +15 more, Fevang BS, Midtvedt Ø, Mahajne J, Batani V, Benanti G, Beyer G, Dagna L, Molberg Ø, Norheim KB, Brunborg C, Schönermarck U, Regel I, Mayerle J, Della-Torre E, Hoffmann-Vold AM
Eur J Intern Med
· 2026 Mar · PMID 41862339
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OBJECTIVES: While glucocorticoids have been considered the standard of care for IgG4-related disease (IgG4-RD), rituximab is increasingly used off-label. We aimed to evaluate the glucocorticoid-sparing ability of rituxim...OBJECTIVES: While glucocorticoids have been considered the standard of care for IgG4-related disease (IgG4-RD), rituximab is increasingly used off-label. We aimed to evaluate the glucocorticoid-sparing ability of rituximab using real-world data. METHODS: This was an observational multicenter study including adult IgG4-RD patients from three European referral centers treated with glucocorticoids or rituximab (± glucocorticoids). The primary endpoint was no glucocorticoid use at 6 months. Secondary endpoints included treatment response (≥ 2-point decline in responder index (RI)), remission (RI = 0) and flare. Key safety measures included infections requiring hospitalization, and death. We applied logistic regression adjusted for potential confounders. FINDINGS: We included 167 patients, 115 (68.9 %) in the rituximab and 52 (31.1 %) in the glucocorticoid group. At baseline, the rituximab group was younger, had longer disease duration, more often relapsing disease and higher RI score than the glucocorticoid group. Despite these indicators of more severe disease, a higher proportion of patients in the rituximab group were free from glucocorticoids by 6 months (OR 3.62, 95 % CI 1.06-12.43, p = 0.040). The median cumulative prednisolone dose at 12 months was 1640.0 mg (IQR 150.0-2578.8) for the rituximab group, and 2950.0 mg (IQR 2302.0-4120.0) for the glucocorticoid group (p < 0.001). The secondary endpoints were similar between groups. INTERPRETATION: While the rituximab-treated patients in this study had more severe IgG4-RD than the glucocorticoid-treated comparators, treatment with rituximab was associated with similar effectiveness endpoints, while significantly reducing glucocorticoid use.
Ageno W, Bertoletti L, Lindhoff-Last E
… +8 more, Lip G, Meijer K, Monreal M, Tran H, Bessada Y, Triller D, Burnett A, Ansell J
Eur J Intern Med
· 2026 May · PMID 41856877
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Antithrombotic drugs are a class of medications with the highest rates of serious and life-threatening adverse events, many of which are preventable with proper knowledge and systems of management. Antithrombotic steward...Antithrombotic drugs are a class of medications with the highest rates of serious and life-threatening adverse events, many of which are preventable with proper knowledge and systems of management. Antithrombotic stewardship is a care model shown to improve outcomes and is gaining traction throughout the world. Stewardship implies a comprehensive system of care employing coordinated, efficient, and sustainable initiatives designed to achieve optimal anticoagulant-related health outcomes and minimize avoidable adverse drug events. Numerous studies from Europe, Asia and elsewhere document the high rate of adverse events associated with prescribing errors, problems of adherence, inappropriate concomitant therapy, and poor follow up. The challenge with antithrombotic stewardship on a global basis is that no single model is applicable to all countries. This manuscript summarizes recent data from a wide range of countries documenting poor outcomes with antithrombotic care, describes the nature and elements of a stewardship program, and advocates for the implementation of such programs, within the context of different country-specific healthcare delivery systems and healthcare cultures.
Therapeutic non-adherence (TNA) significantly contributes to chronic disease burden but remains framed largely as a behavioral issue rather than a pathological process. This conceptual analysis applies the Bradford Hill...Therapeutic non-adherence (TNA) significantly contributes to chronic disease burden but remains framed largely as a behavioral issue rather than a pathological process. This conceptual analysis applies the Bradford Hill criteria assessing whether chronic TNA meets the threshold for recognition as a distinct clinical syndrome. The evidence shows consistent associations between TNA and increased morbidity, mortality, and healthcare costs across multiple chronic diseases. Key features - such as temporality, specificity, dose-response relationship, and emerging biological correlates, particularly in cardiovascular disease - support its pathophysiological plausibility. Intervention studies suggest that modifying TNA alters disease trajectory, and analogies with recognized behavioral syndromes further reinforce a syndromic framing. Reclassifying TNA as a nosological entity would enable systematic identification, coding, and targeted intervention, while potentially reducing stigma and enhancing therapeutic engagement. Though care is needed to avoid overmedicalization, the current approach underestimates the complexity and clinical relevance of chronic TNA. A structured nosological reframing may therefore be conceptually and pragmatically justified. While recent reviews have comprehensively addressed the determinants, consequences, and management of non-adherence, our work offers a complementary perspective by proposing its systematic investigation within a structured nosological framework, supported by the systematic application of the Bradford Hill criteria, thereby extending the current literature from a novel conceptual angle. Further research is required to develop consensus diagnostic criteria, validate phenotypes, and assess etiology-specific interventional strategies before any formal disease classification can be established.
Trotta L, Agozzino F, Berra S
… +13 more, Mascolo R, Rubuano F, Blagova O, Lazaros G, Ceriani E, Pancrazi M, Mauro A, Lazarou E, Marotta N, Casarin F, Sicignano LL, Imazio M, Brucato A
Eur J Intern Med
· 2026 Mar · PMID 41846164
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AIM: To assess the effect of hydroxychloroquine (HCQ) in recurrent pericarditis (RP). METHODS: International longitudinal observational study including 80 patients with idiopathic or post-cardiac injury RP, treated with...AIM: To assess the effect of hydroxychloroquine (HCQ) in recurrent pericarditis (RP). METHODS: International longitudinal observational study including 80 patients with idiopathic or post-cardiac injury RP, treated with HCQ for at least 6 months (April 2014-August 2025); 3 other patients stopped HCQ within 6 months for side-effects. Recurrences, hospitalizations, side effects and therapies were evaluated before and after HCQ. Patient and physician-reported effectiveness were recorded. RESULTS: Females were 57/80 (71 %); median age 51.5 years [IQR 43.8-62.8]. C-reactive protein (CRP) was >10mg/L in 52 (65 %) patients. The median follow-up after starting HCQ was 27.3 [11.7-47.8] months, and the daily dose was 400 mg in 52 patients (65 %) and 200 mg in 28 (35 %). Among the 62 patients treated with HCQ for at least 12 months, recurrences decreased in the 12 months following treatment (median 1 [0-2]) compared with the 12 months preceding it (median 2 [1-3])(p < 0.001), as well as hospitalizations (5 vs 32) (p < 0.001). HCQ was effective either in CRP positive or CRP negative subjects. Fifty-four patients (67.5 %) were on steroids when HCQ was started, but only 21 (26.3 %) continued them at the last follow-up (p < 0.001); the median daily dose of prednisone was reduced from 10.0 mg [7.5-17.5] to 5.0 [2.5-5.0] (p < 0.001). Regarding patients' opinions about HCQ effectiveness, 64 pts (80 %) judged it useful, 16 (20 %) neutral (8 stopped HCQ for lack of effectiveness); the physicians' opinions were similar (concordance rate 74 (93.7 %), k 0.777; p < 0.001). CONCLUSIONS: HCQ reduced recurrences, hospitalizations, and corticosteroid dose in RP, with no relevant side effects.
BACKGROUND: The rise in global prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) has highlighted the importance of developing sex-specific risk profiles for MASLD based on readily available s...BACKGROUND: The rise in global prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD) has highlighted the importance of developing sex-specific risk profiles for MASLD based on readily available self-reported lifestyle characteristics and plasma biomarkers. OBJECTIVES: We aimed to develop sex-specific risk profiles for MASLD according to lifestyle characteristics and plasma biomarkers. METHODS: We included 3282 women and 2167 men from the Copenhagen General Population Study cohort with a computed tomography (CT) scan of the liver. All individuals had information on 17 lifestyle characteristics and plasma biomarkers from standard hospital assays. MASLD was defined by non-contrast CT scan Hounsfield Units (≤48 and ≤56HU) or liver/spleen ratios <1 in addition to at least one cardiometabolic risk factor. RESULTS: For the same value of most lifestyle characteristics and plasma biomarkers, women had less liver fat on CT scans than men. For abnormal categories of most lifestyle characteristics and plasma biomarkers, odds ratios for MASLD were more pronounced in women than in men (p-values for sex-interaction 4 × 10 to 3 × 10). Risk profiles for severe MASLD included waist circumference, smoking, alanine transaminase, and HDL cholesterol for both sexes. For women, risk profiles further included body mass index, systolic blood pressure, and remnant cholesterol, while for men, risk profiles further included diastolic blood pressure. Risk profiles for severe+moderate MASLD and for liver/spleen MASLD included many of the same characteristics; although liver/spleen in women merely included three characteristics. CONCLUSION: Risk profiles for MASLD according to 17 lifestyle characteristics and plasma biomarkers differ by sex.