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Robotic Needle Insertion for CT-guided Percutaneous Biopsy of Thoracoabdominal Lesions: A Prospective Multicenter Randomized Trial.

Purpose To compare safety and feasibility between a novel CT-guided robotic system and the conventional freehand technique for puncture biopsy of thoracoabdominal lesions. Materials and Methods In this prospective multicenter randomized trial, individuals with suspected lesions were enrolled between July 2023 and April 2024 across three university teaching hospitals and randomized to the robot-assisted group (n = 82) or the freehand group (n = 83). Procedure outcomes included the technical success rate, targeting error, number of CT scans and needle adjustments, puncture time, and complications. Descriptive and inferential statistics were calculated. Results A total of 165 participants (mean age, 60 years &#xb1; 10 [SD]; 83 male) were included. Compared with the freehand group, the robot-assisted group demonstrated a higher technical success rate (97.56% [80 of 82] vs 62.65% [52 of 83], P < .001), lower targeting error (mean Euclidean deviation: 1.7 mm &#xb1; 1.1 vs 4.5 mm &#xb1; 3.9, P < .001), and fewer CT scans (mean, 4.3 &#xb1; 1.9 vs 5.2 &#xb1; 2.3; P = .002) and needle adjustments (mean, 0.7 &#xb1; 0.7 vs 1.6 &#xb1; 1.6; P = .003). Despite differences in geometric precision, both groups achieved 100% (82 of 82 and 83 of 83) diagnostic yield. The median puncture time was comparable between groups (5.5 minutes &#xb1; 4.3 vs 4.8 minutes &#xb1; 7.0, P = .50). During lung biopsies, the robot-assisted approach yielded fewer complications compared with the freehand approach (4.88% [four of 82] vs 16.87% [14 of 83], P = .014). Conclusion Compared with the freehand approach, robot-assisted biopsy yielded greater precision and reduced adjustments and complications while demonstrating noninferior diagnostic efficacy and comparable duration. Keywords: Robotic Needle Insertion, Biopsy, Thoracoabdominal Lesions, Robot-assisted Biopsy, CT-guided Intervention, Percutaneous Needle Biopsy, Randomized Controlled Trial, Algorithm Development, CT, Clinical Testing, Interventional-Body, Biopsy/Needle Aspiration, Percutaneous, Thorax, Abdomen/GI, Liver, Lung, Kidney &#xa9;RSNA, 2026.

Humans

Navigated repetitive transcranial magnetic stimulation for post-stroke recovery: A systematic review and meta-analysis of randomized controlled trials.

Repetitive transcranial magnetic stimulation (rTMS) is a subcategory of non-invasive brain stimulation (NIBS), used to modulate brain plasticity and improve post-stroke recovery. Neuronavigation is used to improve the accuracy of stimulation with the aim of achieving a superior clinical outcome than with conventional targeting. The objective of this review is to evaluate the efficacy of navigated rTMS in subacute and chronic stroke patients in comparison to sham stimulation. We conducted a systematic-review and meta-analysis of randomized controlled trials (RCTs) identified from Pubmed, Scopus and Cochrane CENTRAL. Trials employing neuronavigated rTMS were included of these five types; high and low frequency rTMS, intermittent and continuous theta-burst stimulation (TBS) and Hebbian-type stimulation. 13 RCTs were included after a screening of 1900 studies. 606 patients receiving either active (n&#xa0;=&#xa0;360) or sham stimulation (n&#xa0;=&#xa0;246) were assessed. The pooled standardized mean difference (SMD) favored rTMS over sham SMD&#xa0;=&#xa0;0.4 (95&#xa0;%CI: 0.11-0.69), with moderate heterogeneity I2&#xa0;=&#xa0;55&#xa0;%. Among stimulation modalities, continuous TBS showed the largest pooled effect. rTMS was also associated with significant improvements in disability-related outcomes, SMD&#xa0;=&#xa0;0.61 (95&#xa0;% CI 0.14-1.08). Navigated rTMS is associated with modest but significant improvements in motor and disability outcomes in subacute and chronic stroke. Large comparative trials are required to clarify the potential added value over conventional targeting approaches.

Humans

Glycemic and safety outcomes of the insulin-only bionic pancreas in older adults and individuals with impaired awareness of Hypoglycemia: a post hoc analysis of a randomized pivotal trial.

AIMS: Evaluate the efficacy and safety of iLet Bionic Pancreas (BP) in older adults and individuals with impaired awareness of hypoglycemia (IAH). METHODS: This post hoc analysis used individual participant-level data from the Insulin-Only Bionic Pancreas Pivotal Trial (n&#xa0;=&#xa0;440; NCT04200313). Eligible participants (n&#xa0;=&#xa0;96) with type 1 diabetes, aged&#xa0;&#x2265;&#xa0;60&#xa0;years and/or had IAH (Clarke score&#xa0;&#x2265;&#xa0;4), were randomized to BP with aspart/lispro (BP-Asp/Lis; n&#xa0;=&#xa0;45), BP with fast-acting aspart configuration (BP-Fiasp; n&#xa0;=&#xa0;31), or standard care (SC; n&#xa0;=&#xa0;20) for 13&#xa0;weeks. RESULTS: Compared with SC, time-in-range (70-180&#xa0;mg/dL) significantly increased by 7.49&#xa0;% (95&#xa0;% CI: 2.61 to 12.38; &#x223c;1.8&#xa0;h/day) with BP-Asp/Lis and by 8.28&#xa0;% (95&#xa0;% CI: 3.15 to 13.41; &#x223c;2.0&#xa0;h/day) with BP-Fiasp, driven by reduced hyperglycemia. No significant differences were observed in hypoglycemia exposure. Severe hypoglycemia occurred in four participants (four events) on BP-Asp/Lis and one participant (two events) on SC. One diabetic ketoacidosis event occurred on BP-Fiasp due to an infusion set failure. CONCLUSIONS: In high-risk, clinically vulnerable populations, the BP system significantly improved glycemic control while maintaining safety parity with respect to hypoglycemia risk, providing a resilient therapeutic alternative for vulnerable cohorts.

Humans

Ultrasound-guided high-voltage vs conventional pulsed radiofrequency in elderly cervical radiculopathy: A randomized controlled trial.

BACKGROUND: Elderly patients with cervical radiculopathy present therapeutic challenges owing to comorbidities and medication-related risks. Long-term pharmacotherapy and surgical interventions are often suboptimal, necessitating evaluation of optimized pulsed radiofrequency strategies under image guidance. OBJECTIVES: This superiority trial compared the efficacy and safety of ultrasound-guided cervical nerve root high-voltage pulsed radiofrequency (HVP-PRF) versus conventional pulsed radiofrequency (C-PRF) for pain management in elderly patients with cervical radiculopathy. METHODS: This single-center, parallel-group, assessor-blinded randomized controlled trial enrolled patients aged 60-85 years with cervical radiculopathy, randomly assigned (1:1) to HVP-PRF (70 V) or C-PRF (45 V). Procedures were performed under ultrasound guidance with sensory/motor stimulation confirmation and temperature &#x2264;42&#xb0;C. The primary outcome was change in upper-limb radiating pain on the Numeric Rating Scale (&#x394;NRS) from baseline to 3 months. Secondary outcomes included Neck Disability Index (NDI), neck pain NRS, Patient Global Impression of Change, responder rates, rescue analgesia use, and adverse events. Follow-up occurred at 1 week, 1, and 3 months. RESULTS: A total of 104 patients were randomized and 101 received treatment. At 3 months, HVP-PRF demonstrated significantly greater radiating pain improvement versus C-PRF (adjusted mean difference 1.24, 95% CI 0.46-2.02, P=0.002). Functional improvement (NDI) was superior in the HVP-PRF group at 3 months (AMD 6.47, 95% CI 2.11-10.83, P=0.004). Responder rates (&#x2265;50% pain reduction) were higher with HVP-PRF at 3 months (68.75% vs. 42.22%, OR 3.01, P=0.011) and 6 months (65.22% vs. 43.18%, OR 2.52, P=0.035). Rescue analgesic use was lower in the HVP-PRF group during 1-3 months intervals (both P<0.05). Adverse event rates were comparable (27.45% vs. 32.00%). CONCLUSION: Under ultrasound visualization and electrical stimulation-based target confirmation with temperature control &#x2264;42&#xb0;C, HVP-PRF provided greater and more durable relief of upper limb radiating pain compared with C-PRF in elderly patients with cervical radiculopathy, with a comparable safety profile.

Humans

King's Mill anterior-posterior and transverse versus paracervical block in operative outpatient hysteroscopy: a randomised trial.

BACKGROUND: Pain control during operative outpatient hysteroscopy remains a clinical challenge, with the paracervical block (PCB) showing inconsistent efficacy. The King's Mill Anterior-Posterior and Transverse (KAPT) block targets the Lee-Frankenhauser plexus within the uterosacral ligament complex, where the highest density of uterine and cervical sensory fibres lies. We compared the KAPT block with the PCB in operative outpatient hysteroscopy. METHODS: Single-centre, participant- and outcome assessor-blinded randomised controlled trial in a UK district general hospital. Forty-eight women undergoing operative outpatient hysteroscopy were randomised 1:1 to the KAPT block or the PCB, each delivered with 10&#x2009;ml of prilocaine. Pain was measured on a 10-point Visual Analogue Scale (VAS) during the procedure and 10&#x2009;minutes post-procedure (co-primary endpoints), and during cervical dilatation (exploratory). Analyses used the Mann-Whitney U test on an intention-to-treat basis, with Hodges-Lehmann median differences, percentile bootstrap 95% confidence intervals, and a hierarchical fixed-sequence testing strategy. RESULTS: Median intra-procedural VAS was 1 (IQR 0 to 3) with the KAPT block versus 2 (IQR 1 to 6) with the PCB (Hodges-Lehmann median difference -1.00, 95% CI -3.00 to 0.00; p&#x2009;=&#x2009;0.040). At 10&#x2009;minutes post-procedure, median VAS was 0 (IQR 0 to 1.25) versus 2 (IQR 0 to 3.25) (median difference -1.00, 95% CI -2.00 to 0.00; p&#x2009;=&#x2009;0.011). Both co-primary endpoints reached significance under hierarchical testing. Cervical dilatation pain did not differ significantly (p&#x2009;=&#x2009;0.146). Satisfaction was 100% in both arms; willingness to recommend was 100% (KAPT) versus 95.8% (PCB). No serious adverse events occurred. CONCLUSIONS: The KAPT block was associated with lower intra-procedural and post-procedural pain than the PCB, with effect sizes consistent with a clinically meaningful difference. These findings support the KAPT block as a superior, anatomically targeted alternative to the PCB and justify evaluation in a larger multicentre trial.Trial registration: ISRCTN15619382.

Humans

Digital health interventions for diabetes management in the eastern mediterranean region: A systematic review of types and effectiveness.

AIM: The aim of this study was to systematically review and evaluate the types and effectiveness of digital health interventions used for diabetes management in the Eastern Mediterranean Region (EMRO). METHODS: This systematic review, conducted according to PRISMA guidelines, searched PubMed, Web of Science, and Scopus up to May 2025 to identify studies on digital interventions for diabetes management in EMRO countries. Methodological&#xa0;quality of the included studies was evaluated using the EPHPP tool, and findings were categorized by intervention type, outcome measures, and intervention effectiveness. RESULTS: A total of 46 studies were included, mainly from Iran and Saudi Arabia. Phone calls and SMS were the most common digital tools. Digital interventions significantly improved HbA1c, fasting blood sugar, and several behavioral outcomes such as physical activity, medication adherence, and self-efficacy, while effects on psychological outcomes were mixed. CONCLUSION: Digital health interventions, especially phone calls and SMS, effectively improve glycemic control and self-care behaviors, though their impact on psychological outcomes remains inconsistent.

Humans

Infant Dietary Patterns and Early Childhood Weight Outcomes: A Secondary Analysis from the Starting Early Program Trial.

BACKGROUND: The Starting Early Program (StEP) promotes healthy nutrition during early life and leads to healthier child weight, but whether dietary patterns contribute to weight or mediate StEP weight outcomes has not been studied. OBJECTIVES: This secondary analysis identified infant dietary patterns in StEP, determined associations between dietary patterns and child weight outcomes, and examined whether dietary patterns mediated the relationship between StEP and child weight. METHODS: Data were from 377 mother-infant dyads in a randomized trial testing the efficacy of StEP. Dietary patterns at 10 months were identified using latent class analysis. Child weights were abstracted from medical records at 12, 24, and 36 months. Associations between infant dietary patterns and weight-for-age z-score (WFAz) and likelihood of being classified as overweight (WFA &#x2265;85th percentile) were assessed using linear and logistic multivariable regression models. Mediation was used to assess intervention effects on WFAz via impacts on infant dietary patterns. RESULTS: Four classes of infant dietary patterns were identified: Breastfed-High variety, Formula fed-High variety, Formula fed-Low variety, and Mixed fed-Low variety. Compared to the Breastfed-High variety class, infants in the Formula fed-Low variety class had higher WFAz and were more likely to be classified as overweight at 24 and 36 months. Participation in StEP increased membership in Breastfed-High variety, which mediated the association between StEP and lower WFAz at 24 months. CONCLUSIONS: Infant dietary patterns were identified, and some were associated with child overweight. StEP was associated with a dietary pattern most consistent with guidelines, which mediated intervention effects on child weight.

Humans

Cisplatin-Induced Hearing Loss Prevention With Intratympanic Therapy Systematic Review and Meta-Analysis.

INTRODUCTION: Cisplatin-induced hearing loss (CIHL) is a well-described, long-term consequence of cisplatin treatment for malignancy. Intratympanic (IT) injections have been trialed to prevent CIHL in humans. To provide clarity on which agents have been studied through IT injection and to review their efficacy for hearing loss prevention, we performed a systematic review and meta-analysis. DATA SOURCES: OVID Medline, Embase, Web of Science, and Cochrane Library were queried. METHODS: Databases were searched in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Prospective randomized trials were included, and a systematic review was performed for all studies. Demographic, audiometric, and therapeutic data were collected. Random-effects models were used to compare across studies, and subgroup analyses were performed for each IT agent. RESULTS: The initial database search yielded 1017 articles, which were screened according to inclusion and exclusion criteria. Ten studies were identified, involving a total of 284 patients. Studies included data on IT dexamethasone, IT N-acetylcysteine (NAC), and IT sodium thiosulfate (STS). Pooled analysis across all agents and frequencies did not reveal a significant difference in hearing thresholds between treatment and control ears [prediction interval [-3.77, 3.20], negative favors treatment). Subgroup analysis of IT dexamethasone [-1.74, 3.80] and IT NAC [-1.02, 4.64] also did not demonstrate significant differences. STS data were not amenable to pooled analysis; however, one study demonstrated a significant decrease in ASHA-defined ototoxicity (40% vs. 85%, P =0.0027). CONCLUSIONS: To date, no IT agent has consistently prevented CIHL, although limited data suggest that IT STS may decrease ototoxicity. More trials are necessary to fully elucidate these effects.

Humans

Cationic porphyrin covalent organic framework reinforced hydroxypropyl methylcellulose films for photodynamic-photothermal sterilization and food preservation.

Microbial contamination in food necessitates effective antimicrobial packaging. While cellulose-based packaging materials suffer from limited antimicrobial efficacy, lack of active functionality, and susceptibility to inducing microbial resistance. To address these challenges, this study synthesized a cationic porphyrin-based covalent organic framework (Por-ICOF) as a multimodal photosensitizer. Por-ICOF was uniformly dispersed via non-covalent interaction within hydroxypropyl methylcellulose (HPMC), creating an HPMC/Por-ICOF composite film. This integration enhanced mechanical strength (increased by 26%), hydrophobicity (WCA 71&#xb0;), and gas barrier properties (OP reduced by 42%, WVP reduced by 36%). Under visible light, the HPMC/Por ICOF film superior absorption generated reactive oxygen species (ROS) and photothermal effects, inactivating 99.2% of Escherichia coli and 99.95% of Staphylococcus aureus within 20&#xa0;min. The composite film exhibited excellent biocompatibility and effectively extended the shelf life of strawberries. This cationic modification strategy for cellulose-based films offers a novel avenue for the design of high-performance antimicrobial food packaging materials.

Food Preservation

Once-weekly IcoSema versus once-daily insulin glargine U100 in type 2 diabetes management (COMBINE 4): an open-label, multicentre, treat-to-target, randomised, phase 3b trial.

BACKGROUND: Stepwise treatment intensification is recommended for managing type 2 diabetes, including insulin initiation when non-insulin glucose-lowering medications are insufficient. Guidelines recommend combining a GLP-1 receptor agonist with basal insulin to improve glycaemic efficacy while reducing weight gain and hypoglycaemia risk. COMBINE 4 evaluated the efficacy and safety of IcoSema, a once-weekly combination therapy of basal insulin icodec and semaglutide (a GLP-1-receptor agonist) versus insulin glargine U100 (glargine U100) in people with type 2 diabetes on oral glucose-lowering medications. METHODS: COMBINE 4 was a 40-week, randomised, open-label, treat-to-target, phase 3b trial conducted across 97 sites in nine countries. Adults (aged &#x2265;18 years) with type 2 diabetes (HbA1c &#x2265;8&#xb7;0%) receiving oral glucose-lowering medications were randomly allocated in a 1:1 ratio without stratification to IcoSema or once-daily glargine U100. The titration target was 3&#xb7;9-5&#xb7;0 mmol/L (70-90 mg/dL). The primary endpoint was change in HbA1c and the secondary confirmatory endpoint was change in bodyweight, both from baseline to week 40, evaluated in all randomly allocated participants. Adverse events were recorded during weeks 0-45. This trial is registered with ClinicalTrials.gov (NCT06269107) and is complete. FINDINGS: Of 653 individuals screened between Feb 15 and Aug 6, 2024, 151 did not meet screening criteria and 17 withdrew before initiating treatment; 243 were randomised to IcoSema and 242 to glargine U100. Of the 485 randomly allocated participants, 286 (59%) were male and 199 (41%) were female, and median age was 58 years (range 26-82). For HbA1c, from baseline (9&#xb7;57% for IcoSema and 9&#xb7;50% for glargine U100), mean change to week 40 was greater with IcoSema versus glargine U100 (-3&#xb7;32 vs -2&#xb7;44 percentage points; estimated treatment difference [ETD] -0&#xb7;88 percentage points [95% CI -1&#xb7;12 to -0&#xb7;63]), confirming superiority of IcoSema (p<0&#xb7;001). From baseline to week 40, mean bodyweight decreased with IcoSema and increased with glargine U100 (-0&#xb7;79 vs 3&#xb7;81 kg; ETD -4&#xb7;61 kg [95% CI -5&#xb7;46 to -3&#xb7;75]), confirming superiority of IcoSema (p<0&#xb7;001). Rate of combined clinically significant (blood glucose <3&#xb7;0 mmol/L [<54 mg/dL], confirmed with a blood glucose meter) or severe hypoglycaemia (severe cognitive impairment requiring external assistance for recovery) was statistically significantly lower with IcoSema versus glargine U100 (0&#xb7;29 vs 0&#xb7;59 episodes per person-year of exposure; estimated rate ratio 0&#xb7;56 [95% CI 0&#xb7;32 to 0&#xb7;97]; p=0&#xb7;04). Gastrointestinal disorders were the most frequently reported adverse events with IcoSema. INTERPRETATION: Once-weekly IcoSema demonstrated superior HbA1c reduction and bodyweight change, with lower rates of clinically significant or severe hypoglycaemia, versus glargine U100, suggesting that IcoSema might be an effective once-weekly treatment option for insulin-naive individuals with type 2 diabetes inadequately controlled on oral glucose-lowering medications. FUNDING: Novo Nordisk.

Humans

Comparison of a Modified Regimen of Prophylactic Phenylephrine Boluses Versus Variable Rate Infusion During Elective Cesarean Delivery Under Spinal Anesthesia: A Noninferiority Randomized Double-Blind Study.

BACKGROUND: Prophylactic phenylephrine boluses have been found to be as effective as variable rate infusions during elective cesarean delivery but require a higher number of physician interventions to maintain blood pressure near baseline values. Therefore, there is a need to find a feasible regimen of bolus administration that is equally efficacious to the infusion regimen while at the same time requires a comparable number of physician interventions and is thus non-inferior to the infusion regimen. METHODS: Healthy pregnant women with term, uncomplicated, singleton pregnancies undergoing elective cesarean delivery under spinal anesthesia were randomly divided into two groups. The Bolus group received a phenylephrine bolus 100 &#x3bc;g immediately after spinal anesthesia and then at every systolic blood pressure value <90% of the baseline. The infusion group received a prophylactic variable-rate infusion of phenylephrine beginning at 50 &#x3bc;g/min and titrated to maintain systolic blood pressure at 90-99% of baseline. The primary outcome was the number of physician interventions needed to maintain the target systolic blood pressure; the secondary outcomes included phenylephrine requirements, incidence of hypotension/hypertension/bradycardia, umbilical arterial and venous blood gas analysis, Apgar scores, and maternal complications. The primary outcome was analyzed in terms of non-inferiority using a non-inferiority margin of two interventions. RESULTS: Eighty patients were included in the study. The median (interquartile range [IQR]) number of physician interventions was 6 (5-8) in the infusion group and 3 (2-4) in the bolus group (P < .001). The difference of medians (95% confidence interval [CI]) between the two groups was -3 (-4 to -2). Phenylephrine requirements were higher in the infusion group (630 [426-765] &#x3bc;g) compared to the bolus group (300 [200-400] &#x3bc;g; P < .001). Blood pressure was higher at certain time points in the infusion group, but overall accuracy of blood pressure control was not different between the groups. Incidence of hypotension, hypertension, and bradycardia, neonatal outcomes, and maternal complications did not differ between the groups. CONCLUSIONS: The modified regimen of prophylactic boluses is non-inferior to variable rate prophylactic phenylephrine infusion in terms of physician interventions needed to maintain systolic blood pressure within the target range and maternal and neonatal outcomes.

Humans

Comparison of analgesic treatments used for ankle sprains in the emergency department.

BACKGROUND: Ankle sprains (ASs) account for approximately 5% of emergency department visits and 40% of all sports-related injuries, causing significant pain and restriction in the range of motion (ROM). This study aims to observe the clinical outcomes of early administration of intravenously administered paracetamol, ibuprofen, and dexketoprofen, which are frequently used in emergency department practice for ASs. For this purpose, pain monitoring and ROM measurements were performed to demonstrate the effectiveness of early functional analgesia. METHODS: This prospective, randomized, double-blind study was conducted between December 2023 and May 2024 on patients diagnosed with grade 1-2 ASs in the emergency department. Patients were divided into three groups and received intravenous dexketoprofen (Group D, n=52), paracetamol (Group P, n=52), and ibuprofen (Group I, n=51). Pain assessment was performed using the numeric rating scale (NRS) and the Wong-Baker FACES Pain Scale (WBS). ROM was evaluated by measuring dorsiflexion ROM (d-ROM) and plantar flexion ROM (p-ROM) angles using a semicircular goniometer. Pre-treatment and 1-h post-treatment measure-ments were compared. RESULTS: In the post-treatment pain assessment, no significant difference was observed between the groups in terms of NRS scores (p=0.352); however, Group I had the lowest WBS scores (p<0.001). Nevertheless, in all three groups, post-treatment pain scores (NRS and WBS) were significantly lower compared to pre-treatment values (p<0.001). Regarding ROM, pre-treatment d-ROM and p-ROM values were similar among the groups (p=0.196) and p=0.287, respectively). Post-treatment measurements revealed that d-ROM was lower in Group I (p=0.034), whereas p-ROM was higher (p=0.011). However, in all groups, ROM values significantly improved after treatment compared to baseline (p<0.001). When pre- and post-treatment changes (&#x394;) in pain scores and ROM values were compared, no statistically significant differences were found between the groups (&#x394;NRS p=0.264, &#x394;WBS p=0.965, &#x394;d-ROM p=0.099, &#x394;p-ROM p=0.073). CONCLUSION: Paracetamol, ibuprofen, and dexketoprofen demonstrated similar efficacy in reducing pain and improving ankle joint ROM during the acute phase of ASs. These findings suggest that the early initiation of analgesic treatment in ASs contributes to clinical recovery.

Humans

The Effect of Pain Catastrophizing on Acupuncture Treatment for Chronic Pain in Cancer Survivors.

CONTEXT: Pain catastrophizing (PC) predicts worse pain outcomes in cancer survivors. However, little is known whether PC influences pain outcomes of nonpharmacological treatments such as acupuncture. OBJECTIVES: This study aimed to assess the impact of PC on acupuncture efficacy for chronic pain in cancer survivors. METHODS: This secondary analysis of PEACE trial used two-sample t-test and Pearson's chi-squared test to analyze the pain outcomes of cancer survivors who received electroacupuncture (EA) or battlefield acupuncture (BFA). PC was measured using Pain Catastrophizing Scale (PCS). The Brief Pain Inventory (BPI) was used to measure pain severity and interference at the primary endpoint (week 12). RESULTS: Among 266 participants, 41 (15.41%) had a high baseline PC. Among those receiving EA, high PC patients had greater reductions in pain severity (-3.9 vs. -2.1, P = 0.006) and pain interference (-3.8 vs. -2.6, P = 0.04) than low PC. PC was not associated with pain outcomes in BFA group (P > 0.05 for both severity and interference). Among patients with high PC, a greater proportion were responders in the EA group than those in BFA group (83.3% vs. 43.5%, P = 0.009). Among low PC patients, there was no significant difference in the proportion of responders between the EA and BFA groups (66.1% vs. 64.5%, P = 0.8). CONCLUSION: We found that cancer survivors with high baseline PC had greater pain reductions with EA than BFA and compared to low PC patients. These findings suggest that EA may serve as a targeted treatment option for vulnerable patients with high PC and further support precision pain management.

Humans

Sex differences in sleep and alcohol consumption outcomes following a digital insomnia intervention.

BACKGROUND: Poor sleep is a well-established risk factor for heavy drinking, and evidence suggests that sleep could serve as a potential treatment target for reducing alcohol consumption. The relationship between poor sleep and problematic drinking appears to be stronger among females, but no studies to date have assessed sex differences in alcohol consumption following insomnia treatment. Here, we combine the samples from two clinical trials to investigate sex differences in the effects of a digital cognitive behavioral therapy for insomnia (Sleep Healthy Using the Internet; SHUTi) on sleep and alcohol outcomes. METHODS: 184 heavy drinking individuals with insomnia (weekly binge episodes: 4/5&#x2009;+ drinks in one sitting for females/males; AUDIT score >7; ISI score >14) were randomly assigned to either the SHUTi program (n&#x2009;=&#x2009;102) or an active control program (n&#x2009;=&#x2009;82). Participants completed self-report assessments at baseline, immediately following the 9-week intervention period, and at 3 and 6-months post-intervention. RESULTS: Linear mixed effects models showed that SHUTi effects over time were stronger among females than males for improved sleep outcomes and reduced frequency of total and heavy drinking days (ps &#x2264; 0.038). Follow-up comparisons of within-group effect sizes revealed consistently larger reductions in alcohol consumption among SHUTi females (Cohen's d range = 0.92-2.23) than SHUTi males (Cohen's d range = 0.65-1.95). CONCLUSIONS: Findings suggest that SHUTi may be more efficacious in improving sleep and reducing drinking among females with insomnia compared to males. These results could have important implications for sex-specific prevention and treatment efforts for heavy drinking individuals with insomnia.

Humans

CAR-T Cell Therapy: Manufacturing Platforms and Clinical Consequences.

Chimeric antigen receptor (CAR) T-cell therapy has transformed hematological cancer care, yet variability in efficacy, durability, and safety cannot be explained solely by antigen selection or patient factors. We propose that manufacturing platforms are active biological determinants of outcome. Viral vectors, used in all licensed products, provide stable genomic integration and durable expression but are limited by cost, cargo capacity, and centralized production. Nonviral strategies, including transposons, CRISPR knock-ins, and messenger RNA delivery, enable faster, less-expensive manufacturing with larger payloads, while introducing distinct safety and persistence profiles. This review presents a three-layer mechanistic framework that reframes manufacturing as biology: integration biology determines genomic risk and transgene stability; clonal fitness shapes persistence, dominance, and exhaustion; and epigenomic imprinting, influenced by gene transfer method, cytokines, and culture stress, preconfigures functional trajectories. Clinical observations link platform choice to immune recovery, where prolonged B-cell aplasia and delayed T-cell reconstitution contribute to infection-related nonrelapse mortality, and hematopoietic reserve at apheresis emerges as a practical predictor. Finally, manufacturing is positioned as the key to democratizing cell therapy. Decentralized, nonviral production aligned with regulatory standards may enable equitable access and transition CAR-T therapy from innovation to sustainable global care.

Humans

Choice of Anesthesia in Microelectrode Recording-guided Deep Brain Stimulation Surgery for Parkinson's Disease (CHAMPION): A Noninferiority Randomized Controlled Trial.

BACKGROUND: Deep brain stimulation for Parkinson's disease is often performed under conscious sedation or general anesthesia. However, anesthetic agents may influence intraoperative microelectrode recording, and the optimal anesthesia method for microelectrode recording remains unclear. This study compared general anesthesia and conscious sedation in preserving microelectrode recording signal intensity during deep brain stimulation. METHODS: In this prospective, noninferiority randomized controlled trial, patients with Parkinson's disease (United Kingdom Brain Bank criteria) undergoing elective bilateral surgery were randomized 1:1 to the conscious sedation or the general anesthesia group. During surgery, a desflurane anesthetic titrated against the quality of the electrophysiologic signal was applied in the general anesthesia group, whereas patients in the conscious sedation group received dexmedetomidine anesthesia. The primary outcome was the proportion of patients with high-quality microelectrode recording (normalized root mean square greater than 2.0), assessed postoperatively off-line. Secondary outcomes included operation and recording duration, 6-month clinical efficacy, and complication rates. RESULTS: Of 188 randomized patients (94 general anesthesia, 93 conscious sedation), desflurane anesthesia was noninferior for high normalized root mean square proportion (89.4% vs . 90.3%; difference, -0.96%; 95% CI, -9.62 to 7.70). The general anesthesia group had shorter operative time (difference, -9.07&#x2009;min; 95% CI, -13.99 to -4.14; P < 0.001). At 6 months, changes in Unified Parkinson's Disease Rating Scale score (difference, -2.50; 95% CI, -7.20 to 2.20; P = 0.297), levodopa equivalent daily dose (difference, -58.4&#x2009;mg; 95% CI, -133.56 to 16.75; P = 0.128), and complication rates (general anesthesia: 10.9% vs . conscious sedation: 8.9%; P = 0.655) were comparable between the groups. CONCLUSIONS: General anesthesia is noninferior to conscious sedation for microelectrode-guided subthalamic nucleus deep brain stimulation, providing equivalent signal intensity and clinical outcomes while improving procedural efficiency, supporting its use as a valid clinical option.

Humans

Comparison of ultrasound-guided two-point block of the rhomboid intercostal vs. thoracic paravertebral for postoperative analgesia in patients undergoing three-port thoracoscopic surgery: a prospective, randomized, non-inferiority study.

BACKGROUND: The anesthetic characteristics of ultrasound-guided two-point rhomboid intercostal block (RIB) have not been fully established. This study compared the analgesic efficacy of ultrasound-guided two-point RIB with that of two-point thoracic paravertebral block (TPVB) for postoperative pain control and recovery in patients undergoing three-port thoracoscopic surgery. METHODS: Seventy patients aged 18-80&#x2009;years scheduled for three-port thoracoscopic pulmonary resection were block-randomized in a 1:1 ratio to receive either TPVB or RIB. Both techniques were performed using 10&#x2009;mL of 0.5% ropivacaine at each injection site. The primary outcome was the numerical rating scale (NRS) pain score at rest 24&#x2009;h after surgery, with a predefined non-inferiority margin of &#x394;&#x2009;=&#x2009;1. Secondary outcomes included NRS at rest and during coughing at 0.5, 2, 4, 12, 18, 24, and 48&#x2009;h postoperatively, as well as the 24h postoperative Quality of Recovery-40 (QoR-40) score. RESULTS: The final analysis included 34 patients in the TPVB group and 34 in the RIB group. The mean difference in resting NRS scores at 24&#x2009;h between the two groups was 0.088 (95% CI, -0.377 to 0.553), confirming the non-inferiority of RIB. However, the need for rescue analgesia was numerically greater in the RIB group than in the TPVB group (p&#x2009;=&#x2009;0.045). The 24-h postoperative QoR-40 scores and cumulative sufentanil consumption within 48&#x2009;h after surgery were comparable between the groups (both p&#x2009;>&#x2009;0.05). CONCLUSION: Ultrasound-guided two-point RIB provided postoperative analgesia that was non-inferior to TPVB in patients undergoing three-port thoracoscopic surgery.

Adolescent

CoLchicine for Treatment of OsteoArthritis of the Knee (CLOAK): Clinical and biochemical outcomes from a three-month double-blind, placebo-controlled study.

OBJECTIVE: Knee osteoarthritis (KOA) causes pain and progressive disability, but pharmacologic treatments are limited. Colchicine inhibits inflammation that might modulate KOA, but efficacy trials have yielded mixed results. We tested whether colchicine, without concurrent NSAIDs, improved KOA pain, function, synovial effusion size, and OA-associated inflammatory serum biomarkers. METHODS: Participants with symptomatic KOA and radiographic Kellgren-Lawrence grades 2/3 were randomized to receive three months of daily colchicine or placebo in a double-blind manner, with no concurrent NSAID use. The primary outcome was between-group change in visual analog score (VAS) for index knee pain. Secondary outcomes included changes in Knee Osteoarthritis Outcome Scores (KOOS), size (depth in millimeters) of sonographically-identified effusions, acetaminophen use, and changes in OA-related serum biomarkers. RESULTS: From baseline to end of study of 120 enrolled participants, no significant differences were observed in improvement of VAS pain, KOOS scores or effusion size. Subsets of participants with more severe VAS pain, worse radiographic disease, or higher hsCRP or serum urate levels at baseline also showed no significant clinical benefit from colchicine compared to placebo. In contrast to the clinical outcomes, colchicine treatment was associated with significant or trending improvement in multiple OA-related serum biomarkers including hsCRP and &#x3b2;-NGF (p < 0.05) and PGE2, IL-1ra, IL-8, and VEGF (p < 0.16). CONCLUSION: This double-blind placebo-controlled trial of colchicine for KOA failed to demonstrate improvement in pain, function, or synovial effusion size in comparison to placebo at three months. Early improvement in OA-associated inflammatory biomarkers suggests a possible longer-term clinical benefit. Clinical Trials Registration No NCT03913442.

Humans