Citations

Autosomal dominant polycystic kidney disease (ADPKD) often results in ESRD but with a highly variable course. Mutations to PKD1 or PKD2 cause ADPKD; both loci have high levels of allelic heterogeneity. We evaluated genotype-phenotype correlations in 1119 patients (945 families) from the HALT Progression of PKD Study and the Consortium of Radiologic Imaging Study of PKD Study. The population was defined as: 77.7% PKD1, 14.7% PKD2, and 7.6% with no mutation detected (NMD). Phenotypic end points were sex, eGFR, height–adjusted total kidney volume (htTKV), and liver cyst volume. Analysis of the eGFR and htTKV measures showed that the PKD1 group had more severe disease than the PKD2 group, whereas the NMD group had a PKD2-like phenotype. In both the PKD1 and PKD2 populations, men had more severe renal disease, but women had larger liver cyst volumes. Compared with nontruncating PKD1 mutations, truncating PKD1 mutations associated with lower eGFR, but the mutation groups were not differentiated by htTKV. PKD1 nontruncating mutations were evaluated for conservation and chemical change and subdivided into strong (mutation strength group 2 [MSG2]) and weak (MSG3) mutation groups. Analysis of eGFR and htTKV measures showed that patients with MSG3 but not MSG2 mutations had significantly milder disease than patients with truncating cases (MSG1), an association especially evident in extreme decile populations. Overall, we have quantified the contribution of genic and PKD1 allelic effects and sex to the ADPKD phenotype. Intrafamilial correlation analysis showed that other factors shared by families influence htTKV, with these additional genetic/environmental factors significantly affecting the ADPKD phenotype.

Objectives To evaluate the ability of clinical and radiographic features to predict lymph node (pN1) disease among patients with renal cell carcinoma undergoing radical nephrectomy (RN), and to develop a preoperative risk prediction model. Patients and Methods In all, 220 patients with preoperative computed tomography scans available for review underwent RN with lymph node dissection (LND) from 2000 to 2010. Radiographic features were assessed by one genitourinary radiologist blinded to pN status. Associations of features with pN1 disease were evaluated using logistic regression to develop predictive models. Model performance was assessed using area under the receiver operating characteristic curve (AUC) and decision curve analysis. Results The median (interquartile range) lymph node yield was 10 (5–18). In all, 55 patients (25%) had pN1 disease at RN. On univariable analysis, the maximum lymph node (LN) short axis diameter [odds ratio (OR) 1.17; P < 0.001] predicted pN1 disease with an AUC of 0.84. Although several clinical and radiographic features were associated with pN1 disease, only two were retained in the multivariable model: maximum LN short axis diameter (OR 1.19; P <0.001) and radiographic perinephric/sinus fat invasion (OR 44.64; P = 0.01), with an AUC of 0.85. On decision curve analysis, the single variable and multivariable models showed similar net benefit. Conclusion Two radiographic features, maximum LN short axis diameter and perinephric/sinus fat invasion, outperformed traditional clinical variables in predicting pN1 disease. Maximum LN short axis diameter alone showed excellent predictive performance, and, if validated externally, would provide for a simple model to guide patient selection for LND.

Background and Purpose— Emerging evidence demonstrating the high sensitivity of early brain computed tomography (CT) brings into question the necessity of always performing lumbar puncture after a negative CT in the diagnosis of spontaneous subarachnoid hemorrhage (SAH). Our objective was to determine the sensitivity of brain CT using modern scanners (16-slice technology or greater) when performed within 6 hours of headache onset to exclude SAH in neurologically intact patients. Methods— After conducting a comprehensive literature search using Ovid MEDLINE, Ovid EMBASE, Web of Science, and Scopus, we conducted a meta-analysis. We included original research studies of adults presenting with a history concerning for spontaneous SAH and who had noncontrast brain CT scan using a modern generation multidetector CT scanner within 6 hours of symptom onset. Our study adheres to the preferred reporting items for systematic reviews and meta-analyses (PRISMA). Results— A total of 882 titles were reviewed and 5 articles met inclusion criteria, including an estimated 8907 patients. Thirteen had a missed SAH (incidence 1.46 per 1000) on brain CTs within 6 hours. Overall sensitivity of the CT was 0.987 (95% confidence intervals, 0.971–0.994) and specificity was 0.999 (95% confidence intervals, 0.993–1.0). The pooled likelihood ratio of a negative CT was 0.010 (95% confidence intervals, 0.003–0.034). Conclusions— In patients presenting with thunderclap headache and normal neurological examination, normal brain CT within 6 hours of headache is extremely sensitive in ruling out aneurysmal SAH.

© 2016 Heart Rhythm Society, the American College of Cardiology Foundation, and the Society for Cardiovascular Angiography and Interventions

ObjectiveTo develop a new evidence‐based, pharmacologic treatment guideline for rheumatoid arthritis (RA).MethodsWe conducted systematic reviews to synthesize the evidence for the benefits and harms of various treatment options. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the quality of evidence. We employed a group consensus process to grade the strength of recommendations (either strong or conditional). A strong recommendation indicates that clinicians are certain that the benefits of an intervention far outweigh the harms (or vice versa). A conditional recommendation denotes uncertainty over the balance of benefits and harms and/or more significant variability in patient values and preferences.ResultsThe guideline covers the use of traditional disease‐modifying antirheumatic drugs (DMARDs), biologic agents, tofacitinib, and glucocorticoids in early (<6 months) and established (≥6 months) RA. In addition, it provides recommendations on using a treat‐to‐target approach, tapering and discontinuing medications, and the use of biologic agents and DMARDs in patients with hepatitis, congestive heart failure, malignancy, and serious infections. The guideline addresses the use of vaccines in patients starting/receiving DMARDs or biologic agents, screening for tuberculosis in patients starting/receiving biologic agents or tofacitinib, and laboratory monitoring for traditional DMARDs. The guideline includes 74 recommendations: 23% are strong and 77% are conditional.ConclusionThis RA guideline should serve as a tool for clinicians and patients (our two target audiences) for pharmacologic treatment decisions in commonly encountered clinical situations. These recommendations are not prescriptive, and the treatment decisions should be made by physicians and patients through a shared decision‐making process taking into account patients’ values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.

Objective To develop a new evidence‐based, pharmacologic treatment guideline for rheumatoid arthritis (RA). Methods We conducted systematic reviews to synthesize the evidence for the benefits and harms of various treatment options. We used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to rate the quality of evidence. We employed a group consensus process to grade the strength of recommendations (either strong or conditional). A strong recommendation indicates that clinicians are certain that the benefits of an intervention far outweigh the harms (or vice versa). A conditional recommendation denotes uncertainty over the balance of benefits and harms and/or more significant variability in patient values and preferences. Results The guideline covers the use of traditional disease‐modifying antirheumatic drugs (DMARDs), biologic agents, tofacitinib, and glucocorticoids in early (<6 months) and established (≥6 months) RA. In addition, it provides recommendations on using a treat‐to‐target approach, tapering and discontinuing medications, and the use of biologic agents and DMARDs in patients with hepatitis, congestive heart failure, malignancy, and serious infections. The guideline addresses the use of vaccines in patients starting/receiving DMARDs or biologic agents, screening for tuberculosis in patients starting/receiving biologic agents or tofacitinib, and laboratory monitoring for traditional DMARDs. The guideline includes 74 recommendations: 23% are strong and 77% are conditional. Conclusion This RA guideline should serve as a tool for clinicians and patients (our two target audiences) for pharmacologic treatment decisions in commonly encountered clinical situations. These recommendations are not prescriptive, and the treatment decisions should be made by physicians and patients through a shared decision‐making process taking into account patients’ values, preferences, and comorbidities. These recommendations should not be used to limit or deny access to therapies.