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Recombinant Human Thrombopoietin Reduces the Need for Platelet Transfusion in Patients With Chronic Liver Disease and Thrombocytopenia.

Chronic liver disease (CLD)-related thrombocytopenia can limit the feasibility of invasive procedures. Recombinant human thrombopoietin (rhTPO) has demonstrated a favorable safety profile without hepatotoxicity. We evaluated the efficacy and safety of rhTPO in patients with CLD-related thrombocytopenia who were undergoing elective invasive procedures. In this multicenter, randomized (2:1), double-blind, placebo-controlled phase III trial, 120 adult Chinese patients with CLD-related thrombocytopenia (platelet count <&#x2009;50 &#xd7;&#x2009;109/L) received rhTPO (n =&#x2009;80) or placebo (n =&#x2009;40) once daily for up to 5 or 7&#x2009;days. The primary endpoint was the proportion of patients with sustained platelet counts &#x2265;&#x2009;50 &#xd7;&#x2009;109/L from 24 h before invasive procedure to 7&#x2009;days post-procedure, without requiring emergency bleeding management. The primary endpoint was achieved by 85.0% of patients in the rhTPO group versus 12.5% in the placebo group (p&#x2009;<&#x2009;0.0001). Preoperatively, platelet counts &#x2265;&#x2009;50 &#xd7;&#x2009;109/L were achieved in 92.5% and 20.0% of patients in the rhTPO and placebo groups, respectively (p&#x2009;<&#x2009;0.0001). Platelet transfusion was avoided in 92.5% of rhTPO-treated patients versus 25.0% of placebo-treated patients (p&#x2009;<&#x2009;0.0001). The median duration of platelet counts &#x2265;&#x2009;50 &#xd7;&#x2009;109/L was significantly longer with rhTPO than with placebo (21.0 vs. 3.0&#x2009;days, p =&#x2009;0.0007). Treatment-related treatment-emergent adverse events (TEAEs) occurred in 12.5% of patients in both the rhTPO and placebo groups. No treatment-related serious adverse events were reported. Overall, rhTPO was effective and well tolerated in patients with CLD-related thrombocytopenia and may represent a viable therapeutic option for those undergoing elective invasive procedures. Trial Registration: www.chinadrugtrials.org.cn: number CTR20230919.

Humans

Effects of Dynamic Neck Sensorimotor Biofeedback Training in Individuals With Mechanical Neck Pain: A Pilot Randomized Controlled Trial.

Mechanical neck pain (MNP) is commonly accompanied by pain-related functional limitations, sensorimotor disturbances, and fear of movement, which together may contribute to persistent disability. This preliminary randomized controlled trial study investigated the short-term effects of dynamic neck sensorimotor-based biofeedback training in individuals with MNP. 20 MNP patients from outpatient clinics were assigned to a biofeedback training group or a control group. The training group underwent dynamic biofeedback exercises twice weekly for 2&#xa0;weeks, whereas the control group performed repeated cervical movements without biofeedback. Outcomes included cervical kinematics as repositioning errors (RPE), movement units (MU), maximal range of motion (ROM), and subjective measures, including pain intensity, Neck Disability Index (NDI), and Fear-Avoidance Beliefs Questionnaire (FABQ). All participants completed post-intervention assessments; adherence in the training group was 100%, with no missing data and no adverse events reported. Within the biofeedback training group, participants receiving biofeedback training demonstrated greater improvements in cervical repositioning accuracy during flexion (51.95%, p&#xa0;=&#xa0;0.04) and extension (46.67%, p&#xa0;=&#xa0;0.02), along with reductions in fear-avoidance beliefs related to physical activity and work (p&#xa0;<&#xa0;0.05); these changes were less apparent in the active control group. Exploratory regression analyses suggested associations between improvements in repositioning accuracy and pain reduction, and between increased cervical range of motion and improvements in fear-avoidance beliefs related to physical activity. These pilot findings suggest that dynamic sensorimotor biofeedback training may improve proprioceptive acuity and fear-avoidance beliefs in individuals with MNP, supporting further evaluation in an adequately powered randomized trial.

Humans

Effects of aromatherapy on menopausal symptoms: a systematic review and meta-analysis.

BACKGROUND: The postmenopausal period presents a significant challenge to women's health, characterised by vasomotor, psychological, and sleep disturbances. This systematic review and meta-analysis synthesised evidence on aromatherapy for menopausal symptoms. METHODS: We searched Cochrane Library, Web of Science, ScienceDirect, PubMed, Scopus, SID, and Google Scholar until January 2, 2026. The protocol was registered (PROSPERO: CRD420261303084). Randomised controlled trials and quasi-experimental studies were included. The Cochrane Risk of Bias tool and GRADE approach were used for quality assessment and certainty of evidence. Meta-analyses were performed using RevMan 5.3. RESULTS: Of 4435 records, 21 articles from 17 studies (n&#x2009;=&#x2009;1347) were included. Aromatherapy significantly improved sexual function (MD: 7.05, 95% CI: 3.64-10.45), sleep quality (MD: -3.95, 95% CI: -5.94 to -1.97), overall menopausal symptoms (SMD: -1.00, 95% CI: -1.43 to -0.58), vasomotor symptoms (SMD: -0.79, 95% CI: -1.11 to -0.47), physical symptoms (SMD: -0.78, 95% CI: -1.10 to -0.46), somatic symptoms (MD: -1.34, 95% CI: -2.46 to -0.23), psychological symptoms (SMD: -0.59, 95% CI: -0.96 to -0.23), anxiety (SMD: -0.63, 95% CI: -1.10 to -0.16), and depression (SMD: -0.57, 95% CI: -0.85 to -0.28). No significant effect was found for urogenital symptoms. GRADE certainty was 'Very Low' for sexual function and sleep quality, and 'Low' for other outcomes. CONCLUSIONS: Preliminary evidence suggests that aromatherapy may be a beneficial complementary therapy for alleviating some menopausal symptoms. However, given the substantial heterogeneity, methodological limitations, and limited number of studies for subgroup analyses, firm clinical recommendations cannot be made at this time. More rigorous, large-scale, multi-centre randomised controlled trials with standardised interventions and consistent adverse event reporting are required before definitive clinical recommendations can be made.

Humans

Impact of Commercial Artificial Intelligence on Radiologist Reading Time for Pulmonary Nodule Evaluation at Chest CT.

Background Chest CT is a primary method for identifying pulmonary nodules, yet interpreting scans remains time-intensive and demanding. Currently, artificial intelligence (AI) is expected to reduce reading times, but the effect of AI on reporting times in this setting is unknown. Purpose To evaluate the impact of a commercial AI software on radiologists' reading time for pulmonary nodule assessment on chest CT scans within a real-world clinical setting. Materials and Methods This retrospective study included patients who underwent chest CT examinations at a tertiary medical center between September 2021 and May 2024. The study period was divided into pre- and post-AI phases. The primary outcome was radiology reporting time. The association between AI implementation and reporting time was evaluated using a multivariable parametric Weibull shared frailty survival model adjusted for reader function, examination type, patient location, and requesting specialty, with clustering at the radiologist level. Interaction analyses assessed heterogeneity across prespecified subgroups. An exploratory extrapolation estimated projected workforce and financial impact. Results This study included 19&#x2009;433 patients (mean age, 62 years &#xb1; 14.2 [SD]; 21&#x2009;814 men; 39&#x2009;323 chest CT examinations, 19&#x2009;190 pre-AI, and 20&#x2009;133 post-AI). AI implementation was associated with faster report completion (adjusted hazard ratio, 1.17; 95% CI: 1.14, 1.21; P < .001). The adjusted median reporting time decreased from 21.3 minutes pre-AI to 18.2 minutes post-AI (14.6% reduction; P < .001). Heterogeneity was observed across reader function (P < .001), examination type (P = .048), and requesting specialty (P = .03). The largest relative reductions were observed for CT thorax electrocardiogram-gated examinations (-41.1%; P < .001) and thoracic radiologists (-25.0%; P < .001), whereas emergency department examinations showed increased median reporting time (7.1%; P < .001). At institutional scan volumes (approximately 20&#x2009;000-22&#x2009;000 chest CT examinations annually), exploratory modeling suggested an approximate reduction of 0.5 full-time equivalent radiologist workload. Conclusion Implementation of commercial AI-assisted pulmonary nodule assessment on chest CT scans reduced radiologist reporting time in a real-world clinical setting. &#xa9; The Author(s) 2026. Published by the Radiological Society of North America under a CC BY 4.0 license. Supplemental material is available for this article. See also the editorial by Iwasawa in this issue.

Humans

Parent-Mediated Interventions for ASD Under 3 Years: A Systematic Review, Meta Analysis, and Moderator Analyses.

This study aimed to assess the effectiveness of PMIs for ASD under 3&#xa0;years, and explore potential moderators influencing the effectiveness through moderator analyses. The study searched five English databases for randomized controlled trials (RCTs). The meta-analysis was conducted using a random-effects model to calculate Hedges's g. Subgroup analyses and meta regression assessed the effects of potential moderators on PMIs effectiveness, with evidence quality evaluated using GRADE. A total of 31 RCTs were included in the systematic review, with 26 included in the meta-analysis. The results showed a small overall beneficial effect of PMIs on ASD under 3 years (g&#x2009;=&#x2009;0.20). Small to trivial positive effects were found in several subdomains, including adaptive skills (g&#x2009;=&#x2009;0.29), parent responsiveness (g&#x2009;=&#x2009;0.23), parent-child interaction (g&#x2009;=&#x2009;0.35), social communication (g&#x2009;=&#x2009;0.18), and symptoms (g&#x2009;=&#x2009;&#x2009;-&#x2009;0.22). However, PMIs did not show statistically significant effects on children's cognitive competence, language, or motor skills domains. Subgroup analysis and meta-regression explored potential moderators, but none significantly influenced the effectiveness of PMIs. The GRADE assessment showed that the certainty of the evidence ranged from moderate to low. This study confirmed that PMIs demonstrate positive effects on children under 3&#xa0;years old with ASD, and showed beneficial outcomes in most subdomains. However, the evidence was of moderate to low certainty, so these findings should be interpreted with caution. In the future, broader databases and more large-scale, multicenter, high-quality clinical studies are needed to confirm these effects.

Humans

Prevention of postpartum methamphetamine use with micronized progesterone trial (PROMPT): A pilot randomized controlled trial.

OBJECTIVES: Methamphetamine use disorder (MUD) contributes to postpartum morbidity and mortality. Postpartum progesterone decline may destabilize &#x3b3;-aminobutyric acid pathways, increasing craving and return to use. We assessed the feasibility and safety of micronized progesterone, generating efficacy estimates for preventing postpartum methamphetamine use. METHODS: We conducted a double-blind, randomized, placebo-controlled feasibility trial (November 2021-January 2024) at an academic center with a perinatal addiction clinic. Participants &#x2264;&#x2009;12 weeks postpartum with &#x2265;&#x2009;4 weeks of abstinence were randomized 1:1, stratified by opioid use disorder (OUD), to micronized progesterone 400mg (200mg twice daily) or identical placebo for 12 weeks. The primary outcome was feasibility, defined as achieving &#x2265;&#x2009;80% of planned enrollment. Safety outcomes included adverse events (AEs) and serious adverse events (SAEs). Efficacy outcomes were return to methamphetamine use (weekly self-report and every two weeks urine toxicology) and methamphetamine craving. Analyses included intent-to-treat and per-protocol approaches, with loss to follow-up imputed as return to use. Craving trajectories were modeled using adjusted regression with interaction terms for medication for OUD (MOUD). RESULTS: Of 253 screened individuals, 43 were eligible and 34 were enrolled (91.8%; 18 progesterone, 16 placebo). Retention at 12 weeks was 88%. AE frequency was similar between groups (78% vs 81%; p&#x2009;>&#x2009;0.05), and no maternal SAEs occurred. Four infant SAEs were deemed unrelated to treatment. Return to methamphetamine use did not differ between groups. Craving trajectories differed by MOUD type. CONCLUSIONS: Micronized progesterone was feasible and safe for postpartum individuals with MUD. MOUD-specific craving effects support evaluation in larger, multicenter efficacy trials. GOV REGISTRATION NUMBER: NCT05128071 NCT REGISTRATION: Prevention of postpartum methamphetamine use with micronized progesterone trial https://clinicaltrials.gov/study/NCT05128071.

Humans

Weight-bearing locomotion mitigates the progression of post-traumatic knee osteoarthritis in male rodents: A systematic review and meta-analysis.

OBJECTIVE: Although knee post-traumatic osteoarthritis (PTOA) has been associated with altered loading, how weight-bearing (WB) activities should be modulated post-injury to preserve knee health remains unknown. This systematic review and meta-analysis examined the effects of WB locomotion on knee PTOA in rodents to provide insight into potential clinical implications. DESIGN: Studies published in PubMed, Cochrane Library, Embase, and CINAHL through 02/2025 and meeting the following criteria were included: 1) rodents with knee PTOA, 2) compared locomotor exercises (treadmill/wheel) to no exercise, 3) outcome measures of PTOA (OARSI/Mankin OA scores, bone quality, osteophyte condition, cartilage quality/morphology). If significant heterogeneity across studies was observed, locomotion speed, time/number of intervention sessions, frequency and duration of intervention, exercise initiation, follow-up time, animal species, PTOA model were analyzed as potential moderator variables that may influence findings. RESULTS: Twenty-two studies met the criteria, resulting in a total of 156 effect sizes (ESs) for meta-analysis (all males). A positive ES denotes less PTOA. Based on the CAMARADES checklist, 5 studies were ranked low risk of bias and 14 studies were ranked moderate risk of bias. Locomotion significantly reduced PTOA severity evaluated using OARSI/Mankin scores (ES=0.927, 95% CI: [0.590, 1.264]) and improved bone quality (ES=0.379, 95% CI: [-0.023, 0.780]) with substantial heterogeneity across studies. Follow-up analyses indicated that greater ESs for reducing OA scores were associated with a shorter duration of each training session, more training sessions, longer intervention duration, and longer follow-up time (all P&#x2264;0.004). Greater ESs for improving bone quality were associated with a longer follow-up time and later exercise initiation post-injury (both P&#x2264;0.014). Locomotion resulted in small to moderate but non-significant positive effects for isolated measures assessing osteophyte condition (ES=0.379, 95% CI: [-0.023, 0.780]), cartilage quality (ES=0.430, 95% CI: [-0.034, 0.893]), and cartilage morphology (ES=0.464, 95% CI: [-0.006, 0.934]). CONCLUSION: WB locomotion reduced the overall degree of knee PTOA in male rodents. Composite knee OA scores may be more responsive to exercise interventions than isolated cartilage/osteophyte measures. The benefits of locomotion may be more prominent with a longer follow-up time or with exercise protocols consisting of shorter but more individual sessions and longer overall intervention durations.

Animals

Bi-compartmental CSF-serum analysis of NfL and GFAP differentiates central and peripheral pathology in neuroinfectious diseases: A monocentric real-world cohort study.

Neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP), established biomarkers of neuroaxonal injury and astroglial pathology, are frequently only assessed in blood, which limits conclusions regarding their origin. Bi-compartmental analyses of CSF and serum may help differentiate central or peripheral origin of biomarker elevation. Moreover, studies on NfL and GFAP in distinct neuroinfectious disease (NID) phenotypes, particularly those based on real-world cohorts, are limited. This retrospective monocentric study analyzed CSF and serum from patients with (meningo-)encephalitis/myelitis (TI+; n&#xa0;=&#xa0;48), meningitis (TI-; n&#xa0;=&#xa0;80), (cranial) nerve palsies/polyradiculitis (PND; n&#xa0;=&#xa0;61), and 113 non-neuroinflammatory/non-neurodegenerative controls. A bi-compartmental model using scatter plots and simple linear regression was applied to assess the origin of blood biomarker levels and discriminate between central and peripheral pathology. CSF and serum NfL and GFAP z-scores were significantly higher in TI+ compared with TI- (CSF-GFAP p&#xa0;<&#xa0;0.001/sGFAP p&#xa0;=&#xa0;0.0083; CSF-NfL p&#xa0;=&#xa0;0.003/sNfL p&#xa0;=&#xa0;0.0004). TI+ and PND differed only in GFAP levels, which were higher in TI+ (CSF-GFAP p&#xa0;=&#xa0;0.0049/sGFAP p&#xa0;=&#xa0;0.003). The overall group effect (p&#xa0;&#x2264;&#xa0;0.003) and principal findings remained significant after adjustment for age, sex, QAlb, and time since (symptom) onset to LP. Bi-compartmental analysis revealed simultaneous elevation of CSF and serum NfL in TI+, indicating predominantly central origin, whereas PND demonstrated a shift toward higher sNfL levels suggesting peripheral origin. Higher clinical severity (modified Rankin Scale 3-5) was associated with elevated serum and CSF GFAP and NfL (sGFAP p&#xa0;=&#xa0;0.012/sNfL p&#xa0;=&#xa0;0.002; CSF-GFAP p&#xa0;<&#xa0;0.0001/CSF-NfL p&#xa0;=&#xa0;0.0001), which also predicted unfavorable outcome at discharge (sGFAP p&#xa0;=&#xa0;0.006/sNfL p&#xa0;=&#xa0;0.004; CSF-GFAP p&#xa0;=&#xa0;0.003/CSF-NfL p&#xa0;=&#xa0;0.012). NfL and GFAP were associated with brain/myelon involvement in NID, predominantly reflecting central pathology. Despite strong CSF-serum correlations, bi-compartmental approaches provide additional insight into biomarker origin and disease compartment.

Humans

Dual Transcranial Direct Current Stimulation Modulates Hierarchical Functional Network Organization in Post-Stroke Cognitive Impairment: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the clinical efficacy of dual transcranial direct current stimulation (tDCS) in patients with post-stroke cognitive impairment (PSCI) and to explore the effects on the hierarchical organization of functional brain networks, ranging from regional synchronization to inter-regional connectivity and global network topology. METHODS: In this randomized, double-blind, sham-controlled trial, 74 PSCI patients received conventional therapy alongside either active dual-tDCS (n&#x2009;=&#x2009;38) or sham stimulation (n&#x2009;=&#x2009;36). Active tDCS targeted the dorsolateral prefrontal cortex (DLPFC) via anodal-left/cathodal-right nodes (2.0&#x2009;mA, 20&#x2009;min/day, 20 sessions). The primary outcome was the Montreal Cognitive Assessment (MoCA). Secondary outcomes included the Mini-Mental Status Examination (MMSE), Stroop Test (ST), Trail Making Test (TMT), Wechsler Memory Scale (WMS), and Barthel Index (BI). A subgroup of 36 participants (18 per group) underwent resting-state functional magnetic resonance imaging (rs-fMRI) to analyze regional homogeneity (ReHo), functional connectivity (FC), and network topology. Partial correlations assessed the association between neuroimaging alterations and clinical improvements. RESULTS: The tDCS group showed significantly greater improvements in MoCA scores (tDCS: 5.74&#x2009;&#xb1;&#x2009;2.76 vs. sham: 2.69&#x2009;&#xb1;&#x2009;2.69; t&#x2009;=&#x2009;4.799, p&#x2009;<&#x2009;0.001) as well as in attention and memory domains compared to the sham group. The rs-fMRI changes included increased ReHo in the right middle temporal gyrus (MTG) and the left inferior frontal gyrus (IFG), and reduced FC between the right MTG-left superior frontal gyrus and left IFG-cerebellum (p&#x2009;<&#x2009;0.05, FWE-corrected). Additionally, small-worldness and global efficiency increased (p&#x2009;<&#x2009;0.05) with these alterations correlating with clinical recovery. Adverse events were rare and self-limiting. CONCLUSION: Dual-tDCS over bilateral DLPFC safely improves cognitive recovery in PSCI. These clinical gains are associated with rs-fMRI alterations, specifically in regional synchronization, inter-regional connectivity, and global topology, which suggest a potential biomarker for monitoring tDCS efficacy, offering a rationale for precision neuromodulation in stroke rehabilitation.

Humans

Adjunctive intermittent theta-burst stimulation for first-episode schizophrenia: A randomized clinical trial.

BACKGROUND: The efficacy of intermittent theta-burst stimulation (iTBS) combined with pharmacotherapy and psychotherapy in first-episode schizophrenia remains unclear. This study evaluated adjunctive iTBS with risperidone and cognitive behavioral therapy (CBT) and explored serum biomarkers indicating treatment response. METHODS: In this randomized, assessor-blind trial, 100 first-episode schizophrenia patients received either iTBS plus risperidone and CBT (iTBS group, n = 50) or risperidone and CBT alone (control, n = 50) for 3 months. The primary outcome was change in PANSS total score at 4 weeks and 3 months. Response was defined as a &#x2265; 50 % PANSS reduction. Secondary outcomes included cognitive function (MCCB subtests) and serum GDNF, cortisol, and dehydroepiandrosterone sulfate (DHEA-S) levels. RESULTS: The iTBS group showed significantly greater reduction in PANSS total scores than controls at both 4 weeks and 3 months (mean difference at 3 months: -13.3, 95 % CI: -16.8 to -9.8; P < 0.001), with a higher responder rate (76 % vs. 48 %). Significant improvements across all cognitive domains were observed in the iTBS group (all P < 0.001). Post-treatment, the iTBS group exhibited higher GDNF and lower cortisol and DHEA-S levels (all P < 0.001). A combined biomarker panel demonstrated superior discriminative performance for treatment efficacy (AUC=0.865 after cross-validation). Adverse events were comparable between groups. CONCLUSIONS: Adding iTBS to risperidone and CBT significantly improves clinical symptoms and cognitive function in first-episode schizophrenia. The combination of GDNF, cortisol, and DHEA-S shows promise as a composite biomarker for treatment response, though sham-controlled validation is warranted.

Humans

One Year After a Cyberattack: Lessons Learned and Dosimetric Analysis of Contingency Radiotherapy Plans.

PURPOSE: Cyberattacks on health care institutions pose significant risks to patient care, particularly in radiotherapy departments, which are heavily reliant on digital systems. This study examines the impact of a ransomware attack on our hospital and evaluates the effectiveness of the contingency measures implemented to resume radiotherapy treatments. METHODS AND MATERIALS: Following the cyberattack, our radiotherapy department faced a complete shutdown. After an initial estimate considering a shutdown of several weeks, a contingency plan was executed, including manual patient data retrieval and collaboration with a backup hospital. Contingency plans were prepared and delivered within hours, despite a partial lack of information. These plans allowed some patients to restart treatment 3 days after the attack. A dosimetric analysis was performed for the contingency plans, including various pathologies, mainly glioblastoma, head and neck cancers, and lung cancer. We compared the original and contingency plans in terms of dose coverage to the clinical target volume, biological effective dose, and their clinical impact as assessed at the 1&#x2011;year follow&#x2011;up after the cyberattack. RESULTS: Treatments resumed within 12 days at our hospital. Patients with glioblastoma showed good target coverage because of generous margins, resulting in favorable outcomes. In head and neck cases, the lack of detailed imaging led to significant target volume misses, suggesting that more conservative initial treatments could have been beneficial. Lung cases demonstrated accurate peripheral lesion targeting but faced challenges in central lesions because of the absence of positron emission tomography information. In most cases, the approach of using a contingency plan, even with limited information, led to a higher biological effective dose than would have been achieved if treatment had been stopped until full recovery at our hospital. CONCLUSIONS: The study highlights the critical importance of robust contingency planning in radiotherapy departments, emphasizing the need for backup systems and tailored approaches based on tumor location and available diagnostic information. These lessons emphasize that preparedness for digital disruptions should not focus exclusively on information and technology infrastructure.

Humans

Factors associated with additional intervention requirement following ESWL in pediatric patients with urolithiasis.

OBJECTIVE: To identify predictors of additional intervention following extracorporeal shock wave lithotripsy (ESWL) in pediatric patients and to develop a clinically applicable predictive model. MATERIALS AND METHODS: This retrospective cohort study included 647 pediatric patients who underwent ESWL between 2015 and 2025. Demographic, clinical, and radiological variables were analyzed. Univariable and multivariable logistic regression analyses were performed to identify independent predictors of additional intervention. Model performance was evaluated using receiver operating characteristic curve analysis. RESULTS: Additional intervention was required in 65 patients (10.0%). On multivariable analysis, stone size 10-20 mm (OR: 3.04, p = 0.003), moderate (OR: 2.16, p = 0.049) and severe hydronephrosis (OR: 6.05, p < 0.001), and multiple stones (OR: 3.52, p = 0.030) were identified as independent risk factors. Increasing age (OR: 0.84, p = 0.026), history of urolithiasis (OR: 0.41, p = 0.006), and lower calyx location (OR: 0.14, p = 0.034) were associated with a reduced risk. The model demonstrated good discriminative performance (AUC: 0.794), with a sensitivity of 72% and specificity of 75%. Internal validation using bootstrap resampling demonstrated stable model performance, yielding a corrected AUC of 0.732. CONCLUSION: Stone burden, hydronephrosis severity, and stone multiplicity are key determinants of additional intervention after ESWL in pediatric patients. The proposed model shows good predictive performance and may support individualized risk stratification and clinical decision-making.

Humans

Predictors of Efficacy Maintenance After Vunakizumab Discontinuation in Patients With Moderate-to-Severe Plaque Psoriasis: A Post Hoc Analysis of a Randomized Controlled Trial.

BACKGROUND: Efficacy cannot be maintained in some psoriasis patients after biological discontinuation. This study aimed to explore predictors of efficacy maintenance after vunakizumab discontinuation in patients with moderate-to-severe plaque psoriasis. METHODS: This post hoc analysis used data from a phase III trial (NCT04839016); 291 patients with moderate-to-severe plaque psoriasis who achieved 100% improvement in Psoriasis Area and Severity Index (PASI) score at Week 52 were enrolled. Efficacy maintenance was defined as patients who maintained PASI 90 or PASI 100 after 20&#x2009;weeks of vunakizumab discontinuation. RESULTS: There were 44.7% and 72.5% of patients with PASI 100 and PASI 90 maintenance, respectively. In the multivariate logistic regression model, body mass index (BMI) (odds ratio [OR]&#x2009;=&#x2009;0.922, p&#x2009;=&#x2009;0.024) and treatment interruption (OR&#x2009;=&#x2009;0.550, p&#x2009;=&#x2009;0.020) were independently associated with a lower possibility of PASI 100 maintenance; however, the association of family history of psoriasis and the first time of PASI 100 achievement with PASI 100 maintenance did not achieve statistical significance. Duration of psoriasis (OR&#x2009;=&#x2009;0.972, p&#x2009;=&#x2009;0.049) and treatment interruption (OR&#x2009;=&#x2009;0.257, p&#x2009;<&#x2009;0.001) were independently associated with a lower possibility of PASI 90 maintenance. Two nomograms for predicting PASI 90 and PASI 100 maintenance were constructed based on the multivariate models, which disclosed good calibration performance. CONCLUSIONS: PASI 90 and PASI 100 maintenance rates are 72.5% and 44.7% after 20&#x2009;weeks of vunakizumab discontinuation in patients with moderate-to-severe plaque psoriasis. BMI, treatment interruption, and duration of psoriasis predict a lower possibility of efficacy maintenance after vunakizumab discontinuation.

Humans

Systematic Review on the Effectiveness of Photobiomodulation Therapy on Enhancing Musculoskeletal Rehabilitation Outcomes after Total Knee and Hip Arthroplasty.

BACKGROUND: Total knee and hip arthroplasty (TKA/THA) effectively alleviate chronic pain and improve joint function and quality of life. However, postoperative recovery is often hindered by pain, edema, restricted range of motion (ROM), and muscle weakness, necessitating structured physical rehabilitation. Photobiomodulation Therapy (PBMT) has been proposed as an adjunct modality to enhance rehabilitation outcomes. This systematic review evaluates the efficacy of PBMT in reducing postoperative pain and edema as well as improving ROM and functional performance compared with placebo or standard physical therapy in post-arthroplasty patients. METHODS: A systematic search of PubMed, ProQuest, ScienceDirect, and Google Scholar was conducted from inception to May 31, 2025. Only prospective controlled trials assessing PBMT effects on postoperative pain, swelling, ROM, or functional performance following TKA or THA were included. Case reports, uncontrolled studies, and trials focusing on unrelated outcomes were excluded. Article selection involved title, abstract, and full-text screening, with additional studies identified through reference lists. The review is registered in PROSPERO (CRD420251123169). RESULTS: Four randomized controlled trials (RCTs; n = 133 participants) met the inclusion criteria, three studies focused on TKA, and one study examined THA. PBMT significantly improved postoperative pain and edema reduction in three trials, while two studies demonstrated enhanced ROM and functional outcomes compared with control or placebo interventions. PEDro scores ranged from 8 to 10, indicating moderate-to-high methodological quality. CONCLUSIONS: PBMT shows promising short-term benefits in reducing postoperative pain and swelling and improving functional performance after knee or hip arthroplasty. However, due to heterogeneity in treatment parameters and limited high-quality trials, conclusive evidence remains insufficient. Future large-scale RCTs with standardized PBMT parameters and extended follow-up are warranted to confirm its clinical efficacy.

Humans

Alarms and alarm management with automated versus conventional ventilation in neurocritical care patients.

INTRODUCTION: False or clinically irrelevant alarms are a major driver of ICU alarm fatigue and nursing workload. Ventilator alarms make up a large share, and although automated ventilation modes can reduce manual adjustments, their effect on alarm burden is still unclear. This issue can be particularly relevant in neurocritical care patients, where precise ventilator and alarm management is imperative for patient safety. OBJECTIVES: This explorative post hoc analysis of a randomized clinical trial compared alarm frequency and management between automated ventilation and conventional ventilation in neurocritical care patients. METHODS: Ventilator alarms and manual ventilator changes were captured continuously from the ventilator for up to 24&#xa0;h per patient. The primary endpoint was a composite of workload-relevant alarms; with alarm management interventions at the ventilator as a key secondary outcome. Additional endpoints included redundant alarms, alarm duration and ventilator management. RESULTS: 13 patients received automated ventilation and 24 received conventional ventilation. No difference was observed in workload-relevant alarm frequency between automated and conventional ventilation (3.28 [2.87 to 4.30] vs 3.73 [1.66 to 7.33] alarms per hour; P&#xa0;=&#xa0;0.81), while alarm management interventions at the ventilator were lower with automated ventilation (0.14 [0.10 to 0.15] vs 0.21 [0.17 to 0.31] interventions per hour; P&#xa0;=&#xa0;0.01). Other alarm frequencies, duration of alarms and ventilator management were similar. CONCLUSIONS: In this exploratory post hoc analysis of a randomized clinical trial in neurocritical care patients during the early phase of mechanical ventilation, automated ventilation did not reduce the frequency of total or workload-relevant alarms, nor their duration, but was associated with fewer alarm management interventions compared to conventional ventilation. IMPLICATIONS FOR CLINICAL PRACTICE: Automated ventilation may not reduce alarm frequency in neurocritical care patients, but the observed reduction in alarm-related bedside interventions suggests a potential benefit for nursing workload.

Humans

Efficacy and safety of endoscopic ultrasound-guided choledochoduodenostomy compared with endoscopic ultrasound-guided gallbladder drainage for palliation of malignant distal biliary obstruction: a systematic review and meta-analysis.

BACKGROUND AND AIMS: When ERCP is not feasible or fails in the palliation of malignant distal biliary obstruction (MDBO), EUS-guided choledochoduodenostomy (EUS-CDS) and EUS-guided gallbladder drainage (EUS-GBD) are viable alternatives. We conducted a systematic review and meta-analysis comparing the safety and efficacy of the 2 techniques for the palliation of MDBO. METHODS: Multiple databases were searched through November 2025 for studies that reported outcomes of EUS-CDS and EUS-GDB in patients with MDBO. A meta-analysis was performed to determine pooled proportions and relative risk (RR) with 95% CIs. We compared the rates of technical and clinical success, overall adverse events (AEs), and lumen-apposing metal stent dysfunction. A random-effects model was used for our meta-analysis, and heterogeneity was assessed using the I2 (%) statistics. RESULTS: Five studies (352 patients; EUS-CDS: 193 and EUS-GBD: 159) were included. Technical success was 93.3% (95% CI, 70.6-98.8) for EUS-CDS and 95.9% (95% CI, 90.0-98.4) for EUS-GBD (RR, 1.02; 95% CI, 0.94-1.10; P = .6). Clinical success was 90.1% (95% CI, 84.7-93.7) versus 86.6% (95% CI, 80.3-91.0) (RR, 0.97; 95% CI, 0.90-1.05; P = .4). There were no significant differences in overall AEs (19.7% vs 17.6%; RR, 0.93; 95% CI, 0.58-1.48; P = .8), severe AEs (11.0% vs 8.3%; RR, 0.69; 95% CI, 0.33-1.44; P = .3), or stent dysfunction (15.0% vs 14.5%; RR, 0.95; 95% CI, 0.35-2.58; P = .9). CONCLUSIONS: EUS-GBD appears comparable to EUS-CDS in terms of technical and clinical success, AEs, and stent dysfunction. Further prospective studies are warranted to corroborate our findings.

Humans

Understanding FDA's reasons for nonapproval: A systematic review of complete response letters in cell and gene therapy.

BACKGROUND AIMS: Cell and gene therapy products face unique regulatory challenges due to their biological complexity and the stringent expectations for manufacturing control, analytical testing, and clinical assessment. As the pipeline grows, understanding the drivers of FDA non&#x2011;approval is increasingly important for improving first&#x2011;cycle success and reducing development delays. In this study, we aimed to characterize the frequency and impact of refuse&#x2011;to&#x2011;file actions, major amendments, and complete response letters issued for biologics licensing applications; and to identify recurring patterns of deficiencies contributing to delayed approval. METHODS: Publicly available documents were extracted from the FDA website. Data from each approved cell and gene therapy product's regulatory history-including complete responses, major amendments, inspection timing, and cited deficiencies-were compiled and categorized across clinical, quality, and labeling domains. RESULTS: Analysis showed that informational deficiencies were common across modalities. Major amendments occurred in roughly half of applications, and complete responses had the most significant impact. Quality deficiencies appeared in all complete responses and were the predominant barrier, while clinical and labeling issues were less frequent but meaningful when present. CONCLUSION: Overall, these findings highlight the need for proactive FDA engagement, comprehensive readiness, and early inspection preparation to reduce regulatory risk and improve first cycle approval outcomes.

Humans

Criteria for Safe Hospital Discharge in Bronchiolitis: A Systematic Review.

Bronchiolitis is the leading cause of hospital presentation and admission for infants in Australasia. We aimed to synthesise current evidence on the effect of discharge criteria for infants (aged <&#x2009;12&#x2009;months) who are presenting to or are admitted to hospital with bronchiolitis, to inform a binational guideline recommendation update. Systematic searches were conducted on MEDLINE, EMBASE, PubMed, Cochrane Library and CINAHL (last search 19 February 2025) for non-randomised studies evaluating hospital discharge criteria in bronchiolitis. The primary outcomes were length of stay (LOS) and readmission rates. The risk of bias (ROBINS-I) and certainty of the evidence (GRADE) were appraised, and findings were narratively synthesised. GRADE evidence-to-decision methodology, expert consensus voting and interest-holder consultation were used to finalise the recommendation update. Two retrospective observational studies were included (N&#x2009;=&#x2009;2697) (low to very low quality), reporting on unique discharge criteria. In both studies, use of the discharge criteria was associated with a significant reduction in LOS relative to alternative protocols. There was no significant difference in readmission rates observed in either study. There was low to very low certainty evidence across outcomes due to risk of bias, indirectness and imprecision. The review findings informed a recommendation update for safe discharge criteria in the 2025 Australasian Bronchiolitis Guideline update. Updated, prescriptive discharge criteria and flow chart were developed, covering clinical stability, oxygen saturation/support, feeding difficulties, caregiver confidence and education on deterioration, social factors and follow-up. The revised criteria provide clinicians with increased certainty in decision-making in bronchiolitis, albeit with further research needed.

Humans