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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

COMBI-I: Long-Term Overall Survival With Spartalizumab Plus Dabrafenib and Trametinib in BRAF V600-Mutant Advanced Melanoma.

The COMBI-I trial (ClinicalTrials.gov identifier: NCT02967692) evaluating spartalizumab plus dabrafenib and trametinib (sparta-DabTram, n = 267) versus placebo plus dabrafenib and trametinib (placebo-DabTram, n = 265) for BRAF V600-mutant unresectable or metastatic melanoma failed to reach its primary end point of progression-free survival at 24 months. This final analysis reports overall survival (OS) during at least 5 years of extended follow-up. At the end of the trial (August 21, 2024), the median duration of follow-up was 76.9 months (range, 73.7-83.3 months). The median OS was 61.5 months (95% CI, 41.6 to not evaluable) for the sparta-DabTram arm and 41.6 months (95% CI, 30.6 to 56.9) for the placebo-DabTram arm (hazard ratio, 0.760 [95% CI, 0.598 to 0.966]). The safety findings were consistent with the known safety profile for sparta-DabTram. The most common treatment-related adverse event (TRAE) was pyrexia (65.9% v 46.2%, respectively, in the two study arms). Grade ≥3 TRAEs were reported in 57.3% and 36.7% of patients in the two arms, respectively. The combination of sparta-DabTram appears to improve OS compared with dabrafenib and trametinib alone in patients with BRAF V600-mutant metastatic melanoma.

Adult

Risk-Benefit of Phase 2 Monotherapy Trials in Adult Solid Cancers: A Systematic Review and Meta-Analysis.

Phase 2 (and phase 1 dose expansion, which we label phase 2 for the purposes of this study) cancer trials are the first direct tests of a new drug's efficacy. Because efficacy evidence is lacking, the therapeutic status of drug administration during ethical review is uncertain. We compared the efficacy and safety of cancer monotherapies in phase 2&#xa0;with phase 3, where clinical equipoise underwrites a therapeutic status for drug administration. In this systematic review and meta-analysis, we searched Clinicaltrials.gov for phase 2 and 3 investigational monotherapy drug trials in six solid malignancies, with primary completion dates 2015-2020, inclusive. Two independent reviewers completed data extraction. Effects were estimated using an inverse-variance weighted random-effects model meta-analysis of proportions using the R package meta. We analyzed 130 phase 2 and 52 phase 3 trial arms, enrolling 6665 and 18,694 patients. The pooled objective response rate was 7% (95% CI 5%-11%) in phase 2 versus 24% in phase 3 (95% CI 17%-31%; p&#x2009;<&#x2009;0.0001). The median PFS and OS were shorter in phase 2 compared to phase 3 (3.23 vs. 5.43&#x2009;months, p&#x2009;<&#x2009;0.0001; 9.46 vs. 14.44&#x2009;months, p&#x2009;=&#x2009;0.0001). The pooled rate of drug-related grade 3-4 adverse events was 30% (95% CI 23%-37%) in phase 2 and 25% (95% CI 19%-32%) in phase 3. Monotherapies delivered in phase 2 cancer trials present diminished risk-benefit compared with phase 3 and align with historic estimates for phase 1. Though there may be exceptions, risks for drug administration in phase 2 should generally be justified by appeals to research rather than therapeutic value.

Humans

Animal-assisted therapy in pediatric urodynamics.

INTRODUCTION/BACKGROUND: Urodynamics (UDS) is associated with high levels of patient anxiety/discomfort. Children are often unable to complete UDS, with anesthesia needed to place catheters. Animal-assisted therapy (AAT) has been used in a variety of settings, but it has not been studied for UDS before. OBJECTIVE: To determine if AAT can increase success of completing UDS testing without anesthesia in children who were previously unable to perform UDS, along with decreasing distress levels. STUDY DESIGN: We performed a pilot case series of 7 patients (2 female, 5 male) aged 4-16 (mean 9.7) years who previously were unable to complete UDS awake, with AAT prior to and during the UDS procedure. A visual analog scale (VAS) was used to measure patient stress levels before and after AAT. RESULTS: We were able to successfully complete UDS testing with AAT in 6 of the 7 patients (85.7%) without the need for anesthesia. VAS scores decreased from before to after AAT (5.4-3.6, p = 0.020) but with discrepancy when compared to UDS success. DISCUSSION: Our study was the first to describe AAT during UDS. Our preliminary data found AAT to be feasible in UDS. Subjective distress may not correlate with procedural success. AAT in UDS may be more beneficial in certain populations, such as anxious children who previously were unable to tolerate UDS, and not in others such as severe neurodevelopmental conditions. Our study was limited by the small sample size, a single provider, single center, single therapy dog, inclusion of a specific population of patients, and no control group due to this being a pilot study. CONCLUSION: AAT for certain children undergoing UDS testing could help improve the ability to complete the testing without anesthesia. Further studies are needed to fully demonstrate its usefulness in UDS.

Humans

Study of prescription-indication of antivirals for herpesviruses in a Colombian population: a cross-sectional study.

BACKGROUND: To describe the utilization patterns and therapeutic indications of antivirals used for herpesvirus infections in Colombian patients. RESEARCH DESIGN/METHODS: A cross-sectional study on the use of antivirals for treating outpatients with herpesviruses between November 2023 and January 2024 in a Colombian population database. The Micromedex&#xae; database was used to identify Food and Drug Administration (FDA)-approved indications, off-label uses, and potentially inappropriate indications. RESULTS: A total of 14,816 individuals were included (median age:53.0 years [IQR:35.0-65.0]; 60.5% women). Acyclovir was the most frequently prescribed antiviral (oral:77.3%; topical:43.4%). Overall, 56.1% received oral therapy only, 25.2% combined oral and topical therapy, and 18.7% topical therapy only. FDA-approved indications accounted for 29.1% of use (herpes zoster), off-label use for 26.9% (mainly prophylaxis in immunocompromised patients), and potentially inappropriate use for 25.3% (primarily topical treatment of herpes zoster). Acyclovir use (OR:5.93; 95%CI:4.60-7.64) and specialist care (OR:2.17; 95%CI:1.73-2.71) were associated with off-label use. CONCLUSIONS: Antiviral prescribing for herpesvirus infections in a group of patients in Colombia is largely driven by acyclovir, with a substantial proportion of off-label and potentially inappropriate use, particularly involving topical therapies for herpes zoster. These findings highlight significant gaps in adherence to evidence-based recommendations and underscore the need for targeted interventions to optimize prescribing practices.

Humans

Outcomes of Stage IVA Cervical Cancer Treated with Radiation Therapy: A Systematic Review and Meta-Analysis.

FIGO stage IVA cervical cancer, defined by bladder or rectal mucosal invasion without distant metastasis, is an uncommon but clinically challenging disease with limited high-quality evidence to guide management. We performed a systematic review and meta-analysis to evaluate survival outcomes, treatment-related morbidity, and prognostic factors in patients with stage IVA cervical cancer treated with definitive radiotherapy. Following PRISMA 2020 guidelines and PROSPERO registration (CRD42024602426), PubMed, Embase, and Web of Science were searched through February 2025. Eleven studies comprising 492 patients met eligibility criteria. Pooled random-effects analyses demonstrated 2-, 3-, and 5-year disease-free survival rates of 41.5% (95% CI, 28.1-55.0), 34.2% (95% CI, 21.1-47.3), and 30.9% (95% CI, 16.0-45.8), respectively. Corresponding overall survival rates were 56.0% (95% CI, 46.2-65.9), 45.9% (95% CI, 35.9-55.9), and 34.8% (95% CI, 26.4-43.3). Weighted median disease-free survival and overall survival were 15.6 and 33.6 months, respectively. The pooled incidence of vesicovaginal or rectovaginal fistula was 23.7% (95% CI, 12.9-34.6). Adverse prognostic factors included pelvic nodal involvement, hydronephrosis, rectal invasion, omission of brachytherapy, and total EQD2 below 80-85 Gy. Concurrent chemoradiation and completion of brachytherapy were consistently associated with improved outcomes. Despite curative-intent treatment, long-term survival remains poor and treatment-related morbidity substantial. Durable pelvic control remains the principal therapeutic challenge. Concurrent chemoradiation with adequate-dose brachytherapy appears essential for optimal outcomes, while future stage IVA-specific studies incorporating image-guided adaptive brachytherapy, advanced radiotherapy techniques, and systemic treatment intensification are needed to improve survival and reduce treatment-related morbidity.

Humans

Role of nicotine metabolite ratio in pharmacological interventions on smoking cessation: A systematic review and meta-analyses of randomized controlled trials.

BACKGROUND AND OBJECTIVES: Emerging evidence suggests that the nicotine metabolite ratio (NMR) may influence the efficacy of smoking cessation, yet its role across pharmacotherapies remains unclear. This study aims to investigate how NMR affects cessation outcomes under different medications to guide personalized treatment. METHODS: We searched PubMed, Medline, EMBASE, and the Cochrane Central Register of Controlled Trials (inception to September 30, 2024) for randomized controlled trials on pharmacotherapy for smoking cessation with NMR data. Data were synthesized using random-effects models, with heterogeneity assessment. The primary outcome was verified smoking cessation rate at the end of treatment or the closest time-point. RESULTS: Eleven RCTs with accessible full text were included in the qualitative analyses and nine were included in the quantitative synthesis. For non-titratable nicotine replacement therapy (NRT), normal/fast metabolizers demonstrated lower odds of smoking cessation than slow metabolizers (Odds Ratio, OR=0.81, 95% confidence interval, CI=0.68-0.96; 5 studies, I&#xb2;=62.5%). No significant associations were shown between normal/fast and slow metabolizers using titratable NRT (OR=1.04, 95% CI=0.95-1.14; 2 studies, I&#xb2;=0%), bupropion (OR=0.67, 95% CI=0.38-1.16; 2 studies, I&#xb2;=51.4%), or varenicline (OR=1.17, 95% CI=0.79-1.74; 4 studies, I&#xb2;=59.8%). CONCLUSION: Current evidence demonstrates that NMR moderates' treatment efficacy among those who smoke using non-titratable NRT, with slow metabolizers achieving significantly better cessation outcomes than normal/fast metabolizers. Substantial further research is needed to determine optimal medication hierarchies across metabolic profiles.

Humans

Factors Impacting Overall Survival Post-Relapse in High-Risk Neuroblastoma: Children's Oncology Group Outcomes From 2000 to 2019.

PURPOSE: Prior studies of features impacting post-relapse survival in high-risk neuroblastoma (HRNB) evaluated patient cohorts that did not receive contemporary high-risk or relapse therapies. We describe overall survival (OS) after first progression or first relapse of HRNB in a modern cohort. METHODS: Patients with HRNB enrolled on COG ANBL00B1(NCT00904241) between 2000 and 2019, who had relapsed or progressive disease were eligible. Clinical and molecular risk factors at diagnosis, therapy era, clinical trial enrollment, and clinical features at relapse, including site of and time to relapse, were evaluated. OS post-relapse was compared between groups using log-rank tests and Cox models. RESULTS: Among 4253 eligible HRNB patients, 1616 had relapse or progression as a first event. Five-year OS post-relapse was 19.1&#xa0;&#xb1;&#xa0;1.1%. The risk group with the lowest post-relapse survival was observed in patients with INSS Stage 4 or 4S disease <&#xa0;18 months of age at diagnosis with MYCN amplified (MYCN-A) tumors. The other significant most unfavorable factors at diagnosis included diagnosis 2000-2004, tumor MYCN-A, 1p loss of heterozygosity (LOH), and elevated LDH or ferritin. Unfavorable factors at relapse included the time to relapse <&#xa0;36 months from diagnosis, and combined local and metastatic disease at relapse. Multivariable analysis indicated that those with tumors harboring 1p LOH, age &#x2264;&#xa0;5 years at diagnosis, or earlier treatment therapy era (2000-2004) had a higher risk of post-relapse death. CONCLUSIONS: While the 5-year OS rate was low in this cohort, there are subsets of patients with relapsed HRNB who demonstrate long-term survival. TRIALS REGISTRATION: ClinicalTrials.gov identifier: NCT00904241.

Humans

Suction-assisted ureteroscopy compared with traditional ureteroscopy for renal stones &#x2264; 2&#xa0;cm: a systematic review, Bayesian network meta-analysis and meta-regression.

INTRODUCTION AND OBJECTIVE: Suction-enhanced flexible ureteroscopy (URS) aims to improve stone clearance and reduce complications. We performed a Bayesian network meta-analysis to compare the efficacy and safety of flexible aspiration navigable sheaths (FANS) and direct in-scope suction (DISS) for renal calculi &#x2264; 2&#xa0;cm. METHODS: A systematic search of PubMed, MEDLINE, Scopus, Web of Science, and Google Scholar was conducted through June 2026. Comparative studies of FANS, DISS, or conventional access sheaths for renal stones &#x2264; 2&#xa0;cm were included. The primary outcome was 30-day stone-free rate (SFR). Secondary outcomes included operative time, fever, sepsis, and complications. A Bayesian random-effects network meta-analysis synthesized direct and indirect evidence. RESULTS: Seventeen studies including 3,657 patients (1,677 FANS, 56 DISS, 1,924 control) were included. FANS showed higher SFR (OR 2.5, 95% CrI 2.0-3.1), while grouped DISS had a similar but less precise effect (OR 3.1, 95% CrI 1.0-8.8). Calyxo V2 had the highest SFR (OR 5.4, 95% CrI 1.0-29.0), whereas PUSEN showed no significant difference (OR 1.6, 95% CrI 0.41-6.3). FANS reduced postoperative fever and complications. FANS also showed lower odds of postoperative sepsis (OR 0.40, 95% CrI 0.12-0.97). CONCLUSIONS: Suction-assisted ureteroscopy improves SFR for renal calculi &#x2264; 2&#xa0;cm. FANS was associated with shorter operative time, fever, and complications. DISS systems show promising but limited results, with performance differing by technology configuration. Larger prospective trials are needed.

Humans

Endoscopic submucosal dissection for locally recurrent gastric neoplasia following endoscopic resection: a systematic review and meta-analysis.

BACKGROUND AND AIMS: Endoscopic submucosal dissection (ESD) for locally recurrent gastric neoplasia following endoscopic resection (ER) is technically challenging because of scar-related submucosal fibrosis. We performed a systematic review and meta-analysis to evaluate the efficacy and safety of salvage ESD in this setting. METHODS: Multiple databases were searched through December 2025 for studies reporting ESD outcomes for locally recurrent gastric lesions at or contiguous with a prior ER scar. Primary outcome was curative resection and need for surgery. Secondary outcomes were en bloc and R0 resection, local recurrence, delayed bleeding, and perforation. Meta-analyses were performed using a random effects model. Heterogeneity was assessed using I2. RESULTS: Seven studies (259 patients; 265 ESDs) were included. Across 5 studies and 243 ESDs, pooled curative resection rate was 69.7% (95% CI, 60.6-78.1; I2 = 38%), while 8.2% (95% CI, 3.3-14.6; I2 = 38.4%) required surgery. En bloc resection rate was 92.3% (95% CI, 79.1-99.7; I2 = 83.7%) across 6 studies, and pooled R0 resection rate was 87.5% (95% CI, 82.1-92.2; I2 = 0%) across 4 studies. Over a mean follow-up of 42 months, pooled local recurrence was 2.0% (95% CI, 0.0-9.7; I2 = 54.1%) across 6 studies. Delayed bleeding was 4.1% (95% CI, 0.8-9.0; I2 = 40.8%) and perforation was 4.1% (95% CI, 1.6-7.3; I2 = 0%). CONCLUSIONS: ESD for locally recurrent gastric neoplasia after ER achieves acceptable curative resection, high en bloc/R0 resection, and low local recurrence and morbidity. It is a viable organ-preserving option for appropriately selected patients, ideally performed at expert centers with close surveillance.

Humans

Less Invasive Surfactant Administration Using Video Laryngoscope to Decrease Pain in Neonates: A Randomized Controlled Trial.

OBJECTIVES: To assess whether the use of video laryngoscope, when compared to conventional laryngoscope decreases pain (assessed by Faceless Acute Neonatal Pain Scale) in preterm neonates while administering surfactant by LISA. METHODS: Preterm neonates <&#x2009;35 weeks requiring FiO2&#x2009;>&#x2009;0.3 on CPAP pressure of at least 6&#x2009;cm of H2O were administered surfactant by LISA technique either by video laryngoscope (Intervention) or conventional laryngoscope (Control). Faceless Acute Neonatal Pain Scale was used to determine pain 5&#x2009;min before the procedure, immediately, 5&#x2009;min, and 10&#x2009;min after the procedure. The primary outcome was severity of pain; secondary outcomes were time taken to complete the procedure, number of attempts, incidence of IVH, and adverse events during the procedure. RESULTS: In total, 42 neonates of <&#x2009;35 weeks gestation with comparable baseline demographics were randomized into 2 groups. The median (IQR) FANS score immediately post-procedure in the intervention arm was 2 (2-4) versus 2 (1-4) in the control arm, p&#x2009;=&#x2009;0.79. There was no statistical difference in the secondary outcomes studied. CONCLUSION: The two groups had no difference in the pain score. The pain experienced by neonates during the LISA procedure was moderate and of short duration and it did not depend on the type of laryngoscope used. Moderate pain during the procedure can be managed with nonpharmacological measures; thereby, the use of sedatives or analgesics can be avoided, which might be of concern. There was no difference in the number of attempts or in time taken to complete the procedure when performed by neonatologists experienced in using conventional laryngoscopes compared to video laryngoscopes. TRIAL REGISTRATION: Clinical Trial Registry of India: CTRI/2022/09/045204 on 05.09.2022.

Humans

Structured Visualization for Laparoscopic Skill Acquisition:A Randomized Controlled Study.

OBJECTIVE: To evaluate whether structured visualization can support acquisition of basic laparoscopic skills during simulation training and whether this approach can achieve outcomes comparable to repeated physical practice. DESIGN: Prospective randomized comparative study. SETTING: Simulation-based laparoscopic skills training at a university-affiliated teaching center. PARTICIPANTS: Fifty laparoscopy-naive medical students were randomly assigned to a laparoscopic practice group or a visualization group. The laparoscopic practice group performed a validated Gynecological Endoscopic Surgical Education and Assessment (GESEA) Laparoscopic Skills Training and Testing (LASTT) hand-eye coordination task 7 consecutive times. The visualization group performed the same task physically on attempts 1, 4, and 7, while attempts 2, 3, 5, and 6 consisted of guided visualization. Each attempt lasted up to 2 minutes, and performance was scored as the number of correctly placed rings (range 0-12). RESULTS: Baseline performance was comparable between groups (2.92&#x202f;&#xb1;&#x202f;2.14&#x202f;vs 2.88&#x202f;&#xb1;&#x202f;1.72; p&#x202f;=&#x202f;0.94). Both groups improved significantly over time (p&#x202f;<&#x202f;0.001). No statistically significant between-group differences were found on the 4th attempt (6.52&#x202f;&#xb1;&#x202f;3.25&#x202f;vs 5.76&#x202f;&#xb1;&#x202f;2.57; p&#x202f;=&#x202f;0.48) or 7th attempt (8.24&#x202f;&#xb1;&#x202f;2.86&#x202f;vs 7.44&#x202f;&#xb1;&#x202f;2.99; p&#x202f;=&#x202f;0.39). The final physical performance of the visualization group was significantly better than the 3rd physical attempt of the laparoscopic practice group (p&#x202f;=&#x202f;0.025). CONCLUSIONS: Structured visualization may support early laparoscopic skill acquisition and achieve short-term outcomes comparable to repeated hands-on simulator training. Visualization should be considered an adjunct, rather than a replacement, for physical practice in simulation-based laparoscopic education.

Laparoscopy

Pancreatic fat and the risk of future dysglycemia: a systematic review and meta-analysis.

CONTEXT: Pancreatic fat has emerged as a metabolically relevant ectopic fat depot, but its longitudinal association with future dysglycemic outcomes remains incompletely defined. OBJECTIVE: This study aims to evaluate the longitudinal association of pancreatic fat with incident type 2 diabetes (T2D) and glycemic progression, with exploratory narrative synthesis of evidence in lean populations. DATA SOURCES: PubMed, Embase, Web of Science, and the Cochrane Library were searched from inception to March 1, 2026. STUDY SELECTION: Longitudinal observational studies assessing pancreatic fat at baseline and reporting subsequent incident T2D, glycemic progression, or both were included. DATA EXTRACTION: Two reviewers independently screened studies and extracted data. Methodological quality was assessed using the Newcastle-Ottawa Scale. DATA SYNTHESIS: Ten studies were included. In the primary binary meta-analysis (5 studies), higher pancreatic fat burden was associated with incident T2D (pooled effect estimate, 2.56; 95% CI, 1.27-5.14; I2 = 93.3%). Exclusion of 1 influential ultrasound-based study attenuated heterogeneity while preserving the association (pooled effect estimate, 1.45; 95% CI, 1.23-1.73; I2 = 10.2%). A separate continuous analysis (3 studies) also supported an association with incident T2D (1.17; 95% CI, 1.04-1.32; I2 = 79.2%), although exposure scales were not directly comparable. Pancreatic fat was also associated with glycemic progression (2 studies; 1.96; 95% CI, 1.10-3.48; I2 = 73.2%). Exploratory lean-population evidence was limited to 2 analytical contexts, synthesized narratively, and directionally consistent with the overall findings. CONCLUSION: Pancreatic fat was associated with adverse future glycemic outcomes across multiple analytical contexts. These findings support pancreatic fat as a potentially meaningful imaging-derived marker of future dysglycemia, while suggesting that heterogeneity is partly explained by differences in exposure ascertainment.

Humans

Adjuvant apatinib therapy following concurrent chemoradiotherapy in patients with high-risk nasopharyngeal carcinoma: A multicenter, prospective phase 2 study.

PURPOSE: To assess the efficacy and safety of concurrent chemoradiotherapy (CCRT) combined with apatinib in locoregionally advanced nasopharyngeal carcinoma (LA-NPC). METHODS: This multicenter, prospective, phase II study enrolled patients with newly histologically confirmed LA-NPC, who were randomly assigned to receive CCRT followed by adjuvant apatinib (investigational arm) or CCRT alone (control arm). The investigational arm received 250 mg/day of oral apatinib administered every 28 days for up to six cycles after CCRT. The primary endpoint was 3-year progression-free survival (PFS) and secondary endpoints of overall survival (OS), distant metastasis-free survival (DMFS) and local recurrence-free survival (LRFS) of 3-year, and safety. RESULTS: From July 2018 to September 2020, 44 and 44 patients were randomized into the CCRT-alone and CCRT and apatinib groups, respectively. The median follow-up duration 56 (range: 40.0-58.6) months. The survival outcomes were the 3-year PFS, OS, and DMFS rates in the adjuvant apatinib following CCRT group were significantly higher than those observed in the CCRT-alone group((PFS, 78.6%vs. 54.5%, p = 0.027; OS, 88.1% vs. 75.0%, p = 0.029; DMFS, 85.4%vs. 59.1%, p = 0.009). The 3-year LRFS was similar between the groups. The grade 3-4 treatment-related adverse events(TRAEs) were higher in the former group than in the latter. The most common grade 3-4 non-hematology-related adverse events were hypertension (14.3%), hand-foot syndrome (9.5%), increased transaminase levels (7.1%), and headache (7.1%). CONCLUSION: Apatinib significantly improved the treatment effects of CCRT for high-risk LA-NPC patients. Therefore, CCRT and adjuvant apatinib may represent a promising option for this patient population.

Adjuvant therapy

Impacts of climate-driven yield changes on the affordability of healthy diets: a modelling study.

BACKGROUND: Food security is central to global nutrition improvement and public health goals, and healthy diets represent a higher-level aspiration beyond merely avoiding hunger. Climate change poses an increasing threat to food systems by affecting crop yields and food prices. Although climate change-driven risks to hunger have been widely studied, the extent to which climate change undermines the affordability of healthy diets while accounting for socioeconomic responses and regional inequalities remains insufficiently understood. This study aimed to quantify the effects of climate change on the future affordability of healthy diets under alternative socioeconomic and climate scenarios. METHODS: We developed an integrated modelling framework that explicitly couples multimodel crop-yield projections with an integrated assessment model (Global Change Analysis Model [GCAM]). Yield responses from six global gridded crop models driven by four climate models were integrated into GCAM, allowing endogenous socioeconomic adjustments such as land-use shifts, production reallocation, and price responses to emerge under shared socioeconomic pathways (SSPs). Diet affordability was then assessed using the Food and Agriculture Organization of the UN's Cost and Affordability of a Healthy Diet framework across three socioeconomic-climate scenarios (SSP1-2.6, SSP2-4.5, and SSP3-6.0). FINDINGS: Under a high-emissions pathway (ie, SSP3-6.0), climate change was projected to render healthy diets unaffordable for a model-mean of 119 million people globally by 2100, even when CO2 fertilisation effects are included, with the upper end of the model ensemble reaching about 1&#xb7;6 billion people. In contrast, climate-induced affordability losses were found to be negligible under both a low-emissions pathway (ie, SSP1-2.6; -0&#xb7;3 million) and a medium-emission pathway (SSP2-4.5; +0&#xb7;2 million). Under a high-emission pathway, model-mean projections indicated that diet costs could increase by up to 12% in the most affected regions by the end of the century. Under medium emissions, cost increases were projected to remain below 4%, whereas under low emissions, affordability changes were projected to be minimum across regions (within approximately 0&#xb7;5%). Substantial regional disparities emerged, with the largest and most consistent affordability losses concentrated in low-income regions that contributed least to historical greenhouse gas emissions. Under SSP3-6.0, these disparities persisted particularly in regions of Africa and Asia despite projected three-to-five-fold increases in income over the century, with climate-induced disruptions to food systems increasing the number of people unable to afford a healthy diet through mid-century. INTERPRETATION: Climate change is likely to exacerbate global nutritional inequalities by disproportionately increasing the affordability risks of healthy diets in regions that have contributed least to historical greenhouse gas emissions. Under high-warming scenarios, socioeconomic development alone is insufficient to fully offset these risks, highlighting the structural vulnerability of low-income food systems to climate-driven price shocks. These findings suggest that in the absence of targeted interventions, climate change could continue to undermine progress towards equitable and health-oriented nutrition outcomes. FUNDING: Ministry of Science and Technology of the People's Republic of China; National Natural Science Foundation of China; National Aeronautics and Space Administration Goddard Institute for Space Studies Climate Impacts Group; Future of Life Institute; and Global Alliance for Improved Nutrition.

Journal Article

Effect of Smoking in Oropharyngeal Cancer Treated With TORS: Systematic Review and Meta-Analysis.

OBJECTIVE: While smoking has been implicated as a risk factor for recurrence in HPV-associated oropharyngeal squamous cell cancer (OPSCC) treated with definitive chemoradiation, its prognostic impact on surgically treated OPSCC is less clear. DATA SOURCES: MEDLINE, Embase, CENTRAL, and Scopus. REVIEW METHODS: Articles describing patients with HPV-associated OPSCC treated with transoral robotic surgery (TORS), which reported oncologic outcomes by smoking history, were included. RESULTS: 2079 patients were included across 12 studies. Median age was 58.5&#x2009;years, and 1808 (87.0%) were male. HPV-associated disease was reported in 1681 (80.9%) patients. T stage was most commonly T2 in 831 (40.0%) and T1 in 764 (36.7%). N stage was N2 in 854 (41.1%), N1 in 544 (26.2%), and N0 in 307 (14.8%). 931 (44.8%) were considered individuals with a smoking history, while 1045 (50.3%) were considered without a smoking history. Median follow up was 33.7&#x2009;months. Meta-analysis using a fixed effects model demonstrated an overall hazard ratio of 1.4 (95% confidence interval 1.0-2.0) for disease recurrence, 2.7 (95% confidence interval 1.5-4.8) for overall survival, and 1.4 (95% confidence interval 0.4-4.6) for disease specific survival. CONCLUSIONS: In this population of predominantly HPV-associated OPSCC treated with TORS, meta-analysis demonstrated no significant difference in recurrence-free survival or disease-specific survival between individuals with and without a smoking history. Individuals with a smoking history appeared to have worse overall survival, although only five studies reported on this outcome. Further research is required to clarify the prognostic influence of smoking on OPSCC treated with TORS.

Humans

Comparative phylogenomics and transcriptional regulatory networks of AQPs, HSPs, and LEA proteins in salt-stressed Portulaca oleracea.

Soil salinization severely threatens global food security, necessitating systematic investigations of halophytes like Portulaca oleracea to decode the molecular mechanisms of environmental resilience. Utilizing an integrated framework of deep learning-based genome annotation (58,817 predicted genes; 96.5% BUSCO completeness), multi-tissue RNA-Seq, phylogenomics, and gene regulatory network (GRN) inference, the synergistic orchestration of 78 aquaporins (AQPs), 525 heat shock proteins (HSPs), and 119 late embryogenesis abundant (LEA) proteins was elucidated. The active transcriptome, encompassing 39,065 expressed loci, revealed a systemic growth-defense trade-off. Tissues displayed distinct adaptive mechanisms: leaves modulated intracellular water balance via specialized AQPs, whereas adult roots maintained proteostasis through robust HSP20/HSP70 induction. Phylogenomic clustering across 154 species demonstrated that salinity tolerance constitutes an evolutionary mosaic, identifying 81 halophyte-exclusive orthogroups and 1129 species-specific clusters. Comparative topology across six independent GRNs (4.2M-5.3&#x202f;M edges) unmasked a highly modular transcriptional reprogramming strategy governed by a core apparatus of 22 stress-exclusive regulators, with functional enrichment heavily prioritizing protein dimerization and chromatin remodeling. Theoretically, the distinct convergence of Trihelix transcription factors with guard cell differentiation pathways offers a candidate transcriptomic framework to explain the plant's characteristic C4-CAM photosynthetic plasticity under severe osmotic pressure. Practically, these evolutionary blueprints and specific master switches transcend single-gene transgenic limitations. Utilizing these root-sustained and stress-inducible targets under localized promoters provides a naturally optimized, network-level precision engineering roadmap to transfer robust, compartmentalized halotolerance to sensitive glycophytic crops.

Gene Regulatory Networks

Robotic assistance in total hip arthroplasty: a systematic review and meta-analysis of leg length, cup orientation, and early outcomes.

This review examined whether robotic assistance alters postoperative leg-length discrepancy (LLD), acetabular cup orientation, or early hip-specific outcomes relative to conventional total hip arthroplasty (THA). We searched PubMed and Web of Science through May 2026 for comparative English-language reports. Study eligibility, data extraction, and methodological appraisal were undertaken independently by two reviewers. Mean differences (MDs) and 95% confidence intervals (CIs) were calculated in Review Manager 5.4. Model selection was based on the target estimand and anticipated clinical and methodological diversity; leave-one-out and alternative-model sensitivity analyses were undertaken for heterogeneous outcomes. The protocol is registered with PROSPERO (CRD420261454043). The review included seven studies and 968 participants. Compared with conventional THA, robot-assisted THA yielded a smaller postoperative LLD (MD = -2.02, 95% CI -3.46 to -0.58; P = 0.006) and a higher Harris Hip Score (MD = 2.96, 95% CI 1.12 to 4.80; P = 0.002). Mean cup anteversion was lower in the robotic group (MD = -1.52, 95% CI -2.29 to -0.76; P < 0.0001), whereas cup inclination did not differ (MD = -0.71, 95% CI -3.26 to 1.83; P = 0.58). The robotic group also had higher Forgotten Joint Score (MD = 14.68, 95% CI 5.02 to 24.33; P = 0.003) and Oxford Hip Score values (MD = 2.61, 95% CI 0.71 to 4.51; P = 0.007). Robotic assistance was linked to a modest improvement in leg-length restoration and to higher scores on several early functional measures. The limited number of studies, predominance of nonrandomized designs, and marked heterogeneity in some analyses temper the certainty of these findings.

Humans