Operative vs nonoperative treatment of distal radius fractures in adults a systematic review and meta-analysis

Importance No consensus has been reached to date regarding the optimal treatment for distal radius fractures. The international rate of operative treatment has been increasing, despite higher costs and limited functional outcome evidence to support this shift. Objectives To compare functional, clinical, and radiologic outcomes after operative vs nonoperative treatment of distal radius fractures in adults. Data Sources The PubMed/MEDLINE, Embase, CENTRAL (Cochrane Central Register of Controlled Trials), and CINAHL (Cumulative Index to Nursing and Allied Health Literature) databases were searched from inception to June 15, 2019, for studies comparing operative vs nonoperative treatment of distal radius fractures. Study Selection Randomized clinical trials (RCTs) and observational studies reporting on the following: acute distal radius fracture with operative treatment (internal or external fixation) vs nonoperative treatment (cast immobilization, splinting, or bracing); patients 18 years or older; and functional outcome. Studies in a language other than English or reporting treatment for refracture were excluded. Data Extraction and Synthesis Data extraction was performed independently by 2 reviewers. Effect estimates were pooled using random-effects models and presented as risk ratios (RRs) or mean differences (MDs) with 95% CIs. Data were analyzed in September 2019. Main Outcomes and Measures The primary outcome measures included medium-term functional outcome measured with the Disabilities of the Arm, Shoulder and Hand questionnaire (DASH) and the overall complication rate after operative and nonoperative treatment. Results A total of 23 unique studies were included, consisting of 8 RCTs and 15 observational studies, that described 2254 unique patients. Among the studies that presented sex data, 1769 patients were women [80.6%]. Overall weighted mean age was 67 [range, 22-90] years). The RCTs included 656 patients (29.1%); observational studies, 1598 patients (70.9%). The overall pooled effect estimates the showed a significant improvement in medium-term (<= 1 year) DASH score after operative treatment compared with nonoperative treatment (MD, -5.22 [95% CI, -8.87 to -1.57]; P = .005; I-2 = 84%). No difference in complication rate was observed (RR, 1.03 [95% CI, 0.69-1.55]; P = .87; I-2 = 62%). A significant improvement in grip strength was noted after operative treatment, measured in kilograms (MD, 2.73 [95% CI, 0.15-5.32]; P = .04; I-2 = 79%) and as a percentage of the unaffected side (MD, 8.21 [95% CI, 2.26-14.15]; P = .007; I-2 = 76%). No improvement in medium-term DASH score was found in the subgroup of studies that only included patients 60 years or older (MD, -0.98 [95% CI, -3.52 to 1.57]; P = .45; I-2 = 34%]), compared with a larger improvement in medium-term DASH score after operative treatment in the other studies that included patients 18 years or older (MD, -7.50 [95% CI, -12.40 to -2.60]; P = .003; I-2 = 77%); the difference between these subgroups was statically significant (test for subgroup differences, P = .02). Conclusions and Relevance This meta-analysis suggests that operative treatment of distal radius fractures improves the medium-term DASH score and grip strength compared with nonoperative treatment in adults, with no difference in overall complication rate. The findings suggest that operative treatment might be more effective and have a greater effect on the health and well-being of younger, nonelderly patients.This meta-analysis compares functional, clinical, and radiologic outcomes after operative vs nonoperative treatment of distal radial fractures in adults.Question What outcomes are associated with operative vs nonoperative treatment of distal radius fractures in adults? Findings This meta-analysis of 2254 unique participants in 23 unique studies showed that operative treatment of distal radius fractures improved the medium-term Disabilities of the Arm, Shoulder and Hand questionnaire score and grip strength compared with nonoperative treatment in adults, with no difference in overall complication rate. Meaning These findings suggest that operative treatment might be preferred for distal radius fractures.Clinical epidemiolog

Geospatial analyses identify regional hot spots of diffuse gastric cancer in rural Central America

Background: Geospatial technology has facilitated the discovery of disease distributions and etiology and helped target prevention programs. Globally, gastric cancer is the leading infection-associated cancer, and third leading cause of cancer mortality worldwide, with marked geographic variation. Central and South America have a significant burden, particularly in the mountainous regions. In the context of an ongoing population-based case-control study in Central America, our aim was to examine the spatial epidemiology of gastric cancer subtypes and H. pylori virulence factors. Methods: Patients diagnosed with gastric cancer from 2002 to 2013 in western Honduras were identified in the prospective gastric cancer registry at the principal district hospital. Diagnosis was based on endoscopy and confirmatory histopathology. Geospatial methods were applied using the ArcGIS v10.3.1 and SaTScan v9.4.2 platforms to examine regional distributions of the gastric cancer histologic subtypes (Lauren classification), and the H. pylori CagA virulence factor. Getis-Ord-Gi hot spot and Discrete Poisson SaTScan statistics, respectively, were used to explore spatial clustering at the village level (30-50 rural households), with standardization by each village's population. H. pylori and CagA serologic status was determined using the novel H. pylori multiplex assay (DKFZ, Germany). Results: Three hundred seventy-eight incident cases met the inclusion criteria (mean age 63.7, male 66.3%). Areas of higher gastric cancer incidence were identified. Significant spatial clustering of diffuse histology adenocarcinoma was revealed both by the Getis-Ord-GI∗hot spot analysis (P-value < 0.0015; range 0.00003-0.0014; 99%CI), and by the SaTScan statistic (P-value < 0.006; range 0.0026-0.0054). The intestinal subtype was randomly distributed. H. pylori CagA had significant spatial clustering only in association with the diffuse histology cancer hot spot (Getis-Ord-Gi∗P value ≤0.001; range 0.0001-0.0010; SaTScan statistic P value 0.0085). In the diffuse gastric cancer hot spot, the lowest age quartile range was 21-46 years, significantly lower than the intestinal cancers (P = 0.024). Conclusions: Geospatial methods have identified a significant cluster of incident diffuse type adenocarcinoma cases in rural Central America, suggest of a germline genetic association. Further genomic and geospatial analyses to identify potential spatial patterns of genetic, bacterial, and environmental risk factors may be informative

Reporting guideline for the early stage clinical evaluation of decision support systems driven by artificial intelligence: DECIDE-AI

A growing number of artificial intelligence (AI)-based clinical decision support systems are showing promising performance in preclinical, in silico, evaluation, but few have yet demonstrated real benefit to patient care. Early stage clinical evaluation is important to assess an AI system’s actual clinical performance at small scale, ensure its safety, evaluate the human factors surrounding its use, and pave the way to further large scale trials. However, the reporting of these early studies remains inadequate. The present statement provides a multistakeholder, consensus-based reporting guideline for the Developmental and Exploratory Clinical Investigations of DEcision support systems driven by Artificial Intelligence (DECIDE-AI). We conducted a two round, modified Delphi process to collect and analyse expert opinion on the reporting of early clinical evaluation of AI systems. Experts were recruited from 20 predefined stakeholder categories. The final composition and wording of the guideline was determined at a virtual consensus meeting. The checklist and the Explanation & Elaboration (E&E) sections were refined based on feedback from a qualitative evaluation process. 123 experts participated in the first round of Delphi, 138 in the second, 16 in the consensus meeting, and 16 in the qualitative evaluation. The DECIDE-AI reporting guideline comprises 17 AI specific reporting items (made of 28 subitems) and 10 generic reporting items, with an E&E paragraph provided for each. Through consultation and consensus with a range of stakeholders, we have developed a guideline comprising key items that should be reported in early stage clinical studies of AI-based decision support systems in healthcare. By providing an actionable checklist of minimal reporting items, the DECIDE-AI guideline will facilitate the appraisal of these studies and replicability of their findings

Prevention of Gastric Cancer: When is Treatment of Helicobacter Pylori Warranted?

Chronic gastritis induced by Helicobacter pylori (H. pylori) is the strongest known risk factor for adenocarcinoma of the distal stomach, yet the effects of bacterial eradication on carcinogenesis remain unclear. H. pylori isolates possess substantial genotypic diversity, which engenders differential host inflammatory responses that influence clinical outcome. H. pylori strains that possess the cag pathogenicity island and secrete a functional cytotoxin induce more severe gastric injury and further augment the risk for developing distal gastric cancer. Carcinogenesis is also influenced by host genetic diversity, particularly involving immune response genes such as interleukin-1ß and tumor necrosis factor-α. Human trials and anima studies have indicated that eradication of H. pylori prior to the development of atrophic gastritis offers the best chance for prevention of gastric cancer. However, although the timing of intervention influences the magnitude of suppression of premalignant and neoplastic lesions, bacterial eradication, even in longstanding infections, is of clear benefit to the host. It is important to gain insight into the pathogenesis of H. pylori-induced gastritis and adenocarcinoma not only to develop more effective treatments for gastric cancer, but also because it might serve as a paradigm for the role of chronic inflammation in the genesis of other malignancies that arise within the gastrointestinal tract

Pan-genomic analyses identify key Helicobacter pylori pathogenic loci modified by carcinogenic host microenvironments

Objective Helicobacter pylori is the strongest risk factor for gastric cancer; however, the majority of infected individuals do not develop disease. Pathological outcomes are mediated by complex interactions among bacterial, host and environmental constituents, and two dietary factors linked with gastric cancer risk are iron deficiency and high salt. We hypothesised that prolonged adaptation of H. pylori to in vivo carcinogenic microenvironments results in genetic modification important for disease. Design Whole genome sequencing of genetically related H. pylori strains that differ in virulence and targeted H. pylori sequencing following prolonged exposure of bacteria to in vitro carcinogenic conditions were performed. Results A total of 180 unique single nucleotide polymorphisms (SNPs) were identified among the collective genomes when compared with a reference H. pylori genome. Importantly, common SNPs were identified in isolates harvested from iron-depleted and high salt carcinogenic microenvironments, including an SNP within fur (FurR88H). To investigate the direct role of low iron and/or high salt, H. pylori was continuously cultured in vitro under low iron or high salt conditions to assess fur genetic variation. Exposure to low iron or high salt selected for the FurR88H variant after only 5 days. To extend these results, fur was sequenced in 339 clinical H. pylori strains. Among the isolates examined, 17% (40/232) of strains isolated from patients with premalignant lesions harboured the FurR88H variant, compared with only 6% (6/107) of strains from patients with non-atrophic gastritis alone (p=0.0034). Conclusion These results indicate that specific genetic variation arises within H. pylori strains during in vivo adaptation to conditions conducive for gastric carcinogenesis

Helicobacter pylori genetic diversification in the Mongolian gerbil model

Helicobacter pylori requires genetic agility to infect new hosts and establish long-term colonization of changing gastric environments. In this study, we analyzed H. pylori genetic adaptation in the Mongolian gerbil model. This model is of particular interest because H. pylori-infected gerbils develop a high level of gastric inflammation and often develop gastric adenocarcinoma or gastric ulceration. We analyzed the whole genome sequences of H. pylori strains cultured from experimentally infected gerbils, in comparison to the genome sequence of the input strain. The mean annualized single nucleotide polymorphism (SNP) rate per site was 1.5e−5, which is similar to the rates detected previously in H. pylori-infected humans. Many of the mutations occurred within or upstream of genes associated with iron-related functions (fur, tonB1, fecA2, fecA3, and frpB3) or encoding outer membrane proteins (alpA, oipA, fecA2, fecA3, frpB3 and cagY). Most of the SNPs within coding regions (86%) were non-synonymous mutations. Several deletion or insertion mutations led to disruption of open reading frames, suggesting that the corresponding gene products are not required or are deleterious during chronic H. pylori colonization of the gerbil stomach. Five variants (three SNPs and two deletions) were detected in isolates from multiple animals, which suggests that these mutations conferred a selective advantage. One of the mutations (FurR88H) detected in isolates from multiple animals was previously shown to confer increased resistance to oxidative stress, and we now show that this SNP also confers a survival advantage when H. pylori is co-cultured with neutrophils. Collectively, these analyses allow the identification of mutations that are positively selected during H. pylori colonization of the gerbil model