Subgroup Of Patients Research Articles

Efficacy and safety of tildrakizumab in patients with early- vs late-onset psoriasis.

Age of psoriasis onset is bimodally distributed with distinct peaks at <40 (early onset) and ≥40 years (late onset). Although age of psoriasis onset is associated with distinct disease profiles, few well-controlled studies report efficacy of biologics in patients with early- vs late-onset disease. Efficacy and safety of tildrakizumab, an interleukin-23 p19 inhibitor, for the treatment of moderate-to-severe plaque psoriasis were investigated in the Phase 3 trials reSURFACE 1 and reSURFACE 2. To determine efficacy and safety of tildrakizumab in patients with early- vs late-onset psoriasis through 28 weeks of treatment. This was a post hoc subgroup analysis of patients from reSURFACE 1 and reSURFACE 2. Patients ≥50 years of age were grouped by age of psoriasis onset at <40 vs ≥40 years. Efficacy endpoints included absolute Psoriasis Area and Severity Index (PASI) and Dermatology Life Quality Index (DLQI), and proportions of patients who achieved a ≥75%/≥90%/100% improvement from baseline in PASI (PASI 75/90/100), Physician Global Assessment score of 0 or 1 (PGA 0/1), and DLQI of 0 or 1 (DLQI 0/1), adjusted for potential confounders. Safety was assessed from treatment-emergent adverse events (TEAEs). Higher percentages and adjusted responder rate estimates of patients with late- (n = 130) vs early-onset psoriasis (n = 111) achieved absolute PASI <1 (36.2% vs 27.9%; estimate, 32.2% vs 25.0%), PASI 90 (50.8% vs 39.6%; estimate, 49.4% vs 40.2%), and PASI 100 (21.5% vs 8.1%; estimate, 13.7% vs 7.9%) at Week 28 (all P <0.05). Age of onset did not significantly affect change from baseline in absolute PASI or DLQI, or achievement of PASI <5, PASI <3, PASI 75, DLQI 0/1, or PGA 0/1 (all P > 0.05). Efficacy findings were supported in a subset of patients matched by disease duration. Among patients with early- vs late-onset psoriasis, TEAEs and serious TEAEs occurred in 65.8% vs 66.2% and 3.6% vs 6.9%, respectively. Treatment with tildrakizumab was effective with no safety signals in both patient subgroups. Patients with late-onset psoriasis were more likely to achieve complete or near-complete clearance than were patients with early-onset psoriasis. NCT01722331 and NCT01729754.

Fundus autofluorescence lifetimes in age-related macular degeneration versus healthy controls in a pseudophakic population.

To check whether prolonged fundus autofluorescence (FAF) lifetimes in age-related macular degeneration (AMD) could be an artefact resulting from lens fluorescence. Fluorescence lifetime imaging ophthalmoscopy (FLIO) was performed in pseudophakic intermediate AMD as well as healthy controls. The median values of FAF lifetimes in the centre, the inner and the outer ring of the ETDRS grid, obtained as amplitude-weighted mean of the lifetimes from a three-exponential fit of the fluorescence decay over time in two spectral channels, as well as peak emission wavelengths (PEW) were compared between patients and controls. The age dependence of FAF lifetime was checked per group. In the patient cohort, FAF lifetimes of individuals with and without subretinal drusenoid deposits (SDD) were compared. Forty-four AMD patients (mean age 80.0 ± 6.0 years) and 26 controls (mean age 73.0 ± 10.2 years) were included. The FAF lifetimes of a subgroup of patients (N = 25, mean age 76.3 ± 5.6 years), age-matched to the controls, were significantly longer than those of the controls (all grid areas and spectral channels p < 0.001). FAF lifetimes increased with age in the controls (p = 0.006-0.03), but not in the patients. Patients with SDD had longer FAF lifetimes than those without (p = 0.003-0.068). PEW neither showed significant group differences nor age dependence. Although long fluorescence lifetimes of the lens can affect FAF lifetime measurements, prolonged FAF lifetimes in AMD are specific to the disease and not a lens artefact as shown in pseudophakic eyes. The effect of AMD on the lifetimes outweighs that of age. Patients with SDD, who have a higher risk of AMD progression, also show longer FAF lifetimes.

A cross-sectional study of cardiac rehabilitation enrollment barriers in patients at risk for suboptimal outcomes from acute coronary syndrome

Purpose: Cardiac rehabilitation (CR) is an effective treatment to reduce the burden of cardiovascular disease (CVD) but is underutilized. This study characterized CR enrollment barriers and perceived physician endorsement of CR in patient subgroups at increased risk of poor outcomes. Materials and Methods: The association between sociodemographic and clinical characteristics and Cardiac Rehabilitation Barriers Scale (CRBS) item and subscale scores were examined using secondary data analysis of patients with acute coronary syndrome referred to, but not yet enrolled in, a 12-week CR program. Participants rated perceived strength of recommendation to attend CR on 1–5 scale. Results: The three most endorsed CRBS items were inclement weather, travel, and work responsibilities. Additional barriers (e.g. time constraints, already exercising, family responsibilities) emerged in certain patient subgroups. Perceived strength of physician endorsement was high in the overall sample. After statistical adjustment for confounds, depressed mood was positively associated with logistical (b = 0.05, p = 0.002), and comorbidity-related barriers (b = 0.02, p < 0.001). Female sex (b = 0.62, p = 0.004), higher body mass index (b = 0.05, p = 0.009), and diabetes (b = 1.08, p < 0.001), were associated with logistical barriers. Conclusions: Patients require individualized support to address CR enrollment barriers. Given their crucial role in supporting patients to access CR, nurses are well-positioned to identify and address CR barriers.

Effect of extended intravenous diclofenac infusions on brain tissue oxygenation in patients with acute brain injury

BackgroundFever is associated with worse outcomes in patients with acute brain injury. Diclofenac, a non-steroidal anti-inflammatory drug, is commonly used as antipyretic therapy. As evidence emerged that short diclofenac infusions (< 1 h) decrease brain tissue oxygen (PtO2) and cerebral perfusion pressure (CPP), clinical practice has shifted to extended infusions (12 h). The purpose of this study was to investigate the effects of extended diclofenac infusion for the treatment of fever on cerebral perfusion and tissue oxygenation after acute brain injury.ResultsWe conducted a retrospective study of prospectively collected data from a cohort of 18 patients with acute brain injury and PtO2 monitoring admitted between November 2018 and April 2024. The hour before and the 12 h during an extended diclofenac infusion were compared. Additionally, we compared the 12 h prior and 12 h during the diclofenac infusion. Cerebral autoregulation and metabolites obtained by microdialysis were assessed in a subgroup of patients. Thirty-nine interventions were analyzed. Core temperature decreased from 38.1°C in the hour before to 37.4 °C during an extended diclofenac infusion (p < 0.0001). ICP (11.0 vs 10.0 mmHg, p < 0.0001) and heart rate (84 vs. 77 bpm, p < 0.0001) decreased. CPP and PaCO2 did not vary significantly. PtO2 decreased from 23.1 mmHg (IQR 19.0–31.4) during fever peak to 21.7 mmHg (IQR 17.8–27.2) (p < 0.0001). Median PtO2 during the 12 h before diclofenac was 23.3 mmHg (IQR 18.9–30.5). In a multivariable analysis the effect of treatment was significantly influenced by heart rate and temperature (p < 0.0001).ConclusionsExtended diclofenac infusions for the treatment of fever in patients with acute brain injury achieve a clinically significant reduction in temperature but are associated with a small decrease in PtO2, even in the setting of maintained CPP.

Prognostic Effect of CEA Cut-Off in Patients with Resectable Colorectal Liver Metastases: A Meta-Analysis and Meta-Regression.

Although preoperative carcinoembryonic antigen (CEA) is a variable used in most prognostic scores assessing the outcome of patients with colorectal liver metastases (CRLM) undergoing resection, it is unclear what the optimal cut-off is or in which patient subgroups CEA is most relevant. The purpose of this study is to evaluate the prognostic effect of CEA in resected CRLM patients and to explore in which subgroups CEA is most closely associated with overall survival (OS). A systematic literature search was performed, selecting studies that evaluated a relationship between preoperative CEA and OS in patients undergoing CRLM radical surgery. A meta-analysis assessed the overall effect size of the relationship on the selected study cohorts, based on CEA cut-off. An evaluation of 21 baseline variables was performed to explore their possible effect on the relationship between CEA and OS. The study confirms a significant negative prognostic effect of increased CEA on OS (HR 1.46, CI 1.30-1.65), but heterogeneity among studies is significant. The effect is consistent for all CEA cut-offs, although the relationship tends to weaken in more recent studies for cut-offs < 10 ng/mL. Meta-regressions also suggest that the prognostic effect may be more pronounced in the elderly. In addition, the effect of CEA ≥ 20 ng/mL on OS appears significantly reduced in the subgroup with mutated RAS carcinoma. For patients with resectable CRLM, the CEA cut-off should be increased to 20 ng/mL, and evaluation in prospective studies of the more pronounced negative prognostic effect of preoperative CEA in the elderly and wild-type RAS CRLM patients is recommended.

Safety and Efficacy of Vadadustat for the Treatment of CKD-Related Anemia within and outside the United States.

Vadadustat's global clinical program was comprised of four noninferiority trials comparing vadadustat and darbepoetin alfa for CKD-related anemia: two in dialysis-dependent (DD)-CKD and two in non-dialysis-dependent (NDD)-CKD. While vadadustat met prespecified noninferiority criteria for hematological efficacy globally, it did not meet noninferiority criteria for cardiovascular safety in the NDD-CKD trials. The trials considered regional differences in treatment practices, including hemoglobin targets within (10-11 g/dL) and outside the US (10-12 g/dL). To examine region-specific outcomes, we performed prespecified analyses for US and non-US patient subgroups from the vadadustat global program. The primary safety end point was first occurrence of MACE (death from any cause, or nonfatal myocardial infarction or stroke). The primary efficacy end point was change in hemoglobin from baseline to average values during weeks 24-36. 4084/7399 (55%) randomized patients were enrolled in the US. In pooled analyses of all US patients, MACE risk was similar among vadadustat-treated and darbepoetin alfa-treated patients (hazard ratio [HR] 1.03; 95% CI 0.90-1.17). HRs were similar for US patients with DD-CKD (HR 1.00; 95% CI 0.84-1.18) and NDD-CKD (HR 1.06; 95% CI 0.87-1.29). In pooled analyses of non-US patients, MACE risk was numerically higher among vadadustat-treated patients (HR 1.12; 95% CI 0.94-1.33); the higher risk was primarily attributed to the NDD-CKD subgroup (HR 1.29; 95% CI 1.03-1.60). In the non-US DD-CKD subgroup, MACE risk was similar among vadadustat-treated and darbepoetin alfa-treated patients (HR 0.88; 95% CI 0.67-1.17). Changes in hemoglobin were similar among treatment groups in all regions, as were rates of treatment-emergent and serious adverse events. In patients with DD-CKD, safety (vis-à-vis MACE) and efficacy (vis-à-vis change in hemoglobin) of vadadustat and darbepoetin alfa were similar when stratified by region (US versus non-US). In US patients with NDD-CKD, safety and efficacy of vadadustat and darbepoetin alfa were similar.

Our Experience and Literature Update Regarding Concomitant Radiotherapy with CDK4/6 Inhibitors and Hormonal Therapy in Metastatic Breast Cancer

Background and Objectives: Standard treatment in metastatic breast cancer with positive estrogen receptors and negative HER2neu is represented by CDK4 inhibitors combined with aromatase inhibitors or fulvestrant. Palliative radiotherapy is indicated for symptoms or local–regional control. Multiple preclinical data suggest a potential synergistic effect when CDK4/6 inhibitors and radiotherapy are administered concurrently. We are trying to address some questions and/or to establish correlations within a subgroup of patients with unusual toxicities, the safety of combined treatments, the correlation with radiotherapy techniques and fractionation schemas. Also, we are aware that some organs at risk of a rapid turnover are more vulnerable to the occurrence of acute toxicities. Materials and Methods: This retrospective study includes 20 patients with metastatic breast cancer, treated with CDK4 inhibitors and radiotherapy on 29 disease sites; we followed the compliance and toxicities of combined treatments. Results: Regarding the recorded hematological toxicities, grade 1 associated with CDK4 inhibitors, occurring anterior radiotherapy was recorded; grade 2, leucopenia during radiotherapy presented in three cases without radiotherapy interrupting and leucopenia with neutropenia grade 3 presented in one case after pleural secondary lesion’s irradiation. Non-hematological grade 3 toxicities occurred in two cases: one case with grade 3 enteritis, at 2 weeks from bone metastases irradiation—iliac bone (in field toxicity) and one case with radiodermitis during radiotherapy on the breast and lymph node level, in the second week of external radiotherapy (RTE). Conclusions: In all analyzed cases, we obtained control of irradiated lesions. Secondary toxicities occurred only in irradiated areas. A close monitoring of patients during combined treatment must be considered and we are confident that in the future it will be possible to identify the subgroup of patients with a high risk of unusual toxicities occurring; additionally, we hope that using more conforming radiotherapy techniques minimizes the organ being at risk from radiation doses.

Real-World Survival Outcomes in First-Line Ibrutinib-Treated Patients with High-Risk CLL/SLL.

In patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL), high-risk cytogenetic features such as del(17p), del(11q), and unmutated immunoglobulin variable heavy chain (IGHV) may be associated with unfavorable outcomes. In this large retrospective cohort study, data from a nationwide electronic health record-derived deidentified database were analyzed to assess real-world overall survival (rwOS) among patients treated with first-line (IL) ibrutinib with and without high-risk cytogenetic features (i.e., del(17p), del(11q), unmutated IGHV). Inverse probability of treatment weighting was used to account for differences in patient characteristics between cohorts. Of the 1,242 patients included, 969 and 273 had high- and non-high-risk CLL/SLL, with a mean age of 70.0 and 70.8 years, and a median follow up of 32 and 31 months, respectively. Within the high-risk cohort, 32.9%, 36.7%, and 58.7% had the presence of del(17p), del(11q), and unmutated IGHV, respectively. Median rwOS was not reached for either cohort; the hazard ratio (HR; 95% confidence interval [CI]) comparing rwOS between the two cohorts was 1.09 (0.79, 1.51). In a sensitivity analysis where del(11q) was not part of the high-risk definition, similar results were found, with a HR (95% CI) of 1.19 (0.86, 1.64) and median rwOS not reached for either cohort. Similarly, among the subgroup of patients with Medicare coverage, the HR (95% CI) was 0.98 (0.63, 1.53), and median rwOS was not reached. In this real-world study using a large community healthcare dataset, there was no difference in rwOS between patients treated with 1L ibrutinib with and without high-risk cytogenetic features.

Comprehensive Safety Exposure-Response Analysis to Support Ritlecitinib Dose Selection.

Ritlecitinib is a kinase inhibitor drug recently approved for the treatment of alopecia areata (AA) in both adults and adolescents based on a single, combined Phase 2b/3 study. Various QD doses with and without a loading dose have been evaluated in the pivotal Phase 2b/3 study. Therefore, characterization of the ritlecitinib safety profile becomes important to help inform the dose selection within the single Phase 2b/3 trial in conjunction with efficacy analysis. The purpose of this study is to characterize the safety profile of ritlecitinib with comprehensive exposure-response (ER) analyses. The concentration-QTc model was developed using a scientific white paper model, indicating no evidence of ritlecitinib-induced QTc prolongation. The semi-mechanistic PK/PD model well described the longitudinal profile of lymphocytes, indicating ritlecitinib-induced decrease in lymphocytes was marginal and the incidence of Grade 3/4 lymphopenia was predicted to be small across the investigated dose range except for a slight increase in the loading dose regimen. The ritlecitinib-dependent increase in the incidence of infections and rash was successfully described by a Poisson regression model using time-weighted average concentration as an exposure metric, indicating that the dose-dependent increase in the incidence of AEs is not dose-proportionally large in the investigated dose range. Covariate analysis within each model indicated that the safety ER relationship of ritlecitinib is similar across all the patient subgroups and no unique safety risks associated with ritlecitinib are anticipated in adolescent patients. Therefore, this comprehensive safety ER analysis supported the selection of the ritlecitinib 50 mg non-loading dose regimen for AA patients including both adults and adolescents.

Diagnostic performance and safety for robotic-assisted bronchoscopy in pulmonary nodules: a systematic review and meta-analysis.

Diagnostic performance and safety for robotic-assisted bronchoscopy in pulmonary nodules: a systematic review and meta-analysis.

Impact of botulinum therapy on long-term control of cervical dystonia symptoms and patient satisfaction with treatment: results of the international prospective observational study INTEREST IN CD2 in Russian subgroup of patients

To evaluate effect of long-term BTA treatment on cervical dystonia (CD) symptoms control and patient satisfaction with botulinum therapy in real life setting. A total of 1050 patients took part in the international observational study INTEREST IN CD2, the analysis included data from 995 patients (overall population), of which 56 patients were enrolled In Russia. CD clinical assessment was performed at baseline and on the days of BTA injections using the TWSTRS scale and tremor component of the Tsui scale. Patient satisfaction with CD symptoms control was evaluated using 5-point Likert scale on the day of the visit (today satisfaction) and the highest level of satisfaction at any time since the last BTA injection (highest satisfaction). This article presents the results of the analysis of the Russian subgroup of patients in comparison with the overall study population. In 5 Russian investigational sites, 44 (78.6%) women and 12 (21.4%) men were enrolled in the study; the patients' mean age was 51.1±9.6 years, the mean duration of the disease was 7.3±5.6 years. The baseline characteristics of the Russian patients were comparable to the overall population, but severity of CD symptoms was numerically higher in the Russian subgroup: the mean TWSTRS severity scores were 17.4±5.0 and 15.9±5.7, respectively; segmental dystonia was observed more frequently (14.3% and 7.4% of patients), as well as shoulder elevation (73.2% and 50.5%) and jerk (21.4% and 9.6%). The vast majority of Russian patients (82.1%) received treatment with abobotulinumtoxin (Dysport). In the Russian subgroup, higher doses of Dysport (median doses 800.0 U and 500.0 U), larger number of targeted muscles (4.3±1.5 and 3.5±1.5) and injection points (11.7±5.5 and 8.1±5.0) were used compared to the overall population. In the Russian subgroup, the mean TWSTRS total score (assessed at the end of each injection cycle) decreased from 32.3±11.2 to 25.2±15.7 over the 3 years follow-up; there was also decrease in severity score from 17.4±5.0 to 12.6±7.5 and disability score from 9.8±4.0 to 7.4±4.8, comparable to the overall population. Patients' satisfaction with CD symptoms control at peak of the BTA injection effect increased from 92.5% to 98.1% and was higher than in the overall population. At the end of the treatment cycle, patients' satisfaction was consistently lower than at peak effect. The results of the Russian subgroup analysis showed a high level of long-term effectiveness of botulinum therapy in controlling CD symptoms and patients' satisfaction with treatment in real clinical practice. Dysport is the most frequently used BTA preparation In Russia, the optimal level of effectiveness with repeated injections of Dysport remains stable and is maintained within the framework of real-life practice, which supports the clinical guidelines recommendations of its use as the drug of choice in the treatment of patients with CD.

Comparative Assessment of Quality of Life in Hip Fracture Patients Before and After Surgery: A Prospective Longitudinal Observational Study

Background and Objectives: Hip fractures are a leading cause of morbidity in the elderly, often resulting in declining physical function, psychological distress, and diminished quality of life (QoL). This study aimed to evaluate changes in QoL among hip fracture patients preoperatively and postoperatively, comparing diverse patient subgroups to identify factors influencing recovery. Methods: We conducted a prospective longitudinal observational study at Victor Babeș University of Medicine and Pharmacy Timișoara, recruiting 77 adult patients admitted for surgical management of hip fractures between March 2023 and March 2025. Standardized questionnaires, including the Short Form-36 (SF-36), World Health Organization Quality of Life (WHOQOL-BREF), Hospital Anxiety and Depression Scale (HADS), and Generalized Anxiety Disorder-7 (GAD-7), were administered preoperatively and at 3 months postoperatively. Demographic, clinical, and surgical variables were also recorded. Results: Participants’ mean age was 72.6 years (SD 8.1), with 57.1% female. Postoperative QoL scores (SF-36 Physical Function domain mean 52.7 ± 9.2) improved significantly compared to preoperative scores (44.8 ± 8.7, p = 0.012). WHOQOL-BREF physical and psychological domain scores similarly increased (p &lt; 0.05). Anxiety and depression symptoms, as measured by HADS and GAD-7, decreased markedly postoperatively in most subgroups. Subgroup analyses revealed that patients undergoing total hip arthroplasty demonstrated more pronounced QoL improvements than those receiving partial hip replacement. Older patients (≥80 years) exhibited improvements but at a slower rate. Conclusions: Quality of life indicators show notable improvement following surgical treatment of hip fractures, underscoring the significance of timely orthopedic intervention and comprehensive perioperative care. Anxiety and depression levels also declined, highlighting the benefits of a structured follow-up. These findings may guide clinicians toward optimizing patient-centered recovery protocols and targeted interventions, particularly for older adults or those with high baseline anxiety and depression levels.

Seizures influence sleep macrostructure and the sleep-wake circadian rhythm in Dravet syndrome.

Dravet syndrome (DS) is a developmental and epileptic encephalopathy with a wide spectrum of comorbidities comprising sleep disorders, reported in up to 85% of cases. For this, a sleep study is recommended in patients with a sleep complaint. However, no data are available on sleep architecture in DS or on the impact of seizures on sleep quality and macrostructure. We aim to investigate the impact of epileptic phenomena on sleep in DS. In this study, we report seizure type and frequency, seizures during sleep, and concomitant antiseizure medications (ASMs) of 30 patients with clinical diagnosis of DS and confirmed SCN1A pathogenic variant. We obtained 62 whole-night polygraphic sleep recordings (PSGs) and analyzed sleep stages duration, number of arousal events (AEs), arousal index (AI), and number and number/hour of AEs preceded by interictal epileptiform discharges (IEDs; IED-related arousals [IRAs]). In a subgroup of patients, actigraphic recordings and caregiver-reported Sleep Disturbance Scale for Children (SDSC) questionnaires were collected. Mean age at PSG was 9.9 years (range = 1.2-20.8). Mean sleep efficiency was 92.9%, mean AI was 4.2, and the mean IRA index was .5. Patients with tonic seizures during sleep had shorter rapid eye movement sleep duration (p < .05), and those with convulsive seizures during sleep had shorter N3 duration (p < .05). Higher IRA index was also associated with lower total N3 duration (p < .05). In the recordings obtained during treatment with fenfluramine, IRAs were absent (p < .05) or less abundant (p < .05). The actigraphy parameters showed unstable sleep and correlated with PSG-derived data. Our study shows a significant effect of epileptic phenomena on sleep macrostructure in DS. Motor seizures and IEDs influence slow wave sleep, which could be one of the mechanisms that sustain encephalopathy in DS. Interestingly, fenfluramine seems to have a protective effect on this mechanism, both by stabilizing sleep and as an ASM.

Associations between triglyceride-glucose body mass index and all-cause mortality in ICU patients with sepsis and acute heart failure

BackgroundThe triglyceride‒glucose body mass index (TyG-BMI) has been recognized as a significant predictor of cardiovascular disease risk and plays a crucial role in assessing insulin resistance. However, the correlation between the TyG-BMI and clinical outcomes in patients with sepsis and acute heart failure (AHF) has not been sufficiently explored. This study aimed to investigate the associations between TyG-BMI and clinical outcomes in patients with sepsis and AHF.MethodsWe conducted a retrospective analysis of ICU-admitted patients via data from the MIMIC-IV database. Multivariable logistic regression, sensitivity analysis, and restricted cubic spline (RCS) models were used to assess the relationship between TyG-BMI and all-cause mortality. K‒M survival analysis and Boruta analysis were employed to evaluate the predictive value of the TyG-BMI. Subgroup analyses considered the effects of age, sex, ethnicity, and comorbidities.ResultsAmong the 1,729 patients, a higher TyG-BMI was associated with lower all-cause mortality at 90 and 180 days. Each standard deviation increase in the TyG-BMI was linked to 0.2% and 0.3% reductions in 90-day and 180-day all-cause mortality, respectively. Kaplan‒Meier analysis revealed significantly lower all-cause mortality in patients with higher TyG-BMIs (P < 0.0001). The RCS model revealed a nonlinear relationship between the TyG-BMI and mortality. Boruta analysis identified the TyG-BMI as an important clinical feature. Sensitivity analyses revealed that the association remained significant after patients with myocardial infarction, malignancies, or missing data were excluded. The subgroup analysis revealed that for the 90-day and 180-day mortality rates, significant interactions were found only in the subgroup of patients with kidney diseases (P < 0.05).ConclusionThe TyG-BMI may have potential value in predicting mortality in ICU patients with sepsis and AHF, supporting early risk assessment and clinical intervention. This study provides critical insights into patient prognosis.

Automated Cell Counting in CSF Diagnostics Revisited—Friend or Foe?

Background/Objectives: The gold standard for cerebrospinal fluid leukocyte counting is manual counting in a Fuchs–Rosenthal chamber. Recent advances in automated body-fluid-counting systems, offering a time- and labor-saving solution, are challenging this dogma. Yet, the equivalence of diagnostic accuracy is still debated in the community. Methods: We compared manual and automated cell counting of cerebrospinal fluid samples of lumbar punctures and extraventricular drains with both low and high leukocyte counts, shedding light on the variability of results between man and machine. Results: Automated and manual cell counting showed a strong correlation across all samples, particularly in the subgroup of patients with fewer than 20 cells/µl, where outliers could become especially clinically relevant. Conclusions: We found the automated counting system to be highly accurate and not lacking in diagnostic sensitivity even at low cell counts, making it a powerful tool when used in the right clinical setting.

Partial arterial carbon dioxide and oxygen pressure in patients with cardiogenic shock.

In patients with acute cardiovascular diseases, hypocapnia, hypoxia and hyperoxiaare known to be associated with increased mortality. This monocentric prospective registry study included 238 consecutive patients with cardiogenic shock (CS). The study aimed to assess the prognostic impact of partial arterial carbon dioxide (PaCO2) and oxygen pressure (PaO2) on 30-day all-cause mortality. Statistical analyses included t-tests, Spearman´s correlation, Kaplan-Meier and Cox regression analyses. No difference was found between quartiles of PaCO2 (log-rank p = 0.416) and PaO2 (log-rank p = 0.946) in the entire cohort. In the subgroup of patients with ventilation on admission, patients with PaCO2 ≤ 33mmHg showed the highest 30-day all-cause mortality compared to the other quartiles (82.6% vs. 46.9% vs. 54.0% vs. 59.6% log-rank p = 0.026). No differences were found between levels of PaO2, when stratified by quartiles (log-rank p = 0.895). After differentiation between patients with PaCO2 ≤ 33mmHg and PaCO2 > 33mmHg the association with 30-day all-cause mortality remained significant (82.6% vs. 54.5% log-rank p = 0.006) in ventilated patients, whereas still no difference could be seen in the entire cohort (log-rank p = 0.264). Even after multivariable adjustment PaCO2 ≤ 33mmHg remained an independent risk factor for 30-day all-cause mortality (HR 1.936; 95% CI 1.131-3.316; p = 0.016) in ventilated CS-patients. In conclusion, no association was found between different levels of PaCO2 and PaO2 with 30-day all-cause mortalityin patients with CS. However, in the subgroup of CS-patients requiring ventilation, PaCO2 ≤ 33mmHg was associated with an increased 30-day all-cause mortality.

Latent Profile Analysis of Symptom Clusters in Children and Adolescents With Malignant Tumors During Radiotherapy.

Children undergoing treatment for cancer may experience a range of adverse symptoms, yet there is limited information on the symptoms they experience during radiotherapy and the potential heterogeneity among these symptoms. This study aimed to describe the symptom profiles of children during radiotherapy, identify subgroups of children with cancer experiencing similar symptom patterns, and evaluate differences in demographic and clinical characteristics across these subgroups. A total of 154 children were assessed using the Chinese version of the Memorial Symptom Assessment Scale 10-18. Latent profile analysis was used to identify distinct subgroups of patients based on symptom occurrence profiles with a prevalence greater than 40%. Children experienced multiple adverse symptoms during radiotherapy. The best-fitting model identified 3 distinct symptom profiles: low symptom prevalence, high symptom prevalence, and high gastrointestinal symptom prevalence. Significant differences were observed among subgroups based on age, family income, demographic factors, and clinical characteristics, including treatment type, the number of patients currently receiving radiotherapy, radiotherapy site, and recent chemotherapy within the past week. This study found that children experienced various adverse symptoms during radiotherapy, with notable heterogeneity in symptom profiles identified through latent profile analysis. Symptom prevalence varied according to demographic and clinical characteristics. This study highlights the need for healthcare providers to focus on different patient subgroups and provide targeted prevention and early intervention strategies for managing symptoms in children during radiotherapy.

AGE DISPARITY IN COUPLES AND THE SEXUAL AND GENERAL HEALTH OF THE MALE PARTNER

AGE DISPARITY IN COUPLES AND THE SEXUAL AND GENERAL HEALTH OF THE MALE PARTNER

Functional immune profiling of hyper- and hypo-inflammatory subphenotypes of critical illness: a secondary analysis

IntroductionRecent studies of adult sepsis patients demonstrate the existence of two subphenotypes that differ in risk of mortality: a hyper-inflammatory subphenotype with a high risk of mortality, and a hypo-inflammatory or “not hyper-inflamed” subphenotype with a relatively lower risk of mortality. We recently investigated the association of organ dysfunction with ex vivo immune profiling in sixty (60) critically ill adult patients with sepsis. In this secondary analysis we measured cytokine biomarkers with an automated, microfluidic immunoassay device (Ella™) and sought to investigate the functional immune profiles of patients in the hyper/hypo-inflammatory subphenotype groups.MethodsSubjects were consecutively identified adults, older than 18 years, and enrolled within 48 hours of sepsis onset. Whole blood cytokine analysis was performed in all patients. Additionally, ex vivo cytokine production was measured following 4h of stimulation. Cytokine concentrations were measured using the Ella™ automated immunoassay system.ResultsSubjects were divided into hypo-inflammatory (42 patients) and hyper-inflammatory (18 patients) subtypes using a previously validated parsimonious model based on concentrations of IL-6, TNFR1 and bicarbonate. The hyper- and hypo-inflammatory clusters demonstrated a near four-fold difference in 30-day mortality (44.4% vs 11.9%, p=0.0046). Following 4h of ex vivo stimulation with LPS, TNF production was lower in the hyper-inflammatory group as compared with the hypo-inflammatory group (p=0.0159). Ex vivo phorbol 12-myristate 13-acetate (PMA)-stimulated IFN-γ production (4h) by whole blood did not differ between groups.ConclusionsThese data further validate the use of IL-6, TNFR1 and bicarbonate to discern inflammatory sub-groups of patients with critical illness. They also confirm the observation that the presence of the hyper-inflammatory subphenotype is often accompanied by a compensatory anti-inflammatory response syndrome. Future investigations should focus on prospective validation of this panel for prognostic enrichment of clinical research studies.

Effectiveness and Safety of Respiratory Syncytial Virus Vaccine for US Adults Aged 60 Years or Older

ImportanceRespiratory syncytial virus (RSV) is associated with hospitalization and death among older adults. Characterizing the safety and effectiveness of recently introduced vaccines against RSV is critical.ObjectiveTo assess the safety and effectiveness of vaccines against RSV and the major adverse events among patients aged 60 years or older during the 2023-2024 RSV season.Design, Setting, and ParticipantsIn this study using a data platform containing electronic health records for more than 270 million patients across the US, a test-negative case-control design was used to estimate vaccine effectiveness (VE), and a self-controlled case series of vaccine recipients was included to estimate vaccine-associated adverse events. Records from participants aged 60 years or older with acute respiratory infection (ARI) and testing for RSV between October 1, 2023, and April 30, 2024, were included in the VE study. For vaccine safety analysis, all participants aged 60 years or older who received the RSV vaccine from July 1, 2023, to June 30, 2024 were included. Data were analyzed from August 2024 to March 2025.Main Outcomes and MeasuresCases were those patients who tested positive for RSV, and controls were those who tested negative for RSV. Patients were classified as vaccinated if the vaccine was received at least 14 days before testing. VE against RSV-associated ARI diagnosis, emergency department or urgent care visits, or hospitalizations was estimated using (1 − odds ratio) × 100%. Excess risks of immune thrombocytopenic purpura and Guillain-Barré syndrome diagnosis for 6 weeks after vaccine administration were calculated.ResultsOf 787 822 patients tested for RSV, 53 963 were positive (733 859 were controls); 1318 cases (2.4%) and 66 928 controls (9.1%) were vaccinated. Overall, VE was 75.1% (95% CI, 73.6%-76.4%) against ARI and was similar for age groups of 60 to 74 years and 75 years or older and against urgent care visits or hospitalizations. Immunocompromised patients had a VE from 67.0% (95% CI, 62.6%-70.9%) for patients aged 60 to 74 years to 73.1% (95% CI, 69.9%-76.0%) for those aged 75 years or older, and the lowest VE (ie, from 29.4% [95% CI, 3.5%-48.4%] for patients aged 60-74 years to 44.4% [95% CI, 1.0%-68.8%] for those aged ≥75 years) was for a subgroup of patients who received stem cell transplants. Among 4 746 518 vaccine recipients, no excess risk of immune thrombocytopenic purpura diagnosis was detected. An excess of 5.2 cases (RSVPreF3+AS01) or 18.2 cases (RSVPreF) of Guillain-Barré syndrome were diagnosed per 1 000 000 doses of RSV vaccine administered.Conclusions and RelevanceVE for the RSV protein subunit vaccine in this case-control study was similar to the VE in clinical trials. The VE for immunocompromised patients was mildly (overall) to moderately (for stem cell transplant recipients) diminished. Risk of immune thrombocytopenic purpura after vaccination was not elevated, but the risk of Guilain-Barré syndrome was statistically significantly elevated in patients who received the RSVPreF vaccine but not in those who received RSVPreF+AS01 vaccine, although the risk was small. These observations should inform clinicians’ choices and patient instructions.