Comparison of the clinical and economic outcomes between open and minimally invasive appendectomy and colectomy: evidence from a large commercial payer database

Background: Appendectomy and colectomy are commonly performed surgical procedures. Despite evidence demonstrating advantages with the minimally invasive surgical (MIS) approach, open procedures occur with greater prevalence. Therefore, there is still controversy as to whether the MIS approach is safer or more cost effective. Methods: A retrospective analysis was performed using a large commercial payer database. The data included information on 7,532 appendectomies and 2,745 colectomies. Data on the distribution of patient demographic and comorbidity characteristics associated with the MIS and open approaches were reviewed. The corresponding complication rates and expenditures were analyzed. Summary statistics were compared using chi-square tests, and generalized linear models were constructed to estimate expenditures while controlling for patient characteristics. Results: The patients undergoing MIS and open colectomy showed no significant variations in age distribution or marginal age differences for appendectomy. Significantly more patients experienced an infection postoperatively, and procedure-specific complications were more common in the open group for both procedures (P < 0.05). The postsurgical hospital stay was longer for the patients treated using the open techniques, differing an average of half a day for appendectomies and significantly more (4 days) for colectomy (P < 0.05). Readmission rates differed little between the two approaches. Procedures performed through an MIS approach were associated with lower expenditures than for the open technique, with differences ranging from $700 for appendectomy patients (P < 0.05) to$15,200 for colectomy patients (P < 0.05). Conclusions: Minimally invasive appendectomy and colectomy were associated with lower infection rates, fewer complications, shorter hospital stays, and lower expenditures than open surgery

Normal Human Pluripotent Stem Cell Lines Exhibit Pervasive Mosaic Aneuploidy

Human pluripotent stem cell (hPSC) lines have been considered to be homogeneously euploid. Here we report that normal hPSC – including induced pluripotent - lines are karyotypic mosaics of euploid cells intermixed with many cells showing non-clonal aneuploidies as identified by chromosome counting, spectral karyotyping (SKY) and fluorescent in situ hybridization (FISH) of interphase/non-mitotic cells. This mosaic aneuploidy resembles that observed in progenitor cells of the developing brain and preimplantation embryos, suggesting that it is a normal, rather than pathological, feature of stem cell lines. The karyotypic heterogeneity generated by mosaic aneuploidy may contribute to the reported functional and phenotypic heterogeneity of hPSCs lines, as well as their therapeutic efficacy and safety following transplantation

Early experience of COVID-19 vaccination in adults with systemic rheumatic diseases : Results from the COVID-19 Global Rheumatology Alliance Vaccine Survey

Funding Information: Competing interests SES has received funding from the Vasculitis Foundation and the Vasculitis Clinical Research Consortium unrelated to this work. JL has received research grant funding from Pfizer unrelated to this work. ES is a Board Member of the Canadian Arthritis Patient Alliance, a patient run, volunteer-based organisation whose activities are primarily supported by independent grants from pharmaceutical companies. MP was supported by a Rheumatology Research Foundation Scientist Development grant. DA-R is a Scientific Advisor for GlaxoSmithKilne unrelated to this work. FB reports personal fees from Boehringer, Bone Therapeutics, Expanscience, Galapagos, Gilead, GSK, Merck Sereno, MSD, Nordic, Novartis, Pfizer, Regulaxis, Roche, Sandoz, Sanofi, Servier, UCB, Peptinov, TRB Chemedica and 4P Pharma outside of the submitted work. No funding relevant to this manuscript. RC: speakers bureau for Janssen, Roche, Sanofi, AbbVie. KD reports no COI-unpaid volunteer president of the Autoinflammatory Alliance. Any grants or funding from pharma is received by the non-profit organisation only. CLH received funding under a sponsored research agreement unrelated to the data in the paper from Vifor Pharmaceuticals. LeK has received a research grant from Lilly unrelated to this work. AHJK participated in consulting, advisory board or speaker's bureau for Alexion Pharmaceuticals, Aurinia Pharmaceuticals, Annexon Biosciences, Exagen Diagnostics and GlaxoSmithKilne and received funding under a sponsored research agreement unrelated to the data in the paper from GlaxoSmithKline. JSingh has received consultant fees from Crealta/ Horizon, Medisys, Fidia, PK Med, Two Labs, Adept Field Solutions, Clinical Care Options, Clearview Healthcare Partners, Putnam Associates, Focus Forward, Navigant Consulting, Spherix, MedIQ, Jupiter Life Science, UBM, Trio Health, Medscape, WebMD and Practice Point Communications; and the National Institutes of Health and the American College of Rheumatology. JSingh owns stock options in TPT Global Tech, Vaxart Pharmaceuticals and Charlotte’s Web Holdings. JSingh previously owned stock options in Amarin, Viking and Moderna Pharmaceuticals. JSingh is on the speaker’s bureau of Simply Speaking. JSingh is a member of the executive of Outcomes Measures in Rheumatology (OMERACT), an organisation that develops outcome measures in rheumatology and receives arms-length funding from eight companies. JSingh serves on the FDA Arthritis Advisory Committee. JSingh is the chair of the Veterans Affairs Rheumatology Field Advisory Committee. JSingh is the editor and the Director of the University of Alabama at Birmingham (UAB) Cochrane Musculoskeletal Group Satellite Center on Network Meta-analysis. NSingh is supported by funding from the Rheumatology Research Foundation Investigator Award and the American Heart Association. MFU-G has received research support from Pfizer and Janssen, unrelated to this work. SB reports personal fees from Novartis, AbbVie, Pfizer and Horizon Pharma, outside the submitted work. RG reports personal fees from AbbVie New Zealand, Cornerstones, Janssen New Zealand and personal fees and non-financial support Pfizer New Zealand (all <US$10 000) outside the submitted work. PMM reports personal fees from AbbVie, Eli Lilly, Janssen, Novartis, Pfizer and UCB, grants and personal fees from Orphazyme, outside the submitted work. PCR reports personal fees from AbbVie, Gilead, Lilly and Roche, grants and personal fees from Novartis, UCB Pharma, Janssen and Pfizer and non-financial support from BMS, outside the submitted work. PS reports honoraria from Social media editor for @ACR_Journals, outside the submitted work. ZSW reports grants from NIH, BMS and Principia/ Sanofi and personal fees from Viela Bio and MedPace, outside the submitted work. JY reports personal fees from Pfizer and Eli Lilly, and grants and personal fees from AstraZeneca, outside the submitted work. MJL reports grants from American College of Rheumatology, during the conduct of the study and consulting fees from AbbVie, Amgen, Actelion, Boehringer Ingelheim, BMS, Celgene, Gilead, J&J, Mallinckrodt, Novartis, Pfizer, Roche, Sandoz, Sanofi, Sobi and UCB, outside the submitted work. LGR was supported by the Intramural Research Program of the National Institute of Environmental Health Sciences (NIEHS; ZIAES101074) of the National Institutes of Health. JH reports grants from Childhood Arthritis and Rheumatology Research Alliance (CARRA) and Rheumatology Research Alliance, and personal fees from Novartis, Pfizer and Biogen, outside the submitted work. JSimard received research grant funding from the National Institutes of Health unrelated to this work (NIAMS: R01 AR077103 and NIAID R01 AI154533). JSparks has performed consultancy for AbbVie, Boehringer Ingelheim, Bristol-Myers Squibb, Gilead, Inova Diagnostics, Optum and Pfizer unrelated to this work. Funding Information: Funding This study was supported by the European Alliance of Associations for Rheumatology and American College of Rheumatology Research and Education Foundation. Dr. Lisa Rider's involvement was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences. Publisher Copyright: © Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.Background. We describe the early experiences of adults with systemic rheumatic disease who received the COVID-19 vaccine. Methods From 2 April to 30 April 2021, we conducted an online, international survey of adults with systemic rheumatic disease who received COVID-19 vaccination. We collected patient-reported data on clinician communication, beliefs and intent about discontinuing disease-modifying antirheumatic drugs (DMARDs) around the time of vaccination, and patient-reported adverse events after vaccination. Results We analysed 2860 adults with systemic rheumatic diseases who received COVID-19 vaccination (mean age 55.3 years, 86.7% female, 86.3% white). Types of COVID-19 vaccines were Pfizer-BioNTech (53.2%), Oxford/AstraZeneca (22.6%), Moderna (21.3%), Janssen/Johnson & Johnson (1.7%) and others (1.2%). The most common rheumatic disease was rheumatoid arthritis (42.3%), and 81.2% of respondents were on a DMARD. The majority (81.9%) reported communicating with clinicians about vaccination. Most (66.9%) were willing to temporarily discontinue DMARDs to improve vaccine efficacy, although many (44.3%) were concerned about rheumatic disease flares. After vaccination, the most reported patient-reported adverse events were fatigue/somnolence (33.4%), headache (27.7%), muscle/joint pains (22.8%) and fever/chills (19.9%). Rheumatic disease flares that required medication changes occurred in 4.6%. Conclusion. Among adults with systemic rheumatic disease who received COVID-19 vaccination, patient-reported adverse events were typical of those reported in the general population. Most patients were willing to temporarily discontinue DMARDs to improve vaccine efficacy. The relatively low frequency of rheumatic disease flare requiring medications was reassuring.publishersversionPeer reviewe

School Smoking Policy Characteristics and Individual Perceptions of the School Tobacco Context: Are They Linked to Students’ Smoking Status?

The purpose of this study was to explore individual- and school-level policy characteristics on student smoking behavior using an ecological perspective. Participants were 24,213 (51% female) Grade 10–11 students from 81 schools in five Canadian provinces. Data were collected using student self-report surveys, written policies collected from schools, interviews with school administrators, and school property observations to assess multiple dimensions of the school tobacco policy. The multi-level modeling results revealed that the school a student attended was associated with his/her smoking behavior. Individual-level variables that were associated with student smoking included lower school connectedness, a greater number of family and friends who smoked, higher perceptions of student smoking prevalence, lower perceptions of student smoking frequency, and stronger perceptions of the school tobacco context. School-level variables associated with student smoking included weaker policy intention indicating prohibition and assistance to overcome tobacco addiction, weaker policy implementation involving strategies for enforcement, and a higher number of students smoking on school property. These findings suggest that the school environment is important to tobacco control strategies, and that various policy dimensions have unique relationships to student smoking. School tobacco policies should be part of a comprehensive approach to adolescent tobacco use

Insights from the genome of the biotrophic fungal plant pathogen Ustilago maydis

Ustilago maydis is a ubiquitous pathogen of maize and a well-established model organism for the study of plant-microbe interactions. This basidiomycete fungus does not use aggressive virulence strategies to kill its host. U. maydis belongs to the group of biotrophic parasites (the smuts) that depend on living tissue for proliferation and development. Here we report the genome sequence for a member of this economically important group of biotrophic fungi. The 20.5-million-base U. maydis genome assembly contains 6,902 predicted protein-encoding genes and lacks pathogenicity signatures found in the genomes of aggressive pathogenic fungi, for example a battery of cell-wall-degrading enzymes. However, we detected unexpected genomic features responsible for the pathogenicity of this organism. Specifically, we found 12 clusters of genes encoding small secreted proteins with unknown function. A significant fraction of these genes exists in small gene families. Expression analysis showed that most of the genes contained in these clusters are regulated together and induced in infected tissue. Deletion of individual clusters altered the virulence of U. maydis in five cases, ranging from a complete lack of symptoms to hypervirulence. Despite years of research into the mechanism of pathogenicity in U. maydis, no 'true' virulence factors had been previously identified. Thus, the discovery of the secreted protein gene clusters and the functional demonstration of their decisive role in the infection process illuminate previously unknown mechanisms of pathogenicity operating in biotrophic fungi. Genomic analysis is, similarly, likely to open up new avenues for the discovery of virulence determinants in other pathogens. ©2006 Nature Publishing Group.J.K., M. B. and R.K. thank G. Sawers and U. Kämper for critical reading of the manuscript. The genome sequencing of Ustilago maydis strain 521 is part of the fungal genome initiative and was funded by National Human Genome Research Institute (USA) and BayerCropScience AG (Germany). F.B. was supported by a grant from the National Institutes of Health (USA). J.K. and R.K. thank the German Ministry of Education and Science (BMBF) for financing the DNA array setup and the Max Planck Society for their support of the manual genome annotation. F.B. was supported by a grant from the National Institutes of Health, B.J.S. was supported by the Natural Sciences and Engineering Research Council of Canada and the Canada Foundation for Innovation, J.W.K. received funding from the Natural Sciences and Engineering Research Council of Canada, J.R.-H. received funding from CONACYT, México, A.M.-M. was supported by a fellowship from the Humboldt Foundation, and L.M. was supported by an EU grant. Author Contributions All authors were involved in planning and executing the genome sequencing project. B.W.B., J.G., L.-J.M., E.W.M., D.D., C.M.W., J.B., S.Y., D.B.J., S.C., C.N., E.K., G.F., P.H.S., I.H.-H., M. Vaupel, H.V., T.S., J.M., D.P., C.S., A.G., F.C. and V. Vysotskaia contributed to the three independent sequencing projects; M.M., G.M., U.G., D.H., M.O. and H.-W.M. were responsible for gene model refinement, database design and database maintenance; G.M., J. Kämper, R.K., G.S., M. Feldbrügge, J.S., C.W.B., U.F., M.B., B.S., B.J.S., M.J.C., E.C.H.H., S.M., F.B., J.W.K., K.J.B., J. Klose, S.E.G., S.J.K., M.H.P., H.A.B.W., R.deV., H.J.D., J.R.-H., C.G.R.-P., L.O.-C., M.McC., K.S., J.P.-M., J.I.I., W.H., P.G., P.S.-A., M. Farman, J.E.S., R.S., J.M.G.-P., J.C.K., W.L. and D.H. were involved in functional annotation and interpretation; T.B., O.M., L.M., A.M.-M., D.G., K.M., N.R., V. Vincon, M. VraneŠ, M.S. and O.L. performed experiments. J. Kämper, R.K. and M.B. wrote and edited the paper with input from L.-J.M., J.G., F.B., J.W.K., B.J.S. and S.E.G. Individual contributions of authors can be found as Supplementary Notes

IMI - Myopia Genetics Report

The knowledge on the genetic background of refractive error and myopia has expanded dramatically in the past few years. This white paper aims to provide a concise summary of current genetic findings and defines the direction where development is needed. We performed an extensive literature search and conducted informal discussions with key stakeholders. Specific topics reviewed included common refractive error, any and high myopia, and myopia related to syndromes. To date, almost 200 genetic loci have been identified for refractive error and myopia, and risk variants mostly carry low risk but are highly prevalent in the general population. Several genes for secondary syndromic myopia overlap with those for common myopia. Polygenic risk scores show overrepresentation of high myopia in the higher deciles of risk. Annotated genes have a wide variety of functions, and all retinal layers appear to be sites of expression. The current genetic findings offer a world of new molecules involved in myopiagenesis. As the missing heritability is still large, further genetic advances are needed. This Committee recommends expanding large-scale, in-depth genetic studies using complementary big data analytics, consideration of gene-environment effects by thorough measurement of environmental exposures, and focus on subgroups with extreme phenotypes and high familial occurrence. Functional characterization of associated variants is simultaneously needed to bridge the knowledge gap between sequence variance and consequence for eye growth

A framework for human microbiome research

A variety of microbial communities and their genes (the microbiome) exist throughout the human body, with fundamental roles in human health and disease. The National Institutes of Health (NIH)-funded Human Microbiome Project Consortium has established a population-scale framework to develop metagenomic protocols, resulting in a broad range of quality-controlled resources and data including standardized methods for creating, processing and interpreting distinct types of high-throughput metagenomic data available to the scientific community. Here we present resources from a population of 242 healthy adults sampled at 15 or 18 body sites up to three times, which have generated 5,177 microbial taxonomic profiles from 16S ribosomal RNA genes and over 3.5 terabases of metagenomic sequence so far. In parallel, approximately 800 reference strains isolated from the human body have been sequenced. Collectively, these data represent the largest resource describing the abundance and variety of the human microbiome, while providing a framework for current and future studies

Structure, function and diversity of the healthy human microbiome

Author Posting. © The Authors, 2012. This article is posted here by permission of Nature Publishing Group. The definitive version was published in Nature 486 (2012): 207-214, doi:10.1038/nature11234.Studies of the human microbiome have revealed that even healthy individuals differ remarkably in the microbes that occupy habitats such as the gut, skin and vagina. Much of this diversity remains unexplained, although diet, environment, host genetics and early microbial exposure have all been implicated. Accordingly, to characterize the ecology of human-associated microbial communities, the Human Microbiome Project has analysed the largest cohort and set of distinct, clinically relevant body habitats so far. We found the diversity and abundance of each habitat’s signature microbes to vary widely even among healthy subjects, with strong niche specialization both within and among individuals. The project encountered an estimated 81–99% of the genera, enzyme families and community configurations occupied by the healthy Western microbiome. Metagenomic carriage of metabolic pathways was stable among individuals despite variation in community structure, and ethnic/racial background proved to be one of the strongest associations of both pathways and microbes with clinical metadata. These results thus delineate the range of structural and functional configurations normal in the microbial communities of a healthy population, enabling future characterization of the epidemiology, ecology and translational applications of the human microbiome.This research was supported in part by National Institutes of Health grants U54HG004969 to B.W.B.; U54HG003273 to R.A.G.; U54HG004973 to R.A.G., S.K.H. and J.F.P.; U54HG003067 to E.S.Lander; U54AI084844 to K.E.N.; N01AI30071 to R.L.Strausberg; U54HG004968 to G.M.W.; U01HG004866 to O.R.W.; U54HG003079 to R.K.W.; R01HG005969 to C.H.; R01HG004872 to R.K.; R01HG004885 to M.P.; R01HG005975 to P.D.S.; R01HG004908 to Y.Y.; R01HG004900 to M.K.Cho and P. Sankar; R01HG005171 to D.E.H.; R01HG004853 to A.L.M.; R01HG004856 to R.R.; R01HG004877 to R.R.S. and R.F.; R01HG005172 to P. Spicer.; R01HG004857 to M.P.; R01HG004906 to T.M.S.; R21HG005811 to E.A.V.; M.J.B. was supported by UH2AR057506; G.A.B. was supported by UH2AI083263 and UH3AI083263 (G.A.B., C. N. Cornelissen, L. K. Eaves and J. F. Strauss); S.M.H. was supported by UH3DK083993 (V. B. Young, E. B. Chang, F. Meyer, T. M. S., M. L. Sogin, J. M. Tiedje); K.P.R. was supported by UH2DK083990 (J. V.); J.A.S. and H.H.K. were supported by UH2AR057504 and UH3AR057504 (J.A.S.); DP2OD001500 to K.M.A.; N01HG62088 to the Coriell Institute for Medical Research; U01DE016937 to F.E.D.; S.K.H. was supported by RC1DE0202098 and R01DE021574 (S.K.H. and H. Li); J.I. was supported by R21CA139193 (J.I. and D. S. Michaud); K.P.L. was supported by P30DE020751 (D. J. Smith); Army Research Office grant W911NF-11-1-0473 to C.H.; National Science Foundation grants NSF DBI-1053486 to C.H. and NSF IIS-0812111 to M.P.; The Office of Science of the US Department of Energy under Contract No. DE-AC02-05CH11231 for P.S. C.; LANL Laboratory-Directed Research and Development grant 20100034DR and the US Defense Threat Reduction Agency grants B104153I and B084531I to P.S.C.; Research Foundation - Flanders (FWO) grant to K.F. and J.Raes; R.K. is an HHMI Early Career Scientist; Gordon&BettyMoore Foundation funding and institutional funding fromthe J. David Gladstone Institutes to K.S.P.; A.M.S. was supported by fellowships provided by the Rackham Graduate School and the NIH Molecular Mechanisms in Microbial Pathogenesis Training Grant T32AI007528; a Crohn’s and Colitis Foundation of Canada Grant in Aid of Research to E.A.V.; 2010 IBM Faculty Award to K.C.W.; analysis of the HMPdata was performed using National Energy Research Scientific Computing resources, the BluBioU Computational Resource at Rice University

Integrated genomic characterization of oesophageal carcinoma

Oesophageal cancers are prominent worldwide; however, there are few targeted therapies and survival rates for these cancers remain dismal. Here we performed a comprehensive molecular analysis of 164 carcinomas of the oesophagus derived from Western and Eastern populations. Beyond known histopathological and epidemiologic distinctions, molecular features differentiated oesophageal squamous cell carcinomas from oesophageal adenocarcinomas. Oesophageal squamous cell carcinomas resembled squamous carcinomas of other organs more than they did oesophageal adenocarcinomas. Our analyses identified three molecular subclasses of oesophageal squamous cell carcinomas, but none showed evidence for an aetiological role of human papillomavirus. Squamous cell carcinomas showed frequent genomic amplifications of CCND1 and SOX2 and/or TP63, whereas ERBB2, VEGFA and GATA4 and GATA6 were more commonly amplified in adenocarcinomas. Oesophageal adenocarcinomas strongly resembled the chromosomally unstable variant of gastric adenocarcinoma, suggesting that these cancers could be considered a single disease entity. However, some molecular features, including DNA hypermethylation, occurred disproportionally in oesophageal adenocarcinomas. These data provide a framework to facilitate more rational categorization of these tumours and a foundation for new therapies

Comprehensive molecular characterization of gastric adenocarcinoma

Gastric cancer is a leading cause of cancer deaths, but analysis of its molecular and clinical characteristics has been complicated by histological and aetiological heterogeneity. Here we describe a comprehensive molecular evaluation of 295 primary gastric adenocarcinomas as part of The Cancer Genome Atlas (TCGA) project. We propose a molecular classification dividing gastric cancer into four subtypes: tumours positive for Epstein–Barr virus, which display recurrent PIK3CA mutations, extreme DNA hypermethylation, and amplification of JAK2, CD274 (also known as PD-L1) and PDCD1LG2 (also knownasPD-L2); microsatellite unstable tumours, which show elevated mutation rates, including mutations of genes encoding targetable oncogenic signalling proteins; genomically stable tumours, which are enriched for the diffuse histological variant and mutations of RHOA or fusions involving RHO-family GTPase-activating proteins; and tumours with chromosomal instability, which show marked aneuploidy and focal amplification of receptor tyrosine kinases. Identification of these subtypes provides a roadmap for patient stratification and trials of targeted therapies