We aimed to assess markers and risk factors for imminent acute kidney injury (AKI) in emergency patients, as risk stratification in the emergency department is currently not widely used. Using data from a sub-cohort (440 patients) of the prospective multicentre LifePOC study (1434 patients), proenkephalin A 119-159 (penKid) was assessed for early identification of subclinical kidney damage compared to serum creatinine in emergency patients with a qSOFA score ≥1. Logistic regression was applied to assess the usefulness of penKid, four further biomarkers (midregional pro-adrenomedullin, bioactive adrenomedullin, dipeptidyl-peptidase-3, procalcitonin) and clinical risk factors to predict AKI within 24 h, 48 h and 72 h after admission, need for organ support and 28-day mortality. PenKid and bio-adrenomedullin performed moderately to predict AKI within 48 h (AUC 0.645, 95% CI: 0.582-0.703 and AUC 0.647, 95% CI: 0.583-0.707, respectively). Pre-existing chronic kidney disease (OR 2.36, 95% CI: 1.06-5.27), confirmed sepsis (OR 2.41, 95% CI: 1.28-4.56), mechanical ventilation (OR 3.03, 95% CI: 1.48-6.19), and elevated levels of penKid (OR 2.21, 95% CI: 1.60-3.07) at admission were associated with an increased risk of AKI whereas a restrictive fluid management (OR 0.43, 95% CI: 0.26-0.71) was associated with a lower risk of AKI. Patients at high AKI risk may be identified based on specific risk factors, bio-ADM and penKid. The trial was registered in the German Registry for Clinical Trials (DRKS00011188) on 20 October 2016.

The randomised SIRONA trial showed that sirolimus-coated balloon (SCB) angioplasty was non-inferior to paclitaxel-coated balloon angioplasty (PCB) regarding femoropopliteal primary patency. There was no difference in clinically driven target lesion revascularisation (cdTLR) rates between the treatment groups. This post-hoc analysis aimed to assess whether the overall results were consistent across different subgroups and selected post-baseline factors. Primary patency at 12 months was assessed using duplex ultrasound and adjudicated by a core laboratory for 203 and 199 participants in the SCB and PCB groups, respectively (available-case intention-to-treat analysis). Data on 12-month cdTLR were available for 238 and 244 participants in the SCB and PCB groups, respectively. Odds ratios (ORs) for primary patency and hazard ratios (HRs) for cdTLR after SCB compared to PCB in non-pre-specified subgroups were assessed using generalised linear mixed models to control for centre effects, and Cox proportional hazards models, respectively. Primary patency and cdTLR were generally consistent across the analysed subgroups. Two nominal interaction signals were observed. For cdTLR, a nominal interaction with age was identified (interaction p = 0.047); among participants older than 70 years, the estimated hazard ratio favoured SCB (HR 0.52, 95 https://clinicaltrials.gov/study/NCT4475783 .

BACKGROUND:Paclitaxel-coated balloon (PCB) angioplasty is effective for femoropopliteal interventions. However, the increased mortality risk associated with PCB has not yet been cleared, and alternative antiproliferative drugs may offer additional advantages. OBJECTIVES:The authors aimed to investigate whether sirolimus-coated balloon (SCB) angioplasty achieves noninferior primary vessel patency and clinical efficacy and safety compared with PCB angioplasty. METHODS:SIRONA is a multicenter randomized, controlled, noninferiority trial comparing SCB with PCB angioplasty in patients with symptomatic femoropopliteal artery disease. The study was conducted at 25 centers in Germany and Austria. Patients aged 18 years or older with a single target lesion were randomized 1:1 using permuted blocks, stratified by center. Participants and outcome assessors were masked to allocation. Primary endpoints were primary patency and the composite clinical endpoint of freedom from clinically driven target vessel revascularization, major target limb amputation, and device- or procedure-related death at 12 months based on available case intention-to-treat analysis. Prespecified noninferiority margins were 10%. Long-term follow-up is ongoing. RESULTS:Between April 21, 2021, and September 23, 2022, 482 patients were assigned to SCB (n = 238) or PCB (n = 244) groups. The mean age was 68.0 ± 8.9 years; 311 participants (64.5%) were male; and 464 participants (96.3%) presented with intermittent claudication. Mean lesion length was 8.4 ± 6.1 cm and 160 lesions (33.2%) were chronic total occlusions. Primary patency was achieved in 150 of 203 participants (73.9%) with SCBs and in 149 of 199 participants (74.9%) with PCBs (risk difference: -1.0%; 95% CI: -9.6% to 7.6%; Pnoninferiority = 0.019). However, sensitivity analyses revealed that noninferiority was achieved but statistically not robust. The primary clinical endpoint was achieved in 199 of 220 participants (90.5%) with SCBs and in 202 of 218 participants (92.7%) with PCBs (risk difference: -2.2% (95% CI: -7.7% to 3.2%.); Pnoninferiority = 0.003). These results were confirmed by sensitivity analyses. CONCLUSIONS:Among patients with femoropopliteal artery disease, SCBs demonstrated noninferior clinical important outcomes and comparable improvement in vascular quality of life compared with PCBs. Although the noninferiority of primary patency was not statistically robust, this suggests that SCBs may be a valuable alternative to PCBs. (Sirolimus- vs Paclitaxel-Drug Coated Balloons in Patients With Peripheral Artery Disease [SIRONA]; NCT04475783]; Head-to-Head Comparison of Sirolimus vs Paclitaxel Drug-Eluting Balloon Angioplasty in the Femoropopliteal Artery [SIRONA]; DRKS00022452).

BACKGROUND:Drug-coated balloons improve outcomes after femoropopliteal angioplasty, but concerns regarding the long-term safety of paclitaxel-coated devices have prompted interest in alternative antiproliferative strategies. OBJECTIVES:This study sought to evaluate the 2-year patient-centered and clinical outcomes of sirolimus-coated balloon (SCB) versus paclitaxel-coated balloon (PCB) angioplasty. METHODS:SIRONA was a prospective, multicenter, randomized, controlled, noninferiority trial comparing SCB with PCB angioplasty in patients with femoropopliteal artery disease (96.5% intermittent claudication). The present analysis reports prespecified outcomes at 2 years. Effectiveness endpoints included patient-reported outcomes (VascuQol, clinical improvement, and EQ-5D-3L), primary patency, and freedom from clinically driven target lesion revascularization. Safety endpoints included major amputation and all-cause mortality. Longer-term follow-up is ongoing to assess durability and safety up to 5 years. RESULTS:A total of 482 patients was randomized (SCB: n = 238; PCB: n = 244). Improvements in vascular quality of life were sustained through 2 years and were similar between groups (between-group difference: 0.05, 95% CI: -0.15 to 0.24; P = 0.63). Clinical improvement (≥1 Rutherford category) occurred in 88% of the SCB group and 89% of the PCB group (P = 0.89). Kaplan-Meier estimates of primary patency were 64.6% for SCB and 67.2% for PCB (log-rank P = 0.34). Freedom from clinically driven target lesion revascularization was 91.2% for SCB and 88.1% for PCB (log-rank P = 0.42). Major amputation was rare (0.4% in both groups). All-cause mortality occurred in 6.3% and 3.7%, respectively (P = 0.21), with no device- or procedure-related deaths. CONCLUSIONS:SCB angioplasty resulted in sustained patient-reported and clinical outcomes comparable to PCB angioplasty through 2 years, with similar patency, revascularization, and safety.

Abstract Background Sepsis-associated acute kidney injury (SA-AKI) frequently progresses to acute kidney disease (AKD) and is linked to poor outcomes. We evaluated whether combining biomarkers reflecting complementary pathophysiological domains—histone H3.1 nucleosomes (cellular injury), midregional pro-adrenomedullin (MR-proADM; endothelial dysfunction), and kinetic estimated glomerular filtration rate (kinetic eGFR; dynamic renal function)—improves prediction of AKD and renal recovery. Methods This secondary analysis of the multicentre randomized SISPCT trial included 690 patients with sepsis after exclusion of patients with pre-existing renal replacement therapy or missing AKI data. Biomarkers and kinetic eGFR were assessed at baseline, day 2, and day 7. Multivariable logistic regression models adjusted for age, sex, and non-renal SOFA score were used to assess associations with AKD. Predictive performance was evaluated using receiver operating characteristic (ROC) curves and area under the curve (AUC). Calibration for the combined models for each day was evaluated using bootstrap-corrected calibration plots. Clinical utility was assessed using decision curve analysis with fivefold cross-validation. Results AKD occurred in 196 patients (28.4%). At baseline, only MR-proADM was independently associated with AKD (adjusted OR 1.17, 95% CI 1.08–1.28; p < 0.001), whereas H3.1 and kinetic eGFR were not. At day 2 and day 7, only changes in kinetic eGFR were independently associated with AKD (both p < 0.001). Discriminative performance increased over time, with AUCs for the combined model of 0.65 at baseline, 0.70 at day 2, and 0.76 at day 7. At later time points, kinetic eGFR consistently showed the highest discriminative performance based on the point estimates of the AUC. An overall good calibration performance was shown. Decision curve analysis demonstrated only modest and inconsistent additional clinical net benefit of the combined model compared with kinetic eGFR alone. AKD was associated with increased 90-day mortality (55% vs. 24%; risk ratio 2.3, 95% CI 1.9–2.9). Biomarkers showed limited and inconsistent performance for prediction of renal recovery. Conclusions In patients with sepsis, MR-proADM at baseline and dynamic changes in kinetic eGFR during the first week were independently associated with AKD, whereas histone H3.1 nucleosomes provided limited predictive value. Although multimarker models seemed to modestly improve baseline discrimination, this advantage was not sustained over time and added little clinical benefit beyond kinetic eGFR. These findings highlight the value of dynamic renal function assessment for risk stratification of SA-AKI progression to AKD. Trial registration ClinicalTrials.gov Identifier: NCT00832039.

ABSTRACT Invasive Candida infection (ICI) is the most common fungal infection in critically ill patients. This study analyzed the performance of various biomarkers in sera from the CandiSep trial, a randomized, multicenter trial including 342 sepsis patients at high risk for ICI across 18 German intensive care units. ICI and candidemia were diagnosed in 48 (14.0%) and 14 (4.1%) patients, respectively. Sera collected on 2 consecutive days at sepsis onset were analyzed for β-(1→3)-D-glucan (BDG; Fungitell), mannan (Platelia-Candida-Ag-Plus [Platelia-Mn] and Serion-ELISA-antigen-Candida [Serion-Mn]), and anti-Candida antibodies (Platelia-Candida-Ab-Plus, Serion-ELISA-Candida albicans-IgA/IgM/IgG, and Virclia-Candida albicans-germ-tube-antibody-IgG-Monotest). Only antigen levels (BDG, Platelia-Mn, Serion-Mn), but not anti-Candida antibody levels, were significantly elevated in ICI patients. Antigen levels were unaffected by Candida colonization, while antibody levels were significantly increased. Sensitivity and specificity at the manufacturer’s cutoffs were unsatisfactory. Performance improved by adjusting cutoffs: BDG required a 3-fold increase, while all others required lowering. At 80% specificity, sensitivities (95% confidence intervals) for the diagnosis of ICI and candidemia were as follows: BDG (cutoff >280 pg/mL), 46% (31.4–60.8) and 64% (35.1–87.2); Platelia-Mn (cutoff >50 pg/mL), 38% (24.0–52.6) and 64% (35.1–87.2); Serion-Mn (cutoff >0.7 U/mL), 38% (24.0–52.6) and 50% (23.0–77.0), and below 28% and 43% for all antibody assays. Area under the receiver operating characteristic curve comparisons showed no significant differences between antigen assays. Combining biomarkers, either simultaneously or sequentially, offered no diagnostic advantage over single-biomarker use. In conclusion, anti-Candida antibody assays are likely influenced by colonization and have limited diagnostic utility. Antigen assays offer similar diagnostic value but require cutoff optimization. Combining biomarkers did not enhance diagnostic yield in our cohort.IMPORTANCEOur main findings based on our specific ICU cohort were as follows: (i) only Candida antigen levels, not anti-Candida antibody levels, were significantly elevated in ICI and candidemia. (ii) In patients without ICI, Candida colonization was not associated with altered antigen levels, but with elevated antibody levels. (iii) Sensitivity and specificity at the manufacturer’s cutoffs were unsatisfactory, and cutoffs should be significantly adjusted. Potential optimal cutoff values are proposed by us. (iv) The evaluated antigen assays demonstrated overall comparable diagnostic performance in this study. (v) Anti-Candida antibody assays did not provide a meaningful diagnostic contribution. (vi) The combination of biomarkers offered no diagnostic advantage over the use of individual biomarkers, neither simultaneously nor sequentially. Our results suggest that the use of a single Candida antigen test with a cohort-adapted cutoff value may be sufficient. Furthermore, avoiding biomarker combinations could potentially reduce healthcare costs. The clinical implications of these findings should be interpreted with caution, given the limited data with associated large confidence intervals for candidemia and the cohort-specific nature of the study. Our results should therefore be confirmed in larger studies and additionally with other patient groups.

BACKGROUND:Within the PAVA study, we investigated placenta-associated vascular aging in women 15 years after pregnancies complicated by preeclampsia and/or fetal growth restriction. During these pregnancies, blood pressure values >140/90 mmHg were considered to require treatment. Following evidence demonstrating improved pregnancy outcomes with tighter blood pressure control, updated German and international guidelines (International Society for the Study of Hypertension in Pregnancy, ISSHP) now recommend target values below 135/85 mmHg. To evaluate whether blood pressure levels during pregnancy are associated with long-term maternal cardiovascular health, we analyzed the impact of blood pressure control during pregnancy on cardiovascular risk profiles obtained in the PAVA follow-up study. METHODS:Between August 2019 and December 2022, 53 women were examined an average of 15 years after experiencing preeclampsia and/or fetal growth restriction. At the study visit, baseline data were collected, and a comprehensive clinical and functional assessment was performed. This analysis compared 35 women who were hypertensive at follow-up (blood pressure ≥140/90 mmHg and/or antihypertensive medication) with 18 normotensive participants (blood pressure <140/90 mmHg and no antihypertensive medication). Data on blood pressure levels during pregnancy were collected retrospectively from medical records. RESULTS:Blood pressure data during pregnancy were available for the second trimester in 15 women who later developed hypertension and 4 who remained normotensive, and for the third trimester in 19 and 14 participants, respectively. Data from the first trimester were not available. In group comparisons, systolic blood pressure in the second trimester and diastolic blood pressure in the third trimester were significantly higher in women who were hypertensive at follow-up (155 vs. 140 mmHg, p = 0.027; 96 vs. 87 mmHg, p = 0.026). In adjusted analyses, no statistically significant associations were observed; however, effect estimates suggested a potential association between blood pressure control during pregnancy and lower odds of later arterial hypertension (OR 0.22, 95% CI 0.03-1.53) and concentric remodeling (OR 0.37, 95% CI 0.03-4.29). CONCLUSIONS:These findings suggest that blood pressure levels during pregnancy may be associated with long-term maternal cardiovascular health. However, given the limited sample size and exploratory nature of the analysis, these results should be interpreted with caution and require confirmation in larger prospective studies.

Abstract Introduction Low health literacy (HL) can impair decision-making in emergencies. Extending our preceding adult study, this preregistered observational study examined whether parental HL affects accuracy of severity assessments in the pediatric emergency department (PED) and whether the validity of children’s self-reports is age dependent. Methods This single-center prospective cross-sectional study enrolled 182 pediatric patients and parents presenting to a German university hospital PED. Subjective and independent emergency condition severity assessments were obtained from patients, parents, and medical staff. Parental HL was measured using the 16-item European Health Literacy Survey questionnaire (HLS-EU-Q16). Reference standard severity assessment was retrospectively collected by specialists (retrospective chart-based chase assessment). Analyses compared assessment accuracy across three parental HL level groups (adequate, problematic, inadequate). Assessments were adjusted for covariates except for regression analyses, which we performed using unadjusted values. Results Parental HL showed no measurable effect on assessment accuracy, discrepancy or concordance with medical team’s evaluations. Children’s self-reported anxiety emerged as a stronger predictor of actual clinical severity than HL measurements, with this relationship becoming significant at 8 years of age. Children’s severity assessment (OR = 1.38 [1.20, 1.57], p < .001) and less distinctly anxiety (OR = 1.15, 95% CI [1.01, 1.31], p = .037) predicted severe outcome, while the interaction between age and anxiety (B = 0.071, SE = 0.031, p = .022) showed that anxiety becomes a reliable indicator at around early school age. Concordance with the team’s assessment likewise emerged at school age (ρ ≈ 0.30, p < .05). Direct children’s self-assessment provided clinically meaningful information across all HL groups. Nursing assessments remained the strongest predictor of severe outcomes (OR = 1.95, 95% CI [1.37, 2.67], p < .001), followed by physicians (OR = 1.62, 95% CI [1.20, 2.19], p < .001). Parents were in our study not able to predict severe outcome (p = .22). Parental underestimation relative to specialists was consistently linked to severe outcomes (26–33%), regardless of HL level. Conclusion Contrary to common assumptions, parental HL neither impaired nor improved recognition of pediatric emergency severity, and HL did not systematically shift discrepancy patterns. Instead, developmental maturity and professional observation are relevant for severity assessment. From early school age (7–8 years), children’s anxiety appears to provide an increasingly valid, dose-responsive signal of severity. Nurses’ assessments provided the highest predictive accuracy, underscoring their central role in triage. Age-appropriate use of pediatric patients’ self-assessments could further support risk stratification in the PED. Clinical trials registration This observational study was preregistered in the German Clinical Trials Register (DRKS): DRKS00034108, Registration Date: 30th January 2025.

Abstract Background The German Parkinson´s disease multimodal complex treatment (PD-MCT) is a structured multidisciplinary inpatient treatment for people with Parkinson’s disease (PwPD). However, data on its long-term effect are limited. Methods A monocentric, non-blinded, clinical trial with randomized allocation and six-month follow-up was conducted at the Department of Neurology of the Jena University Hospital. At total of 120 patients admitted for PD-MCT were allocated 1:1 to two predefined treatment durations (short: 7–13 days; long: 14–20 days) according to the German Operation and Procedure Classification System (OPS; code 8-97d). The primary outcome was change in the Movement Disorder Society sponsored revision of the unified Parkinson’s disease rating scale (MDS-UPDRS) part II after six months. Secondary outcomes included change in quality of life assessed by the Parkinson’s Disease Questionnaire 8 (PDQ-8) and the influence of treatment duration. Analyses were performed as-treated. Results In 93 PwPD, MDS-UPDRS II improved by 3 points (r = 0.435; p < 0.001), with 52.7% achieving a clinically relevant improvement. Improvement was associated with higher baseline MDS-UPDRS II (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.07–1.27; p < 0.001), lower Hoehn and Yahr stage (OR 0.29, 95% CI 0.09–0.97; p = 0.045), and fewer nonmotor symptoms (OR 0.88, 95% CI 0.77-1.00; p = 0.042) (x 2(3) = 14.94; p = 0.002; R 2 = 0.22). PDQ-8 improved by 8 points (r = 0.524; p < 0.001), with 58.1% showing clinically relevant improvement, which was associated with lower Hoehn and Yahr stage (OR 0.30, 95% CI 0.10–0.92; p = 0.035), and more depressive symptoms (OR 1.17, 95% CI 1.04–1.33; p = 0.012) (x 2(2) = 10.53; p = 0.005; R 2 = 0.15). Treatment duration had no significant influence on MDS-UPDRS II (p = 0.611, Eta² = 0.001) or PDQ-8 (p = 0.809, Eta² = 0.001). Conclusions PD-MCT is an effective multidisciplinary inpatient treatment with clinically relevant long-term effects up to six months. In clinical practice, the shorter treatment duration may be similarly effective in selected patients. Trial registration German Clinical Trials Register, DRKS00025225, registered 30 June 2021, https://drks.de/search/de/trial/DRKS00025225 .

Background: The AML60+ score has been proposed for risk stratification in intensively treated elderly patients with acute myeloid leukemia (AML) or high-risk myelodysplastic neoplasms (MDS). Its prognostic impact in patients treated with hypomethylating agents (HMA) is unknown. Methods: Patients ≥ 60 years of age diagnosed with AML or MDS/AML according to ICC2022 were eligible for this retrospective and multicenter chart review if they had received at least one cycle of HMA-based treatment. Results: A cohort of 142 patients was analyzed. During follow-up (median 8 months), 114 patients died. The molecular Prognostic Score (mPRS) was available for 121 patients, the European Leukemia Net (ELN) 2022 classification for 117 patients, and the AML60+ for 105 patients. According to AML60+, 33 patients (31.4%) were classified as very poor risk, 36 (34.3%) as poor risk, and 34 (32.4%) as intermediate risk. Two patients (1.9%) were classified as favorable. Median overall survival (OS) was 21.7 months (mo) for the combined intermediate/favorable group, 7 mo for the poor risk group and 3 mo for the very poor risk group (p < 0.0001). Cox regression analysis (reference category: very poor) showed a significantly lower risk of death for both intermediate/favorable risk patients (HR 0.17, 95% CI 0.10–0.31, p < 0.001) and poor risk patients (HR 0.47, 95% CI 0.28–0.78, p = 0.004). The concordance score was 0.67 for AML60+, 0.60 for mPRS, and 0.58 for ELN2022. Conclusions: The AML60+ may represent a useful prognostic tool for elderly AML patients treated with HMA-based therapies. In particular, it could help to identify a group with a relatively favorable prognosis that is not clearly identified by the ELN2022 or the mPRS risk classification. However, analyses of larger cohorts are necessary to confirm our findings.

OBJECTIVES:To evaluate whether simultaneous vaccination of the 13-valent pneumococcal conjugate vaccine (PCV13) and the 23-valent polysaccharide vaccine (PPSV23) elicits higher antigen-specific memory B cell responses compared to sequential (PCV13 followed by PPSV23 after 6 months) or single PPSV23 vaccination in elderly. METHODS:In this monocentric, randomized trial, vaccine-naïve adults aged ≥60 years were assigned 1:1:1 to a simultaneous, sequential or single vaccination group. The primary outcome was the change in memory B cells specific for four vaccine-serotypes (ST3, ST14, ST19A, and ST23F) at 27 to 28 weeks after first vaccine dose compared to baseline. Secondary outcomes assessed safety, serotype-specific immunoglobuin G geometric mean fold rise (GMFR) and memory B cells over a 24-month period. RESULTS:Total of 123 persons (41 per group, 65.2 ± 4.4 years, 61.8% females) were randomized. Among 118 evaluable persons, median changes (95% CI) in memory B cells relative to total B cells from baseline to week 27 to 28 were most pronounced for ST19A with 0.022% (0.002%-0.045%) in the simultaneous, 0.022% (-0.006% to 0.068%) in the sequential, and 0.005% (-0.004% to 0.054%) in the single group. There was no evidence of a significant difference in memory B cell responses across all four vaccine-serotypes induced by simultaneous when compared with sequential or single vaccination (e.g. Hodges-Lehmann [HL-] estimator for ST19A, -0.007% [95% CI, -0.038% to 0.021%] for simultaneous vs. sequential; 0.009% [95% CI, -0.017% to 0.036%] for simultaneous versus single), at primary endpoint. Six months after completing the full vaccination schedule, memory B cell response for ST19A was lower in simultaneous than sequential group (HL-estimator, -0.039%; 95% CI, -0.071% to -0.010%). At 24 months, sequential vaccination achieved higher immunoglobulin G against ST3 (GMFR 5.17) than simultaneous (GMFR 2.82) or single vaccination (GMFR 1.94). No serious adverse events occurred. CONCLUSION:Simultaneous vaccination did not elicit higher memory B cell responses compared to sequential or single vaccination. All approaches were safe.

BACKGROUND AND OBJECTIVES:To propose a multiparametric score for discrimination of grade 2/3 from grade 1 intracranial meningiomas (IMs) based on preoperative patient and MRI data. METHODS:A retrospective cohort (n = 463) was used to test patient (age and sex) and MRI characteristics (volume, edema, necrosis, cysts, contrast patterns, edge irregularity, location) to detect a significant correlation with grade 2/3 IMs using binary logistic regression analysis with Hosmer-Lemeshow-test. All IMs were classified according to the 2021 classification. Depending on the variables' strength of correlation, points were assigned based on rounded β-coefficient from binary logistic regression and tallied together to form a total score. A cutoff score was defined by the highest Youden-index. The score was validated in a prospective (n = 211) and DNA methylation-based classification cohort (n = 18). Area under the curve (AUC), sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were calculated. RESULTS:Six variables were significantly correlated with grade 2/3 IMs (edema, location at the convexity, volume >40 cm 3 , male sex, necrosis and cysts). By applying 1 point for male sex, edema, and cysts and 2 points for location at the convexity, volume ≥40 cm 3 , and necrosis, a cutoff value of 3 was identified for discrimination (91 grade 2/3; 372 grade 1 IMs [AUC = 0.791, sensitivity 76.9%, specificity 64.8%, PPV 34.8% and NPV 92%]). The cutoff value 3 was confirmed in the validation cohort (45 grade 2/3 and 166 grade 1 IMs [AUC 0.773, sensitivity 86%, specificity 60.7%, PPV 35.9%, and NPV 95.2%]) and in the DNA methylation-based classification (6 grade 2/3 and 12 grade 1 IMs [AUC 0.750, sensitivity 75%, specificity 83.3%, PPV 90%, and NPV 62.5%]). CONCLUSION:The MEN-CCVol score ( M ale, E dema, N ecrosis, C onvexity, C yst, Vol ume) provides a readily applicable discrimination tool to identify grade 2/3 IMs. It may guide patients' counseling, timing of surgery, and surgical strategy. Further validation using genetic and epigenetic markers is required.

Introduction:Functional decline is a common risk among hospitalized older adults. Comprehensive Geriatric Care (CGC) has been shown to improve clinical outcomes in this population. However, beneficial predictors are not fully known. Methods:This study was conducted at the Department of Geriatrics, University Hospital Jena, Germany. Data were collected from 2014 to 2023. Functional improvement was defined as a positive change in the Barthel Index from admission to discharge. Covariates included age, sex, body mass index (BMI), number of functional disabilities (Lachs screening), cognition, depressive symptoms, mobility, and treatment duration. Statistical analyses were conducted using binominal logistic regression to identify predictors of functional improvement. Results:Of 3,990 patients, functional improvement was observed in 85.2%, which was associated with female sex (OR = 1.352; p = .007), fewer functional disabilities (OR = 0.905; p = .007), better cognition (OR = 1.130; p < .001), better mobility (OR = 1.114; p < .001), lower Barthel Index at admission (OR = 0.964; p < .001), and longer treatment duration (OR = 1.987; p < .001; χ2(6) = 181.32, p < .001, Nagelkerke's R 2 = 0.104). No significant associations were found for age, BMI, or depressive symptoms. Conclusion:Most patients experienced a functional improvement during CGC. However, commonly used predictors explain only a small proportion of the variance, suggesting that additional biopsychosocial factors need to be explored to better predict outcomes after CGC.

AIMS:Studies using peripheral nerve ultrasound have shown moderate nerve enlargement in individuals with diabetic polyneuropathy (DPN). Neither extent, course, consistency, nor clinical significance of this finding is clear. METHOD:We examined 156 people with type 2 diabetes mellitus using nerve ultrasound, nerve conduction studies, and clinical scores. 59 received a follow-up examination after one year and 43 patients after two years. RESULTS:Increase of cross-sectional area (CSA) of the peripheral nerves in DPN was rather negligible compared to normative cut-off values. The CSA of the median nerve at the forearm and wrist and the ulnar nerve at the upper arm, forearm and wrist were significantly larger in individuals with DPN compared to those without DPN. People with DPN had significant changes in most parameters of nerve conduction studies. Ultrasound measurements over time showed a slight increase in CSA in the median nerve at the carpal tunnel and a slight decrease in the fibular nerve at the fibular head. Ultrasound pattern sum score slightly decreased in the DPN group over two years. CONCLUSIONS:Ultrasound measurements alone may be insufficient to detect DPN. Follow up with nerve ultrasound over one or two years was short and did not show substantial changes.

Introduction:Most adults in the United States and Europe have low health literacy (HL), which also has an impact on emergency care. It is unclear, whether low HL impairs the patients' ability to evaluate the seriousness of their emergency and if it increases patient-clinician disagreement. Methods:In this prospective cross-sectional study in a German tertiary-care emergency department (ED), 257 adults (median age = 55 y) self-assessed the severity of their condition on arrival; simultaneously, an ED nurse and physician provided independent assessments. Thirty days later, an expert panel reviewed each case and issued a specialist evaluation. HL was assessed with the 16-item European Health Literacy Survey (HLS-EU-Q16) and categorized as adequate (n = 95), problematic (n = 119), or inadequate (n = 43). Three discrepancy indices were computed from age-, gender-, and education-adjusted assessments. Spearman correlations and Kruskal-Wallis tests compared agreement across HL levels; linear and logistic regressions examined predictors of discrepancy and severe outcome. Results:Patients with adequate HL showed the strongest alignment with clinicians (ρ = 0.24), whereas correlations were weaker in the inadequate group (ρ = 0.18). Discrepancies decreased as HL improved (β = -0.12 to -0.19, p < 0.05), but HL alone explained only up to 7% of variance. Concordant assessments increased with rising HL. Overestimation was most prevalent at inadequate HL level. In multivariable logistic modeling, each one-point increase in the Patient to Medical Team discrepancy raised the odds of a severe outcome by 27% (OR = 1.27, 95% CI [1.04, 1.55]), whereas each additional HL score point lowered the odds by 13% (OR = 0.87, 95% CI [0.77, 0.99]). Conclusion:Lower HL modestly but consistently enlarges the gap between patients' and clinicians' emergency assessments and is associated to a higher likelihood of a severe outcome via this mismatch. Although adequate HL improves agreement, half of these patients still struggle to evaluate severity. Routine teach-back communication might be helpful to identify discrepancies. These findings underscore the need for healthcare professionals to assess patients without prejudice, regardless of presenting symptoms, to ensure optimal medical care. Trial registration:Identifier, DRKS00032962.

Janus kinase inhibitor (JAKi) monotherapy, the standard of care for myelofibrosis (MF), improves splenomegaly and symptom burden but provides limited depth and durability of response. There is a significant unmet need for new combination strategies that adequately address the underlying disease biology and further improve clinical outcomes in MF. Pelabresib (PELA) is an oral, small molecule inhibitor of bromodomain and extraterminal domain (BET) proteins and can act in a complementary manner with the JAK1/2 inhibitor ruxolitinib (RUX) by targeting inflammatory pathways that are regulated by BET-mediated gene expression. PELA+RUX is being investigated in MANIFEST-2 (NCT04603495) in patients (pts) with JAKi-naive MF. The study met its primary endpoint (Rampal RK. Nat Med. 2025). Here, updated 96-wk results from MANIFEST-2 are reported. MANIFEST-2 is a double-blind, randomized, Phase III study in pts with JAKi-naive MF. Pts were randomized 1:1 to PELA or placebo (PBO) once daily with RUX twice daily. Efficacy and safety endpoints were assessed at Wk 96, including ≥35% reduction in spleen volume (SVR35) response, total symptom score (TSS), hemoglobin (Hgb) response, safety, and survival outcomes. As of March 2, 2025, pts had been followed for at least 96 wks, with 56.5% (121/214) of pts in the PELA+RUX arm and 59.3% (128/216) in the PBO+RUX arm completing 96 wks of assigned treatment. With a median follow-up of 115.9 wks at the cutoff date, approximately half of pts were still on assigned treatment (48.6% in the PELA+RUX arm vs 48.1% in the PBO+RUX arm). Most common reasons for discontinuation were adverse events (AE; 21.0% vs 13.4%), physician decision (7.5% vs 14.8%), withdrawal of consent (10.3% vs 6.0%), and protocol-defined disease progression (5.1% vs 6.9%, respectively). At Wk 96, among evaluable pts on treatment, SVR35 response was observed in 91.5% (97/106) in the PELA+RUX arm vs 57.5% (65/113) in the PBO+RUX arm (difference, 34.0%), representing 45.3% (97/214) vs 30.1% (65/216) of the intent-to-treat population in each arm (difference, 15.2%), respectively, and showing sustained benefit in pts remaining on treatment. At Wk 96, absolute change in TSS from baseline was −15.07 in the PELA+RUX arm vs −12.48 in the PBO+RUX arm (difference, −2.59; 95% CI, −5.23 to 0.05); ≥50% reduction in TSS from baseline (TSS50) was achieved by 36.9% (79/214) and 28.2% (61/216) of pts, respectively, demonstrating durable responses in symptom improvement. At Wk 96, dual SVR35 and TSS50 responses were reported in 31.8% (68/214) vs 15.7% (34/216) of pts, respectively. Hgb response was achieved by 17.8% (38/214) vs 11.6% (25/216) of pts in the PELA+RUX vs PBO+RUX arms. By 96 wks from the start of treatment, red blood cell transfusions were required in 33.1% (44/133) vs 39.9% (57/143) of evaluable pts, respectively. Ongoing Wk 96 analyses of exploratory biomarker data, including the dynamics of variant allele frequencies of MF driver genes, will be presented. Treatment-emergent AEs were mainly low grade and remained similar between arms over time (PELA+RUX [n=212] vs PBO+RUX [n=214]: any grade, 99.5% vs 98.1%; Grade ≥3, 67.5% vs 70.1%). Externally and independently adjudicated leukemic transformations were reported in 5.1% (11/216) of pts on PELA+RUX and in 3.7% (8/214) of pts on PBO+RUX by the 96-wk data cutoff. A total of 28 deaths and 22 progression-free survival (PFS) events were reported in the PELA+RUX arm vs 32 deaths and 34 PFS events in the PBO+RUX arm (overall survival [OS] HR, 0.986; 95% CI, 0.590–1.647; PFS HR, 0.746; 95% CI, 0.432–1.291; not powered for OS/PFS). These results represent the longest follow-up to date of a randomized combination trial in MF. After at least 96 wks of follow-up, PELA+RUX continued to show deep and durable improvements in splenic response, TSS, SVR35/TSS50 dual response, and anemia vs PBO+RUX, with stable or improving response rates among pts remaining on long-term treatment. PELA+RUX had a similar safety profile to PBO+RUX. The early imbalance in leukemic transformation cases decreased over time, and the observed frequency was in line with what is historically seen in MF. Longer-term follow-up showed numerically fewer deaths and fewer progression events in the PELA+RUX arm vs the PBO+RUX arm. Overall findings suggest that PELA+RUX provides clinically meaningful benefits vs RUX monotherapy, with potential for disease modification and improving survival in pts with MF.