Citations

Background: Several immune-mediated inflammatory disorders, such as rheumatoid arthritis, psoriatic arthritis, and systemic lupus erythematosus have been linked to an increased risk of venous thromboembolism (VTE). However, the data on ankylosing spondylitis (AS) are limited. Methods: We conducted a systematic review and meta-analysis of observational studies that reported odds ratio, relative risk, hazard ratio, or standardized incidence ratio comparing the risk of VTE and possible pulmonary embolism (PE) in patients with AS versus non-AS participants. Pooled risk ratio and 95% confidence intervals were calculated using a random-effect, generic inverse variance method of DerSimonian and Laird. Results: Of 423 potentially relevant articles, three studies met our inclusion criteria and thus, were included in the data analysis. The pooled risk ratio of VTE in patients with AS was 1.60 (95% confidence interval: 1.05–2.44). The statistical heterogeneity of this study was high with an I 2 of 93%. Conclusion: Our study demonstrated a statistically significant increased VTE risk among patients with AS.

Lung cancer is the deadliest cancer in the United States, killing roughly one of four cancer patients in 2016. While it is well-established that lung cancer is caused primarily by environmental effects (particularly tobacco smoking), there is evidence for genetic susceptibility. Lung cancer has been shown to aggregate in families, and segregation analyses have hypothesized a major susceptibility locus for the disease. Genetic association studies have provided strong evidence for common risk variants of small-to-moderate effect. Rare and highly penetrant alleles have been identified by linkage studies, including on 6q23–25. Though not common, some germline mutations have also been identified via sequencing studies. Ongoing genomics studies aim to identify additional high penetrance germline susceptibility alleles for this deadly disease.

AbstractPurposeThe increase in use of health information technologies (HIT) presents new opportunities for patient engagement and self‐management. Patients in rural areas stand to benefit especially from increased access to health care tools and electronic communication with providers. We assessed the adoption of 4 HIT tools over time by rural or urban residency.MethodsAnalyses were conducted using data from 7 iterations of the National Cancer Institute's Health Information National Trends Survey (HINTS; 2003‐2014). Rural/urban residency was based on the USDA's 2003 Rural‐Urban Continuum Codes. Outcomes of interest included managing personal health information online; whether providers maintain electronic health records (EHRs); e‐mailing health care providers; and purchasing medicine online. Bivariate analyses and logistic regression were used to assess relationships between geography and outcomes, controlling for sociodemographic characteristics.FindingsIn total, 6,043 (17.6%, weighted) of the 33,749 respondents across the 7 administrations of HINTS lived in rural areas. Rural participants were less likely to report regular access to Internet (OR = 0.70, 95% CI = 0.61‐0.80). Rural respondents were neither more nor less likely to report that their health care providers maintained EHRs than were urban respondents; however, they had decreased odds of managing personal health information online (OR = 0.59, 95% CI = 0.40‐0.78) and e‐mailing health care providers (OR = 0.62, 95% CI = 0.49‐0.77).ConclusionsThe digital divide between rural and urban residents extends to HIT. Additional investigation is needed to determine whether the decreased use of HIT may be due to lack of Internet connectivity or awareness of these tools.

Various pathophysiological conditions such as surfactant dysfunction, mechanical ventilation, inflammation, pathogen products, environmental exposures, and gastric acid aspiration stress lung cells, and the compromise of plasma membranes occurs as a result. The mechanisms necessary for cells to repair plasma membrane defects have been extensively investigated in the last two decades, and some of these key repair mechanisms are also shown to occur following lung cell injury. Because it was theorized that lung wounding and repair are involved in the pathogenesis of acute respiratory distress syndrome (ARDS) and idiopathic pulmonary fibrosis (IPF), in this review, we summarized the experimental evidence of lung cell injury in these two devastating syndromes and discuss relevant genetic, physical, and biological injury mechanisms, as well as mechanisms used by lung cells for cell survival and membrane repair. Finally, we discuss relevant signaling pathways that may be activated by chronic or repeated lung cell injury as an extension of our cell injury and repair focus in this review. We hope that a holistic view of injurious stimuli relevant for ARDS and IPF could lead to updated experimental models. In addition, parallel discussion of membrane repair mechanisms in lung cells and injury-activated signaling pathways would encourage research to bridge gaps in current knowledge. Indeed, deep understanding of lung cell wounding and repair, and discovery of relevant repair moieties for lung cells, should inspire the development of new therapies that are likely preventive and broadly effective for targeting injurious pulmonary diseases.

Genome-wide association studies have identified >50 common variants associated with kidney function, but these variants do not fully explain the variation in eGFR. We performed a two-stage meta-analysis of associations between genotypes from the Illumina exome array and eGFR on the basis of serum creatinine (eGFRcrea) among participants of European ancestry from the CKDGen Consortium ( n Stage1 : 111,666; n Stage2 : 48,343). In single-variant analyses, we identified single nucleotide polymorphisms at seven new loci associated with eGFRcrea ( PPM1J , EDEM3, ACP1, SPEG, EYA4, CYP1A1 , and ATXN2L ; P Stage1 <3.7×10 −7 ), of which most were common and annotated as nonsynonymous variants. Gene-based analysis identified associations of functional rare variants in three genes with eGFRcrea, including a novel association with the SOS Ras/Rho guanine nucleotide exchange factor 2 gene, SOS2 ( P =5.4×10 −8 by sequence kernel association test). Experimental follow-up in zebrafish embryos revealed changes in glomerular gene expression and renal tubule morphology in the embryonic kidney of acp1- and sos2 -knockdowns. These developmental abnormalities associated with altered blood clearance rate and heightened prevalence of edema. This study expands the number of loci associated with kidney function and identifies novel genes with potential roles in kidney formation.

The development and utilization of monoclonal antibodies (mAbs) have been of great interest in all fields of medicine. A substantial increase in the production and development of mAbs has occurred because these biologic agents are proving to be effective and less toxic given their targeted mechanism of action. However, data are limited on coadministration of two or more mAbs. With the increasing availability of mAbs and the comorbidities of some patients, assessment is needed of the ability to safely use multiple mAbs for an individual patient. Although the efficacy of coadministered mAbs may be inferred from their specific targets, we could find no literature reporting such a finding. Herein, we report our experience using two different classes of mAbs to treat hypereosinophilic syndrome and ulcerative colitis in a single patient.

Purpose: Traditionally, determination of total lung capacity (TLC) by plethysmography (TLCpleth) has been important in the diagnosis of lung diseases. Alternatively, data acquired from computerized tomography (CT) can be utilized to calculate a measure of TLC (TLCCT). The clinical utility of TLCCT is not certain. We sought to determine, in a clinical setting, whether TLCCT correlates with TLCpleth across a range of lung diseases and scanning techniques. In addition, we determined whether TLCCT affects the interpretation of pulmonary function tests. Subjects and Methods: Records of 118 of 148 consecutive lung transplant recipients were reviewed and determined to have coinciding pulmonary function tests, including plethysmography as well as volumetric chest CT performed supine during full inspiration. CT images acquired with a wide range of scanning protocols were analyzed using CALIPER, a software program for lung and trachea extraction from a CT volume and volumetric tissue characterization of the lung. Segmentation of the lung was achieved by using completely automated dynamic thresholding and region-growing techniques developed to extract the relatively low-density lung and tracheal anatomy from the CT data set without user intervention. Results: TLCpleth and TLCCT were strongly related with a correlation coefficient of 0.88 (P<0.001). The efficacy of the CT-derived measure was not influenced by specific lung diagnoses, age, height, body mass index, or spirometric parameters. TLCCT did not misidentify any diagnosis of restrictive lung disease, nor hyperinflation. Conclusions: In a clinical setting, CT segmentation analysis provides a favorable determination of TLC compared with traditional plethysmography. The technique has general applicability across varying CT data acquisition protocols, lung diseases, and patient characteristics. TLCCT may substitute for TLCpleth in pulmonary function interpretation and may be preferable for some patients in whom plethysmography is difficult to perform, such as transplant subjects with severe pulmonary fibrosis.