Phenotypic relationship and repeatability of methane emissions and performance traits in beef cattle using a GreenFeed system.

Rumen methanogenesis results in the loss of 6% to 10% of gross energy intake in cattle and globally is the single most significant source of anthropogenic methane (CH4) emissions. The purpose of this study was to analyze greenhouse gas traits recorded in a commercial feedlot unit to gain an understanding into the relationships between greenhouse gas traits and production traits. Methane and carbon dioxide (CO2) data recorded via multiple GreenFeed Emission Monitoring (GEM), systems as well as feed intake, live weight, ultrasound scanning data, and slaughter data were available on 1,099 animals destined for beef production, of which 648 were steers, 361 were heifers, and 90 were bulls. Phenotypic relationships between GEM emission measurements with feed intake, weight traits, muscle ultrasound data, and carcass traits were estimated. Utilization of GEM systems, daily patterns of methane output, and repeatability of GEM system measurements across averaging periods were also assessed. Methane concentrations varied with visit number, duration, and time of day of visit to the GEM system. Mean CH4 and CO2 varied between sex, with mean CH4 of 256.1 g/day ± 64.23 for steers, 234.7 g/day ± 59.46 for heifers, and 156.9 g/day ± 55.98 for young bulls. A 10-d average period of GEM system measurements were required for steers and heifers to achieve a minimum repeatability of 0.60; however, higher levels of repeatability were observed in animals that attended the GEM system more frequently. In contrast, CO2 emissions reached repeatability estimates >0.6 for steers and heifers in all averaging periods greater than 2-d, suggesting that cattle have a moderately consistent CO2 emission pattern across time periods. Animals with heavier bodyweights were observed to have higher levels of CH4 (correlation = 0.30) and CO2 production (correlation = 0.61), and when assessing direct methane, higher levels of dry matter intake were associated with higher methane output (correlation = 0.31). Results suggest that reducing CH4 can have a negative impact on growth and body composition of cattle. Methane ratio traits, such as methane yield and intensity were also evaluated, and while easy to understand and compare across populations, ratio traits are undesirable in animal breeding, due to the unpredictable level of response. Methane adjusted for dry matter intake and liveweight (Residual CH4) should be considered as an alternative emission trait when selecting for reduced emissions within breeding goals.

Methane production from cattle digestion results in the loss of 6% to 10% of gross energy intake in cattle and globally is the single most significant source of anthropogenic methane (CH4) emissions. The purpose of this study was to analyze greenhouse gas traits recorded in a commercial feedlot unit to gain an understanding into the relationships between greenhouse gas traits and production traits of economic importance. Methane and carbon dioxide emissions recorded using Greenfeed systems were available on a total of 1,099 animals. In addition, performance indicators such as feed intake, live weight, ultrasound scanning data, and slaughter data were also available on all animals. Phenotypic repeatability of CH4 ranged from 0.13 to 0.74, with a CH4 repeatability of >0.6 achieved by both heifers and steers in 10-d measuring period. Due to the high repeatability of CH4 measures, an accurate portrayal of CH4 production can be observed from a 10-d measuring period when measures are averaged. Methane emission data were positively correlated with traits of economic importance. Phenotypically, animals with heavier body weights and greater feed intake had higher emissions.

A non-human primate model of acute liver failure suitable for testing liver support systems.

Acute hepatic failure is associated with high morbidity and mortality for which the only definitive therapy is liver transplantation. Some fraction of those who undergo emergency transplantation have been shown to recover native liver function when transplanted with an auxiliary hepatic graft that leaves part of the native liver intact. Thus, transplantation could have been averted with the development and use of some form of hepatic support. The costs of developing and testing liver support systems could be dramatically reduced by the availability of a reliable large animal model of hepatic failure with a large therapeutic window that allows the assessment of efficacy and timing of intervention. Non-lethal forms of hepatic injury were examined in combination with liver-directed radiation in non-human primates (NHPs) to develop a model of acute hepatic failure that mimics the human condition. Porcine hepatocyte transplantation was then tested as a potential therapy for acute hepatic failure. After liver-directed radiation therapy, delivery of a non-lethal hepatic ischemia-reperfusion injury reliably and rapidly generated liver failure providing conditions that can enable pre-clinical testing of liver support or replacement therapies. Unfortunately, in preliminary studies, low hepatocyte engraftment and over-immune suppression interfered with the ability to assess the efficacy of transplanted porcine hepatocytes in the model. A model of acute liver failure in NHPs was created that recapitulates the pathophysiology and pathology of the clinical condition, does so with reasonably predictable kinetics, and results in 100% mortality. The model allowed preliminary testing of xenogeneic hepatocyte transplantation as a potential therapy.

Interhospital variability in localization techniques for small pulmonary nodules in children: A pediatric surgical oncology research collaborative study.

BACKGROUND: Pulmonary nodules that are deep within lung parenchyma and/or small in size can be challenging to localize for biopsy. This study describes current trends in performance of image-guided localization techniques for pulmonary nodules in pediatric patients. METHODS: A retrospective review was performed on patients < 21 years of age undergoing localization of pulmonary nodules at 15 institutions. Localization and resection success, time in interventional radiology (IR), operating room (OR) and total anesthesia time, complications, and technical problems were compared between techniques. RESULTS: 225 patients were included with an average of 1.3 lesions (range 1-5). Median nodule size and depth were 4 mm (range 0-30) and 5.4 mm (0-61), respectively. The most common localization techniques were: wire + methylene blue dye (MBD) (28%), MBD only (25%), wire only (14%), technetium-99 only (11%), coil + MBD (7%) and coil only (5%). Localization technique was associated with institution (p < 0.01); technique and institution were significantly associated with mean IR, OR, and anesthesia time (all p < 0.05). Comparing techniques, there was no difference in successful IR localization (range 92-100%, p = 0.75), successful resection (94-100%, p = 0.98), IR technical problems (p = 0.22), or operative complications (p = 0.16). CONCLUSIONS: Many IR localization techniques for small pulmonary nodules in children can be successful, but there is wide variability in application by institution and in procedure time. LEVEL OF EVIDENCE: Retrospective review, Level 3.

Evaluation of partial body weight for predicting body weight and average daily gain in growing beef cattle.

Information on body weight and average daily gain (ADG) of growing animals is key not only to monitoring performance, but also for use in genetic evaluations in the pursuit of achieving sustainable genetic gain. Accurate calculation of ADG, however, requires serial measures of body weight over at least 70 days. This can be resource intensive and thus alternative approaches to predicting individual animal ADG warrant investigation. One such approach is the use of continuously collected individual animal partial body weights. The objective of the present study was to determine the utility of partial body weights in predicting both body weight and ADG; a secondary objective was to deduce the appropriate length of test to determine ADG from partial body weight records. The dataset used consisted of partial body weights, predicted body weights and recorded body weights recorded for 8,972 growing cattle from a range of different breed types in 35 contemporary groups. The relationships among partial body weight, predicted body weight and recorded body weight at the beginning and end of the performance test were determined and calculated ADG per animal from each body weight measure were also compared. On average, partial body weight explained 90.7 ± 2.0% of the variation in recorded body weight at the beginning of the postweaning gain test and 87.9 ± 2.9% of the variation in recorded body weight at its end. The GrowSafe proprietary algorithm to predict body weight from the partial body weight strengthened these coefficients of determination to 95.1 ± 0.9% and 94.9 ± 0.8%, respectively. The ADG calculated from the partial body weight or from the predicted body weight were very strongly correlated (r = 0.95); correlations between these ADG values with those calculated from the recorded body weights were weaker at 0.81 and 0.78, respectively. For some applications, ADG may be measured with sufficient accuracy with a test period of 50 days using partial body weights. The intended inference space is to individual trials which have been represented in this study by contemporary groups of growing cattle from different genotypes.

Genetic parameter estimations and genomic insights for teat and udder structure in young and mature Canadian Angus cows.

Poor teat and udder structure, frequently associated with older cows, impact cow production and health as well as calf morbidity and mortality. However, producer culling, for reasons including age, production, feed availability, and beef markets, creates a bias in teat (TS) and udder scores (US) assessed and submitted to the Canadian Angus Association for genetic evaluations toward improved mammary structure. In addition, due to the infancy of the reporting program, repeated scores are rare. Prior to the adoption of genetic evaluations for TS and US in Canadian Angus cattle, it is imperative to verify that TS and US from young cows are the same traits as TS and US estimated on mature cows. Genetic parameters for TS and US from all cows (n = 4,192) and then from young cows (parities 1 and 2) and from mature cows (parity ≥ 4) were estimated using a single-trait animal model. Genetic correlations for the traits between the two cow age groups were estimated using a two-trait animal model. Estimates of heritability (posterior SD [PSD]) were 0.32 (0.07) and 0.45 (0.07) for young TS and US and 0.27 (0.07) and 0.31 (0.07) for mature TS and US, respectively. Genetic correlation (PSD) between the young and mature traits was 0.87 (0.13) for TS and 0.40 (0.17) for US. Genome-wide association studies were used to further explore the genetic and biological commonalities and differences between the two groups. Although there were no genes in common for the two USs, 12 genes overlapped for TS in the two cow age groups. Interestingly, there were also 23 genes in common between TS and US in mature cows. Based on these findings, it is recommended that producers collect TS and US on their cow herd annually.

Estimation of economic value for efficiency and animal health and welfare traits, teat and udder structure, in Canadian Angus cattle.

The Canadian Angus Association recently developed genetic evaluations for teat and udder structure, which impact efficiencies, and animal health and welfare. Genetic selection tools are most effective incorporated into economic selection indexes. An important factor in the development of economic indexes is the estimation of the economic value and discounted gene expression coefficients, and thereby the economic weight, of each trait. Traditional estimation methods, interrogation of previous studies quantifying the impact of the traits and bioeconomic modelling, were reinforced using producer surveys that employed pairwise ranking methods. Estimates of discounted genetic expression coefficients, economic value and economic weight for teat and udder score in Canadian Angus cattle were 0.31 per sire, $52.47, and $16.91 per score change on a per calf born basis, respectively, indicating that functional traits such as teat and udder structure have a significant impact on profitability and should be included in genetic selection programmes. Limitations in previous studies illustrate the need for longitudinal studies on traits that impact efficiencies and animal health and welfare.

Microcoil localization as an effective adjunct to thoracoscopic resection of pulmonary nodules in children.

BACKGROUND/PURPOSE: Thoracoscopic excision of pulmonary nodules is often required for diagnostic or therapeutic purposes, however subpleural and sub-centimeter nodules can be difficult to visualize. Various CT-guided localization techniques have been described, though there is minimal published pediatric data regarding the use of microcoils. We hypothesize that microcoil localization facilitates thoracoscopic resection of pulmonary nodules in children. METHODS: A multi-institutional retrospective review of children who underwent preoperative CT-guided localization of lung nodules was conducted from 2012 to 2019. A combination of methylene blue dye (MBD), wires, and microcoils were utilized for CT-guided localization. When microcoils were utilized, fluoroscopy assisted in lesion identification and resection. RESULTS: Eighteen patients (mean age 13 years, range 2-21 years) underwent thoracoscopic resection of 24 preoperatively localized pulmonary nodules. Mean size and depth of the lesions were 5.5 mm and 10 mm, respectively. Microcoil placement was successful 95% of the time and assisted in lesion localization in 88% of cases. Wire localization was not a durable technique, as 3 of 5 wires became dislodged upon lung  isolation. CONCLUSIONS: Preoperative CT-guided localization with microcoils can assist in fluoroscopic-guided resection of pulmonary nodules in children. This technique avoids the pitfall of wire dislodgement, and provides surgeons an additional technique to localize sub-centimeter, subpleural nodules. TYPE OF STUDY: Retrospective Review. LEVEL OF EVIDENCE: Level III.

Phase II Trial of Carfilzomib Plus Irinotecan in Patients With Small-cell Lung Cancer Who Have Progressed on Prior Platinum-based Chemotherapy.

INTRODUCTION: The purpose of this study was to evaluate the efficacy and tolerability of carfilzomib plus irinotecan (C/I) in patients with relapsed small-cell lung cancer (SCLC). PATIENTS AND METHODS: Patients with SCLC who progressed after 1 platinum-containing regimen for recurrent or metastatic disease were eligible. Patients were stratified as: sensitive (SS) (progressive disease > 90 days after chemotherapy) or refractory (RS) (progressive disease 30 to 90 days after chemotherapy) and received up to 6 cycles of C/I; imaging was performed every 2 cycles. The primary endpoint was 6-month overall survival (OS). RESULTS: All 62 patients enrolled were evaluable for efficacy and adverse events. 6-month OS was 59% in the platinum SS and 54% in the platinum RS. The overall response rate was 21.6% (2.7% complete response, 18.9% partial response) in SS (n = 37) and 12.5% (all partial response) in RS (n = 25). The disease control rate was 68% (SS) and 56% (RS). Progression-free survival and OS were 3.6 months (95% confidence interval [CI], 2.6-4.6 months) and 6.9 months (95% CI, 4.3-12.3 months) in SS, and 3.3 months (95% CI, 1.8-3.9 months) and 6.8 months (95% CI, 4.1-11 months) in RS. Twenty-nine (47%) patients experienced ≥ grade 3 adverse events; 8 (12.9%) subjects had grade 4 toxicities. Three treatment-related deaths occurred: myocardial infarction (possible), lung infection (possible), and sepsis (probable). CONCLUSION: In patients with relapsed SCLC, C/I was effective in the treatment of SS and RS. With 4.8% grade 5 toxicity, C/I is a viable option for relapsed patients with SCLC with performance status 0 to 1, particularly in platinum-resistant patients, or subjects who cannot receive immunotherapy.

Development of optimal genetic evaluations for teat and udder structure in Canadian Angus cattle.

Despite their heritability and influence on female productivity, there are currently no genetic evaluations for teat and udder structure in Canadian Angus cattle. The objective of this study was to develop optimal genetic evaluations for these traits in the Canadian Angus population. Guidelines recommended by Beef Improvement Federation (BIF) were used to score teat and udder structure in 1,735 Canadian Angus cows from 10 representative herds. Cows scored ranged in parity from 1 to 13; however, >70% of cows were parity ≤4. Scores ranged from 1 (large, bottle shaped) to 9 (very small) for teats and from 1 (very pendulous) to 9 (very tight) for udders. Consistent with parity distribution, >70% of teat and udder scores were ≥6. Teat and udder scores (TS9 and US9, respectively) were modeled using a multiple trait animal model with random effects of contemporary group (herd-year-season) and additive genetic effect, and fixed effects of breed, parity group, and days between calving and scoring. To test good versus poor structure, a binary classification of 1 or 2 (TS2, US2) [comprised of scores 1 to 5 = 1 (poor structure) and scores 6 to 9 = 2 (good structure)] was created. Further, to assess the impact of grouping less frequently observed poor scores, a 1 to 7 scale (TS7, US7) was created by combining teat and udder scores 1 to 3. Analyses for teat and udder scores on scales TS9, US9, TS7, US7, and TS2, US2 were compared. In addition, both threshold and linear animal models were used to estimate variance components for the traits. Data treatment and models were evaluated based on correlation of resulting estimated breeding value (EBV) with corrected phenotypes, Spearman's rank correlation coefficient, average EBV accuracies (r), and deviance information criteria (DIC). TS9, US9 scales for teat and udder scores and linear models performed best. Estimates of heritability (SE) for teat and udder score were 0.32 (0.06) and 0.15 (0.04), respectively, indicating these traits were moderately heritable and that genetic improvement for teat and udder scores was possible. Estimates of phenotypic and genotypic correlations for teat and udder score were 0.46 (0.02) and 0.71 (0.09), respectively. Estimates of genotypic correlations with birth weight (BW), weaning weight (WW), and yearling weight (YW), ranged from -0.04 (0.10) to -0.20 (0.12), verifying the importance of selecting for improved teat and udder score as individual traits, alongside performance traits.

A novel technique for removing a fibrin sheath from a mediport catheter in the pediatric population.

Mediport (also known as port, portacath or Infusaport) is a commonly placed central venous access in pediatric patients. Fibrin sheath formation around the central venous catheter is a common biological response leading to port malfunction in the form of inability to aspirate but preserved capacity for infusion of fluids. If fibrinolytic therapy fails, percutaneous fibrin sheath stripping via transfemoral route or replacement with a new mediport are routine/conventional treatments for a fibrin sheath. We describe a novel technique for removing a fibrin sheath by exteriorizing the catheter through the neck entry site, stripping the fibrin sheath from the catheter manually under sterile conditions and replacing the catheter via a peel-away sheath introduced through the same skin incision as an alternative to complete port replacement or attempted catheter stripping.

Genome-wide association scan for heterotic quantitative trait loci in multi-breed and crossbred beef cattle.

BACKGROUND: Heterosis has been suggested to be caused by dominance effects. We performed a joint genome-wide association analysis (GWAS) using data from multi-breed and crossbred beef cattle to identify single nucleotide polymorphisms (SNPs) with significant dominance effects associated with variation in growth and carcass traits and to understand the mode of action of these associations. METHODS: Illumina BovineSNP50 genotypes and phenotypes for 11 growth and carcass traits were available for 6796 multi-breed and crossbred beef cattle. After performing quality control, 42,610 SNPs and 6794 animals were used for further analyses. A single-SNP GWAS for the joint association of additive and dominance effects was conducted in purebred, crossbred, and combined datasets using the ASReml software. Genomic breed composition predicted from admixture analyses was included in the mixed effect model to account for possible population stratification and breed effects. A threshold of 10% genome-wide false discovery rate was applied to declare associations as significant. The significant SNPs with dominance association were mapped to their corresponding genes at 100 kb. RESULTS: Seven SNPs with significant dominance associations were detected for birth weight, weaning weight, pre-weaning daily gain, yearling weight and marbling score across the three datasets at a false discovery rate of 10%. These SNPs were located on bovine chromosomes 1, 3, 4, 6 and 21 and mapped to six putative candidate genes: U6atac, AGBL4, bta-mir-2888-1, REPIN1, ICA1 and NXPH1. These genes have interesting biological functions related to the regulation of gene expression, glucose and lipid metabolism and body fat mass. For most of the identified loci, we observed over-dominance association with the studied traits, such that the heterozygous individuals at any of these loci had greater genotypic values for the trait than either of the homozygous individuals. CONCLUSIONS: Our results revealed very few regions with significant dominance genetic effects across all the traits studied in the three datasets used. Regarding the SNPs that were detected with dominance associations, further investigation is needed to determine their relevance in crossbreeding programs assuming that dominance effects are the main cause of (or contribute usefully to) heterosis.

The IASLC Lung Cancer Staging Project: A Renewed Call to Participation.

Over the past two decades, the International Association for the Study of Lung Cancer (IASLC) Staging Project has been a steady source of evidence-based recommendations for the TNM classification for lung cancer published by the Union for International Cancer Control and the American Joint Committee on Cancer. The Staging and Prognostic Factors Committee of the IASLC is now issuing a call for participation in the next phase of the project, which is designed to inform the ninth edition of the TNM classification for lung cancer. Following the case recruitment model for the eighth edition database, volunteer site participants are asked to submit data on patients whose lung cancer was diagnosed between January 1, 2011, and December 31, 2019, to the project by means of a secure, electronic data capture system provided by Cancer Research And Biostatistics in Seattle, Washington. Alternatively, participants may transfer existing data sets. The continued success of the IASLC Staging Project in achieving its objectives will depend on the extent of international participation, the degree to which cases are entered directly into the electronic data capture system, and how closely externally submitted cases conform to the data elements for the project.

Meta-analysis of genome-wide association studies for cattle stature identifies common genes that regulate body size in mammals.

Stature is affected by many polymorphisms of small effect in humans 1 . In contrast, variation in dogs, even within breeds, has been suggested to be largely due to variants in a small number of genes2,3. Here we use data from cattle to compare the genetic architecture of stature to those in humans and dogs. We conducted a meta-analysis for stature using 58,265 cattle from 17 populations with 25.4 million imputed whole-genome sequence variants. Results showed that the genetic architecture of stature in cattle is similar to that in humans, as the lead variants in 163 significantly associated genomic regions (P < 5 × 10-8) explained at most 13.8% of the phenotypic variance. Most of these variants were noncoding, including variants that were also expression quantitative trait loci (eQTLs) and in ChIP-seq peaks. There was significant overlap in loci for stature with humans and dogs, suggesting that a set of common genes regulates body size in mammals.

Modeling heterotic effects in beef cattle using genome-wide SNP-marker genotypes.

An objective of commercial beef cattle crossbreeding programs is to simultaneously optimize use of additive (breed differences) and non-additive (heterosis) effects. A total of 6,794 multibreed and crossbred beef cattle with phenotype and Illumina BovineSNP50 genotype data were used to predict genomic heterosis for growth and carcass traits by applying two methods assumed to be linearly proportional to heterosis. The methods were as follows: 1) retained heterozygosity predicted from genomic breed fractions (HET1) and 2) deviation of adjusted crossbred phenotype from midparent value (HET2). Comparison of methods was based on prediction accuracy from cross-validation. Here, a mutually exclusive random sampling of all crossbred animals (n = 5,327) was performed to form five groups replicated five times with approximately 1,065 animals per group. In each run within a replicate, one group was assigned as a validation set, while the remaining four groups were combined to form the reference set. The phenotype of the animals in the validation set was assumed to be unknown; thus, it resulted in every animal having heterosis values that were predicted without using its own phenotype, allowing their adjusted phenotype to be used for validation. The same approach was used to test the impact of predicted heterosis on accuracy of genomic breeding values (GBV). The results showed positive heterotic effects for growth traits but not for carcass traits that reflect the importance of heterosis for growth traits in beef cattle. Heterosis predicted by HET1 method resulted in less variable estimates that were mostly within the range of estimates generated by HET2. Prediction accuracy was greater for HET2 (0.37-0.98) than HET1 (0.34-0.43). Proper consideration of heterosis in genomic evaluation models has debatable effects on accuracy of EBV predictions. However, opportunity exists for predicting heterosis, improving accuracy of genomic selection, and consequently optimizing crossbreeding programs in beef cattle.

The IASLC Lung Cancer Staging Project: External Validation of the Revision of the TNM Stage Groupings in the Eighth Edition of the TNM Classification of Lung Cancer.

INTRODUCTION: Revisions to the TNM stage classifications for lung cancer, informed by the international database (N = 94,708) of the International Association for the Study of Lung Cancer (IASLC) Staging and Prognostic Factors Committee, need external validation. The objective was to externally validate the revisions by using the National Cancer Data Base (NCDB) of the American College of Surgeons. METHODS: Cases presenting from 2000 through 2012 were drawn from the NCDB and reclassified according to the eighth edition stage classification. Clinically and pathologically staged subsets of NSCLC were analyzed separately. The T, N, and overall TNM classifications were evaluated according to clinical, pathologic, and "best" stage (N = 780,294). Multivariate analyses were carried out to adjust for various confounding factors. A combined analysis of the NSCLC cases from both databases was performed to explore differences in overall survival prognosis between the two databases. RESULTS: The databases differed in terms of key factors related to data source. Survival was greater in the IASLC database for all stage categories. However, the eighth edition TNM stage classification system demonstrated consistent ability to discriminate TNM categories and stage groups for clinical and pathologic stage. CONCLUSIONS: The IASLC revisions made for the eighth edition of lung cancer staging are validated by this analysis of the NCDB database by the ordering, statistical differences, and homogeneity within stage groups and by the consistency within analyses of specific cohorts.

Antibiotic resistance among Helicobacter pylori clinical isolates in Lima, Peru.

OBJECTIVES: Gastric carcinoma is the most common cancer and cause of cancer mortality in Peru. Helicobacter pylori, a bacterium that colonizes the human stomach, is a Group 1 carcinogen due to its causal relationship to gastric carcinoma. While eradication of H. pylori can help prevent gastric cancer, characterizing regional antibiotic resistance patterns is necessary to determine targeted treatment for each region. Thus, we examined primary antibiotic resistance in clinical isolates of H. pylori in Lima, Peru. MATERIALS AND METHODS: H. pylori strains were isolated from gastric biopsies of patients with histologically proven H. pylori infection. Primary antibiotic resistance among isolates was examined using E-test strips. Isolates were examined for the presence of the cagA pathogenicity island and the vacA m1/m2 alleles via polymerase chain reaction. RESULTS: Seventy-six isolates were recovered from gastric biopsies. Clinical isolates showed evidence of antibiotic resistance to 1 (27.6%, n=21/76), 2 (28.9%, n=22/76), or ≥3 antibiotics (40.8%). Of 76 isolates, eight (10.5%) were resistant to amoxicillin and clarithromycin, which are part of the standard triple therapy for H. pylori infection. No trends were seen between the presence of cagA, vacA m1, or vacA m2 and antibiotic resistance. CONCLUSION: The rate of antibiotic resistance among H. pylori isolates in Lima, Peru, is higher than expected and presents cause for concern. To develop more targeted eradication therapies for H. pylori in Peru, more research is needed to better characterize antibiotic resistance among a larger number of clinical isolates prospectively.

Correlation of Long-term Results of Imatinib in Advanced Gastrointestinal Stromal Tumors With Next-Generation Sequencing Results: Analysis of Phase 3 SWOG Intergroup Trial S0033.

IMPORTANCE: After identification of activating mutations of the KIT gene in gastrointestinal stromal tumor (GIST)-the most common sarcomaof the gastrointestinal tract-a phase 2 study demonstrated efficacy of imatinib mesylate in patients with metastatic GIST harboring a KIT exon 11 mutation. Initial results of long-term follow-up have found a survival benefit in this subgroup of patients. OBECTIVE: To assess the long-term survival of patients with GIST who were treated in SWOG study S0033 and to present new molecular data regarding treatment outcomes. DESIGN, SETTING, AND PARTICIPANTS: In this follow-up of randomized clinical trial participants (from December 15, 2000, to September 1, 2001), patients were required to have advanced GIST that was not surgically curable. Postprotocol data collection occurred from August 29, 2011, to July 15, 2015. Using modern sequencing technologies, 20 cases originally classified as having wild-type tumors underwent reanalysis. This intergroup study was coordinated by SWOG, a cooperative group member within the National Clinical Trials Network, with participation by member/affiliate institutions. This follow-up was not planned as part of the initial study. INTERVENTIONS: Patients were randomized to 1 of 2 dose levels of imatinib mesylate, including 400 mg once daily (400 mg/d) vs 400 mg twice daily (800 mg/d), and were treated until disease progression or unacceptable toxic effects of the drug occurred. MAIN OUTCOMES AND MEASURES: The primary end point was overall survival. Updated survival data were correlated with clinical and molecular factors, and patterns of postprotocol therapies were enumerated and described in long-term survivors. RESULTS: Of 695 eligible patients (376 men [54.1%]; 319 women [45.9%]; mean [SD] age, 60.1 [14.0] years), 189 survived 8 years or longer, including 95 in the 400-mg/d dose arm and 94 in the 800-mg/d arm. The 10-year estimate of overall survival was 23% (95% CI, 20%-26%). Among 142 long-term survivors, imatinib was the sole therapy administered in 69 (48.6%), with additional systemic agents administered to 54 patients (38.0%). Resequencing studies of 20 cases originally classified as KIT/PDGFRA wild-type GIST revealed that 17 (85.0%) harbored a pathogenic mutation, most commonly a mutation of a subunit of the succinate dehydrogenase complex. CONCLUSIONS AND RELEVANCE: A subset of patients with metastatic GIST experiences durable, long-term overall survival with imatinib treatment. Although this study provides guidance for management of GIST harboring the most common KIT and PDGFRA mutations, optimal management of other genotypic subtypes remains unclear. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00009906.