Contribution of pudendal nerve injury to stress urinary incontinence in a male rat model.

Urinary incontinence is a common complication following radical prostatectomy, as the surgery disturbs critical anatomical structures. This study explored how pudendal nerve (PN) injury affects urinary continence in male rats. In an acute study, leak point pressure (LPP) and external urethral sphincter electromyography (EMG) were performed on six male rats with an intact urethra, the urethra exposed (UE), the PN exposed (NE), and after PN transection (PNT). In a chronic study, LPP and EMG were tested in 67 rats 4 days, 3 weeks, or 6 weeks after sham PN injury, PN crush (PNC), or PNT. Urethras were assessed histologically. Acute PNT caused a significant decrease in LPP and EMG amplitude and firing rate compared to other groups. PNC resulted in a significant reduction in LPP and EMG firing rate 4 days, 3 weeks, and 6 weeks later. EMG amplitude was also significantly reduced 4 days and 6 weeks after PNC. Neuromuscular junctions were less organized and less innervated after PNC or PNT at all timepoints compared to sham injured animals. Collagen infiltration was significantly increased after PNC and PNT compared to sham at all timepoints. This rat model could facilitate preclinical testing of neuroregenerative therapies for post-prostatectomy incontinence.

Variation in risk-adjusted cardiac intensive care unit (CICU) length of stay and the association with in-hospital mortality: An analysis from the Critical Care Cardiology Trials Network (CCCTN) registry.

BACKGROUND: Previous studies have suggested that there is wide variability in cardiac intensive care unit (CICU) length of stay (LOS); however, these studies are limited by the absence of detailed risk assessment at the time of admission. Thus, we evaluated inter-hospital differences in CICU LOS, and the association between LOS and in-hospital mortality. METHODS: Using data from the Critical Care Cardiology Trials Network (CCCTN) registry, we included 22,862 admissions between 2017 and 2022 from 35 primarily tertiary and quaternary CICUs that captured consecutive admissions in annual 2-month snapshots. The primary analysis compared inter-hospital differences in CICU LOS, as well as the association between CICU LOS and all-cause in-hospital mortality using a Fine and Gray competing risk model. RESULTS: The overall median CICU LOS was 2.2 (1.1-4.8) days, and the median hospital LOS was 5.9 (2.8-12.3) days. Admissions in the longest tertile of LOS tended to be younger with higher rates of pre-existing comorbidities, and had higher Sequential Organ Failure Assessment (SOFA) scores, as well as higher rates of mechanical ventilation, intravenous vasopressor use, mechanical circulatory support, and renal replacement therapy. Unadjusted all-cause in-hospital mortality was 9.3%, 6.7%, and 13.4% in the lowest, intermediate, and highest CICU LOS tertiles. In a competing risk analysis, individual patient CICU LOS was correlated (r2 = 0.31) with a higher risk of 30-day in-hospital mortality. The relationship remained significant in admissions with heart failure, ST-elevation myocardial infarction and non-ST segment elevation myocardial infarction. CONCLUSIONS: In a large registry of academic CICUs, we observed significant variation in CICU LOS and report that LOS is independently associated with all-cause in-hospital mortality. These findings could potentially be used to improve CICU resource utilization planning and refine risk prognostication in critically ill cardiovascular patients.

Prognostic performance of the IABP-SHOCK II Risk Score among cardiogenic shock subtypes in the critical care cardiology trials network registry.

BACKGROUND: Risk stratification has potential to guide triage and decision-making in cardiogenic shock (CS). We assessed the prognostic performance of the IABP-SHOCK II score, derived in Europe for acute myocardial infarct-related CS (AMI-CS), in a contemporary North American cohort, including different CS phenotypes. METHODS: The critical care cardiology trials network (CCCTN) coordinated by the TIMI study group is a multicenter network of cardiac intensive care units (CICU). Participating centers annually contribute ≥2 months of consecutive medical CICU admissions. The IABP-SHOCK II risk score includes age > 73 years, prior stroke, admission glucose > 191 mg/dl, creatinine > 1.5 mg/dl, lactate > 5 mmol/l, and post-PCI TIMI flow grade < 3. We assessed the risk score across various CS etiologies. RESULTS: Of 17,852 medical CICU admissions 5,340 patients across 35 sites were admitted with CS. In patients with AMI-CS (n = 912), the IABP-SHOCK II score predicted a >3-fold gradient in in-hospital mortality (low risk = 26.5%, intermediate risk = 52.2%, high risk = 77.5%, P < .0001; c-statistic = 0.67; Hosmer-Lemeshow P = .79). The score showed a similar gradient of in-hospital mortality in patients with non-AMI-related CS (n = 2,517, P < .0001) and mixed shock (n = 923, P < .001), as well as in left ventricular (<0.0001), right ventricular (P = .0163) or biventricular (<0.0001) CS. The correlation between the IABP-SHOCK II score and SOFA was moderate (r2 = 0.17) and the IABP-SHOCK II score revealed a significant risk gradient within each SCAI stage. CONCLUSIONS: In an unselected international multicenter registry of patients admitted with CS, the IABP- SHOCK II score only moderately predicted in-hospital mortality in a broad population of CS regardless of etiology or irrespective of right, left, or bi-ventricular involvement.

Interhospital Variation in Admissions Managed With Critical Care Therapies or Invasive Hemodynamic Monitoring in Tertiary Cardiac Intensive Care Units: An Analysis From the Critical Care Cardiology Trials Network Registry.

BACKGROUND: Wide interhospital variations exist in cardiovascular intensive care unit (CICU) admission practices and the use of critical care restricted therapies (CCRx), but little is known about the differences in patient acuity, CCRx utilization, and the associated outcomes within tertiary centers. METHODS: The Critical Care Cardiology Trials Network is a multicenter registry of tertiary and academic CICUs in the United States and Canada that captured consecutive admissions in 2-month periods between 2017 and 2022. This analysis included 17 843 admissions across 34 sites and compared interhospital tertiles of CCRx (eg, mechanical ventilation, mechanical circulatory support, continuous renal replacement therapy) utilization and its adjusted association with in-hospital survival using logistic regression. The Pratt index was used to quantify patient-related and institutional factors associated with CCRx variability. RESULTS: The median age of the study population was 66 (56-77) years and 37% were female. CCRx was provided to 62.2% (interhospital range of 21.3%-87.1%) of CICU patients. Admissions to CICUs with the highest tertile of CCRx utilization had a greater burden of comorbidities, had more diagnoses of ST-elevation myocardial infarction, cardiac arrest, or cardiogenic shock, and had higher Sequential Organ Failure Assessment scores. The unadjusted in-hospital mortality (median, 12.7%) was 9.6%, 11.1%, and 18.7% in low, intermediate, and high CCRx tertiles, respectively. No clinically meaningful differences in adjusted mortality were observed across tertiles when admissions were stratified by the provision of CCRx. Baseline patient-level variables and institutional differences accounted for 80% and 5.3% of the observed CCRx variability, respectively. CONCLUSIONS: In a large registry of tertiary and academic CICUs, there was a >4-fold interhospital variation in the provision of CCRx that was primarily driven by differences in patient acuity compared with institutional differences. No differences were observed in adjusted mortality between low, intermediate, and high CCRx utilization sites.

Perioperative hemostatic management of patients with type A aortic dissection.

Coagulopathy is common in patients undergoing thoracic aortic repair for Stanford type A aortic dissection. Non-critical administration of blood products may adversely affect the outcome. It is therefore important to be familiar with the pathologic conditions that lead to coagulopathy in complex cardiac surgery. Adequate care of these patients includes the collection of the medical history regarding the use of antithrombotic and anticoagulant drugs, and a sophisticated diagnosis of the coagulopathy with viscoelastic testing and subsequently adapted coagulation therapy with labile and stable blood products. In addition to the above-mentioned measures, intraoperative blood conservation measures as well as good interdisciplinary coordination and communication contribute to a successful hemostatic management strategy.

Distribution and treatment needs of soil-transmitted helminthiasis in Bangladesh: A Bayesian geostatistical analysis of 2017-2020 national survey data.

BACKGROUND: In Bangladesh, preventive chemotherapy targeting soil-transmitted helminth (STH) infections in school-age children has been implemented since 2008. To evaluate the success of this strategy, surveys were conducted between 2017 and 2020 in 10 out of 64 districts. We estimate the geographic distribution of STH infections by species at high spatial resolution, identify risk factors, and estimate treatment needs at different population subgroups. METHODOLOGY: Bayesian geostatistical models were fitted to prevalence data of each STH species. Climatic, environmental, and socioeconomic predictors were extracted from satellite images, open-access, model-based databases, and demographic household surveys, and used to predict the prevalence of infection over a gridded surface at 1 x 1 km spatial resolution across the country, via Bayesian kriging. These estimates were combined with gridded population data to estimate the number of required treatments for different risk groups. PRINCIPAL FINDINGS: The population-adjusted prevalence of Ascaris lumbricoides, Trichuris trichiura, and hookworm across all ages is estimated at 9.9% (95% Bayesian credible interval: 8.0-13.0%), 4.3% (3.0-7.3%), and 0.6% (0.4-0.9%), respectively. There were 24 out of 64 districts with an estimated population-adjusted STH infection prevalence above 20%. The proportion of households with improved sanitation showed a statistically important, protective association for both, A. lumbricoides and T. trichiura prevalence. Precipitation in the driest month of the year was negatively associated with A. lumbricoides prevalence. High organic carbon concentration in the soil's fine earth fraction was related to a high hookworm prevalence. Furthermore, we estimated that 30.5 (27.2; 36.0) million dosages of anthelmintic treatments for school-age children were required per year in Bangladesh. CONCLUSIONS/SIGNIFICANCE: For each of the STH species, the prevalence was reduced by at least 80% since treatment was scaled up more than a decade ago. The current number of deworming dosages could be reduced by up to 61% if the treatment strategy was adapted to the local prevalence.

Hyperoxia-induced deterioration of diastolic function in anaesthetised patients with coronary artery disease - Randomised crossover trial.

Background: There are no current recommendations for oxygen titration in patients with stable coronary artery disease. This study investigates the effect of iatrogenic hyperoxia on cardiac function in patients with coronary artery disease undergoing general anaesthesia. Methods: Patients scheduled for elective coronary artery bypass graft surgery were prospectively recruited into this randomised crossover clinical trial. All patients were exposed to inspired oxygen fractions of 0.3 (normoxaemia) and 0.8 (hyperoxia) in randomised order. A transoesophageal echocardiographic imaging protocol was performed during each exposure. Primary analysis investigated changes in 3D peak strain, whereas secondary analyses investigated other systolic and diastolic responses. Results: There was no statistical difference in systolic function between normoxaemia and hyperoxia. However, the response in systolic function to hyperoxia was dependent on ventricular function at normoxaemia. Patients with a normoxaemic left ventricular (LV) global longitudinal strain (GLS) poorer than the derived cut-off (>-15.4%) improved with hyperoxia (P<0.01), whereas in patients with normoxaemic LV-GLS <-15.4%, LV-GLS worsened with transition to hyperoxia (P<0.01). The same was seen for right ventricular GLS with a cut-off at -24.1%. Diastolic function worsened during hyperoxia indicated by a significant increase of averaged E/e' (8.6 [2.6]. vs 8.2 [2.4], P=0.01) and E/A ratio (1.4 (0.4) vs 1.3 (0.4), P=0.01). Conclusions: Although the response of biventricular systolic variables is dependent on systolic function at normoxaemia, diastolic function consistently worsens under hyperoxia. In coronary artery disease, intraoperative strain analysis may offer guidance for oxygen titration. Clinical trial registration: NCT04424433.

Interdisciplinary Analyses of Bronze Age Communities from Western Hungary Reveal Complex Population Histories.

In this study, we report 21 ancient shotgun genomes from present-day Western Hungary, from previously understudied Late Copper Age Baden, and Bronze Age Somogyvár-Vinkovci, Kisapostag, and Encrusted Pottery archeological cultures (3,530-1,620 cal Bce). Our results indicate the presence of high steppe ancestry in the Somogyvár-Vinkovci culture. They were then replaced by the Kisapostag group, who exhibit an outstandingly high (up to ∼47%) Mesolithic hunter-gatherer ancestry, despite this component being thought to be highly diluted by the time of the Early Bronze Age. The Kisapostag population contributed the genetic basis for the succeeding community of the Encrusted Pottery culture. We also found an elevated hunter-gatherer component in a local Baden culture-associated individual, but no connections were proven to the Bronze Age individuals. The hunter-gatherer ancestry in Kisapostag is likely derived from two main sources, one from a Funnelbeaker or Globular Amphora culture-related population and one from a previously unrecognized source in Eastern Europe. We show that this ancestry not only appeared in various groups in Bronze Age Central Europe but also made contributions to Baltic populations. The social structure of Kisapostag and Encrusted Pottery cultures is patrilocal, similarly to most contemporaneous groups. Furthermore, we developed new methods and method standards for computational analyses of ancient DNA, implemented to our newly developed and freely available bioinformatic package. By analyzing clinical traits, we found carriers of aneuploidy and inheritable genetic diseases. Finally, based on genetic and anthropological data, we present here the first female facial reconstruction from the Bronze Age Carpathian Basin.

Prognostic significance of haemodynamic parameters in patients with cardiogenic shock.

AIMS: Invasive haemodynamic assessment with a pulmonary artery catheter is often used to guide the management of patients with cardiogenic shock (CS) and may provide important prognostic information. We aimed to assess prognostic associations and relationships to end-organ dysfunction of presenting haemodynamic parameters in CS. METHODS AND RESULTS: The Critical Care Cardiology Trials Network is an investigator-initiated multicenter registry of cardiac intensive care units (CICUs) in North America coordinated by the TIMI Study Group. Patients with CS (2018-2022) who underwent invasive haemodynamic assessment within 24 h of CICU admission were included. Associations of haemodynamic parameters with in-hospital mortality were assessed using logistic regression, and associations with presenting serum lactate were assessed using least squares means regression. Sensitivity analyses were performed excluding patients on temporary mechanical circulatory support and adjusted for vasoactive-inotropic score. Among the 3603 admissions with CS, 1473 had haemodynamic data collected within 24 h of CICU admission. The median cardiac index was 1.9 (25th-75th percentile, 1.6-2.4) L/min/m2 and mean arterial pressure (MAP) was 74 (66-86) mmHg. Parameters associated with mortality included low MAP, low systolic blood pressure, low systemic vascular resistance, elevated right atrial pressure (RAP), elevated RAP/pulmonary capillary wedge pressure ratio, and low pulmonary artery pulsatility index. These associations were generally consistent when controlling for the intensity of background pharmacologic and mechanical haemodynamic support. These parameters were also associated with higher presenting serum lactate. CONCLUSION: In a contemporary CS population, presenting haemodynamic parameters reflecting decreased systemic arterial tone and right ventricular dysfunction are associated with adverse outcomes and systemic hypoperfusion.

Determination of selective antegrade perfusion flow rate in aortic arch surgery to restore baseline cerebral near-infrared spectroscopy values: a single-centre observational study.

OBJECTIVES: Neuroprotection during aortic arch surgery involves selective antegrade cerebral perfusion. The parameters of cerebral perfusion, e.g. flow rate, are inconsistent across centres and are subject of debate. The aim of this study was to determine the cerebral perfusion flow rate during hypothermic circulatory arrest required to meet preoperative awake baseline regional cerebral oxygen saturation (rSO2). METHODS: Patients scheduled for aortic arch surgery with hypothermic circulatory arrest were enrolled in this prospective observational study. After initiation of hypothermic circulatory arrest, bilateral selective antegrade cerebral perfusion was established and cerebral flow rate was continuously increased. The primary end point was the difference of cerebral saturation from baseline during cerebral perfusion flow rates of 6, 8 and 10 ml/kg/min. RESULTS: A total of 40 patients were included. During antegrade cerebral perfusion, rSO2 was significantly lower than the baseline at 6 ml/kg/min [-7.3, 95% confidence interval (CI): -1.7, -12.9; P = 0.0015]. In contrast, flow rates of 8 and 10 ml/kg/min resulted in rSO2 that did not significantly differ from the baseline (-2; 95% CI: -4.3, 8.3; P > 0.99 and 1.8; 95% CI: -8.5%, 4.8%; P > 0.99). Cerebral saturation was significantly more likely to meet baseline values during selective antegrade cerebral perfusion with 8 ml/kg/min than at 6 ml/kg/min (44.1%; 95% CI: 27.4%, 60.8% vs 11.8%; 95% CI: 0.9%, 22.6%; P = 0.0001). CONCLUSIONS: At 8 ml/kg/min cerebral flow rate during selective antegrade cerebral perfusion, regional cerebral oximetry baseline values are significantly more likely to be achieved than at 6 ml/kg/min. Further increasing the cerebral flow rate to 10 ml/kg/min does not significantly improve rSO2.

High Coverage Mitogenomes and Y-Chromosomal Typing Reveal Ancient Lineages in the Modern-Day Székely Population in Romania.

Here we present 115 whole mitogenomes and 92 Y-chromosomal Short Tandem Repeat (STR) and Single Nucleotide Polymorphism (SNP) profiles from a Hungarian ethnic group, the Székelys (in Romanian: Secuii, in German: Sekler), living in southeast Transylvania (Romania). The Székelys can be traced back to the 12th century in the region, and numerous scientific theories exist as to their origin. We carefully selected sample providers that had local ancestors inhabiting small villages in the area of Odorheiu Secuiesc/Székelyudvarhely in Romania. The results of our research and the reported data signify a qualitative leap compared to previous studies since it presents the first complete mitochondrial DNA sequences and Y-chromosomal profiles of 23 STRs from the region. We evaluated the results with population genetic and phylogenetic methods in the context of the modern and ancient populations that are either geographically or historically related to the Székelys. Our results demonstrate a predominantly local uniparental make-up of the population that also indicates limited admixture with neighboring populations. Phylogenetic analyses confirmed the presumed eastern origin of certain maternal (A, C, D) and paternal (Q, R1a) lineages, and, in some cases, they could also be linked to ancient DNA data from the Migration Period (5th-9th centuries AD) and Hungarian Conquest Period (10th century AD) populations.

Characteristics, therapies, and outcomes of In-Hospital vs Out-of-Hospital cardiac arrest in patients presenting to cardiac intensive care units: From the critical care Cardiology trials network (CCCTN).

BACKGROUND: Cardiac arrest (CA) is a common reason for admission to the cardiac intensive care unit (CICU), though the relative burden of morbidity, mortality, and resource use between admissions with in-hospital (IH) and out-of-hospital (OH) CA is unknown. We compared characteristics, care patterns, and outcomes of admissions to contemporary CICUs after IHCA or OHCA. METHODS: The Critical Care Cardiology Trials Network is a multicenter network of tertiary CICUs in the US and Canada. Participating centers contributed data from consecutive admissions during 2-month annual snapshots from 2017 to 2021. We analyzed characteristics and outcomes of admissions by IHCA vs OHCA. RESULTS: We analyzed 2,075 admissions across 29 centers (50.3% IHCA, 49.7% OHCA). Admissions with IHCA were older (median 66 vs 62 years), more commonly had coronary disease (38.3% vs 29.7%), atrial fibrillation (26.7% vs 15.6%), and heart failure (36.3% vs 22.1%), and were less commonly comatose on CICU arrival (34.2% vs 71.7%), p < 0.001 for all. IHCA admissions had lower lactate (median 4.3 vs 5.9) but greater utilization of invasive hemodynamics (34.3% vs 23.6%), mechanical circulatory support (28.4% vs 16.8%), and renal replacement therapy (15.5% vs 9.4%); p < 0.001 for all. Comatose IHCA patients underwent targeted temperature management less frequently than OHCA patients (63.3% vs 84.9%, p < 0.001). IHCA admissions had lower unadjusted CICU (30.8% vs 39.0%, p < 0.001) and in-hospital mortality (36.1% vs 44.1%, p < 0.001). CONCLUSION: Despite a greater burden of comorbidities, CICU admissions after IHCA have lower lactate, greater invasive therapy utilization, and lower crude mortality than admissions after OHCA.

Acid citrate dextrose formula A versus unfractionated heparin for anticoagulation of salvaged red blood cells in cardiac surgery.

Red blood cell salvage plays an important role in reducing the use of allogeneic blood transfusion during cardiac surgery. While there is consensus as to the benefit of employing cell salvage systems, there are no clear recommendations on the anticoagulant used for salvaged blood. In eight patients undergoing elective cardiac surgery at our university hospital's cardiovascular center, the authors describe hemodynamic effects of salvaged autologous blood transfusion when either unfractionated heparin or acid citrate dextrose formula A was used as the anticoagulant. Mean arterial pressure, heart rate, central venous pressure and acid-base status of the autologous red blood cell concentrate were compared between patients receiving autologous blood anticoagulated with acid citrate dextrose formula A versus unfractionated heparin. A clinically relevant decrease in mean arterial pressure (median change, - 19 mmHg [min -29; max -1] and marked acidosis [group median <6.30 [<6.30; 6.49] was observed in group acid citrate dextrose formula A. Acid citrate dextrose formula A anticoagulant for autologous red blood cell salvage has the potential to cause major adverse hemodynamic events during free-flowing re-transfusion of autologous red blood cell concentrate. Acute ionized hypocalcemia and acidemia may ensue from residual citrate in the supernatant of red blood cell concentrate reconstituted in unbuffered saline.

Ral GTPases are critical regulators of spinal cord myelination and homeostasis.

Efficient myelination supports nerve conduction and axonal health throughout life. In the central nervous system, oligodendrocytes (OLs) carry out this demanding anabolic duty in part through biosynthetic pathways controlled by mTOR. We identify Ral GTPases as critical regulators of mouse spinal cord myelination and myelin maintenance. Ablation of Ral GTPases (RalA, RalB) in OL-lineage cells impairs timely onset and radial growth of developmental myelination, accompanied by increased endosomal/lysosomal abundance. Further examinations, including transcriptomic analyses of Ral-deficient OLs, were consistent with mTORC1-related deficits. However, deletion of the mTOR signaling-repressor Pten in Ral-deficient OL-lineage cells is unable to rescue mTORC1 activation or developmental myelination deficiencies. Induced deletion of Ral GTPases in OLs of adult mice results in late-onset myelination defects and tissue degeneration. Together, our data indicate critical roles for Ral GTPases to promote developmental spinal cord myelination, to ensure accurate mTORC1 signaling, and to protect the healthy state of myelin-axon units over time.

Tracing genetic connections of ancient Hungarians to the 6th-14th century populations of the Volga-Ural region.

Most of the early Hungarian tribes originated from the Volga-Kama and South-Ural regions, where they were composed of a mixed population based on historical, philological and archaeological data. We present here the uniparental genetic makeup of the mediaeval era of these regions that served as a melting pot for ethnic groups with different linguistic and historical backgrounds. Representing diverse cultural contexts, the new genetic data originate from ancient proto-Ob-Ugric people from Western Siberia (6th-13th century), the pre-Conquest period and subsisting Hungarians from the Volga-Ural region (6th-14th century) and their neighbours. By examining the eastern archaeology traits of Hungarian prehistory, we also study their genetic composition and origin in an interdisciplinary framework. We analyzed 110 deep-sequenced mitogenomes and 42 Y-chromosome haplotypes from 18 archaeological sites in Russia. The results support the studied groups' genetic relationships regardless of geographical distances, suggesting large-scale mobility. We detected long-lasting genetic connections between the sites representing the Kushnarenkovo and Chiyalik cultures and the Carpathian Basin Hungarians and confirmed the Uralic transmission of several East Eurasian uniparental lineages in their gene pool. Based on phylogenetics, we demonstrate and model the connections and splits of the studied Volga-Ural and conqueror groups. Early Hungarians and their alliances conquered the Carpathian Basin around 890 AD. Re-analysis of the Hungarian conquerors' maternal gene pool reveals numerous surviving maternal relationships in both sexes; therefore, we conclude that men and women came to the Carpathian Basin together, and although they were subsequently genetically fused into the local population, certain eastern lineages survived for centuries.

Survival outcomes following radical cystectomy in patients with prior pelvic radiation for prostate cancer: A matched cohort analysis.

OBJECTIVES: To determine the impact of prior pelvic radiation therapy (XRT) on outcomes following radical cystectomy (RC) for bladder cancer. MATERIALS AND METHODS: We performed a retrospective review comparing patients with bladder cancer requiring RC and prior history of XRT for prostate cancer to those undergoing RC without XRT history at our institution from 2011-2018. Propensity score matching was performed with the following variables: age, chronic kidney disease, nutritional deficiency, neoadjuvant chemotherapy use, Charlson comorbidity index, surgical approach, urinary diversion type, and pathologic T-stage. Perioperative, pathologic and oncologic outcomes were analyzed. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Categorical variables were assessed utilizing the Pearson Chi Square Test, and continuous variables with the Wilcoxon rank-sum test. The Kaplan-Meier method with stratified-log rank was used to compare survival outcomes. Multivariable Cox proportional hazards models were utilized to identify predictors of overall and recurrence free survival. RESULTS: 227 patients were included, of which 47 had radiotherapy for prostate cancer. 47% of patients in the radiation cohort received external beam radiation therapy, 47% received brachytherapy and 7% received both. There were no differences in recurrence-free survival (P = 0.82) or overall survival (P = 0.25). Statistically significant differences in perioperative or postoperative outcomes such as 90-day complication, readmission, mortality rates, or ureteroenteric anastomotic stricture rates were not found. Rates of node-positive disease, median lymph node yield, positive surgical margin rates, lymphovascular invasion, or variant histology were not significantly different between cohorts. CONCLUSIONS: After matching for T-stage and other clinical variables, history of pelvic XRT for prostate cancer in patients who later required RC for bladder cancer, was not associated with an increased rate of perioperative complications or an independent predictor of RFS or OS.

The origins and spread of domestic horses from the Western Eurasian steppes.

Domestication of horses fundamentally transformed long-range mobility and warfare1. However, modern domesticated breeds do not descend from the earliest domestic horse lineage associated with archaeological evidence of bridling, milking and corralling2-4 at Botai, Central Asia around 3500 BC3. Other longstanding candidate regions for horse domestication, such as Iberia5 and Anatolia6, have also recently been challenged. Thus, the genetic, geographic and temporal origins of modern domestic horses have remained unknown. Here we pinpoint the Western Eurasian steppes, especially the lower Volga-Don region, as the homeland of modern domestic horses. Furthermore, we map the population changes accompanying domestication from 273 ancient horse genomes. This reveals that modern domestic horses ultimately replaced almost all other local populations as they expanded rapidly across Eurasia from about 2000 BC, synchronously with equestrian material culture, including Sintashta spoke-wheeled chariots. We find that equestrianism involved strong selection for critical locomotor and behavioural adaptations at the GSDMC and ZFPM1 genes. Our results reject the commonly held association7 between horseback riding and the massive expansion of Yamnaya steppe pastoralists into Europe around 3000 BC8,9 driving the spread of Indo-European languages10. This contrasts with the scenario in Asia where Indo-Iranian languages, chariots and horses spread together, following the early second millennium BC Sintashta culture11,12.

De Novo vs Acute-on-Chronic Presentations of Heart Failure-Related Cardiogenic Shock: Insights from the Critical Care Cardiology Trials Network Registry.

BACKGROUND: Heart failure-related cardiogenic shock (HF-CS) accounts for an increasing proportion of cases of CS in contemporary cardiac intensive care units. Whether the chronicity of HF identifies distinct clinical profiles of HF-CS is unknown. METHODS AND RESULTS: We evaluated admissions to cardiac intensive care units for HF-CS in 28 centers using data from the Critical Care Cardiology Trials Network registry (2017-2020). HF-CS was defined as CS due to ventricular failure in the absence of acute myocardial infarction and was classified as de novo vs acute-on-chronic based on the absence or presence of a prior diagnosis of HF, respectively. Clinical features, resource use, and outcomes were compared among groups. Of 1405 admissions with HF-CS, 370 had de novo HF-CS (26.3%), and 1035 had acute-on-chronic HF-CS (73.7%). Patients with de novo HF-CS had a lower prevalence of hypertension, diabetes, coronary artery disease, atrial fibrillation, and chronic kidney disease (all P < 0.01). Median Sequential Organ Failure Assessment (SOFA) scores were higher in those with de novo HF-CS (8; 25th-75th: 5-11) vs acute-on-chronic HF-CS (6; 25th-75th: 4-9, P < 0.01), as was the proportion of Society of Cardiovascular Angiography and Intervention (SCAI) shock stage E (46.1% vs 26.1%, P < 0.01). After adjustment for clinical covariates and preceding cardiac arrest, the risk of in-hospital mortality was higher in patients with de novo HF-CS than in those with acute-on-chronic HF-CS (adjusted hazard ratio 1.36, 95% confidence interval 1.05-1.75, P = 0.02). CONCLUSIONS: Despite having fewer comorbidities, patients with de novo HF-CS had more severe shock presentations and worse in-hospital outcomes. Whether HF disease chronicity is associated with time-dependent compensatory adaptations, unique pathobiological features and responses to treatment in patients presenting with HF-CS warrants further investigation.