Reducing Recurrence of C. difficile Infection.

Clostridium difficile infection (CDI) is facilitated by alteration of the microbiome following antibiotic administration. Antimicrobial therapy directed against the pathogen can treat CDI. Unfortunately, ∼20% of successfully treated patients will suffer recurrence. Bezlotoxumab, a human monoclonal antibody, binds to C. difficile toxin B (TcdB), reducing recurrence presumably by limiting epithelial damage and facilitating microbiome recovery.

A Dietary Fiber-Deprived Gut Microbiota Degrades the Colonic Mucus Barrier and Enhances Pathogen Susceptibility.

Despite the accepted health benefits of consuming dietary fiber, little is known about the mechanisms by which fiber deprivation impacts the gut microbiota and alters disease risk. Using a gnotobiotic mouse model, in which animals were colonized with a synthetic human gut microbiota composed of fully sequenced commensal bacteria, we elucidated the functional interactions between dietary fiber, the gut microbiota, and the colonic mucus barrier, which serves as a primary defense against enteric pathogens. We show that during chronic or intermittent dietary fiber deficiency, the gut microbiota resorts to host-secreted mucus glycoproteins as a nutrient source, leading to erosion of the colonic mucus barrier. Dietary fiber deprivation, together with a fiber-deprived, mucus-eroding microbiota, promotes greater epithelial access and lethal colitis by the mucosal pathogen, Citrobacter rodentium. Our work reveals intricate pathways linking diet, the gut microbiome, and intestinal barrier dysfunction, which could be exploited to improve health using dietary therapeutics.

NLRP12 attenuates colon inflammation by maintaining colonic microbial diversity and promoting protective commensal bacterial growth.

Inflammatory bowel diseases involve the dynamic interaction of host genetics, the microbiome and inflammatory responses. Here we found lower expression of NLRP12 (which encodes a negative regulator of innate immunity) in human ulcerative colitis, by comparing monozygotic twins and other patient cohorts. In parallel, Nlrp12 deficiency in mice caused increased basal colonic inflammation, which led to a less-diverse microbiome and loss of protective gut commensal strains (of the family Lachnospiraceae) and a greater abundance of colitogenic strains (of the family Erysipelotrichaceae). Dysbiosis and susceptibility to colitis associated with Nlrp12 deficency were reversed equally by treatment with antibodies targeting inflammatory cytokines and by the administration of beneficial commensal Lachnospiraceae isolates. Fecal transplants from mice reared in specific-pathogen-free conditions into germ-free Nlrp12-deficient mice showed that NLRP12 and the microbiome each contributed to immunological signaling that culminated in colon inflammation. These findings reveal a feed-forward loop in which NLRP12 promotes specific commensals that can reverse gut inflammation, while cytokine blockade during NLRP12 deficiency can reverse dysbiosis.

Corrigendum: NLRP12 attenuates colon inflammation by maintaining colonic microbial diversity and promoting protective commensal bacterial growth.

This corrects the article DOI: 10.1038/ni.3690.

Gut microbiome-derived metabolites modulate intestinal epithelial cell damage and mitigate graft-versus-host disease.

The effect of alterations in intestinal microbiota on microbial metabolites and on disease processes such as graft-versus-host disease (GVHD) is not known. Here we carried out an unbiased analysis to identify previously unidentified alterations in gastrointestinal microbiota-derived short-chain fatty acids (SCFAs) after allogeneic bone marrow transplant (allo-BMT). Alterations in the amount of only one SCFA, butyrate, were observed only in the intestinal tissue. The reduced butyrate in CD326(+) intestinal epithelial cells (IECs) after allo-BMT resulted in decreased histone acetylation, which was restored after local administration of exogenous butyrate. Butyrate restoration improved IEC junctional integrity, decreased apoptosis and mitigated GVHD. Furthermore, alteration of the indigenous microbiota with 17 rationally selected strains of high butyrate-producing Clostridia also decreased GVHD. These data demonstrate a heretofore unrecognized role of microbial metabolites and suggest that local and specific alteration of microbial metabolites has direct salutary effects on GVHD target tissues and can mitigate disease severity.

Outcomes of the EMDataResource cryo-EM Ligand Modeling Challenge.

The EMDataResource Ligand Model Challenge aimed to assess the reliability and reproducibility of modeling ligands bound to protein and protein-nucleic acid complexes in cryogenic electron microscopy (cryo-EM) maps determined at near-atomic (1.9-2.5 Å) resolution. Three published maps were selected as targets: Escherichia coli beta-galactosidase with inhibitor, SARS-CoV-2 virus RNA-dependent RNA polymerase with covalently bound nucleotide analog and SARS-CoV-2 virus ion channel ORF3a with bound lipid. Sixty-one models were submitted from 17 independent research groups, each with supporting workflow details. The quality of submitted ligand models and surrounding atoms were analyzed by visual inspection and quantification of local map quality, model-to-map fit, geometry, energetics and contact scores. A composite rather than a single score was needed to assess macromolecule+ligand model quality. These observations lead us to recommend best practices for assessing cryo-EM structures of liganded macromolecules reported at near-atomic resolution.

Dosage compensation plans: protein aggregation provides additional insurance against aneuploidy.

Gene dosage alterations caused by aneuploidy are a common feature of most cancers yet pose severe proteotoxic challenges. Therefore, cells have evolved various dosage compensation mechanisms to limit the damage caused by the ensuing protein level imbalances. For instance, for heteromeric protein complexes, excess nonstoichiometric subunits are rapidly recognized and degraded. In this issue of Genes & Development, Brennan et al. (pp. 1031-1047) reveal that sequestration of nonstoichiometric subunits into aggregates is an alternative mechanism for dosage compensation in aneuploid budding yeast and human cell lines. Using a combination of proteomic and genetic techniques, they found that excess proteins undergo either degradation or aggregation but not both. Which route is preferred depends on the half-life of the protein in question. Given the multitude of diseases linked to either aneuploidy or protein aggregation, this study could serve as a springboard for future studies with broad-spanning implications.

Comparison of Daily versus Admission and Discharge Surveillance Cultures for Multidrug-Resistant Organism Detection in an Intensive Care Unit.

BACKGROUND: Admission and discharge screening of patients for asymptomatic gut colonization with multidrug-resistant organisms (MDROs) is a traditional approach to active surveillance, but its sensitivity for detecting colonization is uncertain. METHODS: Daily rectal or fecal swab samples and clinical data were collected over 12 months from patients in one 25-bed intensive care unit (ICU) in Chicago, IL USA and tested for the following multidrug-resistant organisms (MDROs): vancomycin-resistant enterococci (VRE); third-generation cephalosporin-resistant Enterobacterales, including extended-spectrum ß-lactamase-producing Enterobacterales (ESBL); and carbapenem-resistant Enterobacterales (CRE). MDRO detection by (1) admission/discharge surveillance cultures or (2) clinical cultures were compared to daily surveillance cultures. Samples underwent 16S rRNA gene sequencing to measure the relative abundance of operational taxonomic units (OTUs) corresponding to each MDRO. RESULTS: Compared with daily surveillance cultures, admission/discharge cultures detected 91% of prevalent MDRO colonization and 63% of incident MDRO colonization among medical ICU patients. Only a minority (7%) of MDRO carriers were identified by clinical cultures. Higher relative abundance of MDRO-associated OTUs and specific antibiotic exposures were independently associated with higher probability of MDRO detection by culture. CONCLUSION: Admission and discharge surveillance cultures underestimated MDRO acquisitions in an ICU. These limitations should be considered when designing sampling strategies for epidemiologic studies that use culture-based surveillance.

Single-Cell Meta-Analysis of Neutrophil Activation in Kawasaki Disease and Multisystem Inflammatory Syndrome in Children Reveals Potential Shared Immunological Drivers.

BACKGROUND: Kawasaki disease (KD) and multisystem inflammatory syndrome in children (MIS-C) share similar clinical manifestations, including cardiovascular complications, suggesting similar underlying immunopathogenic processes. Aberrant neutrophil activation may play a crucial role in the shared pathologies of KD and MIS-C; however, the associated pathogenic mechanisms and molecular drivers remain unknown. METHODS: We performed a single-cell meta-analysis of neutrophil activation with 103 pediatric single-cell transcriptomic peripheral blood mononuclear cell data across 9 cohorts, including healthy controls, KD, MIS-C, compared with dengue virus infection, juvenile idiopathic arthritis, and pediatric celiac disease. We used a series of computational analyses to investigate the shared neutrophil transcriptional programs of KD and MIS-C that are linked to systemic damage and cardiac pathologies, and suggested Food and Drug Administration-approved drugs to consider as KD and MIS-C treatment. RESULTS: We meta-analyzed 521 950 high-quality cells. We found that blood signatures associated with risks of cardiovascular events are enriched in neutrophils of KD and MIS-C. We revealed the expansion of CD177+ neutrophils harboring hyperactivated effector functions in both KD and MIS-C, but not in healthy controls or in other viral-, inflammatory-, or immune-related pediatric diseases. KD and MIS-C CD177+ neutrophils had highly similar transcriptomes, marked by conserved signatures and pathways related to molecular damage. We found the induction of a shared neutrophil expression program, potentially regulated by SPI1 (Spi-1 proto-oncogene), which confers enhanced effector functions, especially neutrophil degranulation. CD177 and shared neutrophil expression program expressions were associated with acute stages and attenuated during KD intravenous immunoglobulin treatment and MIS-C recovery. Network analysis identified hub genes that correlated with the high activation of CD177+ neutrophils. Disease-gene association analysis revealed that the KD and MIS-C CD177+ neutrophils' shared expression program was associated with the development of coronary and myocardial disorders. Last, we identified and validated TSPO (translocator protein) and S100A12 (S100 calcium-binding protein A12) as main molecular targets, for which the Food and Drug Administration-approved drugs methotrexate, zaleplon, metronidazole, lorazepam, clonazepam, temazepam, and zolpidem, among others, are primary candidates for drug repurposing. CONCLUSIONS: Our findings indicate that CD177+ neutrophils may exert systemic pathological damage contributing to the shared morbidities in KD and MIS-C. We uncovered potential regulatory drivers of CD177+ neutrophil hyperactivation and pathogenicity that may be targeted as a single therapeutic strategy for either KD or MIS-C.

Predicting Long-term Disease-free Survival After Resection of Pancreatic Ductal Adenocarcinoma: A Nationwide Cohort Study.

OBJECTIVE: To develop a prediction model for long-term (≥5 years) disease-free survival (DFS) after the resection of pancreatic ductal adenocarcinoma (PDAC). BACKGROUND: Despite high recurrence rates, ~10% of patients have long-term DFS after PDAC resection. A model to predict long-term DFS may aid individualized prognostication and shared decision-making. METHODS: This nationwide cohort study included all consecutive patients who underwent PDAC resection in the Netherlands (2014-2016). The best-performing prognostic model was selected by Cox-proportional hazard analysis and Akaike's Information Criterion, presented by hazard ratios (HRs) with 95% confidence intervals (CIs). Internal validation was performed, and discrimination and calibration indices were assessed. RESULTS: In all, 836 patients with a median follow-up of 67 months (interquartile range 51-79) were analyzed. Long-term DFS was seen in 118 patients (14%). Factors predictive of long-term DFS were low preoperative carbohydrate antigen 19-9 (logarithmic; HR 1.21; 95% CI 1.10-1.32), no vascular resection (HR 1.33; 95% CI 1.12-1.58), T1 or T2 tumor stage (HR 1.52; 95% CI 1.14-2.04, and HR 1.17; 95% CI 0.98-1.39, respectively), well/moderate tumor differentiation (HR 1.44; 95% CI 1.22-1.68), absence of perineural and lymphovascular invasion (HR 1.42; 95% CI 1.11-1.81 and HR 1.14; 95% CI 0.96-1.36, respectively), N0 or N1 nodal status (HR 1.92; 95% CI 1.54-2.40, and HR 1.33; 95% CI 1.11-1.60, respectively), R0 resection margin status (HR 1.25; 95% CI 1.07-1.46), no major complications (HR 1.14; 95% CI 0.97-1.35) and adjuvant chemotherapy (HR 1.74; 95% CI 1.47-2.06). Moderate performance (concordance index 0.68) with adequate calibration (slope 0.99) was achieved. CONCLUSIONS: The developed prediction model, readily available at www.pancreascalculator.com, can be used to estimate the probability of long-term DFS after resection of pancreatic ductal adenocarcinoma.

Long-Term Outcome of Immediate Versus Postponed Intervention in Patients With Infected Necrotizing Pancreatitis (POINTER): Multicenter Randomized Trial.

OBJECTIVE: To compare the long-term outcomes of immediate drainage versus the postponed-drainage approach in patients with infected necrotizing pancreatitis. BACKGROUND: In the randomized POINTER trial, patients assigned to the postponed-drainage approach using antibiotic treatment required fewer interventions, as compared with immediate drainage, and over a third were treated without any intervention. METHODS: Clinical data of those patients alive after the initial 6-month follow-up were re-evaluated. The primary outcome was a composite of death and major complications. RESULTS: Out of 104 patients, 88 were re-evaluated with a median follow-up of 51 months. After the initial 6-month follow-up, the primary outcome occurred in 7 of 47 patients (15%) in the immediate-drainage group and 7 of 41 patients (17%) in the postponed-drainage group (RR 0.87, 95% CI 0.33-2.28; P =0.78). Additional drainage procedures were performed in 7 patients (15%) versus 3 patients (7%) (RR 2.03; 95% CI 0.56-7.37; P =0.34). The median number of additional interventions was 0 (IQR 0-0) in both groups ( P =0.028). In the total follow-up, the median number of interventions was higher in the immediate-drainage group than in the postponed-drainage group (4 vs. 1, P =0.001). Eventually, 14 of 15 patients (93%) in the postponed-drainage group who were successfully treated in the initial 6-month follow-up with antibiotics and without any intervention remained without intervention. At the end of follow-up, pancreatic function and quality of life were similar. CONCLUSIONS: Also, during long-term follow-up, a postponed-drainage approach using antibiotics in patients with infected necrotizing pancreatitis results in fewer interventions as compared with immediate drainage and should therefore be the preferred approach. TRIAL REGISTRATION: ISRCTN33682933.

Immediate versus Postponed Intervention for Infected Necrotizing Pancreatitis.

BACKGROUND: Infected necrotizing pancreatitis is a potentially lethal disease that is treated with the use of a step-up approach, with catheter drainage often delayed until the infected necrosis is encapsulated. Whether outcomes could be improved by earlier catheter drainage is unknown. METHODS: We conducted a multicenter, randomized superiority trial involving patients with infected necrotizing pancreatitis, in which we compared immediate drainage within 24 hours after randomization once infected necrosis was diagnosed with drainage that was postponed until the stage of walled-off necrosis was reached. The primary end point was the score on the Comprehensive Complication Index, which incorporates all complications over the course of 6 months of follow-up. RESULTS: A total of 104 patients were randomly assigned to immediate drainage (55 patients) or postponed drainage (49 patients). The mean score on the Comprehensive Complication Index (scores range from 0 to 100, with higher scores indicating more severe complications) was 57 in the immediate-drainage group and 58 in the postponed-drainage group (mean difference, -1; 95% confidence interval [CI], -12 to 10; P = 0.90). Mortality was 13% in the immediate-drainage group and 10% in the postponed-drainage group (relative risk, 1.25; 95% CI, 0.42 to 3.68). The mean number of interventions (catheter drainage and necrosectomy) was 4.4 in the immediate-drainage group and 2.6 in the postponed-drainage group (mean difference, 1.8; 95% CI, 0.6 to 3.0). In the postponed-drainage group, 19 patients (39%) were treated conservatively with antibiotics and did not require drainage; 17 of these patients survived. The incidence of adverse events was similar in the two groups. CONCLUSIONS: This trial did not show the superiority of immediate drainage over postponed drainage with regard to complications in patients with infected necrotizing pancreatitis. Patients randomly assigned to the postponed-drainage strategy received fewer invasive interventions. (Funded by Fonds NutsOhra and Amsterdam UMC; POINTER ISRCTN Registry number, ISRCTN33682933.).

Human neutrophil IL1ß directs intestinal epithelial cell extrusion during Salmonella infection.

Infection of the human gut by Salmonella enterica Typhimurium (STM) results in a localized inflammatory disease that is not mimicked in murine infections. To determine mechanisms by which neutrophils, as early responders to bacterial challenge, direct inflammatory programming of human intestinal epithelium, we established a multi-component human intestinal organoid (HIO) model of STM infection. HIOs were micro-injected with STM and seeded with primary human polymorphonuclear leukocytes (PMN-HIOs). PMNs did not significantly alter luminal colonization of Salmonella, but their presence reduced intraepithelial bacterial burden. Adding PMNs to infected HIOs resulted in substantial accumulation of shed TUNEL+ epithelial cells that was driven by PMN Caspase-1 activity. Inhibition of Caspases-1, -3 or -4 abrogated epithelial cell death and extrusion in the infected PMN-HIOs but only Caspase-1 inhibition significantly increased bacterial burden in the PMN-HIO epithelium. Thus, PMNs promote cell death in human intestinal epithelial cells through multiple caspases as a protective response to infection. IL-1ß was necessary and sufficient to induce cell shedding in the infected HIOs. These data support a critical innate immune function for human neutrophils in amplifying cell death and extrusion of human epithelial cells from the Salmonella-infected intestinal monolayer.

Nutritional support in pancreatic cancer patients and its effect on nutritional status: an observational regional HPB network study investigating current practice.

PURPOSE: Preoperative malnutrition is associated with poor postoperative outcomes in patients with pancreatic cancer. This study evaluated the effectiveness of current practice in nutritional support for patients with pancreatic cancer. METHODS: Observational multicenter HPB network study conducted at the Isala Clinics Zwolle, Medical Spectrum Twente, Medical Center Leeuwarden, and University Medical Center Groningen between October 2021 and May 2023. Patients with a suspected pancreatic malignancy scheduled for surgery were screened for malnutrition using the Patient-Generated Subjective Global Assessment (PG-SGA) questionnaire and referred to a dedicated dietician for nutritional support comprising pancreatic enzyme replacement therapy, dietary advice, and nutritional supplements to achieve adequate caloric and protein intake. At baseline, 1 day preoperatively, and 3 months postoperatively, the nutritional status and muscle thickness were evaluated. RESULTS: The study included 30 patients, of whom 12 (40%) classified as malnourished (PG-SGA ≥ 4) at baseline. Compared to well-nourished patients, malnourished patients were younger, were predominantly female, and had a higher body mass index, despite having lost more body weight in the past 6 months. All malnourished patients and 78% of the well-nourished patients received nutritional support. Consequently, a preoperative increase in caloric and protein intake and body weight were observed. Postoperatively, despite a further increase in caloric intake, a considerable decrease in protein intake, body weight, and muscle thickness was observed. CONCLUSION: Malnutrition is prevalent in patients undergoing pancreatic surgery. Nutritional support by a dedicated dietician is effective in enhancing patients' preoperative nutritional status. However, postoperative monitoring of adequate nutritional intake in patients could be improved.

Lessons learned from revision procedures: a case series pleading for reinforcement of the anterior hiatus in recurrent hiatal hernia.

BACKGROUND: Hiatal Hernia (HH) is a common structural defect of the diaphragm. Laparoscopic repair with suturing of the hiatal pillars followed by fundoplication has become standard practice. In an attempt to lower HH recurrence rates, mesh reinforcement, commonly located at the posterior site of the esophageal hiatus, has been used. However, effectiveness of posterior mesh augmentation is still up to debate. There is a lack of understanding of the mechanism of recurrence requiring further investigation. We investigated the anatomic location of HH recurrences in an attempt to assess why HH recurrence rates remain high despite various attempts with mesh reinforcement. METHODS: A retrospective case series of prospectively collected data from patients with hiatal hernia repair between 2012 and 2020 was performed. In total, 54 patients with a recurrent hiatal hernia operation were included in the study. Video clips from the revision procedure were analyzed by a surgical registrar and senior surgeon to assess the anatomic location of recurrent HH. For the assessment, the esophageal hiatus was divided into four equal quadrants. Additionally, patient demographics, hiatal hernia characteristics, and operation details were collected and analyzed. RESULTS: 54 patients were included. The median time between primary repair and revision procedure was 25 months (IQR 13-95, range 0-250). The left-anterior quadrant was involved in 43 patients (80%), the right-anterior quadrant in 21 patients (39%), the left-posterior quadrant in 21 patients (39%), and the right-posterior quadrant in 10 patients (19%). CONCLUSION: In this study, hiatal hernia recurrences occured most commonly at the left-anterior quadrant of the hiatus, however, posterior recurrences were not uncommon. Based on our results, we hypothesize that both posterior and anterior hiatal reinforcement might be a suitable solution to lower the recurrence rate of hiatal hernia. A randomized controlled trial using a circular, bio-absorbable mesh has been initiated to test our hypothesis.

The Gut Microbiome Modulates Body Temperature Both in Sepsis and Health.

Rationale: Among patients with sepsis, variation in temperature trajectories predicts clinical outcomes. In healthy individuals, normal body temperature is variable and has decreased consistently since the 1860s. The biologic underpinnings of this temperature variation in disease and health are unknown. Objectives: To establish and interrogate the role of the gut microbiome in calibrating body temperature. Methods: We performed a series of translational analyses and experiments to determine whether and how variation in gut microbiota explains variation in body temperature in sepsis and in health. We studied patient temperature trajectories using electronic medical record data. We characterized gut microbiota in hospitalized patients using 16S ribosomal RNA gene sequencing. We modeled sepsis using intraperitoneal LPS in mice and modulated the microbiome using antibiotics, germ-free, and gnotobiotic animals. Measurements and Main Results: Consistent with prior work, we identified four temperature trajectories in patients hospitalized with sepsis that predicted clinical outcomes. In a separate cohort of 116 hospitalized patients, we found that the composition of patients' gut microbiota at admission predicted their temperature trajectories. Compared with conventional mice, germ-free mice had reduced temperature loss during experimental sepsis. Among conventional mice, heterogeneity of temperature response in sepsis was strongly explained by variation in gut microbiota. Healthy germ-free and antibiotic-treated mice both had lower basal body temperatures compared with control animals. The Lachnospiraceae family was consistently associated with temperature trajectories in hospitalized patients, experimental sepsis, and antibiotic-treated mice. Conclusions: The gut microbiome is a key modulator of body temperature variation in both health and critical illness and is thus a major, understudied target for modulating physiologic heterogeneity in sepsis.

Comparing 5-Fluorouracil Versus Modified Carnoy's Solution for the Treatment of Odontogenic Keratocysts: A Systematic Review and Meta-Analysis.

PURPOSE: The primary aim of this study was to compare time to odontogenic keratocyst (OKC) recurrence with 5-fluorouracil (5-FU) versus modified Carnoy's solution (MCS) following enucleation and curettage and peripheral ostectomy. The secondary aim was to compare the frequency (%) of permanent peripheral nerve injury characterized by hypoesthesia and neuropathic pain present at 12 months or more after surgery with 5-FU versus MCS. METHODS: The Cox hazard ratio was calculated to compare time to recurrence between the 2 groups. To compare the frequencies of permanent nerve damage, we fitted a fixed-effects model to the data and calculated the risk ratio. Other variables collected were sex, age, follow-up time, and cyst size. RESULTS: No significant differences in sex, age, follow-up time, and cyst size were found. The median follow-up time for all patients was 60 months (range: 12-180 months, Q1 = 32 months, Q3 = 86 months, interquartile range = 54 months). Of the 114 patients treated with MCS, 27 recurrences with a median recurrence time of 42 months (range = 12-108 months, Q1 = 26.3 months, Q3 = 54 months, interquartile range = 27.7 months) were recorded; no recurrences were observed among the 99 patients treated with 5-FU (hazard ratio = 0.02, 95% CI = 0.00018-0.16, P = 2.27e-07). Of the 112 patients treated with MCS, there were 20 (17.86%) instances of permanent peripheral nerve injury; of the 98 patients treated with 5-FU, there were 7 (7.14%) instances of permanent peripheral nerve injury (risk ratio = 0.44, 95% CI = 0.20-0.97, P = .04). CONCLUSION: The results of this meta-analysis significantly favored 5-FU over MCS for lower OKC recurrence and peripheral nerve injury, supporting the use of 5-FU as the superior adjuvant following enucleation and curettage and peripheral ostectomy for the treatment of OKCs.

Is ChatGPT an Accurate and Readable Patient Aid for Third Molar Extractions?

BACKGROUND: Artificial intelligence (AI) platforms such as Chat Generative Pre-Trained Transformer (ChatGPT) (Open AI, San Francisco, California, USA) have the capacity to answer health-related questions. It remains unknown whether AI can be a patient-friendly and accurate resource regarding third molar extraction. PURPOSE: The purpose was to determine the accuracy and readability of AI responses to common patient questions regarding third molar extraction. STUDY DESIGN, SETTING, SAMPLE: This is a cross sectional in-silico assessment of readability and soundness of a computer-generated report. INDEPENDENT VARIABLE: Not applicable. MAIN OUTCOME VARIABLES: Accuracy, or the ability to provide clinically correct and relevant information, was determined subjectively by 2 reviewers using a 5-point Likert scale, and objectively by comparing responses to American Association of Oral and Maxillofacial Surgeons (AAOMS) clinical consensus papers. Readability, or how easy a piece of text is to read, was assessed using the Flesch Kincaid Reading Ease (FKRE) and Flesch Kincaid Grade Level (FKGL). Both assess readability based on mean number of syllables per word, and words per sentence. To be deemed readable, FKRE should be >60 and FKGL should be <8. COVARIATES: Not applicable. ANALYSES: Descriptive statistics were used to analyze the findings of this study. RESULTS: AI-generated responses above the recommended level for the average patient (FKRE: 52; FKGL: 10). The average Likert score was 4.36, suggesting that most responses were accurate with minor inaccuracies or missing information. AI correctly deferred to the provider in instances where no definitive answer exists. Of the responses that addressed content in AAOMS consensus papers, 18/19 responses closely aligned with them. All prompts did not provide citations or references. CONCLUSION AND RELEVANCE: AI was able to provide mostly accurate responses, and content was closely aligned with AAOMS guidelines. However, responses were too complex for the average third molar extraction patient, and were deficient in citations and references. It is important for providers to educate patients on the utility of AI, and to decide whether to recommend using it for information. Ultimately, the best resource for answers is from the practitioners themselves because the AI platform lacks clinical experience.

Comparison of lumen-apposing metal stents versus double-pigtail plastic stents for infected necrotising pancreatitis.

OBJECTIVE: Lumen-apposing metal stents (LAMS) are believed to clinically improve endoscopic transluminal drainage of infected necrosis when compared with double-pigtail plastic stents. However, comparative data from prospective studies are very limited. DESIGN: Patients with infected necrotising pancreatitis, who underwent an endoscopic step-up approach with LAMS within a multicentre prospective cohort study were compared with the data of 51 patients in the randomised TENSION trial who had been assigned to the endoscopic step-up approach with double-pigtail plastic stents. The clinical study protocol was otherwise identical for both groups. Primary end point was the need for endoscopic transluminal necrosectomy. Secondary end points included mortality, major complications, hospital stay and healthcare costs. RESULTS: A total of 53 patients were treated with LAMS in 16 hospitals during 27 months. The need for endoscopic transluminal necrosectomy was 64% (n=34) and was not different from the previous trial using plastic stents (53%, n=27)), also after correction for baseline characteristics (OR 1.21 (95% CI 0.45 to 3.23)). Secondary end points did not differ between groups either, which also included bleeding requiring intervention-5 patients (9%) after LAMS placement vs 11 patients (22%) after placement of plastic stents (relative risk 0.44; 95% CI 0.16 to 1.17). Total healthcare costs were also comparable (mean difference -€6348, bias-corrected and accelerated 95% CI -€26 386 to €10 121). CONCLUSION: Our comparison of two patient groups from two multicentre prospective studies with a similar design suggests that LAMS do not reduce the need for endoscopic transluminal necrosectomy when compared with double-pigtail plastic stents in patients with infected necrotising pancreatitis. Also, the rate of bleeding complications was comparable.