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Multidisciplinary mHealth Rehabilitation for Patients With Abdominal Cancer Who Are Receiving Chemoradiotherapy: Randomized Phase II Trial.

BACKGROUND: Concurrent chemoradiotherapy (CCRT) for abdominal cancer frequently induces muscle loss, weight loss, and malnutrition. OBJECTIVE: This exploratory randomized phase II trial evaluated whether a multidisciplinary, mobile health (mHealth)-based multimodal rehabilitation program could preserve handgrip strength and muscle mass in patients with abdominal cancer undergoing CCRT. METHODS: In this prospective, multicenter, randomized, open-label phase II trial (NCT05325554), 111 eligible patients with abdominal malignancies scheduled for CCRT were randomly assigned (1:1) to receive either multidisciplinary mHealth rehabilitation care (MRC; n=57) or standard care (SC; n=54). The MRC program was delivered by a dedicated multidisciplinary team using the AiNST mHealth platform and wearable heart rate monitors. The primary end point was handgrip strength at the end of CCRT (analyzed with analysis of covariance adjusting for baseline). Secondary end points were exploratory and analyzed without multiplicity adjustment; sensitivity analysis using false discovery rate (FDR) correction was performed. RESULTS: Between February 2022 and April 2023, 111 patients were enrolled. Adherence was high (n=93, 83.9% achieved exercise targets). After adjusting for baseline handgrip strength, the MRC group had significantly higher handgrip strength at the end of CCRT than the SC group (adjusted mean difference 4.87 kg, 95% CI 3.36-6.38; P<.001). Exploratory analyses of secondary end points (without multiplicity adjustment) showed that the MRC group also had better preservation of body weight (P=.005), skeletal muscle mass (P<.001), serum albumin (P=.009), prealbumin (P=.02), and lower rates of hematological toxicity (P<.05), as well as improved psychological status (distress thermometer [DT] and Hospital Anxiety and Depression Scale [HADS]) and nutritional scores (Nutritional Risk Screening 2002 [NRS-2002] and Patient-Generated Subjective Global Assessment [PG-SGA]) at the end of CCRT (all P<.05). All nominally significant secondary end points remained significant after FDR correction (q<.05). These findings are preliminary and should be interpreted with caution due to the open-label design, population heterogeneity, and exploratory secondary analyses. CONCLUSIONS: In this exploratory phase II trial, a multidisciplinary, mHealth-based multimodal rehabilitation program was associated with better preservation of handgrip strength, muscle mass, and nutritional status, as well as lower rates of certain treatment toxicities, compared with SC. However, definitive conclusions are limited by the open-label design, heterogeneity of tumor types, and short follow-up. Larger, blinded phase III trials are needed to confirm these findings.

Humans

Transcranial Motor Evoked Potential Monitoring Using Propofol-Fentanyl Versus Desflurane-Dexmedetomidine Anesthesia During Spinal Cord Tumor Resection: A Randomized Controlled Trial.

BACKGROUND: Patients undergoing resection of spinal cord tumours require intraoperative neuromonitoring. Transcranial electrical stimulation is used to record myogenic responses during surgery. This study aimed to compare the effect of 2 anaesthetic regimens, propofol/fentanyl versus desflurane/dexmedetomidine, on the ability to record MEPs with an amplitude of 50&#xa0;&#xb5;V or greater. Our secondary outcome compared intraoperative haemodynamics, recovery profile, and postoperative analgesia between the groups. METHODS: We conducted a prospective, double-blinded, open-label, single-centre, randomized controlled trial of 50 adult patients undergoing spinal cord tumour resection with TcmMEP monitoring. Patients were randomized to 2 groups: Group P (n=25) received intravenous anaesthesia with propofol and fentanyl; group D (n=25) received desflurane and dexmedetomidine. RESULTS: We recorded TcmMEP's in 80% of group P and 76% group D (95% CI: -23% to 31%, P =1.00). The time in minutes for spontaneous breathing (21.04&#xb1;11.31 vs. 8.00&#xb1;3.42 [8.29-,17.79, P =0.01]), extubation (31.56&#xb1;17.56 vs. 10.84&#xb1;3.99 [13.48-27.96; P =0.01]), emergence (33.68&#xb1;18.11 vs. 10.92&#xb1;4.01 [15.30-30.22, P =0.001]), discharge readiness (45.00&#xb1;25.24 vs. 15.56&#xb1;6.08 [19.00-39.88; P =0.001]) and requirement of first analgesia (136.6&#xb1;108.04 vs. 230.8&#xb1;81.33) (-148.58 to -39.82; P =0.01) was lower in group D compared with group P. Postoperative analgesia assessed using the Visual Analogue Score was lower in group D compared with group P at 12 and 24 hours. (1.68&#xb1;1.18 vs. 0.64&#xb1;1.31 [0.33-1.74 P =0.001]) :1.4&#xb1;0.95 vs. 0.36&#xb1; 0.70 (0.56-1.51; P =0.001). CONCLUSIONS: We found similar rates of successful TcMEP monitoring using desflurane-dexmedetomidine and propofol-fentanyl. Patients who received desflurane-dexmedetomidine had reduced emergence time, discharge readiness, and lower pain scores in the postoperative period.

Humans

Association of hydroxyurea use and sickle cell retinopathy: A systematic review and meta-analysis.

Hydroxyurea (HU) is prescribed to reduce systemic complications of sickle cell disease; however, its association with sickle cell retinopathy (SCR) remains unclear. This meta-analysis (PROSPERO: CRD420251079006) evaluates the pooled association between HU use and SCR. In the primary analysis, HU use was not associated with a statistically significant reduction in SCR (OR = 0.90, 95% CI [0.41, 1.97], p&#x202f;=&#x202f;0.79; I&#xb2; = 77%). In a prespecified leave-one-out analysis, exclusion of the outlier study did not produce a statistically significant association, although the estimate shifted toward a stronger protective effect with reduced heterogeneity (OR = 0.70, 95% CI [0.39, 1.27], p&#x202f;=&#x202f;0.25; I&#xb2; = 67%). In a subgroup analysis excluding high-risk-of-bias studies, HU use was also not associated with a statistically significant reduction in SCR (OR = 0.84, 95% CI [0.39, 1.82], p&#x202f;=&#x202f;0.66; I&#xb2; = 77%). In post hoc analyses, HU use was not associated with a statistically significant reduction in SCR in non-adult populations (OR = 1.14, 95% CI [0.43, 3.05], p&#x202f;=&#x202f;0.79; I&#xb2; = 81%) or genotype-restricted analyses (OR = 1.22, 95% CI [0.81, 1.84], p&#x202f;=&#x202f;0.35; I&#xb2; = 0%). In post hoc analyses restricting studies to retinopathy phenotype, however, HU was associated with statistically significant lower odds of non-proliferative SCR (OR = 0.73, 95% CI [0.54, 0.98], p&#x202f;=&#x202f;0.04; I&#xb2; = 0%) and proliferative SCR (OR = 0.24, 95% CI [0.09, 0.60], p&#x202f;=&#x202f;0.002; I&#xb2; = 12%). Very low-certainty evidence suggests mixed associations between HU and SCR. Prospective studies are needed to clarify its role in SCR prevention.

Humans

A Pilot Study: Developing a Lactating Dairy Goat Model to Study Staphylococcus aureus Mastitis in Women.

INTRODUCTION: Lactational mastitis is common in lactating women, with Staphylococcus aureus as the most commonly isolated agent associated with infectious lactational mastitis. Currently, there are no evidence-based guidelines for antimicrobial treatment due to barriers in obtaining pharmacokinetic data from lactating women. To overcome this barrier, a suitable large animal model is needed. Goats are an ideal translational model for human mastitis due to their anatomical and physiological similarity to humans. The objective of this pilot study was to assess if goats would develop clinical mastitis following intramammary inoculation with a clinical human isolate of S. aureus with the goal of establishing an alternative in&#xa0;vivo model for future research. The hypothesis was that the infected mammary gland half would show similar clinical signs to women with mastitis and demonstrate a similar local immune response when compared to the control mammary gland half. METHODS: One half of the mammary gland of two healthy lactating does was inoculated with a clinical human isolate of S. aureus. The other half of the mammary gland was sham inoculated with sterile buffered saline. Physical examinations, mammary gland assessments, and sterile milk samples were collected every 12 hours post inoculation. At 96 hours post inoculation, the goats were euthanized, and the mammary glands were examined for pathological changes. RESULTS: Goats did not develop systemic signs of disease following inoculation. Focal infected mammary gland changes included warmth, swelling, redness, discoloration, and reduced milk production; the other mammary gland half remained normal throughout the study period. S. aureus was enumerated from only the infected mammary gland half. The microscopic findings of the infected half showed neutrophilic inflammation and cell necrosis consistent with acute mastitis. DISCUSSION: This pilot study demonstrated lactating does can develop clinical signs like those observed in women. Goats have the potential to be a promising animal model to study infectious lactational mastitis.

Animals

Influence of Repeated-Sprint Bout Duration in Sprint Interval Training Intervention on Physical Performance Adaptations of Young Volleyball Players.

The objective of this study was to examine the effects of repeated-sprint training (RST) with varying bout durations on the physical fitness adaptations of young male volleyball players. Forty athletes were randomly allocated to one of three intervention groups performing RST with varying bout durations and similar repetition volumes, all executed at maximal effort. The 3-sec group (n = 10) completed two sets of 30 bouts, the 6-sec group (n = 10) performed two sets of 15 bouts, and the 9-sec group (n = 10) carried out two sets of 10 bouts, each adhering to a 1:3 work to rest ratio. An active control group (n = 10) engaged solely in regular volleyball training without the RST intervention. Physical fitness measures-including countermovement vertical jump (CMVJ), 10-m and 20-m linear sprints, T-test change-of-direction speed (T-CODS), reactive strength index (RSI), and the Wingate anaerobic power test-were assessed pre- and post-a 6-week training intervention (i.e., 18 sessions). All RST groups showed significant post-intervention improvements in physical fitness (main effect of time, p = 0.001), with greater adaptations compared with the control group and effect sizes ranging from small to very large. The 3-sec bout group demonstrated greater gains in CMVJ, 10-m and 20-m sprint performance, RSI, and peak power output compared with the 9-sec group (all, p < 0.05). Conversely, the 9-sec group exhibited superior adaptations in T-CODS and mean power output relative to the 3-sec group (all, p < 0.05). In conclusion, the 3-sec group experienced greater enhancements in explosive and sprint performances, while the 9-sec group showed superior gains in change of direction and mean power output. These findings indicate that manipulation of sprint-bout duration in RST can be used to optimize distinct performance adaptations in young volleyball players.

Humans

Smartphone apps for obesity management: A systematic review using self-determination theory.

BACKGROUND: While bariatric surgery and pharmacotherapy are effective treatments for obesity, ongoing supportive care remains a challenge. Smartphone applications (apps) may assist with symptom management, but their effectiveness and practical use in obesity treatment is unclear. This review evaluated the effectiveness, acceptability, and feasibility of these apps in supporting individuals following obesity treatment. To better understand how these apps may promote sustained engagement and behaviour change, their design was analysed using Self-Determination Theory (SDT). METHODS: A systematic search was conducted across MEDLINE, Embase, PsycINFO, CINAHL, Web of Science, SCOPUS, and CENTRAL databases. Eligible studies included randomised and non-randomised interventions involving adults (&#x2265;18&#xa0;years) with obesity (BMI&#xa0;&#x2265;&#xa0;30&#xa0;kg/m2) who had undergone bariatric surgery or pharmacotherapy. Interventions had to include an app designed to support post-treatment symptom management. Findings were synthesised narratively, and app features were mapped to SDT constructs of autonomy, competence, and relatedness. RESULTS: Five studies (three RCTs, two cohort studies) involving 1,133 participants were included (female: 78&#xa0;%; median age: 47.63&#xa0;years). Most apps targeted post-bariatric surgery care; only one focused on pharmacotherapy. Common features included tracking, reminders, and education, supporting autonomy and competence. Relatedness features such as communication and peer support were least represented. Two studies reported improvements in weight-related outcomes and one in medication adherence. Effects on quality of life, self-efficacy, and healthcare utilisation were not significant. Patient satisfaction was reported in one study, with 95&#xa0;% expressing positive feedback, though formal assessments of feasibility and acceptability were limited. CONCLUSION: Smartphone apps show potential to support obesity management, particularly after bariatric surgery. While some evidence suggests benefits for weight loss and adherence outcomes, the limited studies and variability of reporting prevent conclusive observations in other outcomes. Future app development should integrate behavioural theory to address psychological needs, nutritional risks and promote holistic self-management beyond weight control.

Female

Impact of subthreshold troponin levels and temporal trends on short term adverse cardiovascular outcomes in patients discharged from the emergency department: a RACE-IT trial substudy.

BACKGROUND: High-sensitivity cardiac troponin I assays enable early exclusion of myocardial infarction in the emergency department. However, the clinical implications of detectable troponin values below the 99th percentile upper reference limit (4-18 ng/L) remain unclear. OBJECTIVE: To assess the association between subthreshold troponin levels and 30-day outcomes in patients from the RACE-IT trial, using exact troponin values when available. METHODS: This post-hoc analysis of the RACE-IT stepped-wedge randomized controlled trial included patients with troponin&#x2009;&#x2264;&#x2009;18 ng/L across nine EDs. Patients were stratified by initial troponin, peak value, absolute change, and percent change. The primary outcome was a 30-day composite of all-cause death, acute MI, percutaneous coronary intervention, and coronary artery bypass grafting. Logistic regression analysis after adjusting for age, sex, race, and coronary artery disease was performed. RESULTS: Among 19,194 patients with troponin&#x2009;&#x2264;&#x2009;18 ng/L, 117 (0.6%) experienced the composite outcome. Higher troponin levels were associated with increased event rates in unadjusted analyses. Adjusted analyses showed no independent associations overall, though patients whose highest troponin values fell within the&#x2009;&#x2265;&#x2009;11-&#x2009;&#x2264;&#x2009;18 ng/L range continued to demonstrate significantly worse outcomes than those with lower peak levels. Elevated troponin values correlated with older age, male sex, and greater comorbidity burden. CONCLUSION: In this post-hoc analysis of patients with troponin values below the 99th percentile URL, absolute levels and temporal changes were not independently associated with 30-day adverse outcomes. These findings support the use of subthreshold troponin values in rapid rule-out protocols, emphasizing the need to consider clinical context and comorbidities in risk assessment.

Humans

Integrated miRNA-mRNA profiling reveals candidate regulatory relationships associated with high-fat diet-induced muscle lipid deposition in black seabream (Acanthopagrus schlegelii).

High-fat diets are increasingly used in aquaculture due to their protein-sparing effects; however, the post-transcriptional regulatory mechanisms of fish muscle in response to high-fat diets (HFD) remain unclear. In this study, juvenile black seabream were fed either a normal-fat diet (NFD) or a HFD to investigate the miRNA-mRNA regulatory network associated with diet-induced muscle lipid deposition. Oil Red O staining and biochemical analysis showed that high-fat diet feeding markedly increased lipid droplet accumulation and crude lipid content in muscle, indicating significant induction of muscle lipid deposition. Integrated mRNA and miRNA expression profiling revealed substantial transcriptomic and post-transcriptional responses to high-fat diet challenge. A total of 271 differentially expressed genes were identified, including 120 upregulated and 151 downregulated genes. Through combined target prediction and expression correlation analysis, thirteen candidate inverse miRNA-mRNA relationships were subsequently identified, and RT-qPCR supported the expression patterns of selected miRNAs and mRNAs. These pairs included miR-499-x-dmgdh, miR-499-y-gatm, miR-727-y-ass1, miR-4649-x-foxo4, miR-9129-z-myl7, and several novel miRNA-mediated interactions involving adk, chst11, lypla2, frem2, kcnc4, wars1, bag2, and capn2. Functional analysis suggested that these regulatory pairs were mainly associated with metabolic adaptation, structural remodeling, and cellular stress responses. In particular, gatm, dmgdh, ass1, and adk were associated with energy metabolism-related processes, including pathways previously linked to Ampk regulation, whereas myl7, frem2, and kcnc4 may contribute to muscle structural maintenance and excitability regulation. Overall, this study provides candidate miRNA-mRNA regulatory relationships potentially involved in high-fat diet-induced muscle lipid deposition and adaptive remodeling in black seabream, offering a basis for future functional studies on muscle metabolism and quality regulation in marine fish.

Animals

Malnutrition and adverse outcomes after spine surgery: a systematic review and meta-analysis.

BACKGROUND CONTEXT: Malnutrition is linked to adverse surgical outcomes, but its impact in spine surgery remains unclear due to inconsistent findings and heterogeneous definitions, including use of serum albumin, prealbumin, lymphocyte count, the Geriatric Nutritional Risk Index, and the Prognostic Nutritional Index. We conducted a systematic review and meta-analysis to evaluate the relationship between malnutrition and postoperative outcomes in spine surgery. PURPOSE: To systematically evaluate the association between preoperative malnutrition and postoperative outcomes in patients undergoing spine surgery. STUDY DESIGN: Systematic review and meta-analysis. PATIENT SAMPLE: Patients undergoing elective or urgent spine surgery across included observational studies comparing malnourished vs well-nourished cohorts. OUTCOME MEASURES: Primary outcomes included postoperative mortality and overall surgical complications. Secondary outcomes included infectious complications (sepsis, urinary tract infection, wound complications), delirium, reoperation, 30-day and 90-day readmission, and prolonged length of hospital stay. METHODS: A systematic search of PubMed, Embase, Cochrane Library, and Web of Science was performed on April 7, 2025, following PRISMA guidelines. Studies directly comparing postoperative outcomes in malnourished vs well-nourished spine surgery patients were included. A random-effects model generated pooled odds ratios for complications. Outcomes assessed included mortality, surgical complications, infectious outcomes, readmission, reoperation, delirium, prolonged length of stay, and wound complications. RESULTS: Of 2,851 screened articles, 37 met the inclusion criteria, encompassing 16,987 malnourished patients. Malnutrition was associated with significantly increased odds of mortality (OR: 4.05, 95% CI [2.97-5.54]), delirium (OR: 3.95, 95% CI [2.49-6.27]), sepsis (OR: 2.77, 95% CI [2.31-3.33]), surgical complications (OR: 1.79, 95% CI [1.57-2.04]), urinary tract infection (OR: 1.81, 95% CI [1.59-2.06), wound complications (OR: 2.10, 95% CI [1.80-2.45]), reoperation (OR: 1.70, 95% CI [1.46-1.97]), prolonged length of hospital stay (OR: 3.46, 95% CI [2.57-4.65]), 30-day readmission (OR: 1.59, 95% CI [1.36-1.86]), and 90-day readmission (OR: 2.13, 95% CI [1.67-2.71]). CONCLUSIONS: Malnutrition was consistently associated with adverse outcomes after spine surgery. Routine nutritional assessment and targeted preoperative optimization should be considered a standard component of perioperative spine care to help reduce postoperative complications and improve recovery.

Humans

Webcam-Based Real-Time Visual Feedback During Baduanjin Practice in Older Adults: 6-Week Pilot Randomized Study.

BACKGROUND: Baduanjin qigong is a traditional mind-body exercise used to support balance and physical health in older adults. Age-related changes in proprioception may make accurate self-directed performance difficult without external guidance. OBJECTIVE: The aim of this study is to explore whether webcam-based real-time visual feedback delivered during supervised laboratory sessions was associated with differences in webcam-derived 2D pose discrepancy and movement consistency during Baduanjin practice in older adults. METHODS: A total of 31 older adults were enrolled, and 28 participants with complete analyzable records were included in this complete-case dataset (feedback group, n=14; nonfeedback group, n=14). All sessions were conducted face-to-face in a supervised motion-analysis laboratory. Weekly 2D pose-discrepancy values were analyzed using a linear mixed-effects model with fixed effects for group, categorical week, and the group-by-week interaction and a participant-specific random intercept. Joint- and movement-specific participant-level 6-week means were analyzed exploratorily using Welch independent-samples t tests. Holm correction was applied across 24 exploratory contrasts (6 week-specific, 8 joint-specific, and 10 movement-specific comparisons), and Hedges g and 95% CIs were reported. Participant-specific weekly slopes and within-participant variability were additionally examined to directly assess longitudinal error drift. RESULTS: The linear mixed-effects model showed no significant group-by-week interaction (Wald &#x3c7;25=1.09; P=.96) and no significant overall week effect (Wald &#x3c7;25=6.40; P=.27). Averaged across 6 weeks, the feedback group had an estimated mean 2D pose discrepancy 1.20&#xb0; lower than the nonfeedback group (95% CI -2.38&#xb0; to -0.02&#xb0;; P=.046), although this marginal pilot finding was sensitive to an analytic approach. No week-specific contrast remained significant after Holm adjustment. Nominal right elbow, right shoulder, and right knee differences did not survive global Holm correction. Form 3 showed a lower mean discrepancy in the feedback group (mean difference -3.70&#xb0;, 95% CI -5.86&#xb0; to -1.54&#xb0;; Hedges g=-1.30; unadjusted P=.002; Holm-adjusted P=.04). Direct analyses of participant-specific slopes and within-participant SDs did not support a significant between-group difference in longitudinal error drift. CONCLUSIONS: In this small exploratory pilot study conducted under supervised laboratory conditions, the 6-week trajectories did not differ significantly between groups. A marginally lower average 2D pose discrepancy was observed in the feedback group across the 6 weeks, but no individual week- or joint-specific comparison remained significant after multiplicity adjustment. Form 3 was the only exploratory contrast that remained significant after global Holm correction. Direct longitudinal analyses did not demonstrate prevention of error drift. Larger studies using validated reference measurements, prespecified outcomes, and adequately powered longitudinal designs are required.

Humans

Safety and Tolerability of Oral Islatravir Once Monthly as Pre-exposure Prophylaxis in Cisgender Men and Transgender Women Who Have an Elevated Likelihood of HIV-1 Exposure: Results From the IMPOWER-24 Randomized Phase 3 Study.

BACKGROUND: Islatravir once monthly (qm), a nucleoside reverse transcriptase translocation inhibitor with a long half-life, was evaluated for safety and tolerability in cisgender men and transgender women who have sex with men and are at increased likelihood of HIV-1 (HIV) exposure. METHODS: IMPOWER-24 (NCT04652700) was a double-blind, Phase 3 study. Participants were randomized 2:1 to islatravir 60 mg oral qm or emtricitabine (FTC; 200 mg) coformulated with either tenofovir disoproxil (245 mg) or tenofovir alafenamide (TAF; 25 mg) once daily (qd). After &#x223c;9 months, blinded islatravir was discontinued due to lymphocyte reductions; participants were offered open-label comparator for 20 months. RESULTS: In total, 494 participants were enrolled (328 islatravir; 166 comparator): 91.5% were cisgender men, 41.7% were White, and median age was 27 years. Mean blinded dosing duration was 4.7 months (islatravir) versus 4.3 months (comparator). Overall, 211 participants (64.3%) in the islatravir group and 128 (77.1%) in the comparator group had &#x2265;1 adverse event (AE). Most AEs were mild or moderate, with 1 AE leading to product discontinuation (islatravir; gastroesophageal reflux). Serious AEs occurred in <2%; none were related to study product. Change in total lymphocytes in the islatravir group at Month 3 was -7.4%; a trend toward recovery was observed after islatravir was stopped. Mean total lymphocytes remained within normal range. No HIV infections occurred in either group during the double-blind phase. CONCLUSIONS: Islatravir qm was generally well tolerated; decreases in total lymphocytes were observed with islatravir. Original primary efficacy objectives were not assessed due to early study stoppage.

Humans

Impact of estimated total blood volume on NT-proBNP response to angiotensin receptor-neprilysin inhibition in acute heart failure: Insights from the PREMIER study.

BACKGROUND: Sacubitril/valsartan (Sac/Val) reduces N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels in acute heart failure (AHF), particularly in patients with reduced ejection fraction. However, whether estimated total blood volume (TBV), calculated using anthropometric equations, is associated with heterogeneity in biomarker response remains uncertain. METHODS: This post hoc exploratory sub-analysis of the PREMIER randomized trial evaluated whether baseline estimated TBV was associated with heterogeneity in NT-proBNP reduction after Sac/Val compared with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) therapy. Estimated TBV was calculated using validated anthropometric equations and dichotomized at the median (4.05 L). Patients were further stratified by left ventricular ejection fraction (LVEF <40% vs &#x2265;40%). The primary endpoint was the proportional change in NT-proBNP from baseline to Week 8. RESULTS: Among 376 patients, 372 with baseline estimated TBV data were analyzed. In the high TBV group, Sac/Val was associated with greater NT-proBNP reduction than ACEI/ARB (-56% vs -32%; ratio of change, 0.67; 95% confidence interval, 0.53-0.84; P = .001), whereas no significant difference was observed in the low TBV group (P for heterogeneity = 0.063). In patients with LVEF <40%, Sac/Val was associated with greater NT-proBNP reduction in both TBV groups. In patients with LVEF &#x2265;40%, Sac/Val was associated with greater NT-proBNP reduction in the high TBV group, whereas the point estimate in the low TBV group numerically favored ACEI/ARB. CONCLUSIONS: In this exploratory post hoc analysis, higher estimated TBV was associated with greater NT-proBNP reduction after Sac/Val, particularly among patients with LVEF &#x2265;40%. These findings are hypothesis-generating and require external validation. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05164653; Japan Registry of Clinical Trials, jRCTs021210046.

Humans

Variability in &#x3b2;-human chorionic gonadotropin concentrations following evacuation of a hydatidiform mole pregnancy: A retrospective cohort study from Vietnam.

BackgroundGestational trophoblastic disease refers to a group of tumors defined by abnormal trophoblastic proliferation. This disease produces a distinct tumor marker, beta-human chorionic gonadotropin, which can be useful for diagnosis and follow-up. The objective of this study was to investigate the variations in serum beta-human chorionic gonadotropin levels after uterine evacuation as well and the progression of gestational trophoblastic neoplasia.Materials and methodsThis retrospective cohort study was conducted at Tu Du Hospital, Vietnam, between January 2019 and December 2020. All patients diagnosed with molar pregnancy were analyzed retrospectively based on serial serum beta-human chorionic gonadotropin levels following uterine evacuation. Post-evacuation outcomes, including relapsed molar pregnancy and gestational trophoblastic neoplasia, were also monitored.ResultsWe enrolled 560 patients with molar pregnancy, including 298 with complete hydatidiform mole and 262 with partial hydatidiform mole. Severe symptoms were more common in those with complete hydatidiform mole. Over the follow-up period, 97 cases of gestational trophoblastic neoplasia were noted. The data show that the median time to gestational trophoblastic neoplasia diagnosis was 8.75&#x2009;&#xb1;&#x2009;4.41 (4-26) weeks. In terms of variations in the serum beta-human chorionic gonadotropin levels, the generalized estimating equation model showed a faster decline in the complete hydatidiform mole group than in the partial hydatidiform mole group. Similarly, regression in serum beta-human chorionic gonadotropin levels was significantly more rapid in patients who progressed to gestational trophoblastic neoplasia than in those with relapsed molar pregnancy (-11,593 vs. -20,651.22 and -12,946.26 vs. -46,329.23 mUI/mL, p&#x2009;<&#x2009;0.001).ConclusionsSurveillance of serum beta-human chorionic gonadotropin levels remains essential for gestational trophoblastic neoplasia monitoring in patients with molar pregnancy following surgical evacuation. The post-evacuation serum beta-human chorionic gonadotropin level regression curve helps distinguish gestational trophoblastic neoplasia from hydatidiform moles. Further evidence is required to strengthen these findings.

Humans

Beyond survival: Testicular tissue cryopreservation for fertility preservation during childhood cancer, experiences from a single center.

INTRODUCTION: Approximately 30% of all male childhood cancer survivors receive gonadotoxic therapy increasing their risk for infertility. The only current option for potential fertility preservation in prepubertal males is through testicular tissue cryopreservation (TTC), available through clinical trials. Our aim was to evaluate our experience and identify barriers to enrollment in the TTC study. METHODS: A retrospective review was conducted to describe a single center experience with TTC, including an assessment of factors impacting the decision to enroll or not enroll in the TTC trial. RESULTS: A total of 61 patients were found to be eligible for enrollment in the TTC trial, with 23 patients (34%) choosing to enroll and undergo testicular tissue cryopreservation including 19 (83%) oncology patients. In patients who underwent TTC there were no unexpected delays in starting disease directed therapy. For families that declined enrollment, many did not see fertility preservation as a priority at the time of counseling. (n = 17, 44%). Other barriers included concerns about post-operative complications and a feeling of being overwhelmed at the time of counseling. DISCUSSION: Despite being the only preservation option for pre-pubertal boys facing risk of infertility, TTC enrollment was not pursued by a majority of eligible patients and families. Identifying potential barriers or misconceptions, particularly in regard to post operative complication risks, offer opportunities for improved counseling and education. Early introduction of the Fertility Navigation team allows for procedural coordination success and access for patients that are interested. Success is not measured in how many patients proceed with TTC, rather that all patients have the opportunity for counseling and discussion. CONCLUSION: TTC can be offered and completed safely without delays in disease-directed treatment timelines. A Fertility Navigation Program allows for equal opportunity for education and enrollment on TTC protocol which should be the goal for pediatric institutions, though is not pursued by many patients. A majority of those who declined the study did not see fertility as a priority at the time of treatment while others were concerned regarding peri-operative risks.

Humans

Internet-based acceptance and commitment therapy (iACT) improves professional psychological help-seeking attitudes: A randomized controlled trial.

BACKGROUND: Professional psychological help-seeking attitudes are crucial for addressing mental health challenges, yet the mechanisms underlying their improvement through internet-based interventions remain poorly understood. OBJECTIVE: This randomized controlled trial aimed to (1) evaluate the efficacy of Internet-based Acceptance and Commitment Therapy (iACT) in enhancing professional help-seeking attitudes, and (2) elucidate the longitudinal mediating roles of psychological rigidity and self-stigma. METHODS: A total of 91 male participants (Mean Age&#xa0;=&#xa0;21.09) were randomly assigned to either a 12-day iACT intervention group (n&#xa0;=&#xa0;46) using a self-developed mobile application or a waitlist control group (n&#xa0;=&#xa0;45). Psychological flexibility, rigidity, self-stigma, and help-seeking attitudes were measured at four time points: baseline, mid-intervention (Day 6), post-intervention (Day 12), and 1-month follow-up. Data were analyzed using repeated-measures ANOVA and latent growth modeling. RESULTS: Intention-to-treat analysis revealed the iACT group showed greater improvements in help-seeking attitudes than controls (F (3,87)&#xa0;=&#xa0;5.95, p&#xa0;<&#xa0;0.001), with medium-to-large between-group effects at post-test for reducing psychological rigidity (d&#xa0;=&#xa0;-0.77, 95% CI [-1.19, -0.34]) and self-stigma (d&#xa0;=&#xa0;-0.88, 95% CI [-1.31, -0.45]). Latent growth modeling revealed a sequential mediation effect: the iACT intervention reduced psychological rigidity (&#x3b2;&#xa0;=&#xa0;-0.53, SE&#xa0;=&#xa0;0.12), which in turn reduced self-stigma (&#x3b2;&#xa0;=&#xa0;0.61, SE&#xa0;=&#xa0;0.09) and improved help-seeking attitudes (&#x3b2;&#xa0;=&#xa0;0.47, SE&#xa0;=&#xa0;0.08). CONCLUSION: This study provides the first evidence that a self-guided iACT mobile intervention can effectively enhance professional help-seeking attitudes by reducing psychological rigidity, which in turn alleviates self-stigma. The developed app offers a scalable solution to overcoming stigma-related barriers to mental health care.

Humans

Safety and immunogenicity of an mRNA COVID-19 vaccine administered to adults: A phase 2, randomized, active-controlled trial.

We conducted a phase 2, randomized, active-controlled, observer-blind study (NCT05960097) among healthy adults&#x2009;&#x2265;18 y of age who completed a primary COVID-19 mRNA vaccination series, with or without a booster, &#x2265;3&#x2009;months earlier. Participants were randomized (1:1:1:1:1) to either receive an investigational bivalent mRNA COVID-19 vaccine encoding ancestral D614G and Omicron BA.4-5 spike proteins (CV0701 mRNA vaccine) at one of three dose levels, an investigational monovalent mRNA COVID-19 vaccine encoding the Omicron BA.4-5 spike protein (CV0601 mRNA vaccine), or a licensed Original Wuhan/Omicron BA.4-5 bivalent mRNA COVID-19 vaccine. The primary objectives were to evaluate reactogenicity, safety and immunogenicity post-vaccination. Secondary and tertiary objectives were to further evaluate humoral and cell-mediated immunity post-vaccination. In total, 425 participants were vaccinated and 381 were included in the Day 29 per-protocol immunogenicity analysis. Most solicited events were mild to moderate. No vaccine-related serious adverse events or myocarditis/pericarditis cases were reported. For the CV0701 mRNA vaccine, a dose-dependent increase in Day 29 neutralizing titers against ancestral D614G and Omicron BA.4-5 was observed. Neutralizing titers against ancestral D614G and Omicron BA.4-5 declined by Days 91 and 181, but remained above baseline. Similar immune responses were observed for the CV0601 mRNA vaccine. At Day 8, CD4+ T cells (Th1 profile) increased in all study groups and CD8+ T cells increased in all study groups, except the lowest CV0701 dose group. The CV0701 and CV0601 mRNA vaccines elicited robust humoral and cellular immunity with an acceptable safety profile, comparable to a licensed, bivalent mRNA vaccine. Clinical Trial Registration EU CT number: 2023-504596-25-00 ClinicalTrials.gov: NCT05960097.

Humans

Chronic neurological diseases with acute respiratory failure in a real-life cohort: insights into ICU and long-term survival-A retrospective study.

BACKGROUND: Patients with chronic neurological diseases (CND) are at increased risk of pulmonary complications that often require ICU admission. This study aimed to identify clinical factors associated with ICU mortality and long-term survival in patients with CND who developed acute respiratory failure (ARF). METHODS: This retrospective cohort study was conducted in a level III respiratory ICU. Patients with pre-existing CND admitted to the ICU with ARF were included. ICU mortality was analyzed using multivariable logistic regression. Long-term survival after ICU discharge was evaluated using Kaplan-Meier survival analysis and Cox proportional hazards models. Mortality timing was further characterized using hazard function analysis. RESULTS: A total of 220 patients were included; the most common neurological diagnoses were dementia (37.3%), stroke (22.7%), and amyotrophic lateral sclerosis (14.1%). ICU mortality was 33.6%. Higher APACHE II scores were independently associated with increased ICU mortality (OR 1.076 per point increase; 95% CI 1.029-1.126; p&#xa0;<&#xa0;0.001). Long-term survival differed significantly by post-discharge respiratory support strategy, with Kaplan-Meier analysis demonstrating more favorable survival patterns among patients receiving home non-invasive mechanical ventilation (NIMV) (p&#xa0;=&#xa0;0.003). In Cox regression analysis, age, home NIMV, and feeding modality at discharge were independently associated with long-term outcomes. Survival analyses revealed an early clustering of deaths within the first months after ICU discharge, particularly among patients with dementia. CONCLUSIONS: In patients with CND, acute physiological severity was the main determinant of ICU mortality, whereas long-term survival after ICU discharge was poor, with deaths clustering within the first months thereafter. Post-discharge respiratory support and nutritional management should be individualized according to the expected clinical trajectory and patient values.

Humans

Two-Year Outcomes of a 211 Care Coordination Trial.

BACKGROUND AND OBJECTIVES: Early screening for developmental concerns enables timely diagnosis and referral, yet many families face barriers accessing services. Prior work showed that early childhood care coordination could improve timely service connection. This study assessed developmental outcomes among children participating in a randomized controlled trial of Information and Referral Federation of Los Angeles County (211LA). METHODS: Participants, aged 21-42&#xa0;months, were randomized to usual care or the 211LA intervention. Developmental and behavioral measures, including the Parental Evaluation of Developmental Status Developmental Milestones Assessment Level (PEDS-DM-AL) and the Child Behavior Checklist (CBCL), were collected at baseline and 24&#xa0;months later. The sample included 499 participants, 250 in the 211LA intervention and 249 in usual care. Primary analyses examined changes in PEDS-DM-AL and CBCL scores over the 24-month period by study arm. Post hoc analyses compared family characteristics between intervention and control families who enrolled in services. RESULTS: Developmental and behavioral measures showed some clinically insignificant change over time, but these changes did not differ by condition (expressive/receptive language skills mastered: P&#x2009;>&#x2009;.9; autism, attention, aggression, and externalizing behavior T scores: P&#x2009;>&#x2009;.4). Post hoc analyses identified potentially relevant imbalances between the treatment arms at baseline as well as in the subgroup that enrolled in services, with families assigned to the 211LA intervention being more likely to have a non-US born parent and a parent with limited English proficiency compared with families assigned to usual care. Intervention families enrolled in services also used telehealth more frequently and received a lower duration of services than those receiving usual care. CONCLUSIONS: This study measured the indirect influence of service enrollment through 211LA care coordination on developmental outcomes. Although increased service enrollment through 211LA did not affect developmental outcomes, we hypothesize this may be because of several factors, including overrepresentation of a subset of historically underrepresented families in the 211LA intervention, suboptimal performance of our developmental assessment tool, and complexity of conducting a trial of this magnitude during the COVID-19 pandemic, which may have diminished the ability of this trial to demonstrate developmental benefits despite demonstrated service enrollment gains.

Humans