Summary
The r package ecosystem is rich in tools for the statistics of meta‐analysis. However, there are few resources available to facilitate research synthesis as a whole.
Here, I present the ...metagear package for r. It is a comprehensive, multifunctional toolbox with capabilities aimed to cover much of the research synthesis taxonomy: from applying a systematic review approach to objectively assemble and screen the literature, to extracting data from studies, and to finally summarize and analyse these data with the statistics of meta‐analysis.
Current functionalities of metagear include the following: an screener GUI to efficiently sieve bibliographic information from large numbers of candidate studies; tools to assign screening effort across multiple collaborators/reviewers and to assess inter‐reviewer reliability using kappa statistics; PDF downloader to automate the retrieval of journal articles from online data bases; automated data extractions from scatter‐plots, box‐plots and bar‐plots; PRISMA flow diagrams; simple imputation tools to fill gaps in incomplete or missing study parameters; generation of random‐effects sizes for Hedges' d, log response ratio, odds ratio and correlation coefficients for Monte Carlo experiments; covariance equations for modelling dependencies among multiple effect sizes (e.g. with a common control, phylogenetic correlations); and finally, summaries that replicate analyses and outputs from widely used but no longer updated meta‐analysis software.
Research synthesis practices are vital to many disciplines in the sciences, including ecology and evolutionary biology, and metagear aims to enrich the scope, quality and reproducibility of what can be achieved with the systematic review and meta‐analysis of research outcomes.
The ongoing SARS-CoV-2 pandemic has shocked the world due to its persistence, COVID-19-related morbidity and mortality, and the high mutability of the virus. One of the major concerns is the ...emergence of new viral variants that may increase viral transmission and disease severity. In addition to mutations of spike protein, mutations of viral proteins that affect virulence, such as ORF3a, also must be considered. The purpose of this article is to review the current literature on ORF3a, to summarize the molecular actions of SARS-CoV-2 ORF3a, and its role in viral pathogenesis and COVID-19. ORF3a is a polymorphic, multifunctional viral protein that is specific to SARS-CoV/SARS-CoV-2. It was acquired from β-CoV lineage and likely originated from bats through viral evolution. SARS-CoV-2 ORF3a is a viroporin that interferes with ion channel activities in host plasma and endomembranes. It is likely a virion-associated protein that exerts its effect on the viral life cycle during viral entry through endocytosis, endomembrane-associated viral transcription and replication, and viral release through exocytosis. ORF3a induces cellular innate and pro-inflammatory immune responses that can trigger a cytokine storm, especially under hypoxic conditions, by activating NLRP3 inflammasomes, HMGB1, and HIF-1α to promote the production of pro-inflammatory cytokines and chemokines. ORF3a induces cell death through apoptosis, necrosis, and pyroptosis, which leads to tissue damage that affects the severity of COVID-19. ORF3a continues to evolve along with spike and other viral proteins to adapt in the human cellular environment. How the emerging ORF3a mutations alter the function of SARS-CoV-2 ORF3a and its role in viral pathogenesis and COVID-19 is largely unknown. This review provides an in-depth analysis of ORF3a protein's structure, origin, evolution, and mutant variants, and how these characteristics affect its functional role in viral pathogenesis and COVID-19.
As the technology of three-dimensional (3D) printing becomes more refined and accessible, multiple applications of its use are becoming more commonplace in upper extremity surgery. 3D-printed models ...have been beneficial in preoperative planning of complex cases of acute trauma or malunions, contributing to spatial understanding or even contouring of implants. Custom guides can also be created to assist intraoperatively with precise placement of osteotomies or arthroplasty implants. Finally, custom 3D implants have been described for cases of bone loss in the upper extremity. This can be for relatively small gaps after malunion correction or extensive defects, typically for trauma or tumor. Articular defects can also be addressed with this technology, although special considerations should be given to the implant design and longevity in these situations. Because of the relatively recent nature of 3D implants, long-term data are lacking. However, they show great promise in an expanding range of challenging clinical indications.
Purpose To survey the American Society for Surgery of the Hand membership to determine the nature and distribution of nerve injuries treated after elbow arthroscopy. Methods An online survey was sent ...to all members of the American Society for Surgery of the Hand under an institutional review board–approved protocol. Collected data included the number of nerve injuries observed over a 5-year period, the nature of treatment required for the injuries, and the outcomes observed after any intervention. Responses were anonymous, and results were securely compiled. Results We obtained 372 responses. A total of 222 nerve injuries were reported. The most injured nerves reported were ulnar, radial, and posterior interosseous (38%, 22%, and 19%, respectively). Nearly half of all patients with injuries required operative intervention, including nerve graft, tendon transfer, nerve repair, or nerve transfer. Of the patients who sustained major injuries, those requiring intervention, 77% had partial or no motor recovery. All minor injuries resolved completely. Conclusions Our results suggest that major nerve injuries after elbow arthroscopy are not rare occurrences and the risk of these injuries is likely under-reported in the literature. Furthermore, patients should be counseled on this risk because most nerve injuries show only partial or no functional recovery. With the more widespread practice of elbow arthroscopy, understanding the nature and sequelae of significant complications is critically important in ensuring patient safety and improving outcomes.
Prospective data on the efficacy of a watch-and-wait strategy to achieve organ preservation in patients with locally advanced rectal cancer treated with total neoadjuvant therapy are limited.
In this ...prospective, randomized phase II trial, we assessed the outcomes of 324 patients with stage II or III rectal adenocarcinoma treated with induction chemotherapy followed by chemoradiotherapy (INCT-CRT) or chemoradiotherapy followed by consolidation chemotherapy (CRT-CNCT) and either total mesorectal excision (TME) or watch-and-wait on the basis of tumor response. Patients in both groups received 4 months of infusional fluorouracil-leucovorin-oxaliplatin or capecitabine-oxaliplatin and 5,000 to 5,600 cGy of radiation combined with either continuous infusion fluorouracil or capecitabine during radiotherapy. The trial was designed as two stand-alone studies with disease-free survival (DFS) as the primary end point for both groups, with a comparison to a null hypothesis on the basis of historical data. The secondary end point was TME-free survival.
Median follow-up was 3 years. Three-year DFS was 76% (95% CI, 69 to 84) for the INCT-CRT group and 76% (95% CI, 69 to 83) for the CRT-CNCT group, in line with the 3-year DFS rate (75%) observed historically. Three-year TME-free survival was 41% (95% CI, 33 to 50) in the INCT-CRT group and 53% (95% CI, 45 to 62) in the CRT-CNCT group. No differences were found between groups in local recurrence-free survival, distant metastasis-free survival, or overall survival. Patients who underwent TME after restaging and patients who underwent TME after regrowth had similar DFS rates.
Organ preservation is achievable in half of the patients with rectal cancer treated with total neoadjuvant therapy, without an apparent detriment in survival, compared with historical controls treated with chemoradiotherapy, TME, and postoperative chemotherapy.
Multigene assays have been developed and validated to determine the prognosis of breast cancer. In this study, we assessed the additional predictive value of the 70-gene MammaPrint signature for ...chemotherapy (CT) benefit in addition to endocrine therapy (ET) from pooled study series. For 541 patients who received either ET (n = 315) or ET + CT (n = 226), breast cancer-specific survival (BCSS) and distant disease-free survival (DDFS) at 5 years were assessed separately for the 70-gene high and low risk groups. The 70-gene signature classified 252 patients (47%) as low risk and 289 (53%) as high risk. Within the 70-gene low risk group, BCSS was 97% for the ET group and 99% for the ET + CT group at 5 years with a non-significant univariate hazard ratio (HR) of 0.58 (95% CI 0.07-4.98; P = 0.62). In the 70-gene high risk group, BCSS was 81% (ET group) and 94% (ET + CT group) at 5 years with a significant HR of 0.21 (95% CI 0.07-0.59; P < 0.01). DDFS was 93% (ET) versus 99% (ET + CT), respectively, in the 70-gene low risk group, HR 0.26 (95% CI 0.03-2.02; P = 0.20). In the high risk group DDFS was 76 versus 88%, HR of 0.35 (95% CI 0.17-0.71; P < 0.01). Results were similar in multivariate analysis, showing significant survival benefit by adding CT in the 70-gene high risk group. A significant and clinically meaningful benefit was observed by adding chemotherapy to endocrine treatment in 70-gene high risk patients. This benefit was not significant in low risk patients, who were at such low risk for recurrence and cancer-related death, that adding CT does not appear to be clinically meaningful.
AbstractBackgroundWe conducted a post-hoc analysis of a double blind, randomized, placebo-controlled trial of 13-valent pneumococcal conjugate vaccine (PCV13) among adults aged 65 years or older to ...assess public health impact. MethodsFor all outcomes, we included all randomized subjects, using a modified intention-to-treat (mITT) approach to determine vaccine efficacy (VE), vaccine preventable disease incidence (VPDI) defined as control minus vaccinated group incidence, and numbers needed to vaccinate (NNV) (based on a five-year duration of protection). ResultsResults are reported for, in order, clinical, adjudicated (clinical plus radiologic infiltrate determined by committee), pneumococcal, and vaccine-type pneumococcal (VT-Sp) community-acquired pneumonia; invasive pneumococcal disease (IPD) and VT-IPD. VEs (95% CI) for all hospital episodes were 8.1% (−0.6%, 16.1%), 6.7% (−4.1%, 16.3%), 22.2% (2.0%, 38.3%), 37.5% (14.3%, 54.5%), 49.3% (23.2%, 66.5%), and 75.8% (47.6%, 88.8%). VPDIs per 100,000 person-years of observation (PYOs) were 72, 37, 25, 25, 20, and 15 with NNVs of 277, 535, 816, 798, 1016, and 1342. For clinical CAP, PCV13 was associated with a reduction of 909 (−115, 2013) hospital days per 100,000 PYOs translating to a reduction over 5 years of one hospital day for every 22 people vaccinated. When comparing at-risk persons (defined by self-report of diabetes, chronic lung disease, or other underlying conditions) to not at-risk persons, VEs were similar or lower, but because baseline incidences were higher the VPDIs were approximately 2–10 times higher and NNVs 50–90% lower. ConclusionA public health analysis of pneumonia and IPD outcomes in a randomized controlled trial found substantial burden reduction following adult PCV13 immunization implemented in a setting with an ongoing infant PCV7-PCV10 program. VPDIs were higher among at-risk adults. FundingThe original study and the current analysis were funded by Pfizer.
Background Anastomotic leakage is associated with increased morbidity and mortality after esophagectomy. Calcification of the arteries supplying the gastric tube has been identified as a risk factor ...for leakage of the cervical anastomosis, but its potential contribution to the risk of intrathoracic anastomotic leakage has not been elucidated. This study evaluated the relationship between calcification and the occurrence of leakage of the intrathoracic anastomosis after Ivor-Lewis esophagectomy. Methods Consecutive patients who underwent minimally invasive esophagectomy for cancer at 2 institutions were analyzed. Diagnostic computed tomography images were used to detect calcification of the arteries supplying the gastric tube (eg, aorta, celiac axis). Multivariable logistic regression analysis was used to determine the relationship between vascular calcification and anastomotic leakage. Results Of 167 included patients, anastomotic leakage occurred in 40 (24%). In univariable analysis, leakage was most frequently observed in patients with calcification of the aorta (major calcification: 37% leakage 16 of 43; minor calcification: 32% 18 of 56; no calcification: 9% 6 of 70, p < 0.001). Calcification of other studied arteries was not significantly associated with leakage. A significant association with leakage remained for minor (odds ratio, 5.4; 95% confidence interval, 1.7 to 16.5) and major (odds ratio, 7.0; 95% confidence interval, 1.9 to 26.4) aortic calcifications in multivariable analysis. Conclusions Atherosclerotic calcification of the aorta is an independent risk factor for leakage of the intrathoracic anastomosis after Ivor-Lewis esophagectomy for cancer. The calcification scoring system may aid in patient selection and lead to earlier diagnosis of this potentially fatal complication.
MicroRNAs (miRNAs) are RNA molecules that are involved in the regulation of many cellular processes, including those related to human cancers. The aim of this study was to determine, as a proof of ...principle, whether specific candidate miRNAs could be detected in fine-needle aspirate (FNA) biopsies of pancreatic ductal adenocarcinoma (PDAC) and could accurately differentiate malignant from benign pancreatic tissues.
We used TaqMan(R) assays to quantify miRNA levels in FNA samples collected in RNARetain (n = 16) and compared the results with a training set consisting of frozen macrodissected pancreatic samples (n = 20).
Quantitative reverse-transcription PCR analysis confirmed that miRNA levels are affected in PDAC FNAs and correlate well with the changes observed in the training set of frozen pancreatic samples. Analysis of the amounts produced for a few specific miRNAs enabled identification of PDAC samples. The combination of miR-196a and miR-217 biomarkers further improved the ability to distinguish between healthy tissue, PDAC, and chronic pancreatitis in the training set (P = 8.2 x 10(-10)), as well as segregate PDAC FNA samples from other FNA samples (P = 1.1 x 10(-5)). Furthermore, we showed that miR-196a production is likely specific to PDAC cells and that its incidence paralleled the progression of PDAC.
To the best of our knowledge, this study is the first to evaluate the diagnostic potential of miRNAs in a clinical setting and has shown that miRNA analysis of pancreatic FNA biopsy samples can aid in the pathologic evaluation of suspicious cases and may provide a new strategy for improving the diagnosis of pancreatic diseases.
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