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Analgesic effect of premixed nitrous oxide in postoperative rehabilitation for ankle fractures: a randomized controlled trial.

INTRODUCTION: The global incidence of ankle fractures is on the rise, effective postoperative rehabilitation is a crucial aspect of surgical management. However, the occurrence of severe pain during the rehabilitation continues to pose a substantial clinical challenge. METHODS: The study utilizes a dual-arm, single-center, double-blind, randomized controlled trial design. A total of 100 participants were enrolled. Participants included patients experiencing acute pain (self-reported pain score &#x2265;4) who underwent postoperative rehabilitation for ankle fractures. Participants undergoing rehabilitation training were randomized to receive either 65% nitrous oxide or 100% oxygen. The primary outcome measured was the pain score, while secondary outcomes encompassed anxiety scores, physiological indices, side effects, patient and therapist satisfaction, acceptance, and residual pain. RESULTS: Pain scores were found to be significantly lower in the nitrous oxide group than in the oxygen group (T1: median difference -3.0, [95% CI -3.4 to -2.6]; p&#x2009;<&#x2009;0.001; T2: median difference -2.0, [95% CI -2.8 to -1.2]; p&#x2009;<&#x2009;0.001). Compared with the oxygen group, both therapists (p&#x2009;<&#x2009;0.001) and participants (p&#x2009;<&#x2009;0.001) in the nitrous oxide group reported significantly higher satisfaction levels. Acceptance rate showed significant intergroup differences (p&#x2009;<&#x2009;0.001). No severe adverse effects were observed in either group. Anxiety scores between the two groups did not show a significant difference (p&#x2009;=&#x2009;0.31, &#x3b7;2 = 0.027). CONCLUSION: The safety and analgesic profile of nitrous oxide renders it a suitable option for pain management in postoperative ankle fractures rehabilitation, thus providing a safe and easily manageable alternative to the current available strategies. CLINICAL TRIAL REGISTRATION: We have registered at https://www.chictr.org.cn and the registration number is: ChiCTR2400089379.

Humans

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

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

Humans

Clinical Performance of Bulk-Fill Versus Incremental Composite Placement Approaches in Vital Posterior Teeth: A 24&#x2009;Months Randomized Controlled Trial.

BACKGROUND: Composite resin placement technique may influence marginal integrity, polymerization stress distribution, and long-term clinical performance of posterior restorations. This randomized controlled clinical trial evaluated the 24-month clinical performance of four different placement techniques in Class I posterior composite restorations. METHODS: Fifty patients aged 20-35&#x2009;years presenting with four occlusal carious lesions each were enrolled, resulting in 200 restorations. Cavities (4-5&#x2009;mm depth) were prepared according to caries extension. Restorations were randomly allocated into four equal groups (n&#x2009;=&#x2009;50) according to placement technique: stamp technique, snowplow technique, modified incremental "pizza" technique, and bulk-fill technique. All materials were applied following manufacturers' instructions. Clinical evaluation was performed at baseline and after 6, 12, and 24&#x2009;months using FDI criteria. Functional (fracture/retention, marginal adaptation), esthetic (marginal staining, anatomical form), and biological (postoperative sensitivity, secondary caries) properties were assessed by two calibrated evaluators. Statistical analysis was performed at a significance level of &#x3b1;&#x2009;=&#x2009;0.05. RESULTS: Thirty-eight patients with a total of 152 restorations were evaluated at the end of the 24&#x2009;months in line with FDI at the end of the study with 76% recall rates. No statistically significant differences were observed among groups regarding fracture/retention or secondary caries (p&#x2009;>&#x2009;0.05). Marginal adaptation and marginal staining demonstrated minor deterioration over time across all groups, with statistically significant intergroup differences found (p&#x2009;<&#x2009;0.05). Postoperative sensitivity was minimal and transient in all groups with no significant difference (p&#x2009;=&#x2009;0.181). CONCLUSIONS: Within the limitations of this 24-month follow-up, the four placement techniques demonstrated comparable clinical performance in Class I posterior composite restorations. Selection of technique may therefore be guided by clinical preference and procedural efficiency rather than differences in short-term clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT07415317.

Humans

Comparative efficacy and safety of bi-flanged metal stents versus lumen-apposing metal stents for endoscopic drainage of pancreatic fluid collections: a systematic review and meta-analysis.

INTRODUCTION: Pancreatic fluid collections (PFCs), particularly walled-off necrosis, are common complications of acute pancreatitis that often require endoscopic drainage. Bi-flanged metal stents (BFMS; NAGI; Taewoong Medical, Gyenoggi-do, Korea) and electrocautery-enhanced lumen-apposing metal stents (LAMS; AXIOS, Boston Scientific Corporation, Marlborough, Massachusetts, USA) are frequently used, but comparative data remain limited. This study aims to compare the efficacy and safety of BFMS and LAMS in the endoscopic drainage of PFCs. METHODS: This meta-analysis followed the Cochrane Handbook for Systematic Reviews of Interventions and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Comprehensive database searches were conducted through November 2024 to identify studies comparing BFMS and LAMS for endoscopic ultrasound-guided drainage of PFCs. Outcomes were pooled using a random-effects model with RevMan Web, and statistical significance was defined as a P value less than 0.05. RESULTS: Three studies ( n &#x2005;=&#x2005;627; 329 BFMS and 298 LAMS) met inclusion criteria. No significant differences were observed between BFMS and LAMS for technical success [odds ratio (OR): 1.16; 95% confidence interval (CI): 0.55-2.43] or clinical success (OR: 0.97; 95% CI: 0.51-1.87). Similarly, there were no differences in walled-off necrosis recurrence (OR: 2.01; 95% CI: 0.17-24.02), number of direct endoscopic necrosectomy sessions (OR: 0.52; 95% CI: 0.05-5.12), or mean number of endoscopic procedures (mean difference: 0.18, 95% CI: 2.08-2.45). Adverse events were also comparable between groups, including bleeding (OR: 0.64), infection (OR: 1.18), stent migration (OR: 1.83), and stent occlusion/dysfunction (OR: 1.71). CONCLUSION: BFMS and LAMS provide equivalent efficacy and safety in the endoscopic ultrasound-guided drainage of PFCs. Either stent type represents a viable therapeutic option. Further large-scale prospective studies are warranted to refine stent selection strategies.

Humans

Safety and efficacy of distal versus conventional radial artery cannulation for invasive blood pressure monitoring: a systematic review and meta-analysis.

To compare the safety and effectiveness of distal radial artery (DRA) versus conventional radial artery (CRA) catheterization for invasive arterial blood pressure monitoring. This meta-analysis followed PRISMA guidelines. Randomized controlled trials published up to December 30, 2025 were systematically searched in PubMed, Embase, Web of Science, the Cochrane Library, CINAHL, CNKI, Wanfang, VIP, and SinoMed. Two reviewers independently screened studies, extracted data, and assessed risk of bias. Meta-analyses were conducted using Review Manager 5.4 and Stata 18.0, and evidence quality was evaluated with the GRADE system. 12 randomized controlled trials (RCTs) involving 1,790 participants were included. For the primary outcomes, compared with CRA, DRA was associated with lower incidences of haematoma (RR&#x2009;=&#x2009;0.42, 95% CI: 0.24-0.73), catheter blockage (RR&#x2009;=&#x2009;0.33, 95% CI: 0.14-0.81), and bleeding (RR&#x2009;=&#x2009;0.25, 95% CI: 0.11-0.59), but a longer catheter insertion time (MD&#x2009;=&#x2009;26.89, 95% CI: 5.28-48.50). For the secondary outcomes, DRA was associated with a shorter haemostasis time and reduced waveform instability, with no significant differences in first-attempt success rate or pain scores. Subgroup analysis showed a higher first-attempt success rate in patients aged&#x2009;&#x2264;&#x2009;65 years (RR&#x2009;=&#x2009;1.14, 95% CI: 1.02-1.28). DRA catheterization for invasive arterial blood pressure monitoring appears to be associated with fewer complications and more stable arterial waveform acquisition than CRA catheterization, despite a longer insertion time. DRA may represent a feasible alternative in surgical and intensive care settings; however, further high-quality studies are needed to confirm its long-term safety and generalizability.

Humans

A systematic approach to standardizing the visual appearance of endometriotic lesions for artificial intelligence recognition.

INTRODUCTION: Numerous studies have shown that the diagnostic performance and reproducibility of visual recognition of endometriosis during laparoscopy are poor. The use of artificial intelligence (AI) seems relevant for exhaustive lesion recognition. Standardization of the visual classification of lesions, in the form of an ontology, is an essential prerequisite to enable medical experts to annotate surgical data consistently and subsequently allow engineers to train and build an artificial intelligence tool for endometriosis recognition. MATERIAL AND METHODS: A systematic search was conducted in the MEDLINE (via PubMed), EMBASE, and the Cochrane Library databases up to May 2022, aiming to identify studies describing the laparoscopic visual appearance of superficial endometriosis, endometriomas, and deep infiltrating endometriosis. The accumulated data in the literature concerning the visual appearance of the different forms of endometriosis were used to create an ontology that could be used for artificial intelligence applications. RESULTS: Out of 932 articles screened, 35 studies were selected based on the inclusion criteria of human subjects with histologically confirmed endometriosis lesions visualized via laparoscopy. The selected studies were reviewed to develop a visual ontology of endometriosis lesions observed via laparoscopy. The lesions were categorized into 4 classes and further subdivided into 11 subclasses: superficial (black, red, white, or subtle), adhesions (dense or filmy), deep (obliteration, retraction, or deformation), and ovarian (endometrioma or chocolate fluid). The positive predictive value (PPV) varied across lesion types: black lesions (PPV 47%-97%), red lesions (PPV 33%-100%), white lesions (PPV 20%-81%), and ovarian endometriosis (PPV 42%-98%). Nonspecific lesions such as adhesions (PPV 16%-50%) and subtle superficial lesions (PPV 0%-67%) presented lower PPVs. Deep endometriosis lesions, often buried within organs, required indirect signs (obliteration, retraction, deformation) for identification. CONCLUSIONS: The visual ontology proposed in this systematic search could facilitate the detection and classification of endometriosis lesions using artificial intelligence. This study highlights the challenges of reaching a consensus on lesion recognition and classification in AI projects due to the diverse visual presentations of endometriosis.

Humans

Exercise prehabilitation in head and neck cancer patients proposed for definitive chemoradiotherapy: The FIT4TREAT randomized controlled trial.

BACKGROUND: Patients with head and neck cancer (HNC) initially scheduled for definitive chemoradiotherapy (CRT) often experience early functional decline and deterioration in health-related quality of life (HRQoL) even before treatment initiation. Evidence for prehabilitation in this non-surgical setting remains limited. This study evaluated whether exercise prehabilitation (EP) initiated before CRT improves functional capacity compared with usual care (UC). METHODS: FIT4TREAT (ClinicalTrials.gov: NCT05418842) was a prospective, single-center, randomized clinical trial. Adults with HNC proposed for definitive CRT were randomly assigned (1:1) to EP or UC. EP consisted of supervised combined aerobic and resistance exercise performed three times per week from baseline until radiotherapy initiation. The primary outcome was the six-minute walk distance (6MWD) at the end of the pre-treatment period. Secondary outcomes included muscle strength, lower-limb functionality, body composition, and HRQoL assessed using the EORTC QLQ-C30 and QLQ-HN43. RESULTS: Between May 2021 and February 2025, 47 patients were enrolled; 40 were included in the primary analysis. After adjustment for baseline 6MWD and the randomization stratification variables, EP resulted in a significantly greater pre-treatment 6MWD than UC (adjusted between-group difference, 28.6&#xa0;m; 95&#xa0;% CI, 4.1-53.1; P&#xa0;=&#xa0;0.023). EP also improved lower-limb functionality (P&#xa0;<&#xa0;0.001) and was associated with better preservation in the QLQ-C30 summary score (P&#xa0;=&#xa0;0.008), social functioning (P&#xa0;=&#xa0;0.038) and body image (P&#xa0;=&#xa0;0.011). CONCLUSION: EP before definitive CRT improves functional capacity and may help preserve HRQoL in patients with HNC, supporting its potential integration into routine oncology care.

Humans

Genome-wide identification and expression profiling of HSD3B and SDR42E1 genes in the Pacific oyster (Crassostrea gigas): potential associations with gonadal development.

Sex steroids are lipid-soluble signaling molecules that regulate sex differentiation, reproductive development and physiological homeostasis in animals. 3&#x3b2;-Hydroxysteroid dehydrogenase/&#x394;5-&#x394;4 isomerase (3&#x3b2;-HSD) is a key steroidogenic enzyme, whereas SDR42E1, an extended short-chain dehydrogenase/reductase, has been implicated in sterol- and steroid-related metabolism. However, the composition, evolutionary relationships and expression patterns of the HSD3B- and SDR42E1-related genes in bivalve gonadal development remain poorly characterized. In this study, five PF01073-containing genes, comprising three CgHsd3b and two CgSdr42e1 genes, were identified in the Pacific oyster Crassostrea gigas. Phylogenetic analysis separated the proteins into HSD3B-related and SDR42E1-related groups, and gene-structure and motif analyses indicated subfamily-level divergence. All five proteins retained the SDR domain but differed in exon-intron structure and motif composition. Each contained the extended-SDR TGxxGxxG motif, whereas exact classical [ST]GxxxGxG and NNAG motifs were absent. Tyr- and Lys-equivalent residues were conserved, while the HSD3B1 Ser-equivalent position contained Thr in two C. gigas proteins and Ser in one. These features support their classification as extended-SDR proteins but do not establish enzymatic activity or substrate specificity. The three CgHsd3b genes were dispersed on one chromosome, whereas CgSdr42e1-1 and CgSdr42e1-2 were adjacent on another chromosome, suggesting a possible local duplication event for the CgSdr42e1 pair. Public RNA-seq data showed distinct tissue- and gonadal-stage expression patterns, with several genes displaying gonad-biased or female-stage-associated expression. Independent RT-qPCR profiling of the representative genes CgHsd3b-3 and CgSdr42e1-1 detected stage-dependent expression, although tissue rankings differed from those in the public RNA-seq datasets. These differences may reflect the use of independent biological samples, tissue composition, normalization procedures, and platform-specific measurements. Because enzymatic assays, metabolite measurements, cellular localization, and functional perturbation were not performed, the results identify candidate genes whose expression is associated with gonadal development rather than demonstrating regulatory roles. This study provides a comparative framework for future functional investigation of sterol- and steroid-related metabolism in bivalves.

Animals

A child and young person focused systematic review of scrotal ultrasound with Mitigants to identify missed torsion.

BACKGROUND: Diagnostic accuracy of ultrasound for adults is stated as excellent. Paediatric and adult acute scrotal diseases are different. Findings in adults may not apply in children. The authors have seen overconfidence and interpretation with adult disease in mind in children with scrotal pain and have seen testicular loss as a result. OBJECTIVES: To interrogate the literature methodologically to report diagnostic accuracy of ultrasound (US) for the acute scrotum specifically in CYP with a follow-up methodology which allows identification of missed torsion. STUDY DESIGN: We performed systematic review and meta-analysis of studies reporting true diagnostic accuracy of ultrasound for testicular torsion (TT). PubMed, MEDLINE, Scopus, and Web of Science databases were searched from platform start until September 2023 using MeSH terms with protocol as detailed on PROSPERO. Multiple author search was undertaken. Two authors extracted data for included studies. Study quality was reported through QUADAS-2 methodology. Surgical findings or 12 months follow up in non-operative cases would be the gold standard to identify late atrophy due to missed torsion. Studies with methodology to identify missed torsion outwith the initial consult were included for meta-analysis. RESULTS: A total of 6790 cases were reported from the 38 papers identified. Studies were often flawed with poor definition of outcomes and short follow-up duration. Meta-analysis of the 10 high-quality studies revealed pooled sensitivity and specificity of 0.93 and 0.99. Doppler US by trained individuals demonstrated excellent diagnostic accuracy. Nonetheless, on extrapolation of the data, especially where flow was preserved, 5.6% of torsions were missed. DISCUSSION/CONCLUSION: Our review confirms a high diagnostic accuracy of US for TT in CYP. However, a 5.6% missed torsion rate was found if flow alone was considered diagnostic. The authors suggest US should be used as an adjunct in ambiguous cases, ensuring that clinically obvious torsion goes to theatre immediately and is not delayed by ultrasound. TRIAL REGISTRATION: PROSPERO: CRD42023412619.

Humans

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

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

Humans

Interactive gaming during inhalational induction of anesthesia reduces pediatric patient anxiety and improves induction compliance: A randomized controlled trial.

BACKGROUND: Preoperative anxiety affects up to 75% of pediatric surgical patients and is associated with adverse postoperative outcomes. Traditional anxiolytic strategies with premedication carry drawbacks including delayed recovery and paradoxical reactions, driving interest in non-pharmacologic alternatives. Audiovisual distraction represents one approach, encompassing passive methods (e.g. watching a video) and active modalities (e.g. interactive gaming). The Bedside Entertainment and Relaxation Theater (BERT) is a projection-based environment that enables audiovisual distraction during induction. Whether BERT-based interactive gaming reduces anxiety and improves induction compliance compared to standard perioperative care remains unknown. METHODS: This single-center RCT enrolled 74 pediatric patients aged 4 to 14 undergoing inhalational induction, randomized to standard care (SOC) or interactive gaming via BERT added to SOC during induction (BERT). The primary outcome was change in patient anxiety from baseline to induction, measured using the Modified Yale Preoperative Anxiety Scale (mYPAS). Secondary outcomes included caregiver anxiety, induction compliance, OR efficiency, opioid administration, and OR staff perceptions. RESULTS: Patients in the BERT group experienced significantly smaller increases in anxiety from baseline to induction than SOC (median mYPAS increase [IQR]: 0 [0 to 0] vs 10 [0 to 38], p&#xa0;<&#xa0;0.001). Induction compliance improved, with lower Induction Compliance Checklist (ICC) scores indicating fewer induction-related disruptive behaviors than SOC (median: 0 vs 1, shift -1 [95% CI: -2 to 0]; p&#xa0;=&#xa0;0.004). Caregiver anxiety increased less in the BERT group than SOC (mean STAI increase: 0.18 vs 1.89, difference&#xa0;-&#xa0;1.7, [95% CI: -3.2 to -0.26]; p&#xa0;=&#xa0;0.022). OR staff reported high acceptability, with 97% supporting continued use. No differences were observed in OR efficiency or opioid administration between groups. CONCLUSIONS: Interactive gaming via BERT attenuated increases in patient anxiety, improved induction compliance, and reduced the rise in caregiver anxiety without prolonging OR time. These findings support BERT as an effective, workflow-compatible anxiolytic strategy for pediatric inhalational induction.

Humans

Skin cell suspension autograft as an evidence-based innovation in burn and wound treatment: A systematic review of global evidence across two decades.

BACKGROUND: Skin cell suspension autograft (SCSA) is a point-of-care approach to wound management facilitating epithelialization while reducing burden associated with conventional autografting. Despite growing clinical use of SCSA across diverse wound etiologies, the global clinical evidence describing its use has not yet been comprehensively synthesized. METHODS: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes (PRISMA) guidelines to identify studies between January 2000 and December 2024 reporting clinical use of SCSA for wound closure. Data on patient demographics, wound characteristics, and treatment methods were extracted. Clinical, safety, and health economic outcomes were extracted for comparative studies evaluating SCSA against control treatments. RESULTS: Ninety-nine studies across 13 countries were included. Across the overall dataset, SCSA was used alone or in combination with autografting for burns, surgical wounds, traumatic injuries, inflammatory conditions, and chronic wounds. Among comparative studies (n=27), SCSA consistently reduced donor skin, and healing outcomes favored SCSA in 61%, while 39% reported equivalent outcomes. Pain and esthetic outcomes more frequently favored SCSA, while safety outcomes were generally similar, with some studies favoring comparators. Health-economic outcomes suggested potential reductions in length of stay and resource utilization, although findings were variable across studies. CONCLUSION: The available global evidence supports SCSA as a versatile modality for supporting epidermal coverage across wound types and clinical contexts. However, the findings should be interpreted in the context of the limitations of this review, which include heterogenous study designs, variable outcome reporting, predominance of non-randomized data, and the absence of a formal quantitative analysis. Nevertheless, the demonstrated clinical and economic benefits in comparative studies reinforce the role of SCSA as an evidence-based innovation for burn and wound treatment.

Humans

Diagnostic utility of high-risk HPV polymerase chain reaction-based testing in head and neck FNA specimens with indeterminate cytomorphology.

BACKGROUND: Fine-needle aspiration (FNA) is critical in the initial diagnosis of many high-risk human papillomavirus (HR-HPV)-associated, metastatic oropharyngeal squamous cell carcinomas. Updated guidelines recommend HR-HPV-specific polymerase chain reaction (PCR) analysis over p16 immunohistochemistry on FNA specimens because p16 performs poorly on cytology material. PCR-based assays on liquid cytology material have demonstrated excellent analytic performance; however, the diagnostic utility of a positive HR-HPV PCR result in specimens with indeterminate cytomorphology remains uncharacterized. METHODS: The authors retrospectively identified 279 head and neck FNA specimens that had paired HR-HPV PCR testing on residual liquid cytology material over a 5-year period. The positive predictive value for histopathologically confirmed squamous cell carcinoma on surgical follow-up was calculated within each cytologic interpretive category. RESULTS: The HR-HPV PCR results were positive in 50.2% of specimens, negative in 40.9%, and indeterminate in 9.0%. The HR-HPV positivity rate ranged from 0% in specimens categorized as negative for malignancy to 57.3% in cytologically positive specimens, with 19.0%, 41.2%, and 50.0% positivity in the atypical, suspicious, and nondiagnostic categories, respectively. Among cytologically indeterminate specimens with positive HR-HPV PCR results (n&#xa0;=&#xa0;14), the positive predictive value was 100% (95% confidence interval, 78.5%-100.0%). Blinded slide review additionally identified 15 cytologically positive specimens in which the definitive malignant interpretation depended substantially on HR-HPV positivity; all 15 were confirmed as squamous cell carcinoma. CONCLUSIONS: A positive HR-HPV PCR result on liquid cytology material carries a positive predictive value of 100% for malignancy in cytologically indeterminate head&#xa0;and neck FNA specimens. These findings support integrating HR-HPV PCR analysis into routine cytologic interpretation with the potential to upgrade some indeterminate specimens to malignant when HR-HPV is detected, expediting definitive treatment and sparing patients additional, invasive sampling.

Humans

Acetate- Versus Lactate-Buffered Crystalloids for Prevention of Post-ERCP Pancreatitis in Patients Without Access to Rectal NSAIDs: A Multicentre Double-Blind Randomized Trial.

BACKGROUND: Aggressive peri-procedural intravenous fluid (IVF) therapy with lactated Ringer's solution (LR) reduces the risk of post-ERCP pancreatitis (PEP), but the standard 8-h protocol is impractical in outpatient settings and the optimal fluid type remains uncertain. We compared LR with an acetate-buffered balanced crystalloid (AC) using a symptom-guided 4-h aggressive IVF protocol. METHODS: This multicentre, double-blind, randomized superiority trial was conducted at three academic hospitals in Korea where rectal NSAIDs are unavailable. Adults with native papillae and moderate-to-high PEP risk were randomized to receive LR or AC. The IVF protocol comprised 10&#xa0;mL/kg boluses before and after ERCP, followed by 3&#xa0;mL/kg/h for 4&#xa0;hours and extended to 8&#xa0;hours if abdominal pain developed or worsened. The primary outcome was PEP incidence; secondary outcomes included early post-ERCP pain and adverse events. RESULTS: Of 813 patients (404 LR, 409 AC), PEP occurred in 12.4% of the LR group and 11.5% of the AC group (relative risk [RR] 0.93; 95% CI, 0.64-1.35; P&#xa0;=&#xa0;0.70). Rates of mild (7.9% vs. 7.1%) and moderate (4.5% vs. 4.4%) PEP were similar, and no severe PEP or fluid overload occurred. Among the 68.3% of patients who remained asymptomatic at 4&#xa0;hours and required only 4-h IVF, PEP occurred in 7.4%, with no cases of severe PEP. CONCLUSION: In this superiority trial, acetate-buffered crystalloid did not reduce PEP compared with lactated Ringer's solution, and no significant safety differences were observed between the two agents. Lactated Ringer's remains the recommended first-line crystalloid for aggressive hydration when rectal NSAIDs are unavailable. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05832047).

Humans

Venetoclax added to dose-adjusted EPOCH-R for newly diagnosed double-hit lymphomas: phase 2 results from ALLIANCE A051701, an open-label, randomised, controlled, phase 2-3 trial.

BACKGROUND: High-grade B-cell lymphoma with rearrangements of MYC and BCL2 and/or BCL6, known as double-hit lymphoma, is a highly aggressive malignancy with poor outcomes after standard chemoimmunotherapy. We aimed to study whether the addition of the BCL2-inhibitor venetoclax to chemoimmunotherapy in patients with double-hit lymphoma resulted in superior efficacy compared with chemotherapy alone. METHODS: ALLIANCE A051701 is an open-label, randomised, controlled, phase 2-3 trial in separate cohorts of patients with double-hit lymphoma and patients with double-expressor lymphoma. In this analysis, we report phase 2 results from the double-hit lymphoma cohort. Patients aged 18-80 years with newly diagnosed double-hit lymphoma and Eastern Cooperative Oncology Group (ECOG) performance status 0-2 were recruited from 41 hospitals and outpatient clinics in the USA. Patients were randomly assigned (1:1) to receive DA-EPOCH-R (dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab) either alone (DA-EPOCH-R group) or with venetoclax (DA-EPOCH-R plus venetoclax group) using permuted block randomisation schedule. All patients and investigators were aware of group assignment. DA-EPOCH-R was administered on a 21-day schedule for up to six total cycles. Venetoclax was given as 600 mg by mouth daily on days 4-8 of cycle 1 and on days 1-5 of cycles 2-6. The primary endpoint was progression-free survival in the modified intent-to-treat population inclusive of all eligible patients with centrally confirmed double-hit lymphoma. The safety analysis population consisted of all evaluable patients who received at least one dose of protocol treatment. This trial is registered with ClinicalTrials.gov (NCT03984448) and is closed to enrolment. FINDINGS: 36 patients were randomly assigned to the DA-EPOCH-R group and 37 to the DA-EPOCH-R plus venetoclax group between Oct 22, 2019, and Sept 18, 2020. Median age was 65 years (IQR 56-73) and baseline demographic factors were well balanced between groups, with 30 (45%) female and 36 (55%) male patients. Most patients (59 [89%]) were white, two (3%) were Asian, one (2%) was Black or African American, and four (6%) had unknown or unreported ethnicity. The majority of patients had MYC-BCL2 double-hit lymphoma (59 [89%] patients), advanced stage disease (57 [86%] patients), and high-intermediate/high-risk IPI score (42 [64%] patients). Median follow-up was 34&#xb7;7 months (IQR 30&#xb7;1-36&#xb7;8). Median progression-free survival was 28&#xb7;4 months (95% CI 5&#xb7;2-not estimable) in the DA-EPOCH-R group (n=30) and 7&#xb7;7 months (95% CI 4&#xb7;7-NE) in the DA-EPOCH-R plus venetoclax group (n=36; hazard ratio [HR] 1&#xb7;13, 95% CI 0&#xb7;53-2&#xb7;37; p=0&#xb7;75). Deaths on treatment occurred in one (3%) patient in the DA-EPOCH-R group (due to dyspnoea; possibly related to treatment) and six (17%) patients in the DA-EPOCH-R plus venetoclax group (four due to sepsis [three at least possible related and one unrelated], two due to cardiac arrest [at least possibly related]), prompting early closure of the double-hit lymphoma cohort. The most common grade 3-4 non-haematological adverse event was febrile neutropenia, occurring in 15 (43%) of 35 patients in the DA-EPOCH-R plus venetoclax group and 11 (37%) of 30 patients in the DA-EPOCH-R group. The median overall survival has not been reached in either group. The 24-month overall survival estimates were 72% (95% CI 52-85) in the DA-EPOCH-R group compared with 52% (95% CI 33-68) in the DA-EPOCH-R plus venetoclax group (HR 2&#xb7;49, 95% CI 1&#xb7;03-6&#xb7;04; p=0&#xb7;038). INTERPRETATION: The addition of venetoclax to DA-EPOCH-R resulted in excess mortality, prompting early study closure. Robust accrual shows that prospective multicentre trials are feasible in double-hit lymphoma, and the outcomes in the DA-EPOCH-R group serve as a benchmark for future studies. FUNDING: National Cancer Institute of the National Institutes of Health.

Humans

Critical insights on the application of the theory of planned behaviour to food handlers' food safety practices.

Foodborne diseases remain a significant public health concern, often linked to unsafe food-handling practices. The Theory of Planned Behaviour (TPB) is widely used to predict and explain food safety behaviours, yet its application in this field has not been systematically and in-depth evaluated. This review evaluated how the TPB has been applied to study food handlers' behaviour, focusing on methodological approaches, use of the TACT (Target, Action, Context, and Time) framework, validity, elicitation studies, and reliability. Seventeen studies were included following a systematic search of four databases (Scopus, Web of Science, Wiley Online Library, and Taylor & Francis Online). Data were extracted on behaviour definition, aim of study, main findings, use of indirect and direct TPB measures, use of elicitation studies, internal consistency, content validation, analytical methods used, and any extensions to the original TPB framework. Key elements related to adherence to core TPB principles and measurement practices were extracted using a Checklist. Most studies used direct measures of TPB constructs, and only a few reported procedures for content validation. Considerable variability was found in the reporting of key measurement and psychometric practices. Five studies fully applied the TACT framework, while nine incorporated additional factors such as knowledge and moral norms. Elicitation studies were conducted in five cases where indirect measures were employed. Analytical approaches were mainly based on multiple linear regression, with limited use of more advanced techniques such as structural equation modeling. Twelve studies reported internal consistency results. Overall, the review highlights opportunities to strengthen methodological practices in future TPB research on food safety. Greater attention to conducting and reporting content validation, full application of the TACT framework, reporting of internal consistency, and consistent inclusion of elicitation studies when using indirect measures may enhance transparency, reinforcing the credibility and trustworthiness of research findings. A major methodological limitation of this review was that screening and data extraction were conducted by a single reviewer and no formal quality or risk-of-bias assessment of the included studies was performed. Despite these limitations, the findings provide practical guidance for the development and validation of TPB-based questionnaires and may support more robust food safety research, interventions, and policy initiatives aimed at improving food handlers' practices.

Humans

Comparison of short-term clinical outcomes and patient satisfaction between intraoral scanning and conventional impressions for complete-arch implant prostheses: a pilot RCT.

OBJECTIVE: To compare framework passive fit, subjective evaluations, and short-term clinical outcomes between conventional impressions (CI) and intraoral scanning (IOS) for complete-arch implant-supported fixed dental prostheses (CIFDPs). METHODS: In this randomized controlled trial, 22 patients were allocated to the CI or IOS groups. All participants received a definitive one-piece CIFDP. The primary outcome was framework passive fit, assessed using the Vision and Tactile Score (V&T score), which included framework lift-off, the single-screw test, the full-screw test, smoothness of screw insertion, and radiographic gap assessment. Secondary outcomes included operator evaluation, patient satisfaction using a visual analog scale (VAS), early implant survival, marginal bone loss (MBL), modified Plaque Index (mPII), and complications at the 6-month follow-up. RESULTS: Twenty-two patients were enrolled (CI: n = 11; IOS: n = 11), and one patient in the CI group was lost to follow-up. No statistically significant difference in the V&T score was observed between the CI and IOS groups (4.66 &#xb1; 0.17 vs. 4.65 &#xb1; 0.28; P = 0.93). The operator reported greater nervousness during the CI procedure than during IOS (21.82 &#xb1; 15.69 vs. 8.64 &#xb1; 7.47; P < 0.05). Patients in the CI group reported significantly greater discomfort, including nausea and anxiety, than those in the IOS group (P < 0.05). At the 6-month follow-up, the early implant survival rate was 100% in both groups. No significant differences were found between the groups in MBL (0.09 &#xb1; 0.09 vs. 0.06 &#xb1; 0.10 mm; P = 0.43) or mPII (0.10 &#xb1; 0.12 vs. 0.10 &#xb1; 0.28; P = 0.99). CONCLUSION: IOS and CI achieved comparable short-term clinical outcomes in patients who met the predefined inclusion criteria, including controlled implant number, spacing, and angulation. IOS provided a more favorable experience for both operators and patients. CLINICAL SIGNIFICANCE: In complete-arch implant restorations, intraoral scanning may provide clinical outcomes comparable to those of conventional impressions while improving patient comfort.

Humans

Intraocular Pressure Changes Following Intraluminal Stent Removal From the Paul Glaucoma Implant: A Systematic Review and Meta-Analysis.

PURPOSE: This study aims to systematically review and perform a single-arm meta-analysis to comprehensively evaluate the effect of removal of intraluminal stent from the Paul glaucoma implant (PGI) on intraocular pressure (IOP) changes and to summarize its long-term efficacy and safety. CLINICAL RELEVANCE: Glaucoma remains one of the leading global causes of irreversible vision loss, necessitating effective surgical management for refractory cases. Glaucoma drainage devices are critical for these complex forms, and intraluminal stent removal from the PGI serves as a key strategy to titrate aqueous outflow and optimize long-term IOP control. METHODS: A systematic review was conducted by searching EMBASE, Medline, and CENTRAL. The meta-analysis ultimately included 5 observational studies. The Risk of Bias in Nonrandomized Studies of Interventions (ROBINS-I) tool was used to assess the quality of the included studies. Continuous outcomes (eg, postremoval stent IOP reduction) were analyzed using the mean difference (MD) with 95% confidence intervals (CI); dichotomous outcomes (eg, hypotony incidence) were evaluated using pooled proportion with 95% CI. All meta-analyses employed a random-effects model. RESULTS: Our meta-analysis included 5 studies, involving a total of 283 eyes. The meta-analysis revealed that removal of the stent leads to a significant and immediate IOP reduction. The IOP reduction (immediate postremoval stent IOP minus preremoval stent IOP) was significant, with a pooled MD of -9.09 mm Hg IOP (MD = 9.09; 95% CI = [-11.77, -6.41]). In the preremoval stent high-IOP (>21 mm Hg) subgroup, the IOP reduction is -11.82 (95% CI = [-10.14, -13.51]). This reduction was significantly greater than the preremoval stent low-IOP (<21 mm Hg) subgroup, whose reduction is -6.66 mm Hg (95% CI = [-5.55, -7.77]). Regarding safety, the pooled proportion of clinically hypotony was low and highly consistent (I&#xb2; = 0.00%) at only 0.03 (95% CI = [0.00, 0.15]). CONCLUSIONS: Intraluminal stent removal from the PGI is an effective and safe IOP-lowering intervention. Its IOP reduction effect is significantly more pronounced in patients with preremoval stent high IOP, providing crucial clinical guidance for managing persistently high IOP after PGI implantation.

Humans