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Introduction: After positive findings in clinical trials the time window for endovascular thrombectomy (EVT) for patients with an acute ischemic stroke has been expanded up to 24 h from symptom onset or last seen well (LSW). We aimed to compare EVT patients' characteristics and outcomes in the early versus extended time window and to compare outcomes with the DAWN and DEFUSE 3 trial results., Patients and Methods: Consecutive EVT patients from 16 mostly European comprehensive stroke centers from the EVA-TRISP cohort were included. We compared rates of 90-day good functional outcomes (Modified Rankin Scale 0-2), symptomatic intracranial hemorrhage (sICH), and 90-day mortality between patients treated in the early (<6 h after onset or LSW) versus extended (6-24 h after onset or LSW) time windows., Results: We included 9313 patients, of which 6876 were treated in the early and 2437 in the extended time window. National Institutes of Health Stroke Scale (NIHSS) score at presentation was lower in patients treated in the extended time window (median 13 [IQR 7-18] vs 15 [IQR 9-19], p  < 0.001). The percentage of patients with good functional outcome was slightly lower in the extended time window (37.4% vs 42.2%, p  < 0.001). However, rates of successful recanalization, sICH, and mortality were similar. Good functional outcome rates after EVT were slightly lower for patients in the extended window in the EVA-TRISP cohort as compared to DAWN and DEFUSE 3., Discussion and Conclusion: According to this large multicenter cohort study reflecting daily clinical practice, EVT use in the extended time window appears safe and effective., 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: Ivana Berisavac: speaker honoraria from Medtronic. Visnja Padjen: speaker honoraria from Medtronic and Boehringer Ingelheim. Ronen R. Leker: received speaker honoraria from IscemaView, Boehringer Ingelheim, Pfizer, Jansen, Biogen, Medtronic and Abott and advisory board honoraria from Jansen and Filterlex. Andrea Zini: has received funding for speaker honoraria and consulting fees from Boehringer Ingelheim, Astra Zeneca, Daiichi Sankyo, CSL Behring, for scientific advisory board from Bayer, Astra Zeneca. Mirjam R. Heldner: reports grants from Swiss National Science Foundation, SITEM Research Support Funds and Swiss Heart Foundation, not directly related to this manuscript. Christian H Nolte: has received honoraria for lectures or speaker’s bureau from Alexion, AstraZeneca, BMS, Novartis and Pfizer. The other authors report nothing to disclose.

Background: In the post-COVID-19 era, there is growing concern regarding its impact on cardiovascular health and the following effects on the overall quality of life of affected individuals. This research seeks to investigate cardiac magnetic resonance (CMR) findings following COVID-19 and their impact on the quality of life of affected individuals., Methods: An observational, cross-sectional study was conducted in consecutive patients with persistent cardiovascular symptoms after COVID-19 who were referred to CMR due to suspected myocardial injury. In addition, patients completed a questionnaire about symptoms and the quality of life during the post-COVID-19 period., Results: In this study, 85 patients were included. The study population consisted of patients with a mean age of 42.5 ± 13.4 years, predominantly women, who made up 69.4% of the study population, while men made up 30.6%. CMR findings showed non-ischemic myocardial injury in 78.8% of patients and myocardial edema in 14.1% of patients. Late pericardial enhancement was present in 40% of patients and pericardial effusion in 51.8% of patients. Pericardial effusion ( p = 0.001) was more prevalent in patients who reported more pronounced symptoms in the post-COVID-19 period compared to the acute infection phase. Predictors of lower quality of life in the post-COVID-19 period were the presence of irregular heartbeat ( p = 0.039), cardiovascular problems that last longer than 12 weeks ( p = 0.018), and the presence of pericardial effusion ( p = 0.037)., Conclusion: Acute myocarditis was observed in a minority of patients after COVID-19, while non-ischemic LGE pattern and pericardial effusion were observed in the majority. Quality of life was worse during the post-COVID-19 period in patients with CMR abnormalities, primarily in patients with pericardial effusion. Also, irregular heartbeat, cardiovascular symptoms that last longer than 12 weeks, as well as pericardial effusion were independent predictors of lower quality of life during the post-COVID-19 period.

Type 2 diabetes (T2D) is associated with increased risk for chronic kidney disease (CKD). It is estimated that 40 % of people with diabetes have CKD, which consequently leads to increase in morbidity and mortality from cardiovascular diseases (CVDs). Diabetic kidney disease (DKD) is leading cause of CKD and end-stage renal disease (ESRD) globally. On the other hand, DKD is independent risk factor for CVDs, stroke and overall mortality. According to the guidelines, using spot urine sample and assessing urine albumin-to-creatinine ratio (UACR) and estimated glomerular filtration rate (eGFR) are both mandatory methods for screening of CKD in T2D at diagnosis and at least annually thereafter. Diagnosis of CKD is confirmed by persistent albuminuria followed by a progressive decline in eGFR in two urine samples at an interval of 3 to 6 months. However, many patients with T2D remain underdiagnosed and undertreated, so there is an urgent need to improve the screening by detection of albuminuria at all levels of health care. This review discusses the importance of albuminuria as a marker of CKD and cardiorenal risk and provides insights into the practical aspects of methods for determination of albuminuria in routine clinical care of patients with T2D., Competing Interests: Declaration of competing interest The authors 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 Elsevier B.V. All rights reserved.)

Purpose: The purpose of this study was to evaluate intraocular pressure (IOP) levels in patients suffering from Wilsons disease., Methods: In observational, cross-sectional, non-interventional study, IOP was measured by applanation tonometry in 52 patients with Wilson's disease (WD), and compared to 52 healthy controls (HC)., Results: Patients with Wilsons disease had significantly lower IOPs, compared to control group (CG) (13.20 ± 2.5 versus 14.98 ± 2.0, p  < .000, t test)., Conclusions: We found that IOP is significantly lower in patients with WD., 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.

Neuroactive steroids are a type of steroid hormones produced within the nervous system or in peripheral glands and then transported to the brain to exert their neuromodulatory effects. Neuroactive steroids have pleiotropic effects, that include promoting myelination, neuroplasticity, and brain development. They also regulate important physiological functions, such as metabolism, feeding, reproduction, and stress response. The homoeostatic processes of metabolism and reproduction are closely linked and mutually dependent. Reproductive events, such as pregnancy, bring about significant changes in metabolism, and metabolic status may affect reproductive function in mammals. In females, the regulation of reproduction and energy balance is controlled by the fluctuations of oestradiol and progesterone throughout the menstrual cycle. Neurosteroids play a key role in the neuroendocrine control of reproduction. The synthesis of neuroestradiol and neuroprogesterone within the brain is a crucial process that facilitates the release of GnRH and LH, which in turn, regulate the transition from oestrogen-negative to oestrogen-positive feedback. In addition to their function in the reproductive system, oestrogen has a key role in the regulation of energy homoeostasis by acting at central and peripheral levels. The oestrogenic effects on body weight homoeostasis are primarily mediated by oestrogen receptors-α (ERα), which are abundantly expressed in multiple brain regions that are implicated in the regulation of food intake, basal metabolism, thermogenesis, and brown tissue distribution. The tight interplay between energy balance and reproductive physiology is facilitated by shared regulatory pathways, namely POMC, NPY and kisspeptin neurons, which are targets of oestrogen regulation and likely participate in different aspects of the joint control of energy balance and reproductive function. The aim of this review is to present a summary of the progress made in uncovering shared regulatory pathways that facilitate the tight coupling between energy balance and reproductive physiology, as well as their reciprocal interactions and the modulation induced by neurosteroids., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This narrative review aimed to summarize all adverse outcomes of pregnancy in advanced maternal age (AMA) to assess the age of the mother as a potentially crucial risk factor. AMA refers to women older than 35 years. While expectations and the role of women in society have undergone significant changes today, the biology of aging remains unchanged. Various pathologic changes occur in the human body with age, including chronic noncommunicable diseases, as well as notable changes in reproductive organs, that significantly affect fertility. Despite substantial advancements in technology and medicine, pregnancy in AMA remains a formidable challenge. Although there are some advantages to postponing childbirth, they primarily relate to maternal maturity and economic stability. However, regrettably, there are also many adverse aspects of pregnancy at advanced ages. These include complications affecting both the mother and the fetus. Pregnants in AMA were more prone to suffer from gestational diabetes mellitus, preeclampsia, and eclampsia during pregnancy compared to younger women. In addition, miscarriages and ectopic pregnancies were more prevalent. Delivery was more frequently completed via cesarean section, and postpartum complications and maternal mortality were also higher. Unfortunately, there were also complications concerning the fetus, such as chromosomal abnormalities, premature birth, low birth weight, admission to the neonatal intensive care unit, and stillbirth., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age and is closely associated with chronic low-grade inflammation and insulin resistance. To clarify the contribution of prepubertal weight gain to the development of insulin resistance in PCOS, we investigated the effects of early postnatal overfeeding on inflammatory and energy-sensing pathways as well as on markers of insulin signaling in the liver of the PCOS rat model., Methods: Obesity induced by overfeeding was achieved by reducing litter size, while the PCOS-like condition was developed by treatment with 5α-dihydrotestosterone (DHT). Western blot and qPCR were used to analyze the expression of pro-inflammatory transcription factors and cytokines, as well as markers of the energy sensing and insulin signaling pathways., Results: The results showed that hepatic insulin sensitivity was impaired only in DHT-treated rats raised in small litters, as evidenced by increased phosphorylation of IRS1 on Ser307 and decreased expression of total IRS1. Postnatal overfeeding stimulated JNK1 activation independent of hyperandrogenemia; nevertheless, the synergistic effect of both factors triggered NLRP3 activation and increased IL1β expression in the small litter DHT-treated group. This pro-inflammatory state was accompanied by decreased activatory phosphorylation of AMPK and reduced levels of its protein targets., Conclusions: Overfeeding in the early postnatal period leads to a decrease in hepatic insulin sensitivity in the rat model of PCOS, which is associated with decreased activation of AMPK and stimulation of the hepatic NLRP3-IL1β signaling pathway. Accordingly, the inhibition of NLRP3 activation could provide a basis for the development of new therapeutic strategies for the treatment of insulin resistance in women with PCOS., 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 Veličković, Mićić, Teofilović, Milovanovic, Jovanović, Djordjevic, Macut and Vojnović Milutinović.)

Background and Aims: There is a gap in knowledge about implementing diagnostic tools and therapy for heart failure with preserved ejection fraction (HFpEF) in clinical practice. This survey aimed to assess real-world practice in HFpEF diagnosis and treatment in the international medical community., Methods: An independent academic web-based 29-question survey was designed by a group of heart failure specialists and posted by email and through scientific societies and social networks to a broad community of physicians worldwide., Results: 1.460 physicians from 95 countries answered the survey, with a mean age of 42.2±10.4 years, 39.4 % females, and 85.1 % were cardiologists. The left ventricular ejection fraction cut-off value selected for HFpEF diagnosis was 50 % for 89 % of participants. The scores for the probability of diagnosis of HFpEF were used only by 47.2 %, and H2FPEF was the most used score (31 %). Natriuretic peptides were used by 87.4 % of participants for the diagnostic workup, while the diastolic stress test was only used by 26.2 %. 54.4 % of participants chose SGLT2 inhibitors as their first drug treatment, followed by diuretics (18.6 %) and ACE inhibitors (8.4 %)., Conclusions: In an international academic survey on HFpEF management, the criteria for screening and diagnosis of HFpEF patients remain aligned with classic international guidelines with a low use of diagnostic scores. SGLT2i is the leading therapeutic drug class used for this heterogeneous patient population. These results raise the need to improve education and awareness on diagnosing and managing HFpEF patients., Competing Interests: Declaration of competing interest CS has received honoraria as speaker for Speaker for Novartis, Servier, Merck, Sanofi Pfizer, Astrazeneca, Boehringer Ingelheim, Novo Nordisk, Ely Lilly and as advisor for Bayer, Merck and Novo Nordisk, CF has received travel fees from Pfizer, NM has received consulting fees from Bayer and Amgen and as speaker for Astrazeneca, Novartis and Boehringer Ingelheim, support for attending meetings from Astrazeneca and Novartis, FR has not received personal payments by pharmaceutical companies or device manufacturers in the last 3 years (remuneration for the time spent in activities, such as participation as steering committee member of clinical trials and member of the Pfizer Research Award selection committee in Switzerland, were made directly to the University of Zurich). The Department of Cardiology (University Hospital of Zurich/University of Zurich) reports research-, educational- and/or travel grants from Abbott, Abiomed, Alnylam,Amarin, Amgen, Astra Zeneca, At the Limits Ltd., Bayer, Biotronik, BMS, Boehringer Ingelheim, Boston Scientific, Bracco, CM Microport, Concept Medical, CTI, Daiichi Sankyo, Edwards Lifesciences, FomF GmbH, Hamilton Health Sciences, IHF, Innosuisse, IumiraDX, Kantar, LabPoint, MedAlliance, Medcon International, Medical Education Global Solutions, Medtronic, MicroPort, Monocle, Novartis, Novo Nordisk, OM Pharma, Pfizer, Quintiles Switzerland Sarl, RecorMedical, Roche Diagnostics, Roche Pharma, Sahajanand IN, Sanofi, Sarstedt AG, Servier, Terumo Deutschland, Trama Solutions, V- Wave, Vifor, ZOLL. These grants do not impact on Prof. Ruschitzka`s personal remuneration. IJI received support for travel to meetings from Novartis. DM received payment as a speaker for Novartis, Pfizer, Astra Zeneca and support for attending meetings from Pfizer, Astrazeneca and abbot. GR reports grants and personal fees from Astra Zeneca, personal fees and other from Boheringer Ingelheim, other from Bayer, personal fees from Anlylam, other from Medtronic, grants from Servier, grants and non-financial support from Menarini, personal fees from Viatris, grants from Vifor Pharma, outside the submitted work. GGR reports personal fees from Pfizer, personal fees from CSL Vifor, personal fees from Astra Zeneca, personal fees from PTC therapeutics, personal fees from Bristol MS, personal fees from Boehringer Ingelheim, personal fees from Servier, outside the submitted work; GE reports personal fees from NOVO NORDISK, during the conduct of the study; IM reports grants from Boehringer Ingelheim, during the conduct of the study, SZ Served on advisory boards for, or speaker engagements with Abbott, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Cytokinetics, Eli Lilly, GSK, Medtronic, Merck, Novartis, Novo-Nordisk, Pfizer and Vifor Pharma; and serves on a clinical trial committee or as a national lead for studies sponsored by AstraZeneca, Boehringer Ingelheim, Merck, Novartis, Pfizer, Salubris Bio and Served on advisory boards for, or speaker engagements with Abbott, AstraZeneca, Bayer, BMS, Boehringer Ingelheim, Cytokinetics, Eli Lilly, GSK, Medtronic, Merck, Novartis, Novo-Nordisk, Pfizer and Vifor Pharma., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This study focuses on developing machine learning models to detect subtle alterations in hepatocyte chromatin organization due to Iron (II, III) oxide nanoparticle exposure, hypothesizing that exposure will significantly alter chromatin texture. A total of 2000 hepatocyte nuclear regions of interest (ROIs) from mouse liver tissue were analyzed, and for each ROI, 5 different parameters were calculated: Long Run Emphasis, Short Run Emphasis, Run Length Nonuniformity, and 2 wavelet coefficient energies obtained after the discrete wavelet transform. These parameters served as input for supervised machine learning models, specifically random forest and gradient boosting classifiers. The models demonstrated relatively robust performance in distinguishing hepatocyte chromatin structures belonging to the group exposed to IONPs from the controls. The study's findings suggest that iron oxide nanoparticles induce substantial changes in hepatocyte chromatin distribution and underscore the potential of AI techniques in advancing hepatocyte evaluation in physiological and pathological conditions., (© 2024. The Author(s).)

Background: Gender equity is essential for improving health outcomes globally. Despite comprising 75% of the global health workforce and dominating academic global health programs, women remain underrepresented in leadership positions in global health organizations. Our study aimed to identify potential gender differences in the beliefs and attitudes regarding barriers that women anesthesiologists encounter in pursuing careers and leadership roles in global health and to identify recommendations for improving gender equity in global health., Methods: We conducted a cross-sectional online survey focusing on career leadership opportunities and challenges uniquely faced by women clinicians in global health. We obtained permission from the World Federation of Societies of Anaesthesiologists to distribute our questionnaire to their leadership committee members during 2 months (May-July 2022)., Results: The questionnaire was distributed to 164 study participants with 67 individuals (44.8% female) based in 38 different countries completing the survey (response rate 40.9%). Overall, 47.8% of the participants aspired to a leadership position in global health and 58.2% agreed women face unique barriers to global health leadership (70.0% of women compared to 48.6% of men; P = .081). Female gender (odds ratio [OR], 19.22, P = .004) and divorced marital status (OR, 746.26, P = .004) were positively associated and African ethnicity (OR, 0.002, P = .017) was negatively associated with the perception of gender bias in their career growth. The main challenges included balancing work and family responsibilities, lack of female mentors or role models, gender-based discrimination, and limited opportunities for career advancement. Men acknowledged these challenges but reported personally experiencing them to a lesser extent, particularly concerning lack of opportunities (P = .005), inadequate pay (P = .000), and lack of training (P = .000)., Conclusions: Gender disparities exist in the pursuit of global health careers. This study underscored that more women than men perceive barriers in pursuing leadership roles in global health and that men generally encounter these obstacles to a lesser extent. Female representation in leadership positions could be supported through evidence-informed policies that promote work-life balance, improve mentorship, offer equal opportunities for career advancement and adequate pay, and combat gender-based discrimination., Competing Interests: Conflicts of Interest, Funding: Please see DISCLOSURES at the end of this article., (Copyright © 2024 International Anesthesia Research Society.)

Objectives: The aim of this cross-sectional survey was to gather attitudes and practices of physicians from different countries regarding the implementation of contrast-enhanced ULTRAsound (CEUS) for vascular diseases in clinical practice as well as in academic research., Methods: A web-based survey was developed in English, including 35 questions. Two-hundred sixty physicians were invited by email to fill in the survey anonymously on Google Forms using a dedicated link. The survey started on 25 th February 2024 and was closed on 13 th March 2024 (17 days). A reminder was sent after the first 10 days. In addition to descriptive statistics, sub-analyses of answers according to country of origin (Italy vs other States), years of experience (≤20 years vs > 20 years), and type of institution (Academic/University vs Non-Academic/Private) were also established a priori., Results: A total of 121 practitioners from 20 countries completed our survey (response rate 121/260, 46%). Most responders were males (95/121, 78.5%). Most participants were vascular surgeons (118/121, 97.5%). CEUS was available in 87/121, 70.2% of the centers involved, even though a standardized protocol was present in 54/121, and 44% of surveyed institutions. Italian institutions presented greater CEUS availability (62/72, 86.1% vs 25/49, 51.0%; p = .001) and higher presence of standardized protocols (38/72, 52.8% vs 16/49, 32.6%; p = .022) than foreign institutions. The diagnostic tool was thought to be more useful for carotid artery stenosis in the postoperative phase, while for abdominal aortic aneurysms (AAAs) in the preoperative phase. For diagnosis and/or preoperative management of carotid stenosis 53/121, 44% of physicians believed that CEUS should be performed only in selected cases, while for AAA 42/121, 35% of them believed that it could be useful only for scientific purposes. Similarly, 99/121, 82% of participants answered that CEUS was usually prescribed in 0%-20% of the cases during the preoperative diagnostic pathway of patients with peripheral arterial disease. No differences between country of origin, years of experience, and type of institution were found for the reported items. There was also 106/121, 88% of respondents agreed upon the need for better integration of CEUS in current guidelines and 114/121, 94% of them upon the need for further studies., Conclusions: This ULTRA-VASC survey has demonstrated that CEUS is still rarely used in current practice for many vascular diseases despite the availability of this tool in most centers Future studies are needed, as well as enhanced guidance on the proper implementation of CEUS from guidelines., 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.

Asynclitism, a misalignment of the fetal head with respect to the plane of passage through the birth canal, represents a significant obstetric challenge. High degrees of asynclitism are associated with labor dystocia, difficult operative delivery, and cesarean delivery. Despite its clinical relevance, the diagnosis of asynclitism and its influence on the outcome of labor remain matters of debate. This study analyzes the role of the degree of asynclitism (AD) in assessing labor progress and predicting labor outcome, focusing on its ability to predict intrapartum cesarean delivery (ICD) versus non-cesarean delivery. The study also aims to assess the performance of the AIDA (Artificial Intelligence Dystocia Algorithm) algorithm in integrating AD with other ultrasound parameters for predicting labor outcome. This retrospective study involved 135 full-term nulliparous patients with singleton fetuses in cephalic presentation undergoing neuraxial analgesia. Data were collected at three Italian hospitals between January 2014 and December 2020. In addition to routine digital vaginal examination, all patients underwent intrapartum ultrasound (IU) during protracted second stage of labor (greater than three hours). Four geometric parameters were measured using standard 3.5 MHz transabdominal ultrasound probes: head-to-symphysis distance (HSD), degree of asynclitism (AD), angle of progression (AoP), and midline angle (MLA). The AIDA algorithm, a machine learning-based decision support system, was used to classify patients into five classes (from 0 to 4) based on the values of the four geometric parameters and to predict labor outcome (ICD or non-ICD). Six machine learning algorithms were used: MLP (multi-layer perceptron), RF (random forest), SVM (support vector machine), XGBoost, LR (logistic regression), and DT (decision tree). Pearson's correlation was used to investigate the relationship between AD and the other parameters. A degree of asynclitism greater than 70 mm was found to be significantly associated with an increased rate of cesarean deliveries. Pearson's correlation analysis showed a weak to very weak correlation between AD and AoP (PC = 0.36, p < 0.001), AD and HSD (PC = 0.18, p < 0.05), and AD and MLA (PC = 0.14). The AIDA algorithm demonstrated high accuracy in predicting labor outcome, particularly for AIDA classes 0 and 4, with 100% agreement with physician-practiced labor outcome in two cases (RF and SVM algorithms) and slightly lower agreement with MLP. For AIDA class 3, the RF algorithm performed best, with an accuracy of 92%. AD, in combination with HSD, MLA, and AoP, plays a significant role in predicting labor dystocia and labor outcome. The AIDA algorithm, based on these four geometric parameters, has proven to be a promising decision support tool for predicting labor outcome and may help reduce the need for unnecessary cesarean deliveries, while improving maternal-fetal outcomes. Future studies with larger cohorts are needed to further validate these findings and refine the cut-off thresholds for AD and other parameters in the AIDA algorithm.

Background : Transcatheter aortic valve replacement (TAVR) was developed for inoperable patients with severe aortic stenosis. However, despite TAVR advancements, some patients remain untreated due to complex comorbidities, necessitating less-invasive approaches. Non-invasive ultrasound therapy (NIUT), a new treatment modality, has the potential to address this treatment gap, delivering short ultrasound pulses that create cavitation bubble clouds, aimed at softening embedded calcification in stiffened valve tissue. Methods : In the prospective Valvosoft ® Serbian first-in-human study, we assessed the safety and efficacy of NIUT and its impact on aortic valve hemodynamics, on the left ventricle, and on systemic inflammation in patients with severe symptomatic aortic stenosis not eligible for TAVR or surgery. Results : Ten patients were included. Significant improvements were observed in hemodynamic parameters from baseline to one month, including a 39% increase in the aortic valve area (from 0.5 cm 2 to 0.7 cm 2 , p = 0.001) and a 23% decrease in the mean transvalvular gradient (from 54 mmHg to 38 mmHg, p = 0.01). Additionally, left ventricular global longitudinal strain significantly rose, while global wasted work significantly declined at one month. A dose-response relationship was observed between treatment parameters (peak acoustic power, intensity spatial-peak pulse-average, and mean acoustic energy) and hemodynamic outcomes. NIUT was safely applied, with no clinically relevant changes in high-sensitivity troponin T or C-reactive protein and with a numerical, but not statistically significant, reduction in brain natriuretic peptide (from 471 pg/mL at baseline to 251 pg/mL at one month). Conclusions : This first-in-human study demonstrates that NIUT is safe and confers statistically significant hemodynamic benefits both on the valve and ventricle.

COVID-19, a global epidemic of infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), not only initially refers to acute manifestations but also chronic symptoms known as Long COVID-19. Long COVID-19 represents a significant burden to healthcare systems worldwide. This syndrome encompasses a wide range of continuing health problems with variable durations and consequences for patients' everyday lives. A notable aspect of Long COVID-19 is the emergence of new-onset autoimmune diseases that could be triggered in predisposed patients with altered immune responses. Common autoimmune conditions that arise in post-COVID patients include autoimmune hemolytic anemia, immune thrombocytopenic purpura, autoimmune thyroid diseases, Kawasaki disease, Guillain-Barre syndrome, etc., but with unclear evidence of associated disease occurrence. We present a case of a female rheumatoid arthritis patient who developed autoimmune thyroid disease, latent autoimmune diabetes of adults (LADA), and pernicious anemia after SARS-CoV-2 infection., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Concurrent global increase of prevalence of obesity and male fertility implies link between overweight and obesity with male subfertility. This hypothesis is supported by numerous population-based epidemiological studies. Increase in body mass index (BMI) is associated with poor sperm quality in fertile, and more noticeable in infertile men. Nevertheless, some studies disprove damaging effect of BMI on semen quality. To examine the influence of men's BMI in infertile couples undergoing in vitro fertilization (IVF) on semen analysis parameters and IVF outcomes. Study encompassed all couples who underwent IVF at Gynecology and Obstetrics Clinic Narodni Front in Belgrade during 2018 and 2019. Exclusion criteria were azoospermia, conditions and diseases that could affect the semen analysis parameters (diabetes, malignant diseases treated with radiation and/or chemotherapy, trauma or surgery of the genital organs, mumps or undescended testicles in childhood). Evaluated semen analysis parameters included semen ejaculate volume, sperm pH, sperm count, sperm motility, and sperm morphology. IVF outcomes comprised total number of embryos, number and percentage of obtained good-quality embryos and clinical pregnancy rates. Based on BMI value, participants were divided into a group of underweight (Group 1), normally weight (Group 2), overweight (Group 3), and obese men (Group 4). After applying inclusion and exclusion criteria, 411 men (couples) were included in the analysis. The largest number of men were overweight, while the smallest belonged to the group of underweight participants. There are no significant differences in the semen analysis parameters between study groups. Correlation analysis shown weak and insignificant correlation between BMI and semen analysis parameters. The number and proportion of good quality embryos is significantly lower in overweight and obese study groups compared to normal weight and underweight groups (2.89, 2.91, 2.42, and 2.36, respectively, P = .041). The differences in other IVF outcomes: total number of embryos (3.61, 3.74, 3.21, and 3.37, respectively) and clinical pregnancy rates (41.26%, 43.09%, 42.78%, and 39.95%, respectively) between study groups were not significant (P > .05). BMI does not significantly affect semen analysis parameters, but a higher BMI is associated with a lower number and proportion of good quality embryos in IVF outcomes., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: In the Balkans, rising concerns about invasive fungal infections over the past decade stem from various factors. Primarily, there has been a notable uptick in immunocompromised individuals, including those with chronic illnesses like immunological and hematological diseases. Thus, it is essential to assess the region's laboratory capabilities and the availability of antifungals. This evaluation is vital for gauging the preparedness to diagnose and treat fungal infections effectively, thus minimizing their public health impact., Methods: Data were collected via an online questionnaire targeting healthcare professionals specializing in relevant fields across diverse healthcare settings in Balkan countries. The survey covered various aspects, including diagnostic methods, imaging techniques, and available antifungal armamentarium., Results: Responses were obtained from 50 institutions across the Balkans. While conventional diagnostic methods like microscopy (96 %) and culture (100 %) diagnostics were widely available, access to newer diagnostic tools such as molecular assays (61 %) were limited, often relying on outsourced services. Imaging modalities like ultrasound (100 %) and CT scans (93 %) were universally accessible. A variety of antifungal drugs were available, including amphotericin B formulations (80 %), echinocandins (79 %), and triazoles (100 %). However, access to newer agents like posaconazole (62 %) and isavuconazole (45 %) was inconsistent. Therapeutic drug monitoring (53 %) services were also limited., Conclusion: The study underscores the need for equitable access to diagnostic facilities and antifungal treatments across healthcare settings in the Balkan geographic region. Improving access to molecular diagnostic tools and essential antifungal drugs, as well as implementing therapeutic drug monitoring, would optimize the management of fungal infections in the region., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Conflicts of interest The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Despite improvements over recent years, morbidity and mortality associated with heart failure (HF) are higher in countries in the Central and Eastern Europe and Baltic region than in Western Europe. With the goal of improving the standard of HF care and patient outcomes in the Central and Eastern Europe and Baltic region, this review aimed to identify the main barriers to optimal HF care and potential areas for improvement. This information was used to suggest methods to improve HF management and decrease the burden of HF in the region that can be implemented at the national and regional levels. We performed a literature search to collect information about HF epidemiology in 11 countries in the region (Bulgaria, Croatia, Czechia, Estonia, Hungary, Latvia, Lithuania, Poland, Romania, Serbia, and Slovenia). The prevalence of HF in the region was 1.6-4.7%, and incidence was 3.1-6.0 per 1000 person-years. Owing to the scarcity of published data on HF management in these countries, we also collected insights on local HF care and management practices via two surveys of 11 HF experts representing the 11 countries. Based on the combined results of the literature review and surveys, we created national HF care and management profiles for each country and developed a common patient pathway for HF for the region. We identified five main barriers to optimal HF care: (i) lack of epidemiological data, (ii) low awareness of HF, (iii) lack of national HF strategies, (iv) infrastructure and system gaps, and (v) poor access to novel HF treatments. To overcome these barriers, we propose the following routes to improvement: (i) establish regional and national prospective HF registries for the systematic collection of epidemiological data; (ii) establish education campaigns for the public, patients, caregivers, and healthcare professionals; (iii) establish formal HF strategies to set clear and measurable policy goals and support budget planning; (iv) improve access to quality-of-care centres, multidisciplinary care teams, diagnostic tests, and telemedicine/telemonitoring; and (v) establish national treatment monitoring programmes to develop policies that ensure that adequate proportions of healthcare budgets are reserved for novel therapies. These routes to improvement represent a first step towards improving outcomes in patients with HF in the Central and Eastern Europe and Baltic region by decreasing disparities in HF care within the region and between the region and Western Europe., (© 2024 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Background: In this substudy of the Value of Gated-SPECT MPI for Ischemia- Guided PCI of non-culprit vessels in STEMI Patients with Multi vessel Disease after primary PCI trial after primary PCI we aim to assess if infarct size affects conventional measures of dyssynchrony at rest. Additionally, we explore if there is an independent correlation of stress-inducible ischemia with dyssynchrony at rest., Methods: The 48 patients with imaging at randomization were analyzed. Gated-single-photon emission computed tomography (SPECT) MPI with vasodilator stress and technetium-99m-labeled tracers was performed. The phase histogram bandwidth (HBW), phase SD, and entropy were obtained with the QGS software. Correlation between dyssynchrony at rest and infarct size and inducible ischemia was performed using the Spearman test., Results: According to normal database limits dyssynchrony parameters at rest were abnormal for men. In women only HBW was abnormal. Correlation between the summed rest score with dyssynchrony was significant only for entropy ( P  = 0.035). No correlation was observed for dyssynchrony and stress-induced ischemia., Conclusion: Entropy, as a measure of dyssynchrony, has potential in the assessment of patients with STEMI and multivessel disease after primary PCI. Smaller residual myocardial scars in PCI-reperfused patients with STEMI may contribute to the lack of correlation between dyssynchrony at rest and infarct size and stress-induced ischemia, respectively., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Adenomyosis is an intricate pathological condition that negatively impacts the uterus. It is closely related to the more well-known endometriosis, with which it shares parallels in terms of diagnosis, therapy, and both microscopic and macroscopic features. The purpose of this narrative review is to give a clear univocal definition and outlook on the different, patient-adapted, surgical treatments. MEDLINE and PubMed searches on these topics were conducted from 1990 to 2022 using a mix of selected keywords. Papers and articles were identified and included in this narrative review after authors' revision and evaluation. From the literature analysis, authors reported the following surgical techniques: laparoscopic double/triple-flap method, laparotomic wedge resection of the uterine wall, laparotomic transverse H-incision of the uterine wall, laparotomic wedge-shaped excision, and laparotomic complete debulking excision by asymmetric dissection technique. Each of these techniques has strengths and weaknesses, but the literature data on the pregnancy rate are somewhat limited. The only certain information is the risk of uterine rupture up to 6.0% after surgical treatment for uterine adenomyosis. Over the years, the surgical approach continued to reach a positive result by minimally invasive treatment, with less hospitalization, less postoperative pain, and less blood loss. Over the years, the gynecological surgeon has gained the skills, training and increasingly sophisticated surgical techniques to target effective therapy. That's why a hysterectomy is no longer the only surgical resource to treat adenomyosis, but in patients who wish to preserve the fertility, there is a wide variety of surgical alternatives., (© 2024 International Federation of Gynecology and Obstetrics.)

Background: Patients with ST-segment elevation myocardial infarction (STEMI) and COVID-19 infection have a worse clinical course and prognosis. The prognostic significance of the timing of STEMI in relation to COVID-19 infection was not investigated. Objectives: To assess whether the time of STEMI development in relation to COVID-19 infection (concurrent or following the infection) influenced the short-term prognosis. Methods: This was an observational study of consecutive COVID-19 patients with STEMI admitted to the COVID-hospital Batajnica (February 2021-March 2022). The patients were divided into the "STEMI first" group: patients with STEMI and a positive polymerase chain reaction test for COVID-19, and the "COVID-19 first" group: patients who developed STEMI during COVID-19 treatment. All patients underwent coronary angiography. The primary endpoint was in-hospital all-cause mortality. Results: The study included 87 patients with STEMI and COVID-19 ( M , 66.7 years, 66% male). The "STEMI first" group comprised 54 (62.1%) patients, and the "COVID-19 first" group included 33 (37.9%) patients. Both groups shared a comparatively high burden of comorbidities, similar angiographic and procedural characteristics, and high percentages of performed percutaneous coronary interventions with stent implantation (90.7% vs. 87.9%). In-hospital mortality was significantly higher in the "COVID-19 first" group compared to the "STEMI first" group (51.5% vs. 27.8%). Following adjustment, the "COVID-19 first" group had a hazard ratio of 3.22 (95% confidence interval, 1.18-8.75, age , 66.7 years, 66% male). The "STEMI first" group comprised 54 (62.1%) patients, and the "COVID-19 first" group included 33 (37.9%) patients. Both groups shared a comparatively high burden of comorbidities, similar angiographic and procedural characteristics, and high percentages of performed percutaneous coronary interventions with stent implantation (90.7% vs. 87.9%). In-hospital mortality was significantly higher in the "COVID-19 first" group compared to the "STEMI first" group (51.5% vs. 27.8%). Following adjustment, the "COVID-19 first" group had a hazard ratio of 3.22 (95% confidence interval, 1.18-8.75, p Clinical presentation with COVID-19 infection, followed by STEMI ("COVID-19 first"), was associated with greater short-term mortality compared to patients presenting with STEMI and testing positive for COVID-19 ("STEMI first").Conclusion: Clinical presentation with COVID-19 infection, followed by STEMI ("COVID-19 first"), was associated with greater short-term mortality compared to patients presenting with STEMI and testing positive for COVID-19 ("STEMI first")., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

A budget impact analysis estimates the short-term difference between the cost of the current treatment strategy and a new treatment strategy, in this case to implement population screening for atrial fibrillation (AF). The aim of this study is to estimate the financial impact of implementing population-based AF-screening of 75-year-olds compared with the current setting of no screening from a healthcare payer perspective in eight European countries. The net budget impact of AF-screening was estimated in country-specific settings for Denmark, Germany, Ireland, Italy, Netherlands, Serbia, Spain, and Sweden. Country-specific parameters were used to allow for variations in healthcare systems and to reflect the healthcare sector in the country of interest. Similar results can be seen in all countries AF-screening incurs savings of stroke-related costs since AF treatment reduces the number of strokes. However, the increased number of detected AF and higher drug acquisition will increase the drug costs as well as the costs of physician- and control visits. The net budget impact per invited varied from €10 in Ireland to €122 in the Netherlands. The results showed the increased costs of implementing AF-screening were mainly driven by increased drug costs and screening costs. In conclusion, across Europe, though the initial cost of screening and more frequent use of oral anti-coagulants will increase the healthcare payers' costs, introducing population screening for AF will result in savings of stroke-related costs., Competing Interests: Conflict of interest: M.E., J.L., L.B., and K.A. report no conflicts of interest. L.Å.L. has received lecture fees and advisory board fees from BMS/Pfizer, Bayer, Boehringer Ingelheim, and Zenicor and own stocks in Astra Zeneca. J.H.S. reports to be a member of Medtronic and Vital Beats advisory boards and to have received speaker honoraria and research grants from Medtronic. R.B.S. has received lecture fees and advisory board fees from BMS/Pfizer and Bayer outside this work. D.E. reports no conflicts of interest. C.M. and C.W. are employees of the Institute for Epidemiology, Statistics and Informatics GmbH. The Institute for Epidemiology, Statistics and Informatics GmbH has received grants from Astra Zeneca, Bayer, Bristol-Myers Squibb and CSL Behring outside the submitted work. S.Z.D. reports consultancy fees from VitalBeats, BMS/Pfizer, Cortrium, and Acesion Pharma, speaker grants from BMS/Pfizer and Bayer, and travel grants from Abbott and Boston Scientific. G.B. reports speaker’s fees of small amount from Bayer, Boehringer Ingelheim, Boston, Daiichi Sankyo, Janssen, and Sanofi outside of the submitted work. C.M.B. reports no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

The role of vertical ex vivo dermoscopy relevant to clinical diagnosis has not been investigated yet. Study objectives were defining, describing, and determining the importance of the structures visible using vertical ex vivo dermoscopy in the diagnosis of malignant skin lesions, as well as determining their accuracy in the assessment of tumor margins. A prospective, descriptive study was conducted in two University centers. Digital images of completely excised skin lesions, fixed in formalin, before histopathological diagnosis were used for analysis. BCCs had the most diverse dermoscopic presentation on the vertical section, while SCCs showed a similar presentation in most cases. Vertical dermoscopy of thin melanomas was almost identical, unlike nodular melanomas. Thickness accuracy assessed by dermatologist was 0.753 for BCC, 0.810 for SCC, and 0.800 for melanomas, whereas assessment by pathologist was 0.654, 0.752, and 0.833, respectively. The accuracy of tumor width assessment was 0.819 for BCCs, 0.867 for SCCs and 1.000 for melanoma as estimated by a Dermatologist. Interobserver agreement was 0.71 for BCC, 0.799 for SCC and 0.832 for melanomas. Vertical ex vivo dermoscopy may contribute to the distinction between BCCs, SCCs, and melanomas. Moreover, regardless of the doctor's specialty, it enables a good assessment of the tumor's margins.

Non-somatostatin receptor expressing hypovascular insulinomas can be challenging to prove through imaging. This case highlights the utility of a structured approach to molecular imaging in patients with confirmed endogenous hyperinsulinemia. A 54-year-old woman was admitted because of a sudden loss of consciousness. Her relative reported that she complained of dizziness, intense sweating, blurry vision, and upper extremity tingling before becoming unresponsive for 20 min, after which the patient had little recollection of the event. She experienced similar episodes of shorter duration, trouble recalling everyday events, and unintentional weight gain of over 10 kg during the previous two years. Abdominal magnetic resonance imaging (MRI) and multidetector computerized tomography (MDCT) were unremarkable. Selective arterial calcium stimulation significantly increased hepatic venous insulin concentrations when the superior mesenteric and gastroduodenal arteries were stimulated. Technetium-99m (99mTc) octreotide single-photon emission computed tomography (SPECT) did not localize the lesion. Gallium-68 DOTA-Exendin-4 PET/CT acquisition was performed. A single intense 2 cm hyperperfused pancreatic lesion was located anteriorly in the head of the pancreas. Earlier targeted PET/CT imaging and recognition of significant neuropsychiatric symptoms attributable to the patient's hypoglycemic state might have accelerated the resolution of her condition and obviated the need for unnecessary testing.

(1) Background: Physical activity may cause an imbalance in the major functions of the human body. This study aimed to investigate the effects of endurance running training on the parameters of the antioxidant defense system (SOD, CAT, GPx, GR, GSH), LPO (malondialdehyde, MDA), and stress hormones (A, NA) in young healthy, previously untrained men. (2) Methods: The training program was as follows: 8 weeks of running, three times per week; the duration of a single session was 30-70 min, the intensity was twice a week in the so-called extensive endurance zone, and once a week in the anaerobic threshold zone. Blood samples were collected from the subjects, before and after the running program. (3) Results: The training program resulted in a significant increase in maximal oxygen consumption ( p < 0.001). The activities of SOD, GPx, and GR also increased significantly ( p < 0.05, p < 0.01, and p < 0.05, respectively), while CAT activity and GSH and MDA concentrations remained unchanged. The concentration of A decreased ( p < 0.05), while the NA concentration increased significantly ( p < 0.05). SOD, GPx, GR, and NA positively correlated with VO 2 max ( p < 0.05, p < 0.001, p < 0.01, p < 0.05, respectively), while a negative correlation was detected between A and VO 2 max ( p < 0.05). (4) Conclusions: These results indicate that there is no persistent oxidative stress in response to the applied 8-week running program, probably due to exercise-induced protective alterations in the antioxidant defense system. Furthermore, adaptations occurred at the hormonal level, making the organism more ready for a new challenge.

Purpose: Therapeutic plasma exchange (PLEX) is effective as a second-line treatment of severe relapses of multiple sclerosis (MS) that failed to respond to standard steroid therapy. Our objective was to evaluate the effectiveness of PLEX in the severe MS relapses in a cohort of patients treated at Neurology Clinic, University Clinical Centre of Serbia, Belgrade, from 2007 until 2020., Methods: This retrospective study comprised 107 MS patients with 127 severe relapses treated with PLEX. Majority of our patients suffered from relapsing remitting MS (83.2%), 12.1% had secondary progressive MS and 4.7% had primary progressive MS. Mean age was 39.2 years (range, 19-79 years), female/male ratio 2.3:1. Pulse corticosteroid treatment was used before PLEX in 99.3% of patients. Median EDSS score at nadire during relapse was 6.0 (range 2.0-10.0). After PLEX, 73.8% relapses showed a marked clinical improvement, 7.1% showed mild improvement and in 19.0% there was no improvement. Median EDSS at discharge was 4.0 (6.0 at nadir of relapse vs. 4.0 at discharge; p<0.0001) and it was sustained at the same level, 6 month after PLEX. Multivariate regression analysis showed that higher EDSS at nadir during relapse (OR=0.63, 95% CI 0.41-0.96, p=0.039) and older age (OR=1.07, 95% CI 1.02- 1.12, p=0.010) were significantly associated with poor treatment response after 6- month follow-up. Adverse events occurred in 17.3 of procedures and they were completely resolved., Conclusion: Our study in a large cohort of MS patients confirmed that PLEX is effective., (© 2024. The Author(s) under exclusive licence to Belgian Neurological Society.)

Background/Objectives : Prediction of a difficult airway during pre-anesthetic evaluation is of great importance because it enables an adequate anesthetic approach and airway management. As there is a scarcity of prospective studies evaluating the role of anthropometric measures of the face and neck in predicting difficult airways in infants with an apparently normal airway, we aimed to identify the aforementioned predictors of difficult facemask ventilation and intubation in infants. Methods : A prospective, observational study that included 97 infants requiring general endotracheal anesthesia was conducted. Anthropometric and specific facial measurements were obtained before ventilation and intubation. Results : The incidence of difficult facemask ventilation was 15.5% and 38.1% for difficult intubation. SMD (sternomental distance), TMA (tragus-to-mouth angle distance), NL (neck length) and mouth opening were significantly lower in the difficult facemask ventilation group. HMDn (hyomental distance in neutral head position), HMDe (hyomental distance in neck extension), TMD (thyromental distance), SMD, mandibular development and mouth opening were significantly different in the intubation difficulty group compared to the non-difficult group. HMDn and HMDe showed significantly greater specificities for difficult intubation (83.8% and 76.7%, respectively), while higher sensitivities were observed in TMD, SMD and RHSMD (ratio of height to SMD) (89.2%, 75.7%, and 70.3%, respectively). Regarding difficult facemask ventilation, TMA showed greater sensitivity (86.7%) and SMD showed greater specificity (80%) compared to other anthropometric parameters. In a multivariate model, BMI (body mass index), COPUR (Colorado Pediatric Airway Score), BOV (best oropharyngeal view) and TMA were found to be independent predictors of difficult intubation, while BMI, ASA (The American Society Physical Status Classification System), CL (Cormack-Lehane Score), TMA and SMD predicted difficult facemask ventilation. Conclusions : Preoperative airway assessment is of great importance for ventilation and intubation. Patient's overall condition and facial measurements can be used as predictors of difficult intubation and ventilation.

Increased immune-inflammatory activation has been repeatedly linked to etiopathogenesis and the progression of both major depressive disorder (MDD) and bipolar depression (BD). We explore the role of soluble intercellular cell adhesion molecule-1 (sICAM-1) and soluble vascular cell adhesion molecule-1 (sVCAM-1) in diagnostic differentiation and disorder progression in patients with MDD and BD. Serum levels of sICAM-1 and sVCAM-1 were measured in 137 patients (MDD = 93 and BD = 44) and compared with 73 healthy controls. The severity of psychopathology was assessed using the Hamilton Depression Rating Scale and Clinical Global Impression Scale. After adjustment for multiple confounders, we noticed significant downregulation of sVCAM-1 and upregulation of sICAM-1 levels in both patient groups. Decreased sVCAM-1 levels were detected in patients with acute episodes of BD when compared to MDD. Immune mediators were related to indicators of progression in both mood disorders. They also followed different post-treatment normalization patterns in MDD and BD and in relation to the stage of each disorder. Adhesion molecules could potentially be useful in discriminating between patients with MDD and BD and determining the possible progression of the disorders. Future nosological methods should include time-dependent pathoplasticity and biological correlates, at least for affective disorders.

The skin of newborns is classified as sensitive, with a higher risk of skin barrier disruption and irritation of a diapered area. Despite dermatologist recommendations to use only water and a cloth for cleaning, most of the population still relies on the comforts of modern parenting, which includes intensive daily usage of baby wet wipes. Novel baby formulations are designed following the concept of infant skin health, containing a gentle cleanser, suitable emollient, and buffer system enabling a slightly acidic pH value and they are free of ethyl alcohol. Thus, it is important to understand the chemical background of such a complex liquid formulation, with emphasis on its safety. In line with this, the present paper discusses the scientific background of various chemical compounds found in baby wipe formulations to improve the understanding of wet wipe designs and direct them toward more skin-friendly solutions., (© 2024 the International Society of Dermatology.)

The aims of this study were to examine the effects of pyridoxine administration on the activities of cardiac antioxidant stress enzymes superoxide dismutase (SOD) and catalase (CAT) and enzyme indicators of cardiometabolic status, lactate and malate dehydrogenase (LDH, MDH), as well as LDH and MDH isoforms' distribution in the cardiac tissue of healthy and diabetic Wistar male rats. Experimental animals were divided into five groups: C1-control (0.9% sodium chloride-NaCl-1 mL/kg, intraperitoneally (i.p.), 1 day); C2-second control (0.9% NaCl 1 mL/kg, i.p., 28 days); DM-diabetes mellitus (streptozotocin 100 mg/kg in 0.9% NaCl, i.p., 1 day); P-pyridoxine (7 mg/kg, i.p., 28 days); and DM + P-diabetes mellitus and pyridoxine (streptozotocin 100 mg/kg, i.p., 1 day and pyridoxine 7 mg/kg, i.p., 28 days). Pyridoxine treatment reduced CAT and MDH activity in diabetic rats. In diabetic rats, the administration of pyridoxine increased LDH1 and decreased LDH4 isoform activities, as well as decreased peroxisomal MDH and increased mitochondrial MDH activities. Our findings highlight the positive effects of pyridoxine administration on the complex interplay between oxidative stress, antioxidant enzymes, and metabolic changes in diabetic cardiomyopathy.

Background and Objectives : Partially thrombosed aneurysms represent a subset primarily found within large and giant aneurysms. The presence of an intraluminal thrombus can cause an aneurysm to present in different shapes upon angiographic examination. We present a series of five cases of "donut-shaped" aneurysms observed over the past decade at the Clinic for Neurosurgery in the University Clinical Centre of Serbia. Materials and Methods : The management of "donut-shaped" aneurysms was accomplished through endovascular interventions, employing techniques such as the deployment of flow-diverting stents or a combination of stent placement and coil embolization. Results : Four out of five patients underwent endovascular treatment, yielding positive outcomes with complete thrombosis of the aneurysms during follow-up. The fifth patient was successfully diagnosed; however, due to their deteriorating condition, treatment was not feasible. Conclusions : Given the potential life-threatening complications associated with this entity, accurate diagnosis and appropriate management are crucial. In our cohort, endovascular interventions demonstrated efficacy in the majority of cases, underscoring the significance of this approach in treating "donut-shaped" aneurysms. Nevertheless, considering the rarity of this condition, further research is justified to refine diagnostic and therapeutic strategies for these complex intracranial vascular anomalies.

Autophagy is a lysosome-mediated self-degradation process of central importance for cellular quality control. It also provides macromolecule building blocks and substrates for energy metabolism during nutrient or energy deficiency, which are the main stimuli for autophagy induction. However, like most biological processes, autophagy itself requires ATP, and there is an energy threshold for its initiation and execution. We here present the first comprehensive review of this often-overlooked aspect of autophagy research. The studies in which ATP deficiency suppressed autophagy in vitro and in vivo were classified according to the energy pathway involved (oxidative phosphorylation or glycolysis). A mechanistic insight was provided by pinpointing the critical ATP-consuming autophagic events, including transcription/translation/interaction of autophagy-related molecules, autophagosome formation/elongation, autophagosome fusion with the lysosome, and lysosome acidification. The significance of energy-dependent fine-tuning of autophagic response for preserving the cell homeostasis, and potential implications for the therapy of cancer, autoimmunity, metabolic disorders, and neurodegeneration are discussed., (© 2024 Wiley Periodicals LLC.)

Objective: The mismatch between the demand for and supply of organs for transplantation is steadily growing. Various strategies have been incorporated to improve the availability of organs, including organ use from patients receiving extracorporeal membrane oxygenation (ECMO) at the time of death. However, there is no systematic evidence of the outcome of grafts from these donors., Design: Systematic literature review (Scopus and PubMed, up to October 11, 2023)., Setting: All study designs., Participants: Organ recipients from patients on ECMO at the time of death., Intervention: Outcome of organ donation from ECMO donors., Measurements and Main Results: The search yielded 1,692 publications, with 20 studies ultimately included, comprising 147 donors and 360 organ donations. The most frequently donated organs were kidneys (68%, 244/360), followed by liver (24%, 85/360). In total, 98% (292/299) of recipients survived with a preserved graft function (92%, 319/347) until follow-up within a variable period of up to 3 years., Conclusion: Organ transplantation from donors supported with ECMO at the time of death shows high graft and recipient survival. ECMO could be a suitable approach for expanding the donor pool, helping to alleviate the worldwide organ shortage., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: This survey assessed psychiatry residents'/early-career psychiatrists' attitudes towards the utility of therapeutic drug monitoring (TDM) of antipsychotics., Methods: A previously developed questionnaire on attitudes on TDM utility during antipsychotic treatment was cross-sectionally disseminated by national coordinators between 01/01/2022-31/12/2023. The frequency of using TDM for antipsychotics other than clozapine was the main outcome in a linear regression analysis, including sex, clinical setting, caseload, and factors generated by an exploratory factor analysis. Comparisons between residents and early-career psychiatrists, respondents working in in- and outpatient settings, and low-/middle- and high-income countries were performed., Results: Altogether, 1,237 respondents completed the survey, with 37.9% having never used TDM for antipsychotics. Seven factors explained 41% of response variance; six of them were associated with frequency of TDM use ( p  < 0.05). Items with highest loadings for factors included clinical benefits of TDM (factors A and E: 0.7), negative expectations for beliefs of patients towards TDM (factor B: 0.6-0.7), weak TDM scientific evidence (factor C: 0.8), and TDM availability (factor D: -0.8). Respondents from low-/middle-income countries were less likely to frequently/almost always use TDM compared to high-income countries (9.4% vs. 21.5%, p  < 0.001)., Discussion: TDM use for antipsychotics was poor and associated with limited knowledge and insufficient availability.

Obesity is the best described risk factor for the development of non-alcoholic fatty liver disease (NAFLD)/metabolic dysfunction associated steatotic liver disease (MASLD) and polycystic ovary syndrome (PCOS) while the major pathogenic mechanism linking these entities is insulin resistance (IR). IR is primarily caused by increased secretion of proinflammatory cytokines, adipokines, and lipids from visceral adipose tissue. Increased fatty acid mobilization results in ectopic fat deposition in the liver which causes endoplasmic reticulum stress, mitochondrial dysfunction, and oxidative stress resulting in increased cytokine production and subsequent inflammation. Similarly, IR with hyperinsulinemia cause hyperandrogenism, the hallmark of PCOS, and inflammation in the ovaries. Proinflammatory cytokines from both liver and ovaries aggravate IR thus providing a complex interaction between adipose tissue, liver, and ovaries in inducing metabolic abnormalities in obese subjects. Although many pathogenic mechanisms of IR, NAFLD/MASLD, and PCOS are known, there is still no effective therapy for these entities suggesting the need for further evaluation of their pathogenesis. Extracellular vesicles (EVs) represent a novel cross-talk mechanism between organs and include membrane-bound vesicles containing proteins, lipids, and nucleic acids that may change the phenotype and function of target cells. Adipose tissue releases EVs that promote IR, the development of all stages of NAFLD/MASLD and PCOS, while mesenchymal stem cell-derived AVs may alleviate metabolic abnormalities and may represent a novel therapeutic device in NAFLD/MASLD, and PCOS. The purpose of this review is to summarize the current knowledge on the role of adipose tissue-derived EVs in the pathogenesis of IR, NAFLD/MASLD, and PCOS., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The study aimed to review the role of basal, trigger, and aspiration day progesterone levels (PLs) as predictors of in vitro fertilization (IVF) success for patients with and without endometriosis. A non-systematic review was conducted by searching papers published in English during the period of 1990-2023 in MEDLINE and PubMed, Embase, The Cochrane Library (Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, Cochrane Methodology Register), and Web of Science. The most widely used IVF predictor success was the trigger day progesterone serum level. Many studies utilize the threshold level of 1.5-2.0 ng/ml. However, the predictive power of only progesterone level failed to show high sensitivity and specificity. Contrary, progesterone level on the trigger day combined with the number of mature retrieved oocytes had the highest predictive power. High baseline progesterone level was associated with poor IVF outcomes. Research on progesterone and IVF success in patients with endometriosis is limited but indicates that endometriosis patients seem to benefit from higher progesterone concentrations (≥ 37.1 ng/ml) in IVF cycles. Currently, there is limited data for a definitive insight into the mportance of progesterone in the estimation of IVF success. Nonetheless, this summarized evidence could serve as up-to-date guidance for the role of progesterone in the prediction of IVF outcomes, both in patients with and without endometriosis., (© 2024. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

Objective: Screening for abdominal aortic aneurysm (AAA) is recommended in high risk populations based on local conditions. Differences in lifestyle and risk factors between countries with different income status make risk stratification based on geographic location necessary. The majority of epidemiological studies on AAA have reported data from high income countries. The aim of this study was to explore the prevalence and risk factors for AAA in an upper middle income country in Eastern Europe., Methods: A pilot screening project for AAA, supported by a mass media campaign, was conducted in 2023 in seven cities in Serbia. Ultrasound evaluation of the abdominal aorta was performed by a registered vascular surgeon on individuals who agreed to participate. Participants who attended screening completed a questionnaire on demographic and clinical information. To assess risk factors for AAA, univariable logistic regression analysis was performed to compute the odds ratio (OR) with 95% confidence interval (CI). Multivariable logistic regression was subsequently performed with adjustments for sex, age, family history of AAA, and other relevant factors., Results: A total of 4 046 participants (51.2% male and 48.8% female; mean age 68.8 ± 7.6 years) responded to the campaign. An aneurysm was found in 195 (4.8%) screened individuals (8.2% of men and 1.3% of women). In males aged 50 - 64 years, the prevalence of AAA was 5.4%. Male sex, older age, family history of AAA, being a smoker or ex-smoker, being overweight, and alcohol consumption were predictors of AAA in the univariable analysis. After adjustments in the multivariable analysis, male sex (OR 8.04, 95% CI 4.87 - 13.28), older age (OR 1.04, 95% CI 1.02 - 1.07), positive family history (OR 2.47, 95% CI 1.61 - 3.78), smoker status (OR 3.10, 95% CI 2.10 - 4.59), ex-smoker status (OR 2.13, 95% CI 1.39 - 3.27), and being overweight (OR 1.85, 95% CI 1.25 - 2.74) were independent risk factors for AAA., Conclusion: The prevalence of AAA has not been reduced in all countries, and screening strategies might be changed based on local epidemiological data. The results of this pilot study underline the importance of exploring the prevalence of AAA in populations with a high prevalence of smoking., (Copyright © 2024. Published by Elsevier B.V.)

Spinal muscular atrophy (SMA) is a genetic disorder that causes progressive degeneration of lower motor neurons and the subsequent loss of muscle function throughout the body. It is the second most common recessive disorder in individuals of European descent and is present in all populations. Accurate tools exist for diagnosing SMA from genome sequencing data. However, there are no publicly available tools for GRCh38-aligned data from panel or exome sequencing assays which continue to be used as first line tests for neuromuscular disorders. This deficiency creates a critical gap in our ability to diagnose SMA in large existing rare disease cohorts, as well as newly sequenced exome and panel datasets. We therefore developed and extensively validated a new tool - SMA Finder - that can diagnose SMA not only in genome, but also exome and panel sequencing samples aligned to GRCh37, GRCh38, or T2T-CHM13. It works by evaluating aligned reads that overlap the c.840 position of SMN1 and SMN2 in order to detect the most common molecular causes of SMA. We applied SMA Finder to 16,626 exomes and 3,911 genomes from heterogeneous rare disease cohorts sequenced at the Broad Institute Center for Mendelian Genomics as well as 1,157 exomes and 8,762 panel sequencing samples from Tartu University Hospital. SMA Finder correctly identified all 16 known SMA cases and reported nine novel diagnoses which have since been confirmed by clinical testing, with another four novel diagnoses undergoing validation. Notably, out of the 29 total SMA positive cases, 23 had an initial clinical diagnosis of muscular dystrophy, congenital myasthenic syndrome, or myopathy. This underscored the frequency with which SMA can be misdiagnosed as other neuromuscular disorders and confirmed the utility of using SMA Finder to reanalyze phenotypically diverse neuromuscular disease cohorts. Finally, we evaluated SMA Finder on 198,868 individuals that had both exome and genome sequencing data within the UK Biobank (UKBB) and found that SMA Finder's overall false positive rate was less than 1 / 200,000 exome samples, and its positive predictive value (PPV) was 97%. We also observed 100% concordance between UKBB exome and genome calls. This analysis showed that, even though it is located within a segmental duplication, the most common causal variant for SMA can be detected with comparable accuracy to monogenic disease variants in non-repetitive regions. Additionally, the high PPV demonstrated by SMA Finder, the existence of treatment options for SMA in which early diagnosis is imperative for therapeutic benefit, as well as widespread availability of clinical confirmatory testing for SMA, warrants the addition of SMN1 to the ACMG list of genes with reportable secondary findings after genome and exome sequencing., Competing Interests: HLR receives research funding from Microsoft and previously received funding from Illumina to support rare disease gene discovery and diagnosis. AODL has consulted for Tome Biosciences, Ono Pharma USA Inc, and Addition Therapeutics, and is member of the scientific advisory board for Congenica Inc and the Simons Foundation SPARK for Autism study. AL received honoraria for speaking at educational events for Biogen, PTC and Roche, is a subinvestigator in clinical trials by Roche and PTC, and is involved in a project supported by Biogen (POL-SMA-17-11166). PBK has received research support from ML Bio and Sarepta Therapeutics, and has consulted for Lupin, Neurogene, NS Pharma, and Teneofour.

(1) Background: This study aims to evaluate retinal perfusion by optical coherence tomography angiography (OCTA) in pediatric patients with type 1 diabetes mellitus (T1D) without diabetic retinopathy (DR). (2) Methods: Thirty-one patients affected by T1D were enrolled. All participants were evaluated using OCTA. The foveal avascular zone (FAZ) and superficial and deep macular vessel density (VD) were analyzed. The correlation of these parameters with metabolic factors such as body mass index (BMI), glycated hemoglobin (HbA1c), and the type of insulin therapy (multiple daily injections, MDI vs. continuous subcutaneous insulin infusion, CSII) was determined. (3) Results: None of the OCTA parameters were significantly different between the groups. The patients' HbA1C level did not influence any of the OCTA parameters. The use of MDI tended to reduce the parafoveal and perifoveal deep VD ( p = 0.048 and p = 0.021, respectively) compared to CSII. An elevated BMI tended to increase the deep macular ( p = 0.005) and perifoveal VD ( p = 0.006). (4) Conclusion: VD and FAZ are normal in pubescent children with T1D without signs of DR. Treatment with CSII may be a better choice compared to MDI, as CSII may be protective against retinal microvascular damage. Our results indicate the need for new clinical parameters of glycemic control in addition to HbA1c which could assess the risk of DR.

This prospective case-control study investigated gender-related differences in dry eye symptoms following surgery for involutional ectropion and entropion. A total of 109 patients, aged between 65 and 89, were categorized by eyelid condition and gender. Postoperative assessments included the Tear Film Break-Up Time (TBUT) test, Schirmer I test results, corneal and conjunctival staining, eyelid margin characteristics, and scores from the Ocular Surface Disease Index (OSDI) questionnaire. The analysis revealed notable gender-related differences in dry eye manifestations. Initially, men exhibited lower TBUT scores but higher Schirmer test readings compared to women; however, these disparities diminished over time. No significant gender differences were detected in corneal and conjunctival staining, indicating similar levels of ocular surface damage across genders. Males showed significantly higher values in several eyelid margin characteristics (LMI, LMT) at various postoperative time points. According to the OSDI questionnaire, women experienced more severe symptoms of dry eye both pre- and post-operatively, suggesting a greater subjective symptom burden. When comparing surgical outcomes for ectropion and entropion, both conditions showed improvement in eyelid positioning and dry eye symptoms post-surgery. Despite these improvements, women with either condition reported more severe dry eye symptoms compared to men throughout the postoperative period. This study highlights the gender-specific variations in dry eye symptoms following eyelid malformation surgery and emphasizes the importance of adopting gender-sensitive approaches in postoperative care to improve outcomes and ocular health.

Background: All-cause and AIDS-mortality in Europe has been decreasing between 1996 and 2020. However, regional differences as well as their drivers remain unclear. This study investigates mortality differences and their drivers, including usage of and response to antiretroviral therapy (ART) and active tuberculosis (TB), among people with HIV across Europe., Methods: People with HIV enrolled in EuroSIDA were followed from 2001 through 2020. Immunologic-virologic status (IVS) was categorized as poor (CD4-cell count ≤350 cells/mm 3 and viral load (VL) > 200 copies/ml), good (CD4 ≥ 500 and VL < 200), or intermediate (remaining combinations). Participants missing either CD4-cell count or VL were categorized as unknown. Regional differences in mortality were analyzed using multivariable Poisson regression with interaction analyses between regions of Europe and IVS, ART, or TB status., Findings: 20,364 people with HIV were included: 13,715/20,346 (67.3%) from Western, 3020/20,364 (14.8%) from Central Eastern, and 3629/20,364 (17.8%) from Eastern Europe. At enrolment, median age was 40 years (inter-quartile range (IQR): 33-48), median CD4-cell count 449 cells/mm 3 (IQR: 291-638), and most were male 14,993/20,346 (73.3%). A total of 2639 died during 192,591 person-years of follow-up (crude mortality rate 13.7/1000 person-years, 95% CI: 13.2-14.2), 519/2639 (19.7%) from AIDS (2.7/1000 person-years, 2.5-2.9). All-cause and AIDS-mortality rates decreased over time but remained higher in Eastern Europe after adjusting for confounders. Being off ART (aIRR 2.42; 95% CI 2.14-2.74), poor IVS (aIRR 4.2; 95% CI 3.39-5.20) and prior TB (aIRR 3.33; 95% CI 2.75-4.03) were associated with higher all-cause mortality. For all-cause mortality the effect of ART (test for interaction: p < 0.001) and IVS (p = 0.02), but not TB (p = 0.5) varied across regions., Interpretation: Overall mortality and AIDS-mortality rates decreased over time, but remained higher in Eastern Europe. A poor IVS, being off ART and prior active TB were related to higher mortality. Eastern Europe had the highest proportion of people with poor or unknown IVS, emphasizing the continued need to improve HIV care with a focus on early diagnosis, ART initiation, and adherence., Funding: EuroSIDA has received funding from ViiV Healthcare LLC, Janssen Scientific Affairs, Janssen R&D, Bristol-Myers Squibb Company, Merck Sharp & Dohme Corp, Gilead Sciences and the European Union's Seventh Framework Programme for research, technological development and demonstration under EuroCoord grant agreement n˚ 260694. The study is also supported by a grant from the Danish National Research Foundation and by the International Cohort Consortium of Infectious Disease (RESPOND)., Competing Interests: OK, BS, AC, GM have research grants, personal fees for lectures and consultancy, meeting support from Gilead, MSD and ViiV outside the submitted work. AC has received consulting fees participation on data monitoring board, personal fees for lectures and consultancy, meeting support from Gilead, MSD Jannsen Cilag and ViiV outside the submitted work. CK received payment for a lecture from Gilead outside the submitted work. ET, SS, LØ, GF, SM, KK, AK, JT, JR, RZ, FM, SW, JG, DP, LP, and JR declare no competing interests., (© 2024 The Author(s).)

The association between type 2 diabetes mellitus (T2DM) and heart failure (HF) has been firmly established; however, the entity of diabetic myocardial disorder (previously called diabetic cardiomyopathy) remains a matter of debate. Diabetic myocardial disorder was originally described as the occurrence of myocardial structural/functional abnormalities associated with T2DM in the absence of coronary heart disease, hypertension and/or obesity. However, supporting evidence has been derived from experimental and small clinical studies. Only a minority of T2DM patients are recognized as having this condition in the absence of contributing factors, thereby limiting its clinical utility. Therefore, this concept is increasingly being viewed along the evolving HF trajectory, where patients with T2DM and asymptomatic structural/functional cardiac abnormalities could be considered as having pre-HF. The importance of recognizing this stage has gained interest due to the potential for current treatments to halt or delay the progression to overt HF in some patients. This document is an expert consensus statement of the Heart Failure Association of the ESC and the ESC Working Group on Myocardial & Pericardial Diseases. It summarizes contemporary understanding of the association between T2DM and HF and discuses current knowledge and uncertainties about diabetic myocardial disorder that deserve future research. It also proposes a new definition, whereby diabetic myocardial disorder is defined as systolic and/or diastolic myocardial dysfunction in the presence of diabetes. Diabetes is rarely exclusively responsible for myocardial dysfunction, but usually acts in association with obesity, arterial hypertension, chronic kidney disease and/or coronary artery disease, causing additive myocardial impairment., (© 2024 European Society of Cardiology.)