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Through this study, the synergistic behavior of small-molecular-weight, amphiphilic surfactant molecules and the triblock copolymer Pluronic 188 was extensively evaluated based on their ability to formulate nanocarriers with novel properties for the delivery of class II and IV (biopharmaceutical classification system) chemotherapeutic compounds. The combination of four different surfactants at multiple weight ratios and twelve initially formulated nanosystems resulted in four hybrid delivery platforms, which were further studied in terms of multiple physicochemical characteristics, as well as their stability in protein-rich media (fetal bovine serum/phosphate-buffer saline). Finally, we obtained a single final nanoformulation that exhibited a high loading capacity (%EE ≥ 75%) and a sustained drug release profile under physiological conditions (model drug methotrexate), without altering the original physicochemical characteristics of the carrier. With a mean hydrodynamic radius (Rh) of less than 70 nm, a polydispersity index of 0.219, and no protein complexation, the system is a suitable candidate for in vivo, intravenous, and/or intramuscular administration. The cytotoxicity and genotoxicity of both loaded and unloaded carriers were evaluated through the examination of the upregulation or downregulation of apoptosis-related pathways. Multiple conventional 2D and 3D spheroidal conformations were used for these assessments, including HEK293, HCT-116, and MCF-7 cell lines, the results of which stressed the safety and biocompatibility of the empty nanocarrier. Additionally, experiments on Caenorhabditis elegans were conducted to evaluate the system's in vivo toxicity, focusing on developmental stages, egg-laying behavior, and locomotion. Nanosystems studied in terms of chemotherapeutic encapsulation have mostly focused on the physiochemical aspect of the development of such novel delivery platforms, with only few exceptions proceeding step-by-step from cellular 2D to 3D to in vivo experimentation. The present study offers a holistic view of the behavior of such a novel system, advancing our understanding of the capabilities of polymeric/surfactant-based nanodelivery platforms.

Purpose: Uncertainties remain on the optimal treatment for acute minor stroke with nondisabling symptoms. The two most common therapeutic approaches are intravenous thrombolysis (IVT) and antiplatelet therapy, notably dual antiplatelet therapy (DAPT). We synthesized data from the literature to compare IVT to DAPT and identify the best treatment for this population., Method: We systematically searched Pubmed, Web of Science and the Cochrane Library for randomized trials and observational studies comparing IVT, aspirin, and/or DAPT, started within 24 h of symptom onset in patients with minor stroke (NIHSS ⩽ 5) and nondisabling symptoms. Random-effects Bayesian network meta-analysis was conducted. The primary outcome was excellent functional outcome at 3 months (mRS 0-1). Secondary outcomes included mRS 0-2, symptomatic intracranial hemorrhage, mortality, and recurrent stroke., Findings: Four randomized trials and 2 observational studies (5897 patients for the analysis of the primary outcome) were included. Compared with IVT (alteplase), DAPT (clopidogrel + aspirin) was significantly associated with higher odds of mRS 0-1 (OR = 1.52, 95% CrI, 1.09-2.35), but aspirin alone was not (OR = 1.36, 95% CrI, 0.87-2.30). DAPT was also associated with lower odds of symptomatic intracranial hemorrhage than alteplase (OR = 0.14, 95% CrI, 0.03-0.91). There were no significant differences between treatment groups regarding the other outcomes. For each outcome, the ranking for the best treatment was DAPT, then aspirin, and then IVT., Discussion/conclusion: This network meta-analysis suggests that DAPT may be the optimal treatment for acute nondisabling stroke, with higher odds of excellent functional outcome compared with IVT.Registration: PROSPERO ID: CRD42024522038., Competing Interests: Declaration of conflicting interestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: AHK reports salary support from the Heart and Stroke Foundation Canada and consulting fees from DiaMedica Therapeutics Inc. The other authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background and Aim: Diabetes has been shown in last decades to be associated with a significantly higher mortality among patients with ST-segment elevation myocardial infarction (STEMI) treated with primary PCI (PPCI). Therefore, the aim of current study was to evaluate the impact of diabetes on times delays, reperfusion and mortality in a contemporary STEMI population undergoing PPCI, including treatment during the COVID pandemic., Methods and Results: The ISACS-STEMI COVID-19 is a large-scale retrospective multicenter registry involving PPCI centers from Europe, Latin America, South-East Asia and North-Africa, including patients treated from 1st of March until June 30, 2019 and 2020. Primary study endpoint of this analysis was in-hospital mortality. Secondary endpoints were postprocedural TIMI 0-2 flow and 30-day mortality. Our population is represented by 16083 STEMI patients. A total of 3812 (23,7 %) patients suffered from diabetes. They were older, more often males as compared to non-diabetes. Diabetic patients were less often active smokers and had less often a positive family history of CAD, but they were more often affected by hypertension and hypercholesterolemia, with higher prevalence of previous STEMI and previous CABG. Diabetic patients had longer ischemia time, had more often anterior MI, cardiogenic shock, rescue PCI and multivessel disease. They had less often out-of-hospital cardiac arrest and in-stent thrombosis, received more often a mechanical support, received less often a coronary stent and DES. Diabetes was associated with a significantly impaired postprocedural TIMI flow (TIMI 0-2: 9.8 % vs 7.2 %, adjusted OR [95 % CI] = 1.17 [1.02-1.38], p = 0.024) and higher mortality (in-hospital: 9.1 % vs 4.8 %, Adjusted OR [95 % CI] = 1.70 [1.43-2.02], p < 0.001; 30-day mortality: 10.8 % vs 6 %, Adjusted HR [95 % CI] = 1.46 [1.26-1.68], p < 0.001) as compared to non-diabetes, particularly during the pandemic., Conclusions: Our study showed that in a contemporary STEMI population undergoing PPCI, diabetes is significantly associated with impaired epicardial reperfusion that translates into higher in-hospital and 30-day mortality, particularly during the pandemic., (Copyright © 2024 The Italian Diabetes Society, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.)

Background: Neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS) and adjuvant chemotherapy is a therapeutic choice for women with advanced ovarian cancer. Whether NACT affects the tumor's molecular profile has not been determined., Methods: This was a retrospective study of patients with advanced-stage epithelial ovarian cancer treated with NACT at oncology departments affiliated with the Hellenic Cooperative Oncology Group (HeCOG). Tumor molecular profiling was performed on formalin-fixed and paraffin-embedded (FFPE) tumor pre- and post-NACT tissues. Homologous recombination deficiency (HRD), tumor-infiltrating lymphocytes (TILs), tumor molecular alterations, and tumor mutational burden (TMB) via next-generation sequencing analysis were assessed., Results: Overall, tumors from 36 patients were assessed, and molecular profiling was evaluated in 20 paired tumor samples. HRD positivity exhibited no significant change between pre- and post-NACT tumors. The BRCA1/2 mutational status remained constant, irrespective of the treatment administration. Pre-NACT tumors tended to exhibit a lower percentage of intratumoral TILs compared to post-NACT tumors ( p = 0.004). Differences in the mutation profile between pre- and post-treatment tissue were observed in 33.33% (6/18) of the cases. The mean tumor cell content (TCC) ( p -value: 0.0840) and the mean genomic instability score ( p -value: 0.0636) decreased slightly numerically after therapy. A moderate inverse relationship was observed between the pre-NACT TMB and the chemotherapy response score ( p -value: 0.038), indicating this correlation is statistically significant., Conclusion: This study provides insights into the effect of NACT on the tumor molecular landscape. While BRCA1/2 and HRD status remained stable, an increase in TIL proportion and changes in the mutational profiles were observed post-treatment.

Background: Steroidal mineralocorticoid receptor antagonists reduce morbidity and mortality among patients with heart failure and reduced ejection fraction, but their efficacy in those with heart failure and mildly reduced or preserved ejection fraction has not been established. Data regarding the efficacy and safety of the nonsteroidal mineralocorticoid receptor antagonist finerenone in patients with heart failure and mildly reduced or preserved ejection fraction are needed., Methods: In this international, double-blind trial, we randomly assigned patients with heart failure and a left ventricular ejection fraction of 40% or greater, in a 1:1 ratio, to receive finerenone (at a maximum dose of 20 mg or 40 mg once daily) or matching placebo, in addition to usual therapy. The primary outcome was a composite of total worsening heart failure events (with an event defined as a first or recurrent unplanned hospitalization or urgent visit for heart failure) and death from cardiovascular causes. The components of the primary outcome and safety were also assessed., Results: Over a median follow-up of 32 months, 1083 primary-outcome events occurred in 624 of 3003 patients in the finerenone group, and 1283 primary-outcome events occurred in 719 of 2998 patients in the placebo group (rate ratio, 0.84; 95% confidence interval [CI], 0.74 to 0.95; P = 0.007). The total number of worsening heart failure events was 842 in the finerenone group and 1024 in the placebo group (rate ratio, 0.82; 95% CI, 0.71 to 0.94; P = 0.006). The percentage of patients who died from cardiovascular causes was 8.1% and 8.7%, respectively (hazard ratio, 0.93; 95% CI, 0.78 to 1.11). Finerenone was associated with an increased risk of hyperkalemia and a reduced risk of hypokalemia., Conclusions: In patients with heart failure and mildly reduced or preserved ejection fraction, finerenone resulted in a significantly lower rate of a composite of total worsening heart failure events and death from cardiovascular causes than placebo. (Funded by Bayer; FINEARTS-HF ClinicalTrials.gov number, NCT04435626.)., (Copyright © 2024 Massachusetts Medical Society.)

Introduction: This study aimed to describe the clinical course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with glomerular diseases (GDs) and its impact on the probability of relapse., Methods: Patients with biopsy-proven GD and positive PCR test for SARS-CoV-2 from glomerular clinics across Greece were studied retrospectively. Those who received the GD diagnosis after the SARS-CoV-2 vaccination or coronavirus disease 2019 (COVID-19) or ended in ESKD prior to infection were excluded. Demographics, histopathological diagnoses, past medical history, immunosuppression, and GD activity status were recorded., Results: A total of 219 patients with GDs and documented SARS-CoV-2 infection were included. The mean time from the diagnostic kidney biopsy to SARS-CoV-2 infection was 67.6 ( ± 59.3) months. Among the participants, 82.5% had been vaccinated against SARS-CoV-2 with three doses (range: 2.5-3) without subsequent GD reactivation in 96.2% of them. Twenty-two patients (10%) were hospitalized for COVID-19 and one (0.5%) required mechanical ventilation. Four (1.8%) died due to COVID-19 and one (0.5%) had long COVID-19 symptoms. Among patients in remission prior to SARS-CoV-2 infection, 22 (11.2%) experienced a GD relapse within 2.2 (range: 1.5-3.7) months from the diagnostic test. The relapse-free survival after COVID-19 was significantly shorter for patients with minimal change disease, pauci-immune glomerulonephritis, and focal segmental glomerulosclerosis. No difference was observed in the relapse-free survival post-COVID-19 based on the history of SARS-CoV-2 vaccination., Conclusions: SARS-CoV-2 infection appears to have a symptomatic but uncomplicated sequence in vaccinated patients with GDs, with a significant impact on the clinical course of GD, associated with an increased probability of relapse in certain histopathological types., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lionaki, Dounousi, Marinaki, Kantartzi, Papasotiriou, Galitsiou, Bellos, Sardeli, Kalogeropoulos, Liakopoulos, Mpintas, Goumenos, Flouda, Venetsanopoulou, Voulgari, Andronikidi, Moustakas, Panagoutsos and Boletis.)

Introduction: Wearable Activity Trackers (WATs) offer real-time feedback on activity levels. We assessed the impact of WAT usage on physicians' exercise habits., Methods: Physicians from the Athens Medical Association, Greece (n = 742) responded to a self-administered questionnaire evaluating usage of WAT, demographic characteristics, specialty, and physical exercise habits. WHO guidelines recommend at least 150 min/week of moderate-intensity exercise in all healthy adults. Subjects were divided in Users of WATs (Group A), and Non-Users of WATs (Group B). This is an observational, cross-sectional study., Results: There was no difference in baseline characteristics between the two groups (age, sex, body mass index). WATs were used by 38%. Between Group A and B, there was difference in mean exercise training time (302 ± 304 min vs. 210 ± 268 min, p < 0.001), higher percentage of WHO goal achievement (66.3% vs. 50.7%, p < 0.001), and greater awareness of WHO Guidelines (59.9% vs. 47.4%, p < 0.001). WATs were mostly used by four main specialties, with higher use from Cardiologists: Cardiology (47%), Endocrinology (44%), Surgery (35%) and Internal Medicine (25%), with a p = 0.045. Finally, users of WATs compared to non-users showed higher willingness to reduce body weight (58.5% vs. 48%, p = 0.01), apply dietary restrictions (36.5% vs. 29.6%, p = 0.05), and greater motivation for weekly physical exercise (74.1% vs. 32.4%, p < 0.001); Conclusion: Physicians using WATs demonstrate increased exercise training time, greater awareness of WHO guidelines and a higher propensity to implement dietary restrictions compared to non-users. Variations in WAT usage across medical specialties emphasize the need for targeted interventions to promote physical activity and enhance healthcare professionals' health.

Purpose: Adrenocortical carcinoma (ACC) poses a significant challenge in healthcare due to its aggressive nature and rarity. Prior reports suggest a poorer prognosis associated with hormone-secreting neoplasms. This study aims to assess the impact of ACC hormonal status on patients' oncologic survival., Methods: A comprehensive literature search of the Medline, Embase, Web of Science, CINAHL, CENTRAL and clinicaltrials.gov databases was undertaken. Utilized data involved Hazard Ratios derived from multivariable analysis in order to minimize exposure to confounding bias. Included studies were subsequently meta-analyzed using a Random effects model., Results: Twelve studies incorporating 4483 patients were included in the quantitative analysis. Hormonally active ACCs comprised 48% of the entire pooled patient cohort and were found to be associated with significantly worse Overall Survival (HR 1.57, 95% Confidence Interval 1.39-1.78, p < 0.001). Disease-Free Survival was comparably impacted (HR 1.32, 95% CI 1.11-1.57, p < 0.001). Furthermore, cortisol secreting ACCs specifically, were also found to be associated with a 48% increase in the hazard of death or disease recurrence. Interstudy statistical heterogeneity was minimal among evaluated outcomes., Conclusions: Hormone-producing ACCs exhibit a poorer prognosis compared to non-secreting counterparts, with a 57% increased risk of death and a 32% increased risk of recurrence. These findings support the hypothesis that hormone production signifies an adverse tumor-specific feature, particularly when leading to hypercortisolemia, indicating an aggressive disease phenotype., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: To analyse the new evidence (2018-2022) for the management of systemic lupus erythematosus (SLE) to inform the 2023 update of the European League Against Rheumatism (EULAR) recommendations., Methods: Systematic literature reviews were performed in the Medline and the Cochrane Library databases capturing publications from 1 January 2018 through 31 December 2022, according to the EULAR standardised operating procedures. The research questions focused on five different domains, namely the benefit/harm of SLE treatments, the benefits from the attainment of remission/low disease activity, the risk/benefit from treatment tapering/withdrawal, the management of SLE with antiphospholipid syndrome and the safety of immunisations against varicella zoster virus and SARS-CoV2 infection. A Population, Intervention, Comparison and Outcome framework was used to develop search strings for each research topic., Results: We identified 439 relevant articles, the majority being observational studies of low or moderate quality. High-quality randomised controlled trials (RCTs) documented the efficacy of the type 1 interferon receptor inhibitor, anifrolumab, in non-renal SLE, and belimumab and voclosporin, a novel calcineurin inhibitor, in lupus nephritis (LN), when compared with standard of care. For the treatment of specific organ manifestations outside LN, a lack of high-quality data was documented. Multiple observational studies confirmed the beneficial effects of attaining clinical remission or low disease activity, reducing the risk for multiple adverse outcomes. Two randomised trials with some concerns regarding risk of bias found higher rates of relapse in patients who discontinued glucocorticoids (GC) or immunosuppressants in SLE and LN, respectively, yet observational cohort studies suggest that treatment withdrawal might be feasible in a subset of patients., Conclusion: Anifrolumab and belimumab achieve better disease control than standard of care in extrarenal SLE, while combination therapies with belimumab and voclosporin attained higher response rates in high-quality RCTs in LN. Remission and low disease activity are associated with favourable long-term outcomes. In patients achieving these targets, GC and immunosuppressive therapy may gradually be tapered. Cite Now., Competing Interests: Competing interests: AF reports honoraria and/or consulting fees from Lilly, Boehringer, Novartis, AbbVie, AstraZeneca, GSK, MSD, Pfizer, UCB, Amgen, Aenorasis, support for attending meetings from UCB. MK reports honoraria and/or consulting fees from GSK, participation in advisory boards from GSK, AstraZeneca, Amgen. GB reports grants from GSK, AstraZeneca, Pfizer, honoraria and/or consulting fees from Lilly, Aenorasis, Novartis, AstraZeneca, GSK, SOBI, Pfizer, participation in advisory boards from Novartis. DTB reports unrestricted investigational grants from GSK, honoraria and/or consulting fees from GSK, AstraZeneca, Pfizer. CBM declares no conflict of interest., (© European Alliance of Associations for Rheumatology, EULAR 2024. Re-use permitted under CC BY-NC-ND. No commercial re-use. No derivatives. See rights and permissions. Published by BMJ on behalf of EULAR.)

According to the WHO, more than 90,000 cases of mpox have been reported since the 2022 worldwide outbreak, which resulted in 167 deaths, while a new outbreak in Africa since 2023 has resulted in over 18,000 cases and 617 deaths. Mpox is a zoonosis caused by the monkeypox virus, a double-stranded DNA virus belonging to the Orthopoxvirus genus, which causes smallpox-like illness. Until 2022, cases were predominately located in West and Central Africa, with only sporadic cases and outbreaks reported in other parts of the world. During the 2022 outbreak, the primary mode of transmission was sexual contact among men who have sex with men. The changing epidemiology of mpox resulted in new disease phenotypes and populations at risk, disproportionally affecting people who live with HIV. Commonly presenting as a mild, self-limiting illness, mpox can cause severe and protracted disease in people with HIV with a CD4 count < 200 cell/mm 3 . The global emergence of mpox that followed and intersected with COVID-19 mobilized the scientific community and healthcare stakeholders to provide accurate diagnostics, preventive vaccines and treatment to those most affected. Despite existing gaps, this rapid response helped to contain the outbreak, but challenges remain as new variants emerge. Preparedness and readiness to respond to the next outbreak is crucial in order to minimize the impact to the most vulnerable.

Dietary folate intake has been identified as a potentially modifiable factor of gastric cancer (GC) risk, although the evidence is still inconsistent. We evaluate the association between dietary folate intake and the risk of GC as well as the potential modification effect of alcohol consumption. We pooled data for 2829 histologically confirmed GC cases and 8141 controls from 11 case-control studies from the international Stomach Cancer Pooling Consortium. Dietary folate intake was estimated using food frequency questionnaires. We used linear mixed models with random intercepts for each study to calculate adjusted odds ratios (OR) and 95% confidence interval (CI). Higher folate intake was associated with a lower risk of GC, although this association was not observed among participants who consumed >2.0 alcoholic drinks/day. The OR for the highest quartile of folate intake, compared with the lowest quartile, was 0.78 (95% CI, 0.67-0.90, P-trend = 0.0002). The OR per each quartile increment was 0.92 (95% CI, 0.87-0.96) and, per every 100 μg/day of folate intake, was 0.89 (95% CI, 0.84-0.95). There was a significant interaction between folate intake and alcohol consumption (P-interaction = 0.02). The lower risk of GC associated with higher folate intake was not observed in participants who consumed >2.0 drinks per day, OR Q4v Q1  = 1.15 (95% CI, 0.85-1.56), and the OR 100 μg/day  = 1.02 (95% CI, 0.92-1.15). Our study supports a beneficial effect of folate intake on GC risk, although the consumption of >2.0 alcoholic drinks/day counteracts this beneficial effect., (© 2024 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

This article is the second in a series of two publications on the European Crohn's and Colitis Organisation [ECCO] evidence-based consensus on the management of Crohn's disease. The first article covers medical management; the present article addresses surgical management, including preoperative aspects and drug management before surgery. It also provides technical advice for a variety of common clinical situations. Both articles together represent the evidence-based recommendations of the ECCO for Crohn's disease and an update of prior ECCO Guidelines., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background : Data regarding fungal PJIs of the shoulder are scarce. The present systematic review aims to identify and evaluate all published shoulder fungal PJIs in an effort to better understand the diagnostic and therapeutic approach to these infections. Methods : A systematic review according to the PRISMA guidelines was conducted, locating all shoulder fungal PJIs. The initial search located 1435 articles. Data were collected on demographics, the causative fungus, antifungal treatment (AFT), surgical interventions, and infection outcomes. Results: After screening and implementation of the inclusion criteria, a total of 10 articles, including 10 cases, were eligible. The sample's mean age was 62.44 years. Diabetes mellitus was the most common comorbidity (30%), while 70% were immunocompromised. Candida spp. was the most common causative fungus (nine cases; 90%), while all cases were confirmed with cultures. In three cases (30%), there was bacterial co-infection. The mean duration of antifungal treatment (AFT) was 8.4 weeks, while the preferred agent was fluconazole (60% of cases), followed by amphotericin B (30%). Most cases (50%) underwent resection arthroplasty as part of the treatment, while two-stage revision arthroplasty was performed in 30%. Infection's eradication was reported in 90% of the studied cases. Conclusions : The diagnosis and management of fungal periprosthetic shoulder infections are particularly challenging and require a multidisciplinary approach. The combination of antifungal therapy and tailored surgical strategies is crucial, but further research is needed to refine treatment protocols and address the unique considerations in shoulder PJIs.

Background: Hypertension is the most prevalent cardiovascular risk factor, with several detrimental effects on the cardiovascular system. Contrasting results have been reported so far on its prognostic role in patients admitted for ST-segment elevation myocardial infarction (STEMI). Therefore, we investigated the impact of hypertension on short-term mortality in a large multicenter contemporary registry of STEMI patients, including patients treated during COVID-19 pandemic., Methods: The ISACS-STEMI COVID-19 was a retrospective registry that included STEMI patients treated with primary percutaneous coronary intervention (PCI) between March and June of 2019 and 2020 in 109 high-volume primary PCI centers from 4 continents. We collected data on baseline, clinical and procedural characteristics, in-hospital outcome and 30-day mortality. For this analysis patients were grouped according to history of hypertension at admission., Results: A total of 16083 patients were assessed, including 8813 (54.8%) with history of hypertension. These patients were more often elderly, with a worse cardiovascular risk profile, but were less frequently active smoker. Some procedural differences were observed between the two groups, including lower rate of thrombectomy and use of glycoprotein IIb/IIIa inhibitors or cangrelor but more extensive coronary disease in patients with hypertension. Between patients with and without hypertension, there was no significant difference in SARS-CoV-2 positivity. Hypertensive patients had a significantly higher in-hospital and 30-day mortality, similarly observed in both pre-COVID-19 and COVID-19 era, and confirmed after adjustment for main baseline differences and propensity score (in-hospital mortality: adjusted odds ratio (OR) [95% confidence interval (CI)] =1.673 [1.389-2.014], P < 0.001; 30-day mortality: adjusted hazard ratio (HR) [95% CI] = 1.418 [1.230-1.636], P < 0.001)., Conclusion: This is one of the largest and contemporary study assessing the impact of hypertension in STEMI patients undergoing primary angioplasty, including also the COVID-19 pandemic period. Hypertension was independently associated with significantly higher rates of in-hospital and 30-day mortality., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Current variations in asthma prevalence and clinical characteristics suggest that lifestyle choices including dietary habits, may affect the pathogenesis and/or clinical expression of the disease. The purpose of this study is to evaluate the association between adherence to Mediterranean diet (MD) and asthma control, considering disease severity., Methods: Adherence to MD was assessed through a questionnaire, the MD Adherence Screener (MEDAS), previously validated in Mediterranean populations. Each participant received a score ranging from 0 to 14. A score higher than 10 indicates high MD adherence. The level of asthma control was assessed by the Asthma Control Test and two groups were formed (controlled vs. partly controlled/uncontrolled)., Results: The study sample included 105 participants (34% males). About 45% of participants were severe asthmatics. Adherence to MD was associated with 14% higher, though not statistically significant, probability of controlled asthma in the overall study sample (OR = 1.14; 95% CI = 0.46-2.81) and 60% higher probability of controlled asthma among severe asthmatics (OR = 1.60, 95% CI = 0.46-5.59)., Conclusions: These results indicate a possible association between adherence to MD and asthma control, but findings are restricted by the study's small sample size which does not allow asserting the inference.

Malignant otitis externa (MOE) is a rare but serious condition primarily caused by  Pseudomonas aeruginosa . Fungi, particularly in immunocompromised individuals, can also be a contributing factor. A systematic review was conducted, following PRISMA guidelines, to evaluate the literature on fungal malignant otitis externa (FMOE), focusing on its etiology, patient demographics, clinical presentation, and treatment. Out of 464 articles identified, 10 were analyzed in detail, involving 197 patients with a mean age of 65.9 years. Of the total patients, 143 were male (72.6%), 52 were female (26.4%), and the gender of the remaining two was not specified. One hundred and fifty-five patients (78.7%) had underlying immunosuppressive conditions such as diabetes mellitus, chronic kidney failure, corticosteroid use, chemotherapy, and AIDS. Fungal cultures were positive in 107 cases (54.3%), with  Candida  and  Aspergillus  species being present in nearly equal proportions. There were no significant differences between fungal and non-fungal MOE in terms of clinical presentation and diagnostic methods. Conservative treatment was used in 179 patients (90.8%), with 172 of them (87.3%) receiving antifungals. Itraconazole and voriconazole were the most common antifungals, while amphotericin B was less frequently used due to side effects. In some cases, antifungals were combined with antibiotics. Surgical interventions were performed in 35 patients (17.8%), and hyperbaric oxygen therapy was used in 34 of them (17.3%). Eight patients with FMOE died, and the mortality rate was 4%. Late diagnosis, cranial nerve involvement, and inadequate treatment may contribute to higher mortality. Given the potential underdiagnosis of FMOE, early incorporation of antifungal medications into empirical treatment protocols could improve outcomes for patients with a poor prognosis., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Sideris et al.)

Background/objectives: Prostate cancer (PCa) is a significant global health issue. The relationship between alcohol consumption and PCa risk has been the subject of extensive research, yet findings remain inconsistent. This review aims to clarify the association between alcohol intake and PCa risk, its aggressiveness, and the potential metabolic pathways involved in PCa onset., Methods: A comprehensive literature search was conducted across multiple databases, including PubMed and MEDLINE, focusing on epidemiological studies, meta-analyses, cohort studies, and case-control studies. Studies evaluating alcohol consumption, prostate-specific antigen (PSA) levels, and PCa risk were included. The review also explored the roles of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in alcohol metabolism., Results: The analysis reveals a complex relationship between alcohol consumption and PCa. Heavy alcohol intake is associated with an increased risk of PCa, particularly more aggressive forms, and higher mortality rates. However, studies also show weak or no association between moderate alcohol consumption and PCa. The variability in findings may be attributed to differences in alcohol types, regional factors, and study methodologies., Conclusions: The link between alcohol consumption and PCa risk is multifaceted. While heavy drinking appears to increase the risk of aggressive PCa, the overall relationship remains unclear. Further research is needed to better understand these associations and inform public health recommendations and cancer prevention strategies.

Central nervous system (CNS) tumors represent a formidable clinical challenge due to their molecular complexity and varied prognostic outcomes. This review delves into the pivotal role of the epigenetic marker H3K27me3 in the development and treatment of CNS tumors. H3K27me3, specifically the trimethylation of lysine 27 on the histone H3 protein, plays a crucial role in regulating gene expression and maintaining chromatin architecture (e.g., in X-chromosome inactivation). Notably, a reduction in H3K27me3 levels, frequently tied to mutations in the H3 gene family such as H3F3A and HIST1H3B, is evident in diverse brain tumor variants, including the diffuse midline glioma characterized by the H3K27M mutation and certain pediatric high-grade gliomas. The loss of H3K27me3 has been linked to more aggressive behavior in meningiomas, with the trimethylation loss associated with significantly shorter recurrence-free survival (RFS) among grade 2 meningiomas, albeit not within grade 1 tumors. Pediatric posterior fossa ependymomas characterized by a lowered H3K27me3 and DNA hypomethylation exhibit poor prognosis, underscoring the prognostic significance of these epigenetic alterations in CNS tumors. Comprehending the role of H3K27me3 in CNS tumors is vital for advancing diagnostic tools and therapeutic interventions, with the goal of enhancing patient outcomes and quality of life. This review underscores the importance of ongoing investigations into H3K27me to refine and optimize management strategies for CNS tumors, paving the way for improved personalized medicine practices in oncology.

Polycystic Ovarian Syndrome (PCOS) is a prevalent endocrine disorder affecting women of reproductive age, with significant variations in presentation characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovarian morphology. Beyond reproductive health, it may also pose crucial long-term cardiometabolic risks, especially for women with specific types of PCOS, contributing to early subclinical cardiovascular atherosclerotic alterations such as endothelial dysfunction, increased arterial stiffness, and coronary artery calcium levels, respectively. Moreover, the precise relationship between clinical cardiovascular disease (CVD) and PCOS remains debated, with studies demonstrating an elevated risk while others report no significant association. This review investigates the pathophysiology of PCOS, focusing on insulin resistance and its link to subclinical and clinical cardiovascular disease. Diagnostic challenges and novel management strategies, including lifestyle interventions, medications like metformin and glucagon-like peptide-1 receptor agonists (GLP-1RAs), hormonal contraceptives, and bariatric surgery, are further discussed. Recognizing the cardiometabolic risks associated with PCOS, a comprehensive approach and early intervention should address both the reproductive and cardiometabolic dimensions of the syndrome.

Background/Objectives: Multiple sclerosis (MS) frequently results in both urinary and sexual dysfunction, which significantly impairs quality of life. Conventional treatments for bladder dysfunction often prove insufficient, leading to the exploration of alternative therapies such as percutaneous tibial nerve stimulation (PTNS). This study aimed to assess the impact of PTNS on sexual function and bladder symptoms in female MS patients with neurogenic detrusor overactivity (NDO) and female sexual dysfunction (FSD). Methods: A total of 65 female MS patients with NDO were evaluated and underwent 12 weeks of standardized PTNS treatment. Sexual function was assessed using the Female Sexual Function Index (FSFI) and the Female Sexual Distress Scale-Revised (FSDS-R), while bladder symptoms were evaluated using the OAB-v8 questionnaire. Participants were grouped based on the presence of sexual dysfunction and distress and compared to a control group of 20 patients who declined PTNS. Results: Significant improvements were observed in FSFI scores across multiple domains (desire, arousal, lubrication, orgasm, satisfaction, and pain) in the treatment groups ( p < 0.05). Additionally, 58.46% of patients showed positive responses to PTNS regarding overactive bladder symptoms (OAB-v8 score), while the control group showed no significant changes. Conclusions: PTNS appears to be an effective therapeutic option for improving sexual function and urinary symptoms in female MS patients with NDO and FSD, offering a promising non-invasive alternative for managing these conditions.

Aim: Arterial stiffness hallmarks age-related cardiovascular diseases, precedes their onset and strongly links to accelerated disease progression. However, whether carotid-to-femoral pulse wave velocity (PWV), a proxy of arterial stiffness, predicts cardiovascular risk over and above SCORE2, a newly introduced risk score remains to be investigated., Methods: We measured PWV among 747 individuals without established atheromatosis. Study participants were followed up over a 6-year period for the incidence of cardiovascular events [[MACE)-cardiovascular mortality, stroke and myocardial infarction]., Results: PWV emerged as an independent and additive predictor of first cardiovascular events when added in a model encompassing SCORE2 (hazard ratio = 1.10; 95% confidence interval (95% CI) = 1.07-1.14; P < 0.001, Brier score changed from 0.073 (0.060-0.086) to 0.067 (0.055-0.081); P < 0.001, c-statistic increased from 0.71 to 0.75; P = 0.017; likelihood ratio: 20.22; P < 0.001; the overall net reclassification improvement (NRI): 0.577; P < 0.001, AICc changed from 697.81 to 679.60; BIC changed from 702.42 to 688.82]. An increase in PWV predicted a greater risk of future MACEs additively to conventional risk factors (P < 0.05). We performed Kaplan-Meier survival analysis for the tertiles of PWV [first tertile < 8.04 m/s; the second tertile: (8.04-10 m/s); the third tertile: (10-17.10 m/s); (P < 0.05 for all comparisons between the tertiles). PWV tertiles also predicted MACE when added to SCORE2 [for the second tertile: hazard ratio: 5.87 (95% CI: 1.73-19.92); P = 0.004 and for the third tertile: hazard ratio: 9.69 (95% CI: 2.97-31.55); P < 0.001 with the respective change of c-statistic from 0.739 to 0.772; P = 0.012 and continuous NRI = 0.598]., Conclusion: PWV confers additive prognostic value to the newly introduced SCORE2 for adverse outcome in primary prevention., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Guidelines recommend low-dose colchicine for secondary prevention in cardiovascular disease, but uncertainty remains concerning its efficacy for stroke, efficacy in key subgroups and about uncommon but serious safety outcomes., Methods: In this trial-level meta-analysis, we searched bibliographic databases and trial registries form inception to May 16, 2024. We included randomised trials of colchicine for secondary prevention of ischaemic stroke and major adverse cardiovascular events (MACE: ischaemic stroke, myocardial infarction, coronary revascularisation, or cardiovascular death). Secondary outcomes were serious safety outcomes and mortality. A fixed-effect inverse-variance model was used to generate a pooled estimate of relative risk (RR) with 95% confidence intervals (CI). This study is registered with PROSPERO, CRD42024540320., Findings: Six trials involving 14,934 patients with prior stroke or coronary disease were included. In all patients, colchicine compared with placebo or no colchicine reduced the risk for ischaemic stroke by 27% (132 [1.8%] events versus 186 [2.5%] events, RR 0.73 [95% CI 0.58-0.90]) and MACE by 27% (505 [6.8%] events versus 693 [9.4%] events, with RR 0.73 [0.65-0.81]). Efficacy was consistent in key subgroups (females versus males, age below versus above 70, with versus without diabetes, statin versus non-statin users). Colchicine was not associated with an increase in serious safety outcomes: hospitalisation for pneumonia (109 [1.5%] versus 106 [1.5%], RR 0.99 [0.76-1.30]), cancer (247 [3.5%] versus 255 [3.6%], RR 0.97 [0.82-1.15]), and gastro-intestinal events (153 [2.1%] versus 135 [1.9%]), RR 1.15 [0.91-1.44]. There was no difference in all-cause death (201 [2.7%] versus 181 [2.4%], RR 1.09 [0.89-1.33]), cardiovascular death (70 [0.9%] versus 80 [1.1%], RR 0.89 [0.65-1.23]), or non-cardiovascular death (131 [1.8%] versus 101 [1.4%], RR 1.26 [0.98-1.64])., Interpretation: In patients with prior stroke or coronary disease, colchicine reduced ischaemic stroke and MACE, with consistent treatment effect in key subgroups, and did not increase serious safety events or death., Funding: There was no funding source for this study., Competing Interests: Funding: Michiel Poorthuis reports support for travel to Dublin from Dr. Jan Meerwaldt stichting. Pierre Amarenco reports grants from the French Government for Reducing Inflammation in Ischemic Stroke with Colchicine (RIISC); Ticagrelor in High-risk patients-Extended Treatment in Ischemic Stroke (THETIS); Treat Stroke to Target 40; Treat Stroke to Target Cholesterol and Colchicine in Cerebral Small Vessel Disease (TST 3C SVD), from Pfizer for Treat Stroke to Target Trial, consulties fees from Neuraltide for TIDE-IN Trial, honoraria from Novartis, Sanofi, and Viatris, support from Novartis, Participation on a Data Safety Monitoring Board or Advisory Board for Cell Prothera, and from AstraZeneca for Ticagrelor supply (Ticagrelor in High-risk patients-Extended Treatment in Ischemic Stroke (THETIS)). Kevin Boczar reports grants from Novartis paid to his institution. Noel Chan is supported by a Heart and Stroke of Canada New Investigator Award, and received a project grant from the Canadian Institutes of Health Research for a randomized trial investigating the risk-benefit of colchicine in peripheral artery disease. Sanjit Jolly reports honoraria from Pharmascience. Binita Shah reports grants from NIH NHLBI and VA Office of Research and Development paid to her institution, support for attending meetings and/or travel from NovoNordisk as US national leader and co-chair of the global expert panel for the ARTEMIS trial, leadership or fiduciary role for the Society of Cardiovascular Angiography and Interventions (Board of Trustees) and the American Heart Association (Associate Editor for Circulation Cardiovascular Intervention), and from Philips Volcano (advisory board). Jean-Claude Tardif reports grants from Amarin, AstraZeneca, Ceapro, DalCor Pharmaceuticals, Esperion, Ionis, Merck, Novartis, Pfizer paid tot his institution, consulting fees from DalCor Pharmaceuticals paid to him, honoraria for lectures from HLS Pharmaceuticals, Pendopharm, Pfizer paid to him, patent for Pharmacogenomics-guided CETP inhibition (waived his right in this patent), patent for Use of colchicine after myocardial infarction (his institution submitted a patent on this topic and he was an author, but waived his rights in this patent and did not stand to gain financially), and a minor equity interest in DalCor Pharmaceuticals. John Eikelboom reports grants from Anthos, Bayer, BI, BMS, Daiichi-Sankyo, Ionis, Janssen, Merck, Pfizer, USV; consulting fees from Anthos, Bayer, BI, BMS, Daiichi-Sankyo, Ionis, Janssen, Merck, Pfizer, USV., (© 2024 The Authors.)

Aims: Hypokalaemia is associated with cardiovascular events and mortality in patients with chronic kidney disease (CKD). This exploratory FIDELITY analysis, a prespecified pooled patient-dataset from FIDELIO-DKD and FIGARO-DKD, investigated the incidence and effect of hypokalaemia in patients with CKD and type 2 diabetes (T2D) treated with finerenone vs. placebo., Methods: Outcomes include the incidence of treatment-emergent hypokalaemia (serum potassium < 4.0 or < 3.5 mmol/L) and the effect of finerenone on cardiovascular composite outcome (cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or hospitalization for heart failure) and arrhythmia composite outcome (new diagnosis of atrial fibrillation/atrial flutter, hospitalization due to arrhythmia, or sudden cardiac death) by baseline serum potassium subgroups., Results: In the FIDELITY population, treatment-emergent hypokalaemia with serum potassium < 4.0 and < 3.5 mmol/L occurred in 41.1% and 7.5%, respectively. Hazards of cardiovascular and arrhythmia composite outcomes were higher in patients with baseline serum potassium < 4.0 vs. 4.0-4.5 mmol/L (hazard ratio [HR] 1.16; 95% confidence interval [CI] 1.02-1.32, P = 0.022 and HR 1.20; 95% CI 1.00-1.44, P = 0.055, respectively). Finerenone reduced the incidence of hypokalaemia with serum potassium < 4.0 mmol/L (HR 0.63; 95% CI 0.60-0.66) and < 3.5 mmol/L (HR 0.46; 95% CI 0.40-0.53) vs. placebo. Finerenone lessened the hazard of cardiovascular and arrhythmia events vs. placebo, irrespective of baseline serum potassium., Conclusion: A substantial proportion of patients with CKD and T2D experienced hypokalaemia, which was associated with an increased hazard of adverse cardiovascular outcomes. Finerenone reduced the incidence of hypokalaemia. Finerenone reduced the hazard of cardiovascular and arrhythmia outcomes irrespective of serum potassium subgroups. Clinical trials registration: FIDELIO-DKD and FIGARO-DKD are registered with ClinicalTrials.gov, numbers NCT02540993 and NCT02545049, respectively (funded by Bayer AG)., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Recent studies have suggested that certain combinations of KRAS or BRAF biomarkers with clinical factors are associated with poor outcomes and may indicate that surgery could be "biologically" futile in otherwise technically resectable colorectal liver metastasis (CRLM). However, these combinations have yet to be validated through external studies., Patients and Methods: We conducted a systematic search to identify these studies. The overall survival (OS) of patients with these combinations was evaluated in a cohort of patients treated at 11 tertiary centers. Additionally, the study investigated whether using high-risk KRAS point mutations in these combinations could be associated with particularly poor outcomes., Results: The recommendations of four studies were validated in 1661 patients. The first three studies utilized KRAS, and their validation showed the following median and 5-year OS: (1) 30 months and 16.9%, (2) 24.3 months and 21.6%, and (3) 46.8 months and 44.4%, respectively. When analyzing only patients with high-risk KRAS mutations, median and 5-year OS decreased to: (1) 26.2 months and 0%, (2) 22.3 months and 15.1%, and (3) not reached and 44.9%, respectively. The fourth study utilized BRAF, and its validation showed a median OS of 10.4 months, with no survivors beyond 21 months., Conclusion: The combinations of biomarkers and clinical factors proposed to render surgery for CRLM futile, as presented in studies 1 (KRAS high-risk mutations) and 4, appear justified. In these studies, there were no long-term survivors, and survival was similar to that of historic cohorts with similar mutational profiles that received systemic therapies alone for unresectable disease., (© 2024. Society of Surgical Oncology.)

Background and Objectives: Limited data exist on the safety of IV thrombolysis (IVT) for acute ischemic stroke (AIS) after dabigatran reversal with idarucizumab. We sought to evaluate the safety and efficacy of idarucizumab pretreatment in patients with AIS receiving IVT., Methods: A national registry-based study evaluated the safety and efficacy of IVT in this specific subgroup. We also conducted a systematic review and meta-analysis of cohort studies and case series, aiming to document the pooled rates of (1) symptomatic intracranial hemorrhage (sICH), (2) any intracranial hemorrhage, (3) 3-month mortality, and (4) the proportion of excellent (modified Rankin Scale [mRS] scores 0-1) and (5) good (mRS scores 0-2) functional outcome at 3 months among patients with AIS, who received IVT after dabigatran reversal with idarucizumab. Moreover, we sought to compare these outcomes between IVT-treated patients after dabigatran reversal with idarucizumab and IVT-treated patients without dabigatran pretreatment., Results: Thirteen cohorts including our nation-wide registry-based cohort and 1 case series comprising 553 patients with AIS (mean age: 75 years; male sex: 65%; median baseline NIH Stroke Scale score: 11 points) receiving idarucizumab before IVT were included in this meta-analysis. The pooled rate of sICH after IVT after idarucizumab administration was 4% (95% CI 1-9; I 2 = 26%), while the pooled rates of any intracranial hemorrhage and 3-month mortality were 10% (95% CI 5-16; I 2 = 24%) and 18% (95% CI 10-27; I 2 = 0%), respectively. The pooled rates of excellent and good functional outcomes at 3 months were 56% (95% CI 27-83; I 2 = 69%) and 70% (95% CI 57-81; I 2 = 40%), respectively. The risk of sICH (risk ratio [RR] 1.86; 95% CI 0.91-3.80; I 2 = 0%), any intracranial hemorrhage (RR 1.76; 95% CI 0.99-3.11; I 2 = 8%), and 3-month mortality (RR 1.50; 95% CI 0.91-2.48; I 2 = 0%) did not differ between patients with AIS receiving IVT with and without idarucizumab. Moreover, idarucizumab administration was associated with higher likelihood of achieving a 3-month good functional outcome (RR 1.35; 95% CI 1.11-1.65; I 2 = 27%)., Discussion: IVT for AIS after dabigatran reversal with idarucizumab seems to be safe and effective in observational studies with limited number of patients. Randomized-controlled clinical trials are warranted to provide robust evidence on the safety and efficacy of IVT in this specific AIS subgroup.

Aims: Cardiogenic shock (CS) is linked to high morbidity and mortality rates, posing a challenge for clinicians. Interventions to improve tissue perfusion and blood pressure are crucial to prevent further deterioration. Unfortunately, current inotropes, which act through adrenergic receptor stimulation, are associated with malignant arrhythmias and poorer outcomes. Due to its unique mechanism of action, istaroxime should improve haemodynamics without adrenergic overactivation. The SEISMiC study is designed to examine the safety and efficacy (haemodynamic effect) of istaroxime administrated in pre-CS patients., Methods and Results: The SEISMiC study is a multinational, multicentre, randomized, double-blind, placebo-controlled safety and efficacy study with two parts (A and B). The study enrols patients hospitalized for decompensated heart failure (pre-CS, not related to myocardial ischaemia) with persistent hypotension [systolic blood pressure (SBP) 70-100 mmHg for at least 2 h] and clinically confirmed congestion, NT-proBNP ≥1400 pg/mL, and LVEF≤40%. Subjects must not have taken intravenous (iv) vasopressors, inotropes or digoxin in the past 6 h. Eligible patients are randomized to receive IV infusion of istaroxime (different doses and regimens in Parts A and B) or placebo for up to 60 h. Central haemodynamics, ECG Holter monitoring, cardiac ultrasound and biomarkers are recorded at predefined time points during the trial. The study's primary efficacy endpoint is the SBP area under the curve from baseline curve from baseline to 6 and 24 h in the combined SEISMiC Parts A and B population. Key secondary efficacy endpoints include haemodynamic, laboratory and clinical measures in SEISMiC B alone in the combined SEISMiC A and B studies., Conclusions: The study results will contribute to our understanding of the role of istaroxime in pre-CS patients and potentially provide insight into the drug's haemodynamic effects and safety in this population., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background and Aims: Evidence is lacking that correcting iron deficiency (ID) has clinically important benefits for patients with heart failure with preserved ejection fraction (HFpEF)., Methods: FAIR-HFpEF was a multicentre, randomized, double-blind trial designed to compare intravenous ferric carboxymaltose (FCM) with placebo (saline) in 200 patients with symptomatic HFpEF and ID (serum ferritin < 100 ng/mL or ferritin 100-299 ng/mL with transferrin saturation < 20%). The primary endpoint was change in 6-min walking test distance (6MWTD) from baseline to week 24. Secondary endpoints included changes in New York Heart Association class, patient global assessment, and health-related quality of life (QoL)., Results: The trial was stopped because of slow recruitment after 39 patients had been included (median age 80 years, 62% women). The change in 6MWTD from baseline to week 24 was greater for those assigned to FCM compared to placebo [least square mean difference 49 m, 95% confidence interval (CI) 5-93; P = .029]. Changes in secondary endpoints were not significantly different between groups. The total number of adverse events (76 vs. 114) and serious adverse events (5 vs. 19; rate ratio 0.27, 95% CI 0.07-0.96; P = .043) was lower with FCM than placebo., Conclusions: In patients with HFpEF and markers of ID, intravenous FCM improved 6MWTD and was associated with fewer serious adverse events. However, the trial lacked sufficient power to identify or refute effects on symptoms or QoL. The potential benefits of intravenous iron in HFpEF with ID should be investigated further in a larger cohort., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Introduction: To investigate whether synthetic (s) glucocorticoids (GCs) administered between the 24th and the 34th gestational weeks in pre-term labor might precipitate labor, studies on sGCs administration were reviewed. The physiology of endogenous glucocorticoid-related increase in fetal-maternal circulation and its association with labor, followed by a scoping review of studies on exogenous sGCs administered for fetal lung maturation and the timing of labor, were included., Materials and Methods: The methodology of systematic reviews was followed. MEDLINE, Cochrane Library, and Google Scholar databases were searched until October 2023, for original studies investigating the administration of sGCs in pregnancies risking pre-term labor. Duplicates were removed, and 1867 abstracts were excluded as irrelevant. Six controlled and four non-controlled studies were included. The index group consisted of 6001 subjects and 7691 controls in the former, while in the latter, the index group consisted of 2069 subjects., Results: In three out of the six controlled studies, gestational age at labor was significantly lower in sGC-treated women than in controls, while in three studies, gestational age at labor was lower in sGC-treated women than in controls, with a trend toward statistical significance. In one study, gestational age at labor was significantly lower in controls than in sGC-treated women. In the non-controlled studies, the majority of women delivered less than 1 week from the day of sGC administration., Conclusions: In this scoping review, studies lack homogeneity. However, in the controlled studies, a pattern of earlier labor emerges among sGC-treated pregnant women. The use of multiple courses of antenatal sGCs appears to be associated with precipitated labor. Their use should be carefully weighed. Carefully designed trials should examine this ongoing scientific query.

Infective endocarditis (IE) is a disease associated with significant morbidity and mortality. It is more commonly caused by Gram-positive cocci, but Gram-positive bacilli may seldom cause the disease. Listeria monocytogenes is an aerobic Gram-positive coccobacillus and a foodborne and opportunistic pathogen most commonly causing gastrointestinal infections, even though bacteremia, sepsis, meningitis, and fetal infections may also occur. Listeria IE has rarely been described, with most reports being case reports or case series. Thus, the characteristics of this disease remain largely unknown. This systematic review aimed to present all published Listeria IE studies and describe their characteristics. A search of PubMed, Scopus, and the Cochrane Library for studies providing information on epidemiology, clinical findings, treatment, and outcome of Listeria IE cases was performed. A total of 54 studies containing data from 62 patients were included. Among all patients, 64.5% were male; the median age was 69 years. Among all patients, 54.8% had a history of a prosthetic valve. The aortic valve was the most commonly affected, followed by the mitral. Fever, heart failure, and embolic phenomena were the most commonly encountered clinical findings. The only isolated species was L. monocytogenes . Antimicrobial resistance was relatively low for aminopenicillins and aminoglycosides, the most commonly used antimicrobials for treating L. monocytogenes IE. Surgery was performed in 27.4% of patients. Mortality was 37.1%. Patients who survived were more likely to have had a prosthetic valve, to have necessitated transesophageal echocardiography for the diagnosis, to have mitral valve IE, and to have had surgical management; however, no factor was identified in a multivariate logistic regression model as an independent factor for overall mortality.

Background: Transperitoneal laparoscopic adrenalectomy (TLA) is the most frequently chosen approach in adrenal surgery. At present, impact of obesity on patient outcomes following adrenal surgery is frequently under discussion. We intended to offer updated evidence thanks to a comparison between intraoperative and perioperative outcomes in non-obese and obese patients, who underwent TLA for benign or malignant adrenal diseases., Methods: Our systematic review made use of Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) guidelines. Articles of interest turned out from a search with PubMed/MEDLINE, Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials-CENTRAL), Web of Science (Science and Social Science Citation Index), and Scopus databases. We evaluated two groups of outcomes: intraoperative (operative time, intraoperative complications rate, estimated blood loss (EBL), transfusion rate, conversion to open surgery rate) and postoperative (overall postoperative complications rate, major postoperative complications rate, length of hospital stay). RevMan (Computer program) Version 5.4 was used to perform the meta-analysis. The heterogeneity of the included studies in the meta-analysis was assessed by using the I2 statist., Results: The 8 included comparative studies (1,646 patients: 995 non-obese versus 651 obese) had a time frame of approximately 30 years (1994-2020) and an observational nature. Meta-analysis showed no differences in terms of operative time, intraoperative complications rate, EBL, transfusion rate, conversion to open surgery rate, overall postoperative complications rate, major (Clavien-Dindo ≥ III) postoperative complications rate, length of hospital stay between non-obese and obese populations., Conclusions: We can say that obesity does not impact TLA safety and effectiveness. Due to biases among meta-analyzed studies (small overall sample size and small number of events analyzed, in particular), careful interpretation is needed to interpret our results. Additional randomized, possibly multi-center trials may contribute to confirm our results.

Summary: Pneumatosis intestinalis (PI) is characterised by pathological gas infiltration into the submucosa and subserosa of the gastrointestinal tract, sometimes with an unclear pathogenesis. The clinical presentation of PI varies, with the diagnosis established via computed tomography (CT), where PI manifests as linear or bubbly gas patterns within the bowel wall. Management often necessitates surgical intervention to address potential life-threatening causes like mesenteric ischemia or bowel necrosis. This case report discusses a 69-year-old male who presented with abdominal pain and distension alongside worrisome radiological features indicative of extensive PI, who underwent an exploratory laparotomy that revealed no pathological findings and with an eventual uneventful recovery., (Copyright© Authors.)

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and is regarded as a liver manifestation of metabolic syndrome. It is linked to insulin resistance, obesity, and diabetes mellitus, all of which increase the risk of cardiovascular complications. Endothelial dysfunction (EnD) constitutes the main driver in the progression of atherosclerosis and coronary artery disease (CAD). Several pathophysiological alterations and molecular mechanisms are involved in the development of EnD in patients with NAFLD. Our aim is to examine the association of NAFLD and CAD with the parallel assessment of EnD, discussing the pathophysiological mechanisms and the genetic background that underpin this relationship. This review delves into the management of the condition, exploring potential clinical implications and available medical treatment options to facilitate the deployment of optimal treatment strategies for these patients.

Background: Herein, we evaluated the attributable fraction (AF) of human papillomavirus (HPV)-mediated (HPV+) oropharyngeal carcinomas (OPCs) in Greece over a recent calendar period., Patients and Methods: ORPHEAS, a retrospective, observational, multicenter, cross-sectional study with prospective recruitment, included adult patients with OPC in 2017-2022, each of them with a high-quality, treatment-naïve tumor specimen. The primary endpoint was the HPV-AF, defined as combined positivity for p16 INK4a (p16) overexpression and HPV DNA presence by central laboratory testing, among included patients. Other endpoints evaluated the HPV+/HPV- patient/disease characteristics at OPC diagnosis and the HPV subtypes for HPV+ patients., Results: 144/147 patients with available HPV status by central laboratory testing were analyzed [median age: 60.0 years; males: 111 (77.1%)]. The most common tumor anatomical sites were the tonsils (70/147, 48.6%) and the base of the tongue (51, 35.4%), and most patients were at the American Joint Committee on Cancer eighth edition TNM (tumor-node-metastasis) stages III (25, 22.7%) and IV (43, 39.1%). The HPV-AF was 52.1% (75/144; 95% confidence interval 43.6% to 60.5%). Most HPV+ patients were infected by an HPV type targeted by the 9-valent HPV vaccine (72/75, 96.0%), especially HPV16 (70/75, 93.3%). HPV+ compared with HPV- patients were younger (median age 58.0 versus 64.0 years; P = 0.003); more likely to have tumors in the tonsils (65.0% versus 30.4%; P < 0.001); less likely to have tumors in the base of the tongue (25.3% versus 46.4%; P = 0.008); and less frequently at TNM stage IV (20.4% versus 57.1%; overall P < 0.001)., Conclusions: In Greece, we observed a high HPV-AF (52.1%) in OPC, approximating the AFs reported for some Northern European countries. HPV+ versus HPV- patients were younger, more frequently with tonsillar tumors, and less frequently at TNM stage IV. Since most patients were infected by ≥1 HPV type targeted by the 9-valent vaccine, the HPV+ OPC burden could be mitigated through a routine HPV gender-neutral vaccination program., (Copyright © 2024 Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA., The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Introduction: Esophageal inflammatory fibroid polyp (IFP) is a rare benign tumor of the gastrointestinal tract with limited available data on clinicopathologic features and treatment strategies., Evidence Acquisition: A systematic review of the literature in PubMed/Medline and Scopus databases was performed for articles concerning esophageal IFP in adult population., Evidence Synthesis: A total of 16 studies were identified, involving 16 patients with a Male-Female Ratio of 3:1 and mean age of 50.38 years. Clinical presentation of esophageal IFP included progressive dysphagia in 56.3% of cases, with additional symptoms such as epigastric and retrosternal pain, weight loss, vomiting, and melena. Diagnostic modalities involved endoscopy in all cases, with endoscopic ultrasound (EUS) employed in 50% of cases and tissue biopsy performed during endoscopy in 87.5% of the patients. Therapeutic approach of esophageal IFP consisted of surgical resection in 75% of the patients and endoscopic resection in the remaining 25%, with various surgical procedures employed based on tumor location. Follow-up data, available for 11 patients over a median duration of 15.5 months, indicated two instances of recurrence following endoscopic resection, while the other nine patients remained asymptomatic with no evidence of recurrence., Conclusions: Esophageal IFP is a rare benign tumor of the gastrointestinal tract presenting with dysphagia, regurgitation, and heartburn. Resection, either endoscopic or surgical, is the primary treatment approach. Prognosis for esophageal IFP is favorable, with low recurrence rates. Further research is required to investigate potential risk factors and etiology for this lesion, and to explore novel therapeutic approaches that may improve patient outcomes.

Aims: Burst steroid therapy, effective in acute respiratory diseases, may benefit patients with acute heart failure (AHF) in whom inflammatory activation is associated with adverse outcomes., Methods and Results: CORTAHF assessed whether burst steroid therapy reduces inflammation and results in better quality of life and clinical outcomes in AHF. Patients with AHF, N-terminal pro-B-type natriuretic peptide >1500 pg/ml, and high-sensitivity C-reactive protein (hsCRP) >20 mg/L were randomized 1:1 to oral, once daily 40 mg prednisone for 7 days or usual care, without blinding. Patients were followed for 90 days. A total of 101 patients were randomized. At day 7 the primary endpoint, hsCRP decreased in both arms - adjusted geometric mean ratios (GMRs) were 0.30 and 0.40 in the prednisone and usual care arms (ratio of GMRs 0.75, 95% confidence interval [CI] 0.56-1.00, p = 0.0498). The 90-day risk of worsening heart failure (HF), HF readmission or death as reported by the unblinded investigators was significantly lower in the prednisone group (10.4%) than in usual care (30.8%) (hazard ratio 0.31, 95% CI 0.11-0.86, p = 0.016). The EQ-5D visual analogue scale score as reported by the unblinded patients increased more in the prednisone group on day 7 (least squares mean difference 2.57, 95% CI 0.12-5.01 points, p = 0.040). All effects were statistically significant in the pre-specified subgroup with centrally-measured interleukin-6 >13 pg/ml. Adverse events, particularly hyperglycaemia, occurred more in the prednisone group with no difference in infection rate., Conclusion: In this small open-label study of patients with AHF, burst steroid therapy was associated with reduced inflammation as measured by hsCRP levels at day 7 (primary endpoint). Secondary endpoints showed improved quality of life at day 7 and reduced 90-day risk of death or worsening HF. Large prospective studies are needed to evaluate these findings., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: Biologic asthma therapies reduce exacerbations and long-term oral corticosteroids (LTOCS) use in randomized controlled trials (RCTs); however, there are limited data on outcomes among patients ineligible for RCTs. Hence, we investigated responsiveness to biologics in a real-world population of adults with severe asthma., Methods: Adults in the International Severe Asthma Registry (ISAR) with ≥24 weeks of follow-up were grouped into those who did, or did not, initiate biologics (anti-IgE, anti-IL5/IL5R, anti-IL4/13). Treatment responses were examined across four domains: forced expiratory volume in 1 second (FEV 1 ) increase by ≥100 mL, improved asthma control, annualized exacerbation rate (AER) reduction ≥50%, and any LTOCS dose reduction. Super-response criteria were: FEV 1 increase by ≥500 mL, new well-controlled asthma, no exacerbations, and LTOCS cessation or tapering to ≤5 mg/day., Results: 5.3% of ISAR patients met basic RCT inclusion criteria; 2116/8451 started biologics. Biologic initiators had worse baseline impairment than non-initiators, despite having similar biomarker levels. Half or more of initiators had treatment responses: 59% AER reduction, 54% FEV 1 increase, 49% improved control, 49% reduced LTOCS, of which 32%, 19%, 30%, and 39%, respectively, were super-responses. Responses/super-responses were more frequent in biologic initiators than in non-initiators; nevertheless, ~40-50% of initiators did not meet response criteria., Conclusions: Most patients with severe asthma are ineligible for RCTs of biologic therapies. Biologics are initiated in patients who have worse baseline impairments than non-initiators despite similar biomarker levels. Although biologic initiators exhibited clinical responses and super-responses in all outcome domains, 40-50% did not meet the response criteria., (© 2024 The Author(s). Allergy published by European Academy of Allergy and Clinical Immunology and John Wiley & Sons Ltd.)

The Child and Adolescent Mental Health Initiative (CAMHI) aims to enhance mental health care capacity for children and adolescents across Greece. Considering the need for evidence-based policy, the program developed an open-resource dataset for researching the field within the country. A comprehensive, mixed-method, community-based research was conducted in 2022/2023 assessing the current state, needs, barriers, and opportunities according to multiple viewpoints. We surveyed geographically distributed samples of 1,756 caregivers, 1,201 children/adolescents, 404 schoolteachers, and 475 health professionals using validated instruments to assess mental health symptoms, mental health needs, literacy and stigma, service use and access, professional practices, training background, and training needs and preferences. Fourteen focus groups were conducted with informants from diverse populations (including underrepresented minorities) to reach an in-depth understanding of those topics. A dataset with quantitative and qualitative findings is now available for researchers, policymakers, and society [ https://osf.io/crz6h/ and https://rpubs.com/camhi/sdashboard ]. This resource offers valuable data for assessing the needs and priorities for child and adolescent mental health care in Greece. It is now freely available to consult, and is expected to inform upcoming research and evidence-based professional training. This initiative may inspire similar ones in other countries, informing methodological strategies for researching mental health needs., Competing Interests: Declarations Conflicts of interest AC has acted as a consultant for Knight Therapeutics in the past year. All other authors declare no conflicts of interest., (© 2024. The Author(s).)

Background and Aim: Hepatocellular carcinoma (HCC) diagnosis mainly relies on its pathognomonic radiological profile, obviating the need for biopsy. The project of incorporating artificial intelligence (AI) techniques in HCC aims to improve the performance of image recognition. Herein, we thoroughly analyze and evaluate proposed AI models in the field of HCC diagnosis., Methods: A comprehensive review of the literature was performed utilizing MEDLINE/PubMed and Web of Science databases with the end of search date being the 30th of September 2023. The MESH terms "Artificial Intelligence," "Liver Cancer," "Hepatocellular Carcinoma," "Machine Learning," and "Deep Learning" were searched in the title and/or abstract. All references of the obtained articles were also evaluated for any additional information., Results: Our search resulted in 183 studies meeting our inclusion criteria. Across all diagnostic modalities, reported area under the curve (AUC) of most developed models surpassed 0.900. A B-mode US and a contrast-enhanced US model achieved AUCs of 0.947 and 0.957, respectively. Regarding the more challenging task of HCC diagnosis, a 2021 deep learning model, trained with CT scans, classified hepatic malignant lesions with an AUC of 0.986. Finally, a MRI machine learning model developed in 2021 displayed an AUC of 0.975 when differentiating small HCCs from benign lesions, while another MRI-based model achieved HCC diagnosis with an AUC of 0.970., Conclusions: AI tools may lead to significant improvement in diagnostic management of HCC. Many models fared better or comparable to experienced radiologists while proving capable of elevating radiologists' accuracy, demonstrating promising results for AI implementation in HCC-related diagnostic tasks., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Evidence-based information is essential for effective mental health care, yet the extent and accessibility of the scientific literature are critical barriers for professionals and policymakers. To map the necessities and make validated resources accessible, we undertook a systematic review of scientific evidence on child and adolescent mental health in Greece encompassing three research topics: prevalence estimates, assessment instruments, and interventions. We searched Pubmed, Web of Science, PsycINFO, Google Scholar, and IATPOTEK from inception to December 16th, 2021. We included studies assessing the prevalence of conditions, reporting data on assessment tools, and experimental interventions. For each area, manuals informed data extraction and the methodological quality were ascertained using validated tools. This review was registered in protocols.io [68583]. We included 104 studies reporting 533 prevalence estimates, 223 studies informing data on 261 assessment instruments, and 34 intervention studies. We report the prevalence of conditions according to regions within the country. A repository of locally validated instruments and their psychometrics was compiled. An overview of interventions provided data on their effectiveness. The outcomes are made available in an interactive resource online [ https://rpubs.com/camhi/sysrev&#95;table ]. Scientific evidence on child and adolescent mental health in Greece has now been cataloged and appraised. This timely and accessible compendium of up-to-date evidence offers valuable resources for clinical practice and policymaking in Greece and may encourage similar assessments in other countries., Competing Interests: Declarations Conflict of interest AC has acted as a consultant for Knight Therapeutics in the past year. All other authors declare no conflicts of interest., (© 2023. The Author(s).)

Clinical studies have previously established the role of olive products in cardiovascular disease (CVD) prevention, whilst the identification of the responsible constituents for the beneficial effects is still pending. We sought to assess and compare the cardioprotective potential of oleuropein (OL), hydroxytyrosol (HT), oleocanthal (OC) and oleanolic Acid (OA), regarding Ischemia/Reperfusion Injury (IRI) and CVD risk factors alleviation. The scope of the study was to design a potent and safe combinatorial therapy for high-cardiovascular-risk patients on a bench-to-bedside approach. We evaluated the IRI-limiting potential of 6-weeks treatment with OL, HT, OC or OA at nutritional doses, in healthy and metabolic syndrome (MS)-burdened mice. Three combinatorial regimens were designed and the mixture with preponderant benefits (OL-HT-OC, Combo 2), including infarct sparing and antiglycemic potency, compared to the isolated compounds, was further investigated for its anti-atherosclerotic effects. In vivo experiments revealed that the combination regimen of Combo 2 presented the most favorable effects in limiting infarct size and hyperglycemia, which was selected to be further investigated in the clinical setting in Chronic Coronary Artery Syndrome (CCAS) patients. Cardiac function, inflammation markers and oxidative stress were assessed at baseline and after 4 weeks of treatment with the OL-HT-OC supplement in the clinical study. We found that OL, OC and OA significantly reduced infarct size in vivo compared to Controls. OL exhibited antihyperglycemic properties and OA attenuated hypercholesterolemia. OL-HT-OA, OL-HT-OC and OL-HT-OC-OA combination regimens were cardioprotective, whereas only OL-HT-OC mitigated hyperglycemia. Combo 2 cardioprotection was attributed to apoptosis suppression, enhanced antioxidant effects and upregulation of antioxidant enzymes. Additionally, it reduced atherosclerotic plaque extent in vivo. OL-HT-OC supplement ameliorated cardiac, vascular and endothelial function in the small-scale clinical study. Conclusively, OL-HT-OC combination therapy exerts potent cardioprotective, antihyperglycemic and anti-atherosclerotic properties in vivo, with remarkable and clinically translatable cardiovascular benefits in high-risk patients., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Andreadou Ioanna has patent “Composition based on olive extract suitable for cardioprotection” pending to Uni-Pharma S.A. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The advent of immunological therapies has revolutionized the treatment of solid and haematological cancers over the last decade. Licensed therapies which activate the immune system to target cancer cells can be broadly divided into two classes. The first class are antibodies that inhibit immune checkpoint signalling, known as immune checkpoint inhibitors (ICIs). The second class are cell-based immune therapies including chimeric antigen receptor T lymphocyte (CAR-T) cell therapies, natural killer (NK) cell therapies, and tumour infiltrating lymphocyte (TIL) therapies. The clinical efficacy of all these treatments generally outweighs the risks, but there is a high rate of immune-related adverse events (irAEs), which are often unpredictable in timing with clinical sequalae ranging from mild (e.g. rash) to severe or even fatal (e.g. myocarditis, cytokine release syndrome) and reversible to permanent (e.g. endocrinopathies).The mechanisms underpinning irAE pathology vary across different irAE complications and syndromes, reflecting the broad clinical phenotypes observed and the variability of different individual immune responses, and are poorly understood overall. Immune-related cardiovascular toxicities have emerged, and our understanding has evolved from focussing initially on rare but fatal ICI-related myocarditis with cardiogenic shock to more common complications including less severe ICI-related myocarditis, pericarditis, arrhythmias, including conduction system disease and heart block, non-inflammatory heart failure, takotsubo syndrome and coronary artery disease. In this scientific statement on the cardiovascular toxicities of immune therapies for cancer, we summarize the pathophysiology, epidemiology, diagnosis, and management of ICI, CAR-T, NK, and TIL therapies. We also highlight gaps in the literature and where future research should focus., (© 2024 European Society of Cardiology.)

The traditional healthcare model is focused on diseases (medicine and natural science) and does not acknowledge patients' resources and abilities to be experts in their own lives based on their lived experiences. Improving healthcare safety, quality, and coordination, as well as quality of life, is an important aim in the care of patients with chronic conditions. Person-centered care needs to ensure that people's values and preferences guide clinical decisions. This paper reviews current knowledge to develop (1) digital care pathways for rhinitis and asthma multimorbidity and (2) digitally enabled, person-centered care. 1 It combines all relevant research evidence, including the so-called real-world evidence, with the ultimate goal to develop digitally enabled, patient-centered care. The paper includes (1) Allergic Rhinitis and its Impact on Asthma (ARIA), a 2-decade journey, (2) Grading of Recommendations, Assessment, Development and Evaluation (GRADE), the evidence-based model of guidelines in airway diseases, (3) mHealth impact on airway diseases, (4) From guidelines to digital care pathways, (5) Embedding Planetary Health, (6) Novel classification of rhinitis and asthma, (7) Embedding real-life data with population-based studies, (8) The ARIA-EAACI (European Academy of Allergy and Clinical Immunology) strategy for the management of airway diseases using digital biomarkers, (9) Artificial intelligence, (10) The development of digitally enabled, ARIA person-centered care, and (11) The political agenda. The ultimate goal is to propose ARIA 2024 guidelines centered around the patient to make them more applicable and sustainable., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background and Purpose: Cervical artery dissection (CAD) represents a leading cause of unilateral lower cranial nerve IX-XII palsy, known as Collet-Sicard syndrome (CSS). High-resolution magnetic resonance imaging (HR-MRI) is widely used in the evaluation of patients with CAD, providing information regarding vessel wall abnormalities and intraluminal thrombus., Methods: We present a patient with palsy of multiple lower cranial nerves in the context of CSS, attributed to unilateral spontaneous internal carotid artery dissection., Results: We describe a 68-year-old man with unremarkable previous history, who presented with subacute, gradually worsening dysphagia and hoarse voice. Clinical examination revealed right-sided palsy of cranial nerves IX-XII. Three-dimensional fat-saturated black-blood T1-weighted high-resolution vessel wall imaging disclosed spontaneous dissection with intramural hematoma along the distal right internal carotid artery. Neck MRI showed inward displacement of right aryepiglottic fold, right pyriform sinus dilatation, and right true vocal cord in middle position, indicative of right vagus nerve palsy, atrophy of right trapezius and sternocleidomastoid muscles, due to right spinal accessory nerve palsy, and unilateral tongue atrophy with fatty infiltration, characteristic for right hypoglossal nerve palsy., Conclusions: This case highlights the utility of high-resolution vessel wall imaging and especially fat-saturated T1-weighted black-blood SPACE (sampling perfection with application-optimized contrast using different flip-angle evolutions) sequences in the accurate diagnosis of CAD, revealing the characteristic mural hematoma and intimal flap. HR-MRI is also valuable in the recognition of indirect signs of lower cranial nerve compression., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Aims: Inflammation has emerged as a potential key pathophysiological mechanism in heart failure (HF) in general and acute HF (AHF) specifically, with inflammatory biomarkers shown to be highly predictive of adverse outcomes in these patients. The CORTAHF study builds on both these data and the fact that steroid burst therapy has been shown to be effective in the treatment of respiratory diseases and COVID-19. Our hypothesis is that in patients with AHF and elevated C-reactive protein (CRP) levels without symptoms or signs of infection, a 7-day course of steroid therapy will lead to reduced inflammation and short-term improvement in quality of life and a reduced risk of worsening HF (WHF) events., Methods and Results: The study, which is currently ongoing, will include 100 patients with AHF ages 18-85, regardless of ejection fraction, screened within 12 h of presentation. Patients will be included who have NT-proBNP > 1500 pg/mL and CRP > 20 mg/L at screening. Exclusion criteria include haemodynamic instability and symptoms and signs of infection. After signed consent, eligible patients will be randomized according to a central randomization scheme stratified by centre 1:1 to either treatment once daily for 7 days with 40 mg prednisone orally or to standard care. Patients will be assessed at study day 2, day 4 or at discharge if earlier, and at days 7 and 31 at the hospital; and at day 91 through a telephone follow-up. The primary endpoint is the change in CRP level from baseline to day 7, estimated from a mixed model for repeated measures (MMRM) including all measured timepoints, in patients without a major protocol violation. Secondary endpoints include the time to the first event of WHF adverse event, readmission for HF, or death through day 91; and changes to day 7 in EQ-5D visual analogue scale score and utility index. Additional clinical and laboratory measures will be assessed., Conclusions: The results of the study will add to the knowledge of the role of inflammation in AHF and potentially inform the design of larger studies with possibly longer duration of anti-inflammatory therapies in AHF., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Objective: Skin involvement is common in systemic lupus erythematosus (SLE), but may be resistant to conventional treatment. We sought to evaluate the efficacy of anifrolumab (ANI) in refractory cutaneous manifestations of SLE., Methods: Case series of patients with refractory cutaneous SLE from three Rheumatology Departments in Greece. Outcome measures were improvement in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K), physician global assessment (PGA) and Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI). Clinically relevant improvement in skin was defined as decrease ≥50% (CLASI50) from baseline values., Results: Eighteen patients received ANI; all had active skin involvement at baseline. Mean (SD) SLEDAI and PGA at ANI initiation were 7.4 (2.7) and 1.4 (0.5), respectively, with a mean prednisone dose 4.9 (4.5) mg/day. Mean CLASI (Activity/Damage) at baseline was 13.9 (9.7)/2.9 (4.6). Patients were refractory to a mean 6.3 (1.5) immunomodulatory agents (including hydroxychloroquine and glucocorticoids) before the initiation of ANI. After a mean 8.5 (4.6) months, 89% ( n = 16/18) of patients demonstrated significant improvement in general lupus and cutaneous disease activity, and glucocorticoid tapering. Mean SLEDAI and mean CLASI at last visit were 3.4 (1.9) and 2.1 (2.4)/1.4 (2.2), respectively, and mean daily prednisone dose decreased to 2.4 (2.2). Of note, in this group of highly refractory patients CLASI50 was achieved in 16/18 (89%) patients. One patient discontinued ANI after 4 infusions due to a varicella-zoster virus infection and one patient, who initially responded to treatment with ANI, experienced a skin flare due to temporary discontinuation due to Covid 19 infection. DORIS remission and LLDAS were attained in two (11.1%) and eleven (61.1%) patients, respectively., Conclusion: Anifrolumab is highly effective in various skin manifestations of SLE, even after prior failure to multiple treatments., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.