The role of glomerular filtration rate in AVF success: Should we intervene earlier?

INTRODUCTION: End-stage kidney disease (ESKD) patients require life-sustaining kidney replacement therapies, with the natural arteriovenous fistula (AVF) being the preferred vascular access due to its low infection risk, high patency, and fewer complications. Factors like vessel diameter, gender, diabetes, age, and surgical technique influence AVF maturation. METHOD: Our study focused on short-term AVF creation success, specifically examining estimated glomerular filtration rate (eGFR) levels using the CKD-EPI formula. Patients were categorized according to their eGFR levels to observe the effects of fistula timing and the severity of kidney disease. RESULTS: No significant demographic or outcome differences between eGFR groups have been observed except for gender. AVF maturation was notably associated with distal vein diameter (>2 mm), while other factors did not significantly impact maturation rates. As a secondary outcome, it was concluded that the recording of patients' blood pressure values at preoperative and perioperative levels led to the conclusion that blood pressure levels may have an impact on fistula maturation. CONCLUSION: To ensure vascular access effectiveness, optimizing blood pressure, determining vein diameter, strategic AVF timing, and reducing catheter usage are crucial. Our study aimed to identify eGFR levels conducive to optimal AVF outcomes. Although significant results could not be obtained in this regard, it is considered worthwhile to re-examine the effect of blood pressure in secondary outcomes. Additionally, prospective studies may be appropriate for reevaluating the effect of GFR.

Does prior PCNL affect RIRS? A retrospective analysis of a single center data.

PURPOSE: The aim of this study is to investigate the results and safety of retrograde intrarenal surgery (RIRS) in patients who have previously undergone percutaneous nephrolithotomy (PCNL). METHODS: A retrospective analysis included patients who underwent RIRS for kidney stones between August 2018 and April 2023. Group 1 comprised 396 patients who underwent primary RIRS, while Group 2 included 231 individuals who had RIRS after previous PCNL. Evaluation parameters included preoperative characteristics, stone attributes, operative details, treatment outcomes, stone-free status, and complications. Statistical analysis utilized Student's t test, Mann-Whitney U test, and Pearson Chi-square test (p < 0.05). RESULTS: The mean age, body mass index, stone number, mean stone burden, and SFS were not statistically different between the groups. Lower pole stones were identified in 144 patients in Group 1 and 88 patients in Group 2 (p = 0.315). In Group 1 and Group 2, the mean operation time and fluoroscopy time were 65.23 ± 18.1 min, 81.32 ± 14.3 min, 26.34 ± 8.31 s, 46.61 ± 7.6 s, respectively, showing statistically significant differences between the groups (p = 0.013, p < 0.001, respectively). Infundibulum stenosis was identified and treated with a laser in 12% of Group 2 cases. Complications occurred in 12 patients in Group 1 and 14 patients in Group 2 (p = 0.136). CONCLUSION: A history of PCNL may contribute to extended operation times and increased fluoroscopy exposure in subsequent RIRS without significantly affecting postoperative SFS or complication rates.

Gerdy's tubercle as a novel anatomical landmark for the proximal tibial cut in total knee arthroplasty.

OBJECTIVES: This study aimed to explore the use of Gerdy's tubercle (GT) as an innovative and dependable anatomical landmark for the proximal tibial cut in total knee arthroplasty (TKA) in cases with extensive knee degeneration. MATERIALS AND METHODS: One hundred dry tibia bones and 10 formalin-fixed cadaveric knee specimens of both sexes were examined. A Zimmer NexGen tibial cutting guide and a Mitutoyo digital caliper were utilized to align the guide with the tibia's mechanical axis. The procedure was replicated on cadaver knees using a standardized medial parapatellar arthrotomy approach. Measurements included the distance from GT superior border to the resection line and the length of the tibia. A radiological study involving magnetic resonance imaging examinations of 48 patients, which were evaluated focusing on the upper border of GT and the least degenerated segment of the posterolateral part of the lateral tibial condyle, was conducted. RESULTS: Anatomical measurements of GT and proximal tibial areas in 110 specimens showed slight but consistent variations with cadaver measurements. Magnetic resonance imaging analysis of 48 patients revealed notable sex differences in the distance between the superior border of GT and the tibia's posterolateral surface. There was also a significant negative correlation between the distance from GT to the posterolateral corner and cartilage thickness. CONCLUSION: Proper alignment in TKA is crucial for success, but identifying an extra-articular landmark for horizontal tibial resection remains challenging, particularly in severely arthritic knees. This study introduces GT as a novel anatomical landmark for TKA, offering a more reliable reference for achieving desired joint levels in knees with significant degenerative changes.

Deciphering mortality risk of diabetes medications in heart failure patients with diabetes mellitus under triple guideline-directed medical therapy.

BACKGROUND: Scientific evidence regarding the impact of different combinations of diabetes medications in heart failure patients with diabetes mellitus (HFwDM) remains limited. AIM: We aimed to investigate the effect of monotherapy and combination therapy for DM on all-cause mortality in HFwDM under triple guideline-directed medical therapy (GDMT). METHOD: This nationwide retrospective cohort study included adult HFwDM under triple GDMT between January 1, 2016 and December 31, 2022.We collected the data from the National Electronic Database of the Turkish Ministry of Health.We created various combination including different diabetes medications based on the current guidelines for DM.The primary endpoint was all-cause mortality. RESULTS: A total of 321,525 HFwDM under triple GDMT (female:49%, median age:68[61-75] years) were included. The highest rate of prescribed combination therapy was metformin and sulfonylureas (n = 55,266). In Cox regression analysis, insülin monotherapy had the highest risk for all-cause mortality (HR:2.25, 95CI%:2.06 - 2.45), whereas combination therapy including metformin, SGLT2i, and sulfonylureas provided the most beneficial effect on survival (HR:0.29, 95CI%:0.22-0.39) when compared to patients not receiving diabetes medication. Among patients taking diabetes medications, the inclusion of SGLT2i demonstrated a survival benefit (p < 0.05), despite concurrent use of volume-retaining medications such as insulin and thiazolidinediones. Conversely, combinations of diabetes medications without SGLT2i did not demonstrate any survival benefit compared to patients not taking diabetes medication (p > 0.05). CONCLUSION: This study underscored the use of SGLT2i as monotherapy or as a part of combination diabetes medications to improve survival among HFwDM, while also highlighting that combinations lacking SGLT2i did not confer any survival benefit.

Digoxin is Not Related to Mortality in Patients with Heart Failure: Results from the SELFIE-TR Registry.

AIMS: Digoxin has been used in the treatment for heart failure for centuries, but the role of this drug in the modern era is controversial. A particular concern is the recent observational findings suggesting an increase in all-cause mortality with digoxin, although such observations suffer from biased results since these studies usually do not provide adequate compensation for the severity of disease. Using a nationwide registry database, we aimed to investigate whether digoxin is associated with 1-year all-cause mortality in patients with heart failure irrespective of phenotype. METHODS: A total of 1014 out of 1054 patients in the registry, of whom 110 patients were on digoxin, were included in the study. Multivariable adjustments were done and propensity scores were calculated for various prognostic indicators, including signs and symptoms of heart failure and functional capacity. Crude mortality, mortality adjusted for covariates, mortality in the propensity score-matched cohort, and Bayesian factors (BFs) were analyzed. RESULTS: Crude 1-year mortality rate did not differ between patients on and off digoxin (17.3% vs 20.1%, log-rank p = 0.46), and digoxin was not related to mortality following multivariable adjustment (hazard ratio 0.87, 95% confidence interval 0.539-1.402, p = 0.57). Similarly, all-cause mortality was similar in 220 propensity-score adjusted patients (17.3% vs 20.0%, log-rank p = 0.55). On Bayesian analyses, there was moderate to strong evidence suggesting a lack of difference between in unmatched cohort (BF10 0.091) and weak-to-moderate evidence in the matched cohort (BF10 0.296). CONCLUSIONS: In this nationwide cohort, we did not find any evidence for an increased 1-year mortality in heart failure patients on digoxin.

Investigation of stair ascending and descending activities on the lifespan of hip implants.

Total hip arthroplasty (THA) surgeries among young patients are on the increase, so it is crucial to predict the lifespan of hip implants correctly and produce solutions to improve longevity. Current implants are designed and tested against walking conditions to predict the wear rates. However, it would be reasonable to include the additional effects of other daily life activities on wear rates to predict convergent results to clinical outputs. In this study, 14 participants are recruited to perform stair ascending (AS), descending (DS), and walking activities to obtain kinematic and kinetic data for each cycle using marker based Qualisys motion capture (MOCAP) system. AnyBody Modeling System using the Calibrated Anatomical System Technique (CAST) full body marker set are performed Multibody simulations. The 3D generic musculoskeletal model used in this study is a marker-based full-body motion capture model (AMMR,2.3.1 MoCapModel) consisting of the upper extremity and the Twente Lower Extremity Model (TLEM2). The dynamic wear prediction model detailing the intermittent and overall wear rates for CoCr-on-XLPE bearing couple is developed to investigate the wear mechanism under 3D loading for AS, DS, and walking activities over 5 million cycles (Mc) by using finite element modelling technique. The volumetric wear rates of XLPE liner under AS, DS, and walking activities over 5-Mc are predicted as 27.43, 23.22, and 18.84 mm3/Mc respectively. Additionally, the wear rate was predicted by combining stair activities and gait cycles based on the walk-to-stair ratio. By adding the effect of stair activities, the volumetric wear rate of XLPE is predicted as 22.02 mm3/Mc which is equivalent to 19.41% of walking. In conclusion, in this study, the effect of including other daily life activities is demonstrated and evidence is provided by matching them to the clinical data as opposed to simulator test results of implants under ISO 14242 boundary conditions.

Association between left-sided varicocele and epididymo-orchitis with sonographic findings.

OBJECTIVE: The aim of this study was to investigate the relationship between left-sided varicocele and epididymitis or epididymo-orchitis. MATERIALS AND METHODS: The study included 72 patients with left side epididymitis (EP) or epididymo-orchitis (EPO) (Group 1) and a control group of 72 patients without EP or EPO (Group 2). Those with right EP-EPO were excluded due to possible other underlying retroperitoneal pathologies causing varicocele. Groups were evaluated for presence of left side varicocele, varicocele grade and pampiniform plexus vein diameter. RESULTS: The average age was 38 ± 8.4 years (range, 18-50 years) in Group 1, and 36 ± 9.1 years (range, 16-47 years) in Group 2. Varicocele was significantly more common in patients with EP or EPO (p < .001). The rate of varicocele was 66.7% (48/72) in Group 1, and 22.3% (16/72) in Group 2. The median grade of varicocele was 2 in Group 1, and 0 in Group 2. Pampiniform plexus vein diameters were found to be significantly larger in patients with EP or EPO compare to patients without EP and EPO. The median vein diameter was 3.3 mm with the 25th and 75th percentiles at 2.7 and 3.8 mm, and was 1.9 mm with the 25th and 75th percentiles at 1.7 and 2.3 mm, respectively (p < .001). CONCLUSIONS: Left-sided varicocele was significantly more common in patients with EP or EPO and it is an important cause for the development of EP/EPO because of chronic venous stasis.

The effect of ureteral double J stent insertion on work performance in patients undergoing endoscopic stone treatment.

Introduction: Despite the developments in the material of the double J (DJ) stents and the production of thinner ones of desired sizes, patients continue to experience troublesome DJ stent-related symptoms in their lives. This study aimed to determine how DJ stenting affects patients' work performance after endoscopic stone surgery. Material and methods: A total of 107 patients underwent placement of a ureteral stent after ureterorenoscopy (URS)/retrograde intrarenal surgery (RIRS), and only active and full-time working patients were included. All patients were asked to complete the validated Turkish version of the work performance score (WPS) questionnaire in the Ureteral Stent Symptom Questionnaire (USSQ) the day before stent removal and again one month after stent removal. Results: Of the participants, 32.7% (n = 35) were female and 67.3% (n = 72) were male; the mean age was 41 (19-80) years. The workday loss had no statistically significant correlation with patient BMI, stone size, or stent indwelling time (p >0.005); however, a statistically significant negative correlation was detected with patient age (r = -0.335, p <0.001). The medians of WPSs with the stent and without the stent were 6 (3-15) and 3 (3-12), respectively (p <0.001). Conclusions: Although DJ catheterization is a crucial tool for urological practice, it may increase the social and economic burden of patients due to reduced work performance and lost workdays. Therefore, limiting the duration of the DJ stent's stay and providing treatments to minimize patient symptoms will positively impact their professional lives. It would be beneficial to avoid DJ stenting in routine practice unless medically necessary.

Single versus double Hem-o-lok clips to secure the apendiceal stump during laparoscopic appendectomy: a prospective randomized multicentric clinical trial.

PURPOSE: Polymeric clips (Hem-o-lok ligation system) are now widely used to securing the base of the appendix during laparoscopic appendectomy. Studies comparing the use of single or double hem-o-lok clips are limited. The aim of this study was to compare the reliability of a single hem-o-lok clips with a double hem-o-lok clips for closure of an appendiceal stump. METHODS: This prospective randomized study includes patients from two centers who underwent laparoscopic appendectomy with the diagnosis of appendicitis between September 2020 and March 2023. Demographic, operative and clinical outcomes of the use of single or double hem-o-lok clips for closure of the appendiceal stump were compared. Factors affecting long postoperative hospital stay were investigated using univariate and multivariate analyzes. RESULTS: One hundred forty two (48.3%) patients in the single hem-o-lok arm and 152 (51.7%) patients in the double hem-o-lok arm were included in the analysis.The shortest operative time was noted in the single hem-o-lok group (52.1 ± 19.9 versus 61.6 ± 24.9 min, p < 0.001). The median hospital stay was 1 day (range 1-10) in the single hem-o-lok group and 1 day (range 1-12) in the double hem-o-lok group, and was shorter in the single hem-o-lok arm (1.61 ± 1.56 vs 1.84 ± 1.69, p = 0.019). Based on multivariate analysis, drain placement was identified as an independent predictive factor for long hospital stay. CONCLUSIONS: The use of single hem-o-lok clips for appendiceal stump closure during laparoscopic appendectomy is safe and effective. Trial registration NCT04387370 ( http://www. CLINICALTRIALS: gov ).

Tibial nerve branching pattern and compatibility of branches for the deep fibular nerve.

PURPOSE: In individuals who develop drop foot due to nerve loss, several methods such as foot-leg orthosis, tendon transfer, and nerve grafting are used. Nerve transfer, on the other hand, has been explored in recent years. The purpose of this study was to look at the tibial nerve's branching pattern and the features of its branches in order to determine the suitability of the tibial nerve motor branches, particularly the plantaris muscle motor nerve, for deep fibular nerve transfer. METHODS: There were 36 fixed cadavers used. Tibial nerve motor branches were observed and measured, as were the lengths, distributions, and thicknesses of the common fibular nerve and its branches at the bifurcation region. RESULT: The motor branches of the tibial nerve that supply the soleus muscle, lateral head, and medial head of the gastrocnemius were studied, and three distinct forms of distribution were discovered. The motor branch of the gastrocnemius medial head was commonly observed as the first branch to divide, and it appeared as a single root. The nerve of the plantaris muscle was shown to be split from many origins. When the thickness and length of the motor branches measured were compared, the nerve of the soleus muscle was determined to be the most physically suited for neurotization. CONCLUSION: In today drop foot is very common. Traditional methods of treatment are insufficient. Nerve transfer is viewed as an application that can both improve patient outcomes and hasten the patient's return to society. The nerve of the soleus muscle was shown to be the best candidate for transfer in our investigation.

The efficacy and safety of soluble guanylate cyclase modulation in patients with heart failure: a comprehensive meta-analysis of randomized controlled trials.

Soluble guanylate cyclase (sGC) modulation has been scrutinized in several disease states including heart failure (HF). Recently, it was shown that an sGC modulator improved HF-related hospitalization significantly, though, there was no benefit related to mortality. Herein, a comprehensive meta-analysis of randomized controlled trials (RCTs) for sGC modulation in HF patients was provided in agreement with the PRISMA statement. A total of 10 RCTs yielding 12 papers were included. There were 7526 patients with heart failure of each phenotype, 4253 in the sGC modulator group and 3273 in the placebo group. Use of sGC modulators in HF patients yielded no significant difference in the risk of all-cause mortality compared to placebo (RR = 0.97, 95% CI 0.88-1.08, p = 0.62). The use of sGC modulators was associated with a trend toward a considerable but non-significant increase in the incidence of SAEs (RR = 1.10, 95% CI 0.99-1.22, p = 0.07), as well as an increased incidence of hypotension and anemia. There was an overall neutral effect of sGC modulation on NT-proBNP levels, 6MWD and mortality, at a cost of slight increase in hypotension and anemia. Of note, the improvement in EQ-5D-based quality of life was significant. Hence, the benefit seems to be driven by distinctive domains of quality of life.

Association of soluble ST2 Level with 6-month Mortality and/or Recurrent Cardiovascular-Related Hospitalization in Pulmonary Embolism. / Associação do Nível de ST2 Solúvel com Mortalidade em 6 Meses e/ou Hospitalização Recorrente Relacionada a Doenças Cardiovasculares em Embolia Pulmonar.

BACKGROUND: The association of soluble suppression of tumorigenesis-2 (sST2) levels with prognosis in pulmonary embolism (PE) is unknown. OBJECTIVE: This study aimed to investigate the relationship between sST2 levels in patients with acute PE and 6-month mortality and recurrent hospitalizations. METHODS: This prospective study included 100 patients with acute PE. Patients were classified into two groups according to 6-month mortality and the presence of recurrent Cardiovascular-Related hospitalizations. Two groups were compared. A p-value of 0.05 was considered statistically significant. RESULTS: Soluble ST2 levels were significantly higher in the group with mortality and recurrent hospitalizations. (138.6 ng/mL (56.7-236.8) vs. 38 ng/mL (26.3-75.4); p<0.001) The best cut-off threshold for sST2 levels in the prediction of a composite outcome of 6-month mortality and/or recurrent Cardiovascular-Related hospitalization was found to be >89.9 with a specificity of 90.6% and a sensitivity of 65.2%, according to the receiver operating characteristic curve (area under the curve = 0.798; 95% CI, 0.705-0.891; p <0.0001). After adjusting for confounding factors that were either statistically significant in the univariate analysis or for the variables correlated with the sST2 levels, sST2 level (OR = 1.019, 95% CI: 1.009-1.028, p 0.001) and C-reactive protein (CRP ) (OR = 1.010, 95% CI: 1.001-1.021, p = 0.046) continued to be significant predictors of 6-month mortality and/or recurrent Cardiovascular-Related hospitalization in the multiple logistic regression model via backward stepwise method. CONCLUSION: Soluble ST2 level seems to be a biomarker to predict 6-month mortality and/or recurrent Cardiovascular-Related hospitalization in patients with acute PE.

FUNDAMENTO: A associação de supressão solúvel da tumorigênese-2 (sST2) com prognóstico em embolia pulmonar (EP) é desconhecida. OBJETIVO: Este estudo teve como objetivo investigar a relação entre os níveis de sST2 em pacientes com EP aguda e mortalidade em 6 meses e hospitalizações recorrentes. MÉTODOS: Este estudo prospectivo incluiu 100 pacientes com EP aguda. Os pacientes foram classificados em dois grupos de acordo com a mortalidade em 6 meses e a presença de hospitalizações recorrentes relacionadas a doenças cardiovasculares. Dois grupos foram comparados. Um valor de p de 0,05 foi considerado estatisticamente significativo. RESULTADOS: Os níveis de ST2 solúvel foram significativamente maiores no grupo com mortalidade e internações recorrentes. (138,6 ng/mL (56,7-236,8) vs. 38 ng/mL (26,3-75,4); p<0,001) O melhor limite de corte para níveis de sST2 na previsão de um desfecho composto de mortalidade em 6 meses e/ou a hospitalização recorrente relacionada a doenças cardiovasculares foi >89,9, com especificidade de 90,6% e sensibilidade de 65,2%, de acordo com a curva Receiver Operating Characteristic (área sob a curva = 0,798; IC 95%, 0,705­0,891; p <0,0001). Após ajuste para fatores de confusão que foram estatisticamente significativos na análise univariada ou para as variáveis correlacionadas com os níveis de sST2, nível de sST2 (OR = 1,019, IC 95%: 1,009-1,028, p 0,001) e proteína C reativa (PCR). (OR = 1,010, IC 95%: 1,001-1,021, p = 0,046) continuaram a ser preditores significativos de mortalidade em 6 meses e/ou hospitalização recorrente relacionada a doenças cardiovasculares no modelo de regressão logística múltipla através do método backward stepwise. CONCLUSÕES: O nível de ST2 solúvel parece ser um biomarcador para prever mortalidade em 6 meses e/ou hospitalização recorrente relacionada a doenças cardiovasculares em pacientes com EP aguda.

Interleukin-6 And Interleukin-10 Polymorphisms In Chronic Lymphoid Leukemia Patients.

OBJECTIVE: A major part of the cytokines secreted from the immune system are interleukins (IL) and their main role is to stimulate the immune system cells. Therefore the genotypic effects of IL-6 and IL-10 on the immune system in CLL were investigated in the study. METHOD: For this purpose 100 patients diagnosed with CLL and 70 healthy individuals with no cancer history were included in the study. Polymorphisms at IL10 and IL 6 promoter regions (1082 A\G and 819 C\T) and IL6 (174 G\C) polymorphisms were analyzed with RT-PCR. Genotype and allele frequencies were directly calculated. RESULT: In 100 CLL patients, 45 wild type AA, 40 AG and 15 mutant type GG genotypes were found for the IL 10 1082 A\G region. Genotypic distribution of IL10 819 C\T region was determined as CC, BT and TT genotypes in 37, 50 and 13 patients, respectively. In IL 6 174 G\C region, GG, GC and CC genotypes were determined in 62, 30 and 8 patients, respectively. There is no statistically significant difference between the CLL patients and control groups in terms of IL10 1082 A\G, 819 C\T and IL 6 174 G/C regions (p> 0.05). As a result of the allele frequency calculation of the IL 10 1082 region, the values obtained were A (0.65), G (0.35) for the patient group and (0.61) and G (0.31) for the control group. 819 region allele frequencies were C (0.57) and T (0.33) in the patient group and C (0.48) and T (0.32) in the control group. The IL6 174 region was calculated as G (0.82), C (0.28) in the patient group and G (0.63), C (0.23) in the control group. Given the number of patients within the limits of this study, IL 10 and IL 6 genotype frequencies do not seem to be statistically related to CLL patients. CONCLUSION: Mutant alleles of all interleukin SNPs were determined at a higher frequency in the patient group as compared to the control group. Therefore, a potential correlation between the SNPs of these interleukins and CLL can be determined in future studies with a higher number of samples.

Patient Perception, Knowledge and Adaptation in The Management of Heart Failure: A Multicenter, Cross-Sectional, Observational, Questionnaire-Based Study: ADAPTATION HF.

OBJECTIVE: The aim of this study is to reveal the perception levels of heart failure (HF) patients about the disease, their adaptation to the disease process, their compliance with the treatment, and their knowledge and thoughts about the disease from the patient's perspective. METHOD: Patients with a diagnosis of HF for at least 6 months who applied to the cardiology clinics of 10 different centers were included in this cross-sectional, multicenter and questionnaire-based study. A questionnaire consisting of sections that included demographic information, evaluation of the patient's symptoms, knowledge and experience of clinical follow-up, knowledge of HF, compliance and awareness of treatment was applied to the patients. RESULTS: 504 patients with a mean age of 59.8 ± 14.9 years (M/F: 360/144, 71.4%/28.6%) were included in the study. 61.2% of the patients stated that they knew about HF disease before. Most of the patients knew that the complaints of shortness of breath, fatigue and palpitation could develop due to HF (95.4%; 92.7%; 89.7%, respectively). The patients reported that they were mostly worried about not being able to provide their own self-care without the support of another person (67.5%). While the majority of patients (37.6%) thought that the worst disease was to have a cerebrovascular disease; only 10.9% stated that HF was the worst disease. While 98.8% of the patients stated that they used HF drugs regularly, a relatively large part of the patients did not know that the drugs were effective on kidney functions (68.5%) and blood pressure (76.9%). In the daily practice of the patients, the rate of weight follow-up was 35.5%, the rate of blood pressure monitoring was 26.9%, and the rate of patients who exercised was 27%. Among the patients, 73.3% said that they pay attention to the amount of salt they take with diet, and 33.5% have a completely salt.free diet. There was no difference between the groups with low and high knowledge scores in terms of Pittsburgh Sleep Quality Index (P > 0.005). The knowledge level score was significantly higher in patients with previous myocardial infarction (P = 0.002). CONCLUSION: Most of the HF patients participating in the study are aware of the signs and symptoms of HF, follow the recommendations of their physicians, and use drugs regularly. These patients should have more information about blood pressure monitoring, weight monitoring, diet and sodium restriction, exercise, which are included in the non-pharmacological part of treatment management.

Navigating Heart Failure: Unveiling Sex Disparities in Guideline-Directed Medical Therapy Combinations.

Major heart failure (HF) trials remain insufficient in terms of assessing the differences in clinical characteristics, biomarkers, treatment efficacy, and safety because of the under-representation of women. The study aimed to present sex-related disparities in HF management, including differences in demographics, co-morbidities, cardiac biomarkers, prescribed medications, and treatment outcomes. The study utilized anonymized data from the Turkish Ministry of Health's National Electronic Database between January 1, 2016, and December 31, 2022. The cohort analysis included 2,501,231 adult patients with HF. Specific therapeutic combinations were analyzed using a Cox regression model to obtain relative risk reduction for all-cause death. The primary end point was all-cause mortality. In the cohort, 48.7% (n = 1,218,911) were male, whereas 51.3% (n = 1,282,320) were female. Female patients exhibited a higher median age (71 vs 68 years) and manifested higher prevalence of diabetes mellitus, anemia, atrial fibrillation, anxiety, and ischemic stroke. Male patients demonstrated higher rates of previous myocardial infarction, dyslipidemia, chronic obstructive pulmonary disease, and chronic kidney disease. Higher concentrations of natriuretic peptides were observed in female patients. Renin-angiotensin aldosterone inhibitor, ß blockers, mineralocorticoid receptor antagonists, sodium/glucose cotransporter 2 inhibitor (SGLT2i), and ivabradine were more commonly prescribed in male patients, whereas loop diuretics, digoxin, and ferric carboxymaltose were more frequent in female patients. Male patients had higher rates of cardiac resynchronization therapy and implantable cardioverter defibrillator implantation rates. All-cause mortality and hospitalization rates were higher in male patients. Compared with monotherapy, all combinations, including SGLT2i, showed a beneficial effect on all-cause mortality in both female and male patients with HF. In hospitalized patients with HF, the addition of digoxin to renin-angiotensin aldosterone inhibitor, mineralocorticoid receptor antagonists, and ß blockers was superior to monotherapy regarding all-cause mortality in female patients with HF compared with male patients with HF. In conclusion, this study highlights that sex-specific responses to HF medication combinations compared with monotherapy and differences in co-morbidities underscore the importance of tailored management strategies. Digoxin showed a contrasting effect on all-cause mortality between both sexes after hospitalization, whereas SGLT2i exhibited a consistent beneficial effect in both sexes when added to all combinations.

Integration of implantable device therapy in patients with heart failure. A clinical consensus statement from the Heart Failure Association (HFA) and European Heart Rhythm Association (EHRA) of the European Society of Cardiology (ESC).

Implantable devices form an integral part of the management of patients with heart failure (HF) and provide adjunctive therapies in addition to cornerstone drug treatment. Although the number of these devices is growing, only few are supported by robust evidence. Current devices aim to improve haemodynamics, improve reverse remodelling, or provide electrical therapy. A number of these devices have guideline recommendations and some have been shown to improve outcomes such as cardiac resynchronization therapy, implantable cardioverter-defibrillators and long-term mechanical support. For others, more evidence is still needed before large-scale implementation can be strongly advised. Of note, devices and drugs can work synergistically in HF as improved disease control with devices can allow for further optimization of drug therapy. Therefore, some devices might already be considered early in the disease trajectory of HF patients, while others might only be reserved for advanced HF. As such, device therapy should be integrated into HF care programmes. Unfortunately, implementation of devices, including those with the greatest evidence, in clinical care pathways is still suboptimal. This clinical consensus document of the Heart Failure Association (HFA) and European Heart Rhythm Association (EHRA) of the European Society of Cardiology (ESC) describes the physiological rationale behind device-provided therapy and also device-guided management, offers an overview of current implantable device options recommended by the guidelines and proposes a new integrated model of device therapy as a part of HF care.

Exploring Regional Disparities in Heart Failure Epidemiology and Outcomes: A Comprehensive Study Across Geographical Regions in Türkiye.

Background: Heart failure (HF) is a common condition that affects 1-3% of the general population. Its prevalence exhibits notable international and intranational disparities, partly explained by socioeconomic status, religion, ethnic diversity, and geographic factors. A comprehensive understanding of the epidemiological symptoms of HF in different regions of Türkiye has yet to be revealed. Aims: To examine epidemiological data from 2016 to 2022, focusing on crucial patient characteristics and geographical regions, to determine the incidence and prevalence of HF in Türkiye across seven diverse geographical regions. Study Design: A nationwide population-based retrospective cohort study. Methods: The comprehensive National Electronic Database of the Turkish Ministry of Health was used in this study to obtain data that covers the whole Turkish population from January 1, 2016, to December 31, 2022. The International Classification of Diseases-10 (ICD-10) codes were used to identify adults with HF (n = 2,701,099) and associated comorbidities. Türkiye is divided into seven geographically distinct regions. Epidemiological characteristics and survival data of these regions were analyzed separately. All-cause mortality was set as the primary outcome. Results: In , the total estimated prevalence of adult patients with HF is 2.939%, ranging from 2.442% in Southeastern Anatolia to 4.382% in the Black Sea Region. Except for the Eastern Anatolia Region, the three most often reported comorbidities were hypertension, dyslipidemia, and anxiety disorders. The rates of prescribing guideline-directed medical therapy (GDMT) for HF and other medications varied significantly. GDMT prescription rates were lowest in the Eastern Anatolia Region (82.6% for beta-blockers, 48.7% for RASi, 31.8% for mineralocorticoid receptor antagonists, and 9.4% for SGLT2i). The Mediterranean and Aegean regions had the highest median N-terminal brain natriuretic peptide (NT-proBNP) levels of 1,990,0 pg/ml (518.0-6,636,0) and 1,441,0 pg/ml (363.0-5,000,0), respectively. From 2016 to 2022, 915,897 (33.9%) of 2,701,099 patients died. The Eastern Anatolia Region had the lowest all-cause mortality rate of 26.5%, whereas the Black Sea Region had the highest all-cause mortality rate of 35.3%. Conclusion: Our real-world analysis revealed geographic disparities in HF characteristics, such as decreased mortality in socioeconomically challenged regions. Higher stress susceptibility in developed regions may increase the likelihood of adverse outcomes.

ECOLE: Learning to call copy number variants on whole exome sequencing data.

Copy number variants (CNV) are shown to contribute to the etiology of several genetic disorders. Accurate detection of CNVs on whole exome sequencing (WES) data has been a long sought-after goal for use in clinics. This was not possible despite recent improvements in performance because algorithms mostly suffer from low precision and even lower recall on expert-curated gold standard call sets. Here, we present a deep learning-based somatic and germline CNV caller for WES data, named ECOLE. Based on a variant of the transformer architecture, the model learns to call CNVs per exon, using high-confidence calls made on matched WGS samples. We further train and fine-tune the model with a small set of expert calls via transfer learning. We show that ECOLE achieves high performance on human expert labelled data for the first time with 68.7% precision and 49.6% recall. This corresponds to precision and recall improvements of 18.7% and 30.8% over the next best-performing methods, respectively. We also show that the same fine-tuning strategy using tumor samples enables ECOLE to detect RT-qPCR-validated variations in bladder cancer samples without the need for a control sample. ECOLE is available at https://github.com/ciceklab/ECOLE .

Expert Recommendations to Bridge Gaps in Heart Failure Patient Support in the Middle East and Africa Region.

Heart failure (HF) remains a serious health and socioeconomic problem in the Middle East and Africa (MEA). The age-standardized prevalence rate for HF in the MEA region is higher compared to countries in Eastern Europe, Latin America, and Southeast Asia. Also cardiovascular-related deaths remain high compared to their global counterparts. Moreover, in MEA, 66% of HF readmissions are elicited by potentially preventable factors, including delay in seeking medical attention, nonadherence to HF medication, suboptimal discharge planning, inadequate follow-up, and poor social support. Patient support in the form of activation, counseling, and caregiver education has been shown to improve outcomes in patients with HF. A multidisciplinary meeting with experts from different countries across the MEA region was convened to identify the current gaps and unmet needs for patient support for HF in the region. The panel provided insights into the real-world challenges in HF patient support and contributed strategic recommendations for optimizing HF care.

Turkish Real Life Atrial Fibrillation in Clinical Practice: TRAFFIC Study.

BACKGROUND: Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia worldwide and is associated with an increased risk of thromboembolism, ischemic stroke, impaired quality of life, and mortality. The latest research that shows the prevalence and incidence of AF patients in Türkiye was the Turkish Adults' Heart Disease and Risk Factors study, which included 3,450 patients and collected data until 2006/07.The Turkish Real Life Atrial Fibrillation in Clinical Practice (TRAFFIC) study is planned to present current prevalence data, reveal the reflection of new treatment and risk approaches in our country, and develop new prediction models in terms of outcomes. METHODS: The TRAFFIC study is a national, prospective, multicenter, observational registry. The study aims to collect data from at least 1900 patients diagnosed with atrial fibrillation, with the participation of 40 centers from Türkiye. The following data will be collected from patients: baseline demographic characteristics, medical history, vital signs, symptoms of AF, ECG and echocardiographic findings, CHADS2-VASC2 and HAS-BLED (1-year risk of major bleeding) risk scores, interventional treatments, antithrombotic and antiarrhythmic medications, or other medications used by the patients. For patients who use warfarin, international normalized ratio levels will be monitored. Follow-up data will be collected at 6, 12, 18, and 24 months. Primary endpoints are defined as systemic embolism or major safety endpoints (major bleeding, clinically relevant nonmajor bleeding, and minor bleeding as defined by the International Society on Thrombosis and Hemostasis). The main secondary endpoints include major adverse cardiovascular events (systemic embolism, myocardial infarction, and cardiovascular death), all-cause mortality, and hospitalizations due to all causes or specific reasons. RESULTS: The results of the 12-month follow-up of the study are planned to be shared by the end of 2023. CONCLUSION: The TRAFFIC study will reveal the prevalence and incidence, demographic characteristics, and risk profiles of AF patients in Türkiye. Additionally, it will provide insights into how current treatments are reflected in this population. Furthermore, risk prediction modeling and risk scoring can be conducted for patients with AF.