Citations

ABSTRACT Introduction Publication bias (PB) threatens the validity of meta‐analyses by distorting effect size estimates, potentially leading to misleading conclusions. With advanced pattern recognition and multimodal capabilities, large language models (LLMs) may be able to evaluate PB and make the systematic review process more efficient. Methods We evaluated the ability of two state‐of‐the‐art multimodal LLMs, GPT‐4o and Llama 3.2 Vision, to detect PB using funnel plots alone and in combination with quantitative inputs. We simulated meta‐analyses under varying conditions, including the absence of PB, different levels of presence of PB, varying total number of studies within a meta‐analysis, and differing degrees of between‐study heterogeneity. Results Neither GPT‐4o nor Llama 3.2 Vision consistently detected the presence of PB across various settings. Under no‐publication‐bias conditions, GPT‐4o achieved a higher specificity outperforming Llama 3.2 Vision, with the difference most shown in the meta‐analyses with 20 or more studies. The inclusion of quantitative inputs alongside funnel plots did not significantly improve performance. Additionally, between‐study heterogeneity and patterns of non‐reported studies had minimal impact on the models’ assessments. Conclusions The ability of LLMs to detect PB without fine‐tuning is limited at the present time. This study highlights the need for specialized model adaptation before LLMs can be effectively integrated into meta‐analysis workflows. Future research can focus on targeted refinements to enhance LLM performance and utility in evidence synthesis.

Campylobacter species are considered to be the leading bacterial cause of human gastroenteritis globally. Consumption of undercooked or contaminated food, such as chicken, is the main cause of human campylobacteriosis. Despite this significant zoonotic link, comparative data on virulence determinants in Campylobacter isolates across avian and human sources remain limited. This study aimed to characterize the prevalence and expression of virulence determinants in Campylobacter jejuni and Campylobacter coli isolates from chicken and human sources in Ismailia governorate, Egypt. A total of twenty C. jejuni and C. coli isolates (ten of each species) were screened for 14 virulence genes using PCR. All isolates harbored virB11, iam, racR, and tetO. Chicken isolates exhibited a significantly higher prevalence: C. jejuni (chicken): pldA, dnaJ, flaA (100%), cdtB (80%), ciaB (60%), and wlaN (0%); C. coli (chicken): pldA, dnaJ (100%), flaA (60%), cdtB (60%), ciaB (40%), and wlaN (20%). In contrast, human isolates showed a markedly lower prevalence: C. jejuni (human): dnaJ, flaA, and cdtB (20%); C. coli (human): dnaJ, flaA, and cdtB (40%). Crucially, pldA, ciaB, and wlaN were absent in all human isolates. plda and dnaJ genes showed statistically significant prevalence differences. qPCR revealed a significant upregulation (p < 0.05) of dnaJ, virB11, flaA, and iam in chicken isolates compared to human isolates, with log2 fold changes of 3.52, 2.84, 2.43, and 1.90 for C. jejuni and 3.06, 2.38, 1.51, and 1.32 for C. coli. Differential expressions of racR, cdtB, and tetO were not significant, with log2 fold changes ranging from −0.51 to 0.14. Ganglioside mimicry genes (Cst11, wlaN, Waac, ggt, and cgtB) and the carbon storage regulator gene (csrA) were absent in all human isolates. These findings underscore the significant variability in virulence gene profiles in chicken and human C. jejuni and C. coli isolates and highlight the importance of molecular characterization in the risk assessment and epidemiological surveillance of Campylobacter infections.

ABSTRACT Biofilms hinder wound infection healing, making wound infections a healthcare challenge for which innovative treatments are needed. A 1.77 cm 2 electrochemical bandage (e-bandage), which generates the biocide hypochlorous acid (HOCl), has shown promising anti-biofilm activity in vitro , ex vivo , and in vivo . The e-bandage is a three-electrode system operationalized by a hydrogel. In addition to providing a conductive electrolyte for the electrodes, the hydrogel provides a protective barrier for the wound. How different hydrogels impact e-bandage functionality is not completely defined. Here, the in vitro activity of seven clinically available hydrogels (xanthan gum, 3M, Duoderm, Prontosan, Purilon, Skintegrity, and Solosite) was evaluated with 1.77 cm 2 HOCl-generating e-bandages using a potentiostat with a multiplexer in a membrane biofilm model against methicillin-resistant Staphylococcus aureus IDRL-6169 and Acinetobacter baumannii ATCC-17978. When applied with polarized HOCl-producing e-bandages, all evaluated hydrogels except Solosite yielded ≥5.5 log 10 CFU/cm 2 reductions in bacterial quantities after 6 h of treatment, with most being below the detection limit at that time point. Prontosan exhibited antibacterial activity independent of e-bandage. Results of this study inform the selection of clinically available hydrogels that may be suitable for use with a 1.77 cm 2 HOCl-producing e-bandage. IMPORTANCE In this study, it was shown that some clinically available hydrogels, combined with a 1.77 cm 2 HOCl-generating electrochemical bandage, deliver time-dependent antimicrobial activity against methicillin-resistant Staphylococcus aureus and Acinetobacter baumannii biofilms, offering a potential approach to treat wound infections, including those caused by antimicrobial-resistant bacteria.

SUMMARY Periprosthetic joint infection (PJI) is a significant complication of arthroplasty. Implicit in the diagnosis of PJI is the presence of organisms in what should be a sterile milieu. Given limits to culture-based PJI diagnosis, optimal utilization of culture in the diagnostic approach to PJI needs clarification. Culture is important in confirming a PJI diagnosis and characterizing the infecting microorganism(s) to inform management. As part of the development of a unified definition of PJI (by a group representing multiple scientific societies), a systematic review was performed to inform the role of culture in the definition of PJI. In addition, a comprehensive review on synovial fluid and periprosthetic tissue collection for culture, and associated culture methodology and results interpretation, was performed to inform best practices. Gaps in the literature were identified to develop research priorities.

Abstract Objective The objective of this study is to characterize contemporary surgical management practices and factors influencing surgical decision‐making in the management of Lennox–Gastaut Syndrome (LGS) across pediatric epilepsy centers in the United States. Methods A 45‐item cross‐sectional survey was developed and distributed to Pediatric Epilepsy Research Consortium centers. Domains included institutional demographics, surgical evaluation timing and goals, presurgical workup, procedural utilization and outcomes, and barriers to surgery. Descriptive statistics and thematic analysis were performed. Results Thirty‐two pediatric epilepsy centers participated (38% response), the majority comprising pediatric epileptologists at Level 4 National Association of Epilepsy Centers. Most centers (66%) considered surgery after failure of 3–4 antiseizure medications. Presurgical workup typically included brain magnetic resonance imaging (MRI), long‐term electroencephalography (EEG) monitoring, and neuropsychological assessment, while use of functional imaging, magnetoencephalography, and intracranial EEG varied considerably. All centers offered vagus nerve stimulation and corpus callosotomy; 80%–90% offered resection, hemispherectomy, responsive neurostimulation (RNS); 60%–65% offered deep brain stimulation (DBS) and laser ablation. Among centers offering RNS, half targeted thalamic structures exclusively, and the remainder targeted cortical or combined cortical‐thalamic structures; the centromedian nucleus was the preferred thalamic target for RNS and DBS. Surgical decision‐making was influenced by patient characteristics, procedural considerations, and systemic factors. Seizure frequency, family preference, and multidisciplinary input were highly rated across all interventions. Etiology was critical for resection and hemispherectomy, while financial constraints, insurance barriers, and the need for future neuroimaging impacted neuromodulation selection. Scenario‐specific trends included less frequent consideration of DBS and RNS in children under five years, less use of hemispherectomy in older children, preference for corpus callosotomy in children with predominantly drop seizures, and procedural selection based on MRI findings. Significance Substantial variability exists in the surgical management of LGS. These findings highlight critical opportunities to harmonize practices, reduce disparities, and guide comparative effectiveness research to optimize outcomes. Plain Language Summary Lennox–Gastaut Syndrome (LGS) is a severe form of epilepsy that may require surgery when medications are not effective. This study found that surgical care for LGS varies widely across pediatric epilepsy centers in the United States, including when surgery is recommended, how patients are evaluated, and which procedures are available. Newer approaches such as brain stimulation are being used more often, although access remains inconsistent. These findings highlight the need for clearer treatment pathways to ensure that children with LGS have equitable access to the best possible care.

Abstract A workgroup assembled by the Alzheimer’s Association recently described a conceptual framework for Alzheimer’s disease biological staging based on amyloid and tau PET imaging. However, specific tau PET cut points were left to be determined, a step necessary prior to clinical application. We sought to operationalize and evaluate Alzheimer’s disease biological staging by identifying meaningful tau PET cut points to define the four biological stages in a well-characterized participant cohort and describe the features of individuals placed into the different biological stages. The primary analysis included 896 participants in the Mayo Clinic Study of Aging or the Mayo Clinic Alzheimer’s Disease Research Center longitudinal cohorts. A validation cohort consisted of 328 participants in the Alzheimer’s Disease Neuroimaging Initiative. Both cognitively normal and impaired individuals with positive amyloid PET and evaluable tau PET imaging were included. Tau PET cut points were identified with Gaussian mixture models to characterize Alzheimer’s disease biological stage in study participants with different clinical diagnoses and objective degrees of cognitive impairment as measured by Mini-Mental State Examination. A tau PET cut point in the medial temporal region and two cut points in the temporoparietal region were identified to produce, collectively, the four Alzheimer’s disease biological stages described in the revised criteria. Increasing stage was associated with greater likelihood of mild cognitive impairment and dementia diagnosis and worsening cognitive performance on Mini-Mental State Examination and Clinical Dementia Rating Sum of Boxes, a result that was reproduced in the independent Alzheimer’s Disease Neuroimaging Initiative cohort. This study provided empirical validation for the concept of using amyloid PET and tau PET to separate subjects with biomarker-proven Alzheimer’s disease into four biological stages with distinct characteristics.

Abstract Background Lung adenocarcinoma in never-smokers is a major public health burden, especially among East Asian women. Polygenic risk scores (PRSs) are promising for risk stratification but are primarily developed in European-ancestry populations. We aimed to develop and validate single- and multi-ancestry PRSs for East Asian never-smokers to improve lung adenocarcinoma risk prediction. Methods PRSs were developed using genome-wide association study summary statistics from East Asian (8002 cases; 20 782 controls) and European (2058 cases; 5575 controls) populations. Single-ancestry models included a PRS with 25 single nucleotide variants (PRS-25), PRS clumping and thresholding (CT), and LDpred2; multi-ancestry models included LDpred2 plus European PRS-128, PRS-CSx, and clumping and thresholding, super learning, empirical Bayes (CT-SLEB). Performance was evaluated in independent East Asian data from the Female Lung Cancer Consortium and externally validated in the Nanjing Lung Cancer Cohort. We assessed predictive accuracy via area under the curve operating procedure (AUC), with 10-year and (ages 30-80 years) absolute risks estimates. Results The best multi-ancestry PRS, using East Asian and European data via CT-SLEB, outperformed the best East Asian-only (LDpred2; AUC = 0.629, 95% confidence interval [CI] = 0.618 to 0.641), achieving an AUC of 0.640 (95% CI = 0.629 to 0.653) and odds ratio of 1.71 (95% CI = 1.61 to 1.82) per standard deviation increase. Nanjing Lung Cancer Cohort validation confirmed robust performance (AUC = 0.649, 95% CI = 0.623 to 0.676). The top 20% PRS group had a 3.92-fold higher lung adenocarcinoma risk than the bottom 20%. Further, the top 5% PRS group reached a 6.69% lifetime absolute risk. Notably, this group reached the average population 10-year lung adenocarcinoma risk at age 50 years (0.42%) by age 41 years, 9 years earlier. Conclusions Multi-ancestry PRS approaches enhance lung adenocarcinoma risk stratification in East Asian never-smokers, with consistent external validation, suggesting future clinical utility.

Abstract Background The past two decades have witnessed tremendous growth in the appreciation and treatment of sacroiliac joint (SIJ) complex pain, including anatomical dissections that shed light on innervation, an appreciation for the contribution of extra-articular components to SIJ complex pain, the advent of radiofrequency ablation (RFA) and a host of minimally invasive surgical techniques. Yet, there is no standardization on diagnosis and treatment paradigms. Methods In February 2023, the Boards of Directors for the American Academy of Pain Medicine (AAPM) and American Society of Regional Anesthesia & Pain Medicine (ASRA-PM) approved the development of multispecialty guidelines on SIJ complex pain. Thirty partner organizations with clinical and scientific interests in SIJ complex pain were identified, and formal letters of request-for-participation were sent to each, along with a request for nominees to serve on the committee. Twenty five organizations agreed to participate in addition to the Departments of Defense and Veterans Affairs. A steering committee developed 21 questions, which spanned criteria for diagnosis, non-interventional and interventional treatments including surgery, technical parameters on how to optimize results, and what constitutes positive outcomes. Questions were methodically assigned to specialized modules comprising 4-5 members with complementary expertise, who collaborated with the Subcommittee Lead and one of three Committee Chairs to develop preliminary drafts. Following thorough revisions, these drafts were subsequently submitted to the full committee for comprehensive review. A modified Delphi method was used in which the answers to questions were sent to the committee en bloc and comments were returned in a non-blinded fashion to the Chairs, who incorporated the comments and sent out revised versions until consensus was achieved. During a committee meeting before commencement, it was agreed that recommendations would be noted when there was &gt;50% agreement among committee members, but that a formal recommendation would require ≥75% consensus. Results Twenty-one organizations formally endorsed the guidelines. The American Society of Anesthesiologists, and American Academy of Physical Medicine & Rehabilitation, and the North American Spine Society affirmed the benefit of the guidelines but did not officially endorse them. The American Academy of Neurology declined to affirm the benefit of the guidelines citing “lack of relevance to their membership.” Per policies, while the Departments of Defense and Veterans Affairs did not formally review the guidelines for endorsement, their representatives approved them. In addition to being endorsed or the benefit affirmed by all voting organizations, complete consensus from committee members was obtained on all 21 questions. On 2 recommendations, there were dissensions from 3 societies who thought that selecting patients for sacral lateral branch RFA and minimally invasive fusion should be based on ≥75% relief from 2 blocks instead of at least 50% relief from a single block before RFA, and greater than 50% pain relief with documented functional improvement after a single block before fusion. One additional society (Latin American Society of Regional Anesthesia) abstained on the statement that the evidence is stronger for extra-articular than intra-articular injections. The committee found that a battery of physical exam tests has reasonable sensitivity, but lower specificity, for identifying intra-articular but not extra-articular pathology, with negative tests having greater predictive value than positive ones. Intra-articular injections have diagnostic validity for SIJ intra-articular, but not extra-articular pain. There is unclear or negative evidence for imaging. The prevalence rates of intra-articular and extra-articular pathology are comparable, with both intra- and extra-articular steroid injections providing at least 4 weeks of relief in well-selected patients. However, the evidence is slightly stronger for extra-articular corticosteroid injections to provide short-term relief. The evidence base for non-interventional therapies is indirect, extrapolated mostly from low back pain studies. There is weak evidence supporting dextrose-based prolotherapy and platelet-rich plasma to provide at least 3 months of pain relief. There is strong evidence for sacral lateral branch RFA to provide relief for at least 6 months in individuals with extra-articular pathology, with face validity and indirect evidence from randomized trials supporting sacral lateral branch blocks as a prognostic tool. There is stronger evidence for larger lesions or more aggressive lesioning strategies than for less stringent techniques. There is weak evidence to support non-steroidal anti-inflammatory drugs to prevent neuritis after RFA, and in most cases anticoagulation does not require cessation in the periprocedural perioid. With an aggressive lesioning strategy, sensory stimulation provides minimal therapeutic benefit, with weak, extrapolated evidence that motor stimulation can provide safety benefit. The cutoff to designate diagnostic or prognostic blocks as positive is most commonly set at 50%, with higher values not shown to improve outcomes for more definitive procedures; for therapeutic treatment outcomes, the evidence supports a lower threshold of ≥30% pain relief or meaningful benefit on non-pain outcomes (eg, opioid cessation) for designation of a positive response. For carefully selected patients with intra-articular SIJ complex pain based on controlled blocks who have failed conservative therapies, there is weak or very weak evidence that minimally invasive SIJ fusion can provide benefit for at least one year. Conclusions SIJ complex pain remains an underappreciated source of chronic low back pain, affecting between 15% and 30% of patients with axial pain predominantly below L5. Answers to many questions were limited by low-quality evidence, indicating the need for better research. SIJ complex pain is a multifarious condition (ie, pain can be from different portions of both the intra- and extra-articular components of the joint) for which an interdisciplinary, multimodal treatment plan can optimize treatment outcomes.