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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.)

Background: There has been a large discussion in literature regarding the proper management of asymptomatic patients with significant carotid artery stenosis. This study aims to identify potential risk factors associated with high-risk carotid plaques., Methods: This is a retrospective study based on a prospective database. Eligible patients had medium to severe symptomatic or asymptomatic carotid stenosis (≥50%, North American Symptomatic Carotid Endarterectomy Trial criteria). This study will analyze patients recruited by our institution as part of the multicenter TAXINOMISIS project (NCT03495830). According to protocol, all patients underwent a colored Duplex ultrasound examination and a magnetic resonance angiography at baseline. Carotid plaques were classified according to Gray-Weale ultrasonographic criteria (types I-V). Main outcomes included the occurrence of symptoms, the high/low echogenicity of the plaque, the existence of intraplaque hemorrhage and the existence of lipidic/necrotic core. Secondary, risk factors associated with the aforementioned outcomes were evaluated., Results: A total of 62 patients (mean age: 68.7 ± 9.3 years, 66.1% males, 24.2% symptomatic) were recruited by our department. Mean carotid stenosis was 70.81% ± 13.53%. In multivariate regression analysis, C-reactive protein > 2 mg/l was strongly associated with symptomatic stenosis (odds ratio [OR] = 9.92 [1.12-88.178]; P = 0.039), and low high-density lipoprotein levels (<1200 mmol/l) were associated with lipidic/necrotic plaque core (OR = 16.88 [1.10-259.30]; P = 0.043). Low high-density lipoprotein levels (OR = 7.22 [1.00-51.95], P = 0.049) and HbA1c >7% (OR = 0.08 [0.01-0.93], P = 0.044) were associated with type III/IV plaques whereas HgAbc1 >7% (OR = 14.26 [1.21-168.34], P = 0.035) was associated with type V plaques., Conclusions: This preliminary study has revealed some potential risk factors associated with unstable carotid plaques. These data could help the future development of prognostic models for early detection patients that could benefit from further intervention., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aims: This systematic review was aimed to assess the association between magnitude of body weight loss (BWL) in type 2 diabetes (T2D) patients and cardiovascular (CV) risk in CV outcome trials (CVOTs)., Methods: We searched electronic databases (PubMed, Cochrane and Scopus) for available CVOTs, observational cohort studies or post hoc analyses of clinical trials of adult T2D patients investigated the association of BWL with CV outcomes and/or all-cause mortality., Results: 19 RCTs of novel glucose-lowering drugs (GLP-1RA, DPP-4i and SGLT2i) and 6 RCT or observational trial of different strategies (intensive treatment or standard care) were included (379.904 T2D patients). Higher BWL during GLP-1RA treatment, in comaprison to lower BWL, was associated with higher decrease in risk of MACE, while DPP-4i had not that effect. With SGLT2i the higher decrease in risk of MACE was associated with lower BWL. In contrast, in other different strategies, higher BWL lead to increase in risk for MACE and all-cause mortality., Conclusions: In CVOTs, treatment of T2D patients resulted in BWL, which correlated with reduction in risk for CV outcomes, particularly with GLP-1 RAs. However, interventional non-CVOTs are warning that in the absence of structured behavioral intervention and relevant medication, the large BWL might be harmful for CV outcomes., 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.)

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.)

Background: In 2020, the COVID-19 pandemic caused disruptions in kidney replacement therapy (KRT) services worldwide. The aim of this study was to assess the effect of the COVID-19 pandemic in 2020 on the incidence of KRT, kidney transplantation activity, mortality and prevalence of KRT across Europe., Methods: Patients receiving KRT were included from 17 countries providing data to the European Renal Association Registry. The epidemiology of KRT in 2020 was compared with average data from the period 2017-2019. Also changes occurring during the first and second wave of the pandemic were explored., Results: The incidence of KRT was 6.2% lower in 2020 compared with 2017-2019, with the lowest point (-22.7%) during the first wave in April. The decrease varied across countries, was smaller in males (-5.2%) than in females (-8.2%), and was moderate for peritoneal dialysis (-3.7%) and haemodialysis (-5.4%), but substantial for pre-emptive kidney transplantation (-23.6%). The kidney transplantation rate decreased by 22.5%, reaching a nadir of -80.1% during the first wave, and most for living donor kidney transplants (-30.5%). While in most countries the kidney transplantation rate decreased, in the Nordic/Baltic countries and Greece there was no clear decline. In dialysis patients, mortality increased by 11.4%, and was highest in those aged 65-74 years (16.1%), in those with diabetes as primary renal disease (15.1%), and in those on haemodialysis (12.4%). In transplant recipients, the mortality was 25.8% higher, but there were no subgroups that stood out. In contrast to the rising prevalence of KRT observed over the past decades across Europe, the prevalence at the end of 2020 (N=317787) resembled that of 2019 (N=317077)., Conclusion: The COVID-19 pandemic has had a substantial impact on the incidence of KRT, kidney transplant activity, mortality of KRT, and prevalence of KRT in Europe with variations across countries., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Cytoplasmic and nuclear iron-sulfur (Fe-S) enzymes that are essential for genome maintenance and replication depend on the cytoplasmic Fe-S assembly (CIA) machinery for cluster acquisition. The core of the CIA machinery consists of a complex of CIAO1, MMS19 and FAM96B. The physiological consequences of loss of function in the components of the CIA pathway have thus far remained uncharacterized. Our study revealed that patients with biallelic loss of function in CIAO1 developed proximal and axial muscle weakness, fluctuating creatine kinase elevation, and respiratory insufficiency. In addition, they presented with CNS symptoms including learning difficulties and neurobehavioral comorbidities, along with iron deposition in deep brain nuclei, mild normocytic to macrocytic anemia, and gastrointestinal symptoms. Mutational analysis revealed reduced stability of the variants compared with WT CIAO1. Functional assays demonstrated failure of the variants identified in patients to recruit Fe-S recipient proteins, resulting in compromised activities of DNA helicases, polymerases, and repair enzymes that rely on the CIA complex to acquire their Fe-S cofactors. Lentivirus-mediated restoration of CIAO1 expression reversed all patient-derived cellular abnormalities. Our study identifies CIAO1 as a human disease gene and provides insights into the broader implications of the cytosolic Fe-S assembly pathway in human health and disease.

Mixed epithelial and stromal tumors (MESTs) of the kidney are rare renal neoplasms, primarily affecting middle-aged women. These tumors are characterized by a mix of epithelial and stromal components. While generally benign, MESTs require accurate diagnosis and appropriate management due to the potential for malignant transformation. The present study reports the case of a 75-year-old male patient who underwent a partial nephrectomy following the incidental discovery of a kidney tumor. Histopathological examination revealed a partially cystic tumor with solid areas, measuring 26 mm in diameter. The tumor had cysts lined with cuboidal cells and an ovarian-like stroma. The solid component consisted of elongated cells with eosinophilic cytoplasm and oval nuclei, showing angiocentric growth around small blood vessels without nuclear atypia or mitoses. Since the morphology of the solid component could not reveal the differentiation of those cells, immunohistochemical staining was performed and a myopericytoma/myofibroma component was established, mostly based on the positivity of smooth muscle actin, muscle-specific actin, h-caldesmon, estrogen receptor, progesterone receptor, solute carrier family 2 facilitated glucose transporter member 1 and collagen IV, along with a lack of staining for desmin, CD34, CD31 and CD99. Thus, to the best of our knowledge, for the first time in the literature, MEST with myopericytoma/myofibroma stromal component in a male patient was reported., Competing Interests: The authors declare that they have no competing interests., (Copyright: © 2024 Nikolić et al.)

Macrophage inhibitory factor (MIF) is a multipotent cytokine, involved in the inflammatory response to infections or injuries. This study investigates the role of MIF in liver fibrosis and the modulating effect of betaine on MIF in thioacetamide (TAA)-induced liver fibrosis. The wild-type and knockout MIF-/- C57BL/6 mice were divided into the following groups: control; Bet group, which received betaine; MIF-/-; MIF-/-+Bet; TAA group, which received TAA; TAA+Bet; MIF-/-+TAA; and MIF-/-+TAA+Bet group. After eight weeks of treatment, liver tissue was collected for further analysis. The results revealed that TAA-treated MIF-deficient mice had elevated levels of hepatic TGF-β1 and PDGF-BB, as well as MMP-2, MMP-9, and TIMP-1 compared to TAA-treated wild-type mice. However, the administration of betaine to TAA-treated MIF-deficient mice reduced hepatic TGF-β1 and PDGF-BB levels and also the relative activities of MMP-2, MMP-9 and TIMP-1, albeit less effectively than in TAA-treated mice without MIF deficiency. Furthermore, the antifibrogenic effect of MIF was demonstrated by an increase in MMP2/TIMP1 and MMP9/TIMP1 ratios. The changes in the hepatic levels of fibrogenic factors were confirmed by a histological examination of liver tissue. Overall, the dual nature of MIF highlights its involvement in the progression of liver fibrosis. Its prooxidant and proinflammatory effects may exacerbate tissue damage and inflammation initially, but its antifibrogenic activity suggests a potential protective role against fibrosis development. The study showed that betaine modulates the antifibrogenic effects of MIF in TAA-induced liver fibrosis, by decreasing TGF-β1, PDGF-BB, MMP-2, MMP-9, TIMP-1, and the deposition of ECM (Coll1 and Coll3) in the liver.

Background: Cytarabine-anthracycline-based induction chemotherapy remains the standard of care for remission induction among patients with newly diagnosed acute myeloid leukaemia (AML). There are remarkable differences in therapy response among AML patients. This fact could be partly explained by the patients' genetic variability related to the metabolic paths of cytarabine and anthracyclines. This study aims to evaluate the effect of variants in pharmacogenes SLC29A1, DCK, ABCB1, GSTM1, and GSTT1, as well as laboratory and AML-related parameters on clinical outcomes in adult AML patients., Methods: A total of 100 AML patients were included in the study. Pharmacogenetic variants SLC29A1 rs9394992, DCK rs12648166, ABCB1 rs2032582, and GSTM1 and GSTT1 gene deletions were detected by methodology based on PCR, fragment analysis and direct sequencing. The methods of descriptive and analytic statistics were used. Survival analysis was done using the Kaplan-Meier method using the Log-Rank test., Results: This is the first study of adult AML pharmacogenetics in the Serbian population. Clinical outcomes in our cohort of AML patients were not impacted by analysed variants in SLC29A1, DCK, ABCB1 and GSTT1, and GSTM1 genes, independently or in combinations. Achievement of complete remission was identified as an independent prognostic indicator of clinical outcome., Conclusions: The population-specific genomic profile has to be considered in pharmacogenetics. Since the data on AML pharmacogenetics in European populations is limited, our results contribute to knowledge in this field and strongly indicate that a high-throughput approach must be applied to find particular pharmacogenetic markers of AML in the European population., Competing Interests: All the authors declare that they have no conflict of interest in this work., (2024 Zlatko Pravdić, Nada Suvajdžić-Vuković, Marijana Virijević, Mirjana Mitrović, Nikola Pantić, Nikica Sabljić, Đorđe Pavlović, Irena Marjanović, Zoran Bukumirić, Ana Vidović, Ljubomir Jaković, Sonja Pavlović, Vladimir Gašić, published by CEON/CEES.)

Background: In contemporary clinical practice, carotid artery stenting (CAS) is increasingly becoming a multispecialty field, joining operators of various training backgrounds, which bring forth their unique expertise, patient management philosophies, and procedural preferences. The best practices and approaches, however, are still debated. Therefore, real-world insights on different operator preferences and related outcomes are of utmost value, yet still rather scarce in the available literature., Methods: Using the data collected in the ROADSAVER observational, European multicenter CAS study, a prespecified comparative analysis evaluating the impact of the operator's specialization was performed. We used major adverse event (MAE) rate at 30-day follow-up, defined as the cumulative incidence of any death or stroke, and its components as outcome measures., Results: A total of 1965 procedures were analyzed; almost half 878 (44.7%) were performed by radiologists (interventional/neuro), 717 (36.5%) by cardiologists or angiologists, and 370 (18.8%) by surgeons (vascular/neuro). Patients treated by surgeons were the oldest (72.9±8.5), while radiologists treated most symptomatic patients (58.1%) and more often used radial access (37.2%). The 30-day MAE incidence achieved by cardiologists/angiologists was 2.0%, radiologists 2.5%, and surgeons 1.9%; the observed differences in rates were statistically not-significant (P=0.7027), even when adjusted for baseline patient/lesion and procedural disparities across groups. The corresponding incidence rates for death from any cause were 1.0%, 0.8%, and 0.3%, P=0.4880, and for any stroke: 1.4%, 2.3%, and 1.9%, P=0.4477, respectively., Conclusions: Despite the disparities in patient selection and procedural preferences, the outcomes achieved by different specialties in real-world, contemporary CAS practice remain similar when using modern devices and techniques.

Background: The aim of this cohort study was to report the proportion of patients who develop periprocedural acute kidney injury (AKI) after endovascular repair (ER) and open surgery (OS) in patients with juxta/pararenal abdominal aortic aneurysm and to assess potential risk factors for AKI. The study also aimed to report the short- and long-term outcomes of patients with and without AKI., Methods: This was a multicenter cohort study of five European academic high-volume centers (>50 OS or 50 ER infrarenal AAA repairs, plus >15 complex AAA repairs per year). All consecutively treated patients were extracted from a prospective vascular surgical registry and the data were scrutinized retrospectively. The primary end point for this study was the development of AKI. AKI was diagnosed when there is a two-fold increase of serum creatinine or decrease of glomerular filtration rate of >50% within 1 week of AAA repair. Secondary end points included long-term mortality and end-stage renal disease (ESRD)., Results: AKI occurred in 16.6% of patients in the ER group vs 30.3% in the OS group (P < .001). The 30-day mortality rate was higher among patients with AKI in both ER (15.4% vs 3.1%; P = .006) and OS (13.2% vs 5.3%; P = .001) groups. Age, chronic kidney disease, presence of significant thrombus burden in the pararenal region, >1000 mL blood loss in ER group were associated with development of AKI. Age, diabetes mellitus, chronic kidney disease, presence of significant thrombus burden in the pararenal region, and a proximal clamping time of >30 minutes in the OS group were associated with the development of AKI, whereas renal perfusion during clamping was the protective factor against AKI development. After a median follow-up of 91 months, AKI was associated with higher mortality rates in both the ER group (58.9% vs 29.7%; P < .001) and the OS group (61.5% vs 27.3%; P < .001). After the same follow-up period, AKI was associated with a higher incidence of ESRD in both the ER group (12.8% vs 3.6%; P = .009) and the OS group (9.9% vs 2.9%; P < .001)., Conclusions: The current study identified important pre and postoperative factors associated with AKI after juxta/pararenal abdominal aortic aneurysm repair. Patients with postoperative AKI had significantly higher short- and long term mortality and higher incidence of ESRD than patients without AKI., Competing Interests: Disclosures None., (Copyright © 2024 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Introduction: Although the overall quality of medicine has improved in recent decades, the functional capacity in many hip fracture patients remains insufficient. The goal of the present study was to identify significant predictors of Instrumental Activities of Daily Living (IADL) measured by the Lawton-Brody scale at 3- and 6-month follow-up in patients with hip fractures admitted to a hospital., Methods: This observational cohort study included 191 patients with acute hip fractures. IADL was measured at baseline and after 3 and 6 months using the Lawton-Brody scale. Multivariable logistic regression analysis was carried out using pre-fracture functional status, sociodemographic variables, hand grip strength (HGS), surgical procedure, complications, and length of hospital stay, Short Physical Performance Battery, and Barthel Index (BI) on the fifth postoperative day as potential predictors for IADL after a hip fracture surgery., Results: The mean age of the participants was 80.3 ± 6.8 years, and 77.0% of our cohort were women. Multivariate regression analysis revealed that pre-fracture functional status and early functional recovery were independent predictors of IADL after hip fracture surgery., Conclusions: Clinicians should take steps to improve functional outcomes by changing how patients are rehabilitated in the first days after hip fracture surgery, especially for the group of patients with a lower functional status before the fracture., 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.)

Polymorphisms located within NOS3 gene have been investigated as susceptibility variants for diabetic nephropathy (DN) in type 2 diabetes mellitus (T2DM) in a large number of studies. However, these previous articles yielded inconsistent results and we aimed at elucidating the impact of NOS3 variants on DN risk in T2DM by conducting an updated systematic data synthesis. A total of 36 studies (12,807 participants) were selected for qualitative data synthesis, while 33 records with 11,649 subjects were included in the meta-analysis. The pooled analysis demonstrated the association of minor alleles of rs2070744 and rs1799983 with an increased susceptibility to DN (P < 0.001 and P = 0.015 for allelic model, respectively). For both of these variants, a significant effect of subgrouping according to ethnicity was found. Rs869109213 displayed an association with DN susceptibility, with pooled effect measures indicating a predisposing effect of the minor allele a (P rec  = 0.002, OR rec  = 1.960, 95%CI 1.288-2.983; P aa vs. bb  = 2.014, 95%CI 1.316-3.083). These findings support the effects of NOS3 variants on the risk of developing DN in T2DM.aa vs. bb  = 2.014, 95%CI 1.316-3.083). These findings support the effects of NOS3 variants on the risk of developing DN in T2DM., 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: While pharmacologic therapy remains the cornerstone of lung emphysema treatment, surgery is an additional therapeutic option in selected patient groups with advanced emphysema. The aim of lung volume reduction surgery (LVRS) is to improve lung function, exercise capacity, quality of life and survival. We sought to determine the therapeutic value of surgical resection in specific patients with lung emphysema., Patients and Methods: A retrospective study was performed consisting of 58 patients with lung emphysema who underwent surgical intervention over a 10-year period and were followed for 2 years postoperatively. The clinical characteristics recorded were FEV 1 (forced expiratory volume in 1 s), the 6-min walk test (6-MWT), the Modified Medical Research Council (mMRC), body mass index (BMI) and quality of life prior to and 6, 12 and 24 months after surgical intervention. Moreover, all peri- and post-operative complications were noted., Results: Out of 58 emphysema patients (72% male, FEV 1 (L) 2.21 ± 0.17, RV (L) 3.39 ± 0.55), 19 underwent surgical bullectomy, 31 unilateral LVRS and 8 sequential bilateral LVRS. Six months after surgery, there was a statistically significant improvement in FEV 1 , RV, TLC, 6-MWT and mMRC. Over a period of 12 to 24 months postoperatively, clinical benefit gradually declines most likely due to COPD progression but patients still experienced a significant improvement in FEV 1 . The most common postoperative complications were persistent air leakage (> 7 days), arrhythmia and subcutaneous emphysema in 60%, 51.6% and 22.4%, respectively. No deaths were observed after surgical intervention., Conclusion: In a selected patient population, surgery led to significant improvement of lung function parameters, exercise capacity and quality of life. Over a period of 12 to 24 months postoperatively, clinical benefit gradually decreased most likely due to COPD progression., (© 2024. The Author(s).)

Introduction: Biomarkers capable of reflecting disease onset and short- and long-term therapeutic effects in individuals with spinal muscular atrophy (SMA) are still an unmet need and phosphorylated neurofilament heavy chain (pNF-H) holds significant promise., Methods: We conducted a longitudinal prospective study to evaluate pNF-H levels in the cerebrospinal fluid (CSF) and plasma of 29 individuals with childhood-onset SMA treated with Nuinersen (SMA type 1: n  = 6, 2: n  = 17, 3: n  = 6). pNF-H levels before and during treatment were compared with the levels of controls ( n  = 22), patients with Duchenne muscular dystrophy ( n  = 17), myotonic dystrophy type 1 ( n  = 11), untreated SMA individuals with chronic type 3 disease ( n  = 8), and children with presymptomatic SMA ( n  = 3)., Results: SMA type 1 showed the highest mean CSF pNF-H levels before treatment initiation. All Nusinersen-treated individuals (types 1, 2, and 3) showed significantly elevated mean baseline CSF pNF-H compared to controls, which inversely correlated with age at disease onset, age at first dose, disease duration and the initial CHOP INTEND result (SMA type 1 and 2). During 22 months of treatment, CSF pNF-H levels declined during loading doses, stabilizing at reduced levels from the initial maintenance dose in all individuals. Baseline plasma pNF-H levels in type 1 and 2 SMA were significantly increased compared to other cohorts and decreased notably in type 1 after 2 months of treatment and type 2 after 14 months. Conversely, SMA type 3, characterized by lower baseline pNF-H levels, did not show significant fluctuations in plasma pNF-H levels after 14 months of treatment., Conclusion: Our findings suggest that CSF pNF-H levels in untreated SMA individuals are significantly higher than in controls and that monitoring of CSF pNF-H levels may serve as an indicator of rapid short-term treatment response in childhood-onset SMA individuals, irrespective of the subtype of the disease, while also suggesting its potential for assessing long-term suppression of neurodegeneration. Plasma pNF-H may serve as an appropriate outcome measure for disease progression and/or response to treatment in types 1 and 2 but not in type 3. Presymptomatic infants with SMA may show elevated pNF-H levels, confirming early neuronal degeneration., 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 Brkušanin, Kosać, Branković-Srećković, Jovanović, Perić, Karanović, Matijašević Joković, Garai, Pešović, Nikolić, Stević, Brajušković, Milić-Rašić and Savić-Pavićević.)

Diabetic retinopathy is not cured efficiently and changes of lifestyle measures may delay early retinal injury in diabetes. The aim of our study was to investigate the effects of reduced daily light exposure on retinal vascular changes in streptozotocin (STZ)-induced model of DM with emphasis on inflammation, Aqp4 expression, visual cycle and cholesterol metabolism-related gene expression in rat retina and RPE. Male Wistar rats were divided into the following groups: 1. control; 2. diabetic group (DM) treated with streptozotocin (100 mg/kg); 3. group exposed to light/dark cycle 6/18 h (6/18); 4. diabetic group exposed to light/dark cycle 6/18 h (DM+6/18). Retinal vascular abnormalities were estimated based on lectin staining, while the expression of genes involved in the visual cycle, cholesterol metabolism, and inflammation was determined by qRT-PCR. Reduced light exposure alleviated vasculopathy, gliosis and the expression of IL-1 and TNF-α in the retina with increased perivascular Aqp4 expression. The expression of genes involved in visual cycle and cholesterol metabolism was significantly up-regulated in RPE in DM+6/18 vs. DM group. In the retina only the expression of APOE was significantly higher in DM+6/18 vs. DM group. Reduced light exposure mitigates vascular changes and gliosis in DM via its anti-inflammatory effect, increased retinal cholesterol turnover and perivascular Aqp4 expression., 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.)

Background: Chronic rhinosinusitis (CRS) is one of the most common health disorders in humans and has a major impact on health-related quality of life (HRQoL). Of the many factors contributing to the etiology of CRS, less is known about the correlation between CRS and bacterial biofilms and their impact on HRQoL., Objective: The aim of this prospective study was to investigate the relationship between biofilm-producing bacteria and patients' objective findings and HRQoL., Methods: Forty-eight patients with CRSwNP were enrolled in a 12-month prospective study. The Lund-Mackay (LM) CT and endoscopic Lund-Kennedy (LK) scores were obtained before endoscopic sinus surgery (ESS), and patients completed the HRQoL instruments: the 22-item Sinonasal Outcome Test (SNOT-22), the 36-item Short Questionnaire (SF-36), and the visual analog scale (VAS). A sinus culture was obtained at ESS, bacteria were isolated, and in vitro quantification of the biofilm was performed. The LK score and HRQoL were determined postoperatively at months 1, 3, 6, and 12., Results: The most common bacterial isolates in patients with CRSwNP were Staphylococcus aureus (28%), coagulase-negative staphylococci (52%), and Pseudomonas aeruginosa (8%). Preoperatively, the highest LM and LK scores were found in patients with strong biofilm producers . Postoperative LK scores were significantly reduced in all patients. Postoperative VAS scores were significantly reduced from month 1 to month 12 postoperatively. Patients with strong biofilm producers had significantly worse nasal blockage, secretion, headache, facial pressure and pain, and loss of smell preoperatively, compared to patients with low biofilm producers. The most significant reduction in preoperative scores SNOT-22 and SF-36 (excluding physical functioning) was seen in patients with S. aureus and P. aeruginosa., Conclusions: Patients with strong biofilm producers had higher LK and LM scores preoperatively, and greater improvement in LK and HRQoL scores postoperatively. Microbiologic surveillance of all CRS patients is recommended., 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.

Background: The aim of the study was to assess socio-demographical characteristics, clinical presentation, and outcomes in patients diagnosed with mpox., Methods: A survey on patients diagnosed with mpox was performed in 14 countries from Central and Eastern Europe. Data was compared according to HIV status and country of origin (EU vs. non-EU). Mpox diagnosis was confirmed by RT-PCR from oropharyngeal swabs, skin lesions, and other body fluids., Results: Out of 154 patients confirmed with mpox in 2022, 99.3% were males, with a median age (years) of 35 (IQR 30-39), 90.2% MSM and 48.7% PLWH. Compared to HIV-negative subjects, PLWH had more frequent high-risk behaviours:chemsex (p = 0.015), group sex (p = 0.027), and a history of sexually transmitted infections (STIs) (p = 0.004). Persons from EU were more often PLWH (p = 0.042), MSM (p < 0.0001), had multiple sexual partners (p = 0.025), practiced chemsex (p = 0.008) or group-sex (p = 0.005) and had more often history of STIs (p < 0.0001). The median CD4 cell count/mL at mpox diagnosis was 713 (IQR 486-996) and 73.5% had undetectable HIV VL. The commonest clinical features were fever (108 cases), lymphadenopathy (78), and vesiculo-pustular rash: penile (76), perianal (48), limbs (67). Fifty-one (31%) persons were hospitalized due to complications or epidemiological reasons. Three patients received tecovirimat or cidofovir. The outcome was favorable for all patients, including 4 with severe forms., Conclusions: Mpox was diagnosed predominantly in young MSM, with high-risk behaviors and history of STIs. Effective contact tracing and vaccination are important strategic pillars to control mpox outbreaks., 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 The Authors. Published by Elsevier Ltd.. All rights reserved.)

The conceptualization of mental disorders varies among professionals, impacting diagnosis, treatment, and research. This cross-disciplinary study aimed to understand how various professionals, including psychiatrists, psychologists, medical students, philosophers, and social sciences experts, perceive mental disorders, their attitudes towards the disease status of certain mental states, and their emphasis on biological versus social explanatory attributions. A survey of 371 participants assessed their agreement on a variety of conceptual statements and the relative influence of biological or social explanatory attribution for different mental states. Our findings revealed a consensus on the need for multiple explanatory perspectives in understanding psychiatric conditions and the influence of social, cultural, moral, and political values on diagnosis and classification. Psychiatrists demonstrated balanced bio-social explanatory attributions for various mental conditions, indicating a potential shift from the biological attribution predominantly observed among medical students and residents in psychiatry. Further research into factors influencing these differing perspectives is necessary., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

This research explores the association between ABO blood groups and susceptibility to SARS-CoV-2 infection, analyzing Convalescent COVID-19 plasma (CCP) donors ( n = 500) and healthy whole blood donors (BDs) ( n = 9678) during the pandemic (1 May 2020 to 30 April 2021). A comparison is made with pre-pandemic BDs ( n = 11,892) from 1 May 2018 to 30 April 2019. Significant differences in blood group distribution are observed, with blood group A individuals being three times more likely to be CCP donors. Conversely, blood groups B, O, and AB are less associated with CCP donation. Notably, blood group O is more prevalent among regular BDs, suggesting potential resistance to SARS-CoV-2 infection. This study underscores variations in blood group distribution during the pandemic compared to pre-pandemic periods. The findings support previous research indicating a link between blood group antigens and viral susceptibility, including SARS-CoV-2. Understanding these associations has implications for public health strategies, with potential for predicting COVID-19 outcomes and transmission patterns. Further research is crucial to explore molecular and immunological mechanisms, providing valuable insights for targeted preventive strategies and personalized healthcare in managing the impact of COVID-19.

Background: Achalasia is an esophageal motor disorder characterized by aperistalsis and the failure of the relaxation of the lower esophageal sphincter. We want to find out whether external compression or recurrent micro-aspiration of undigested food has a functional effect on the airway., Methods: The aim of this research was to analyze the influence of achalasia on the peak expiratory flow and flow-volume curve. All of the 110 patients performed spirometry., Results: The mean diameter of the esophagus was 5.4 ± 2.1 cm, and nine of the patients had mega-esophagus. Seven patients had a plateau in the inspiratory part of the flow-volume curve, which coincides with the patients who had mega-esophagus. The rest of the patients had a plateau in the expiration part of the curve. The existence of a plateau in the diameter of the esophagus of more than 5 cm was significant ( p 0.003). Statistical significance between the existence of a plateau and a lowered PEF (PEF < 80) has been proven ( p 0.001). Also, a statistical significance between the subtype and diameter of more than 4 cm has been proved. There was no significant improvement in the PEF values after operation. In total, 20.9% of patients had a spirometry abnormality finding. The frequency of the improvement in the spirometry values after surgery did not differ significantly by achalasia subtype. The improvement in FEV1 was statistically significant compared to the FVC values., Conclusions: Awareness of the influence of achalasia on the pulmonary parameters is important because low values of PEF with a plateau on the spirometry loop can lead to misdiagnosis. The recognition of various patterns of the spirometry loop may help in identifying airway obstruction caused by another non-pulmonary disease such as achalasia.

Complex perianal fistula is a common complication of Crohn's disease (CD) which leads to negative impact on patient's quality of life. Successful management of the disease requires a multidisciplinary approach, including a gastroenterologist and a colorectal surgeon, applying combined surgical and medical therapy. One of frequently practiced surgical procedures is seton placement in the fistula tract, which is used to control perianal sepsis and drain the fistula, while preventing recurrent abscess formation.Darvadstrocel, a suspension of expanded, allogeneic, adipose-derived, mesenchymal stem cells, is safe and effective for treatment-refractory complex perianal fistulas in patients with Crohn's disease. Following approval of darvadstrocel, the INSPIRE registry is being conducted in order to evaluate long-term safety and effectiveness of the drug on a large, heterogenous population.An online expert meeting was held from March 20 to March 30, 2023, which provided relevant insights into the decision-making process regarding seton use and obtained feedback on the first experiences with darvadstrocel. The aim of this article is to present the perspectives from gastroenterologists and colorectal surgeons practicing in Czechia, Hungary, Israel, Lithuania, Serbia, and Slovenia in topics such as diagnosis and treatment options for patients with complex Crohn's perianal fistulas (CPF), specifically focusing on the use of setons and darvadstrocel.During this virtual session, unavailability of comprehensive data on safety and efficacy of available treatment procedures was emphasized as an important obstacle towards development of standardized recommendations and improvement of outcomes in treatment of (CPF). Furthermore, achieving consensus in seton use, duration of its placement, and frequency of change is recognized as one of CPF treatments major challenges. Despite these issues, it is important to promote better understanding and treatment of complex perianal fistulas in order to improve the quality of life of those affected by this condition., (© 2024. The Author(s).)

Chronic kidney disease (CKD) is a global health concern affecting approximately one billion individuals worldwide. End-stage kidney disease (ESKD), the most severe form of CKD, is often accompanied by anemia. Peritoneal dialysis (PD), a common treatment for ESKD, utilizes the peritoneum for solute transfer but is associated with complications including protein loss, including transferrin (Tf) a key protein involved in iron transport. This study investigated Tf characteristics in ESKD patients compared to healthy individuals using lectin microarray, spectroscopic techniques and immunocytochemical analysis to assess Tf interaction with transferrin receptors (TfRs). ESKD patients exhibited altered Tf glycosylation patterns, evidenced by significant changes in lectin reactivity compared to healthy controls. However, structural analyses revealed no significant differences in the Tf secondary or tertiary structures between the two groups. A functional analysis demonstrated comparable Tf-TfR interaction in both PD and healthy samples. Despite significant alterations in Tf glycosylation, structural integrity and Tf-TfR interaction remained preserved in PD patients. These findings suggest that while glycosylation changes may influence iron metabolism, they do not impair Tf function. The study highlights the importance of a glucose-free dialysis solutions in managing anemia exacerbation in PD patients with poorly controlled anemia, potentially offering a targeted therapeutic approach to improve patient outcomes.

Introduction: Patient-reported treatment burden (TBN) refers to the patient's time and effort invested in the management of their chronic health conditions. The aim of this research was to explore TBN in patients with coronary artery disease (CAD)., Methods: Consecutive patients with chronic medical condition(s) were invited to complete the study questionnaires (TBN and EQ-5D)., Results: Of 514 enrolled patients, 116 (22.6%) patients had CAD. The mean TBN score for CAD vs. non-CAD was 40.49 ±21.54 and 46.17 ±21.44 ( p = 0.023), respectively., Conclusions: Patients with CAD could have a lower TBN in comparison to patients with other chronic medical conditions., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2024 Termedia & Banach.)

This retrospective study aimed to compare risk factors for vascular calcification (VC) between pre-hemodialysis (HD) and prevalent HD adult patients while investigating associations with calcification biomarkers. Baseline data from 30 pre-HD and 85 HD patients were analyzed, including iPTH, vitamin D, FGF 23, fetuin-A, sclerostin, and VC scores (Adragao method). Prevalence of VC was similar in both groups, but HD patients had more frequent VC scores ≥ 6. Pre-HD patients were older, with higher prevalence of hypertension and less frequent use of calcium phosphate binders. Both groups showed similar patterns of hyperphosphatemia, low vitamin D, and iPTH. Fetuin-A and sclerostin levels were higher in pre-HD, while FGF 23 was elevated in HD patients. Higher VC risk in pre-HD patients was associated with male gender, older age, lower fetuin-A and higher sclerostin, lower ferritin, and no vitamin D treatment, while in HD patients with higher sclerostin, FGF 23 and urea, and lower iPTH. Conclusion: Biomarkers could be measurable indicators of biological processes underlying VC in CKD patients that may serve as a potential guide for considering personalized therapeutic approaches. Further studies are needed to elucidate the underlying pathways.

Although not regarded as an oncogenic pathogen, the human cytomegalovirus (HCMV) has been associated with a wide array of malignancies. Conversely, a number of studies report on possible anti-tumor properties of the virus, apparently mediated via HCMV-galvanized T-cell tumor killing; these were recently being investigated in clinical trials for the purposes of anti-cancer treatment by means of dendritic cell vaccines and HCMV-specific cytotoxic T cells. In the present study, we have analyzed the relation between a complement of head-and-neck tumors and HCMV infection across 73 countries worldwide using Spearman correlation, univariate and multivariate regression analysis. Intriguingly, HCMV was found to be pro-oncogenic in patients with nasopharyngeal carcinoma; contrarywise, the virus manifested an inverse (i.e., anti-tumor) association with the tumors of the lip/oral region and the salivary glands. Although this putative protective effect was noted initially for thyroid neoplasia and hypopharyngeal tumors as well, after multivariate regression analysis the connection did not hold. There was no association between laryngeal cancer and HCMV infection. It would appear that, depending on the tissue, HCMV may exert both protective and oncogenic effects. The globally observed protective feature of the virus could potentially be utilized in future therapeutic approaches for salivary tumors and neoplasia in the lip/oral region. As correlation does not necessarily imply causation, more in-depth molecular analyses from comprehensive clinical studies are warranted to substantiate our findings.

The aim of this retrospective study was to identify myocardial injury after COVID-19 inflammation and explore whether myocardial damage could be a possible cause of the persistent symptoms following COVID-19 infection in previously healthy individuals. This study included 139 patients who were enrolled between January and June 2021, with a mean age of 46.7 ± 15.2 years, of whom 68 were men and 71 were women without known cardiac or pulmonary diseases. All patients underwent clinical work-up, laboratory analysis, cardiac ultrasound, and CMR on a 1.5 T scanner using a recommended protocol for morphological and functional assessment before and after contrast media application with multi-parametric sequences. In 39% of patients, late gadolinium enhancement (LGE) was found as a sign of myocarditis. Fibrinogen was statistically significantly higher in patients with LGE than in those without LGE (4.3 ± 0.23 vs. 3.2 ± 0.14 g/L, p < 0.05, respectively), as well as D-dimer (1.8 ± 0.3 vs. 0.8 ± 0.1 mg/L FEU). Also, troponin was statistically significantly higher in patients with myocardial LGE (13.1 ± 0.4 ng/L) compared to those with normal myocardium (4.9 ± 0.3 ng/L, p < 0.001). We demonstrated chest pain, fatigue, and elevated troponin to be independent predictors for LGE. Septal LGE was shown to be a predictor for arrhythmias. The use of CMR is a potential risk stratification tool in evaluating outcomes following COVID-19 myocarditis.