Citations

AbstractObjectiveTo conduct a systematic literature review of dorsal root ganglion (DRG) stimulation for pain.DesignGrade the evidence for DRG stimulation.MethodsAn international, interdisciplinary work group conducted a literature search for DRG stimulation. Abstracts were reviewed to select studies for grading. General inclusion criteria were prospective trials (randomized controlled trials and observational studies) that were not part of a larger or previously reported group. Excluded studies were retrospective, too small, or existed only as abstracts. Studies were graded using the modified Interventional Pain Management Techniques–Quality Appraisal of Reliability and Risk of Bias Assessment, the Cochrane Collaborations Risk of Bias assessment, and the US Preventative Services Task Force level-of-evidence criteria.ResultsDRG stimulation has Level II evidence (moderate) based upon one high-quality pivotal randomized controlled trial and two lower-quality studies.ConclusionsModerate-level evidence supports DRG stimulation for treating chronic focal neuropathic pain and complex regional pain syndrome.

Abstract Background: Results from epidemiologic studies examining polyunsaturated fatty acids (PUFA) and colorectal cancer risk are inconsistent. Mendelian randomization may strengthen causal inference from observational studies. Given their shared metabolic pathway, examining the combined effects of aspirin/NSAID use with PUFAs could help elucidate an association between PUFAs and colorectal cancer risk. Methods: Information was leveraged from genome-wide association studies (GWAS) regarding PUFA-associated SNPs to create weighted genetic scores (wGS) representing genetically predicted circulating blood PUFAs for 11,016 non-Hispanic white colorectal cancer cases and 13,732 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Associations per SD increase in the wGS were estimated using unconditional logistic regression. Interactions between PUFA wGSs and aspirin/NSAID use on colorectal cancer risk were also examined. Results: Modest colorectal cancer risk reductions were observed per SD increase in circulating linoleic acid [ORLA = 0.96; 95% confidence interval (CI) = 0.93–0.98; P = 5.2 × 10−4] and α-linolenic acid (ORALA = 0.95; 95% CI = 0.92–0.97; P = 5.4 × 10−5), whereas modest increased risks were observed for arachidonic (ORAA = 1.06; 95% CI = 1.03–1.08; P = 3.3 × 10−5), eicosapentaenoic (OREPA = 1.04; 95% CI = 1.01–1.07; P = 2.5 × 10−3), and docosapentaenoic acids (ORDPA = 1.03; 95% CI = 1.01–1.06; P = 1.2 × 10−2). Each of these effects was stronger among aspirin/NSAID nonusers in the stratified analyses. Conclusions: Our study suggests that higher circulating shorter-chain PUFAs (i.e., LA and ALA) were associated with reduced colorectal cancer risk, whereas longer-chain PUFAs (i.e., AA, EPA, and DPA) were associated with an increased colorectal cancer risk. Impact: The interaction of PUFAs with aspirin/NSAID use indicates a shared colorectal cancer inflammatory pathway. Future research should continue to improve PUFA genetic instruments to elucidate the independent effects of PUFAs on colorectal cancer.

AbstractObjectivesTo investigate metabolic features that may predispose to GCA in a nested case–control study.MethodsIndividuals who developed GCA after inclusion in a population-based health survey (the Malmö Preventive Medicine Project; N = 33 346) were identified and validated through a structured review of medical records. Four controls for every validated case were selected from the database.ResultsA total of 76 cases with a confirmed incident diagnosis of GCA (61% female, 65% biopsy positive, mean age at diagnosis 70 years) were identified. The median time from screening to diagnosis was 20.7 years (range 3.0–32.1). Cases had significantly lower fasting blood glucose (FBG) at baseline screening compared with controls [mean 4.7 vs 5.1 mmol/l (S.d. overall 1.5), odds ratio (OR) 0.35 per mmol/l (95% CI 0.17, 0.71)] and the association remained significant when adjusted for smoking [OR 0.33 per mmol/l (95% CI 0.16, 0.68)]. Current smokers had a reduced risk of GCA [OR 0.35 (95% CI 0.18, 0.70)]. Both cholesterol [mean 5.6 vs 6.0 mmol/l (S.d. overall 1.0)] and triglyceride levels [median 1.0 vs 1.2 mmol/l (S.d. overall 0.8)] were lower among the cases at baseline screening, with significant negative associations with subsequent GCA in crude and smoking-adjusted models [OR 0.62 per mmol/l (95% CI 0.43, 0.90) for cholesterol; 0.46 per mmol/l (95% CI 0.27, 0.81) for triglycerides].ConclusionDevelopment of GCA was associated with lower FBG and lower cholesterol and triglyceride levels at baseline, all adjusted for current smoking, suggesting that metabolic features predispose to GCA.

Goals: To develop an encounter decision aid [Barrett’s esophagus Choice (BE-Choice)] for patients and clinicians to engage in shared decision making (SDM) for management of BE with low-grade dysplasia (BE-LGD) and assess its impact on patient-important outcomes. Background: Currently, there are 2 strategies for management of BE-LGD—endoscopic surveillance and ablation. SDM can help patients decide on their preferred management option. Study: Phase-I: Patients and clinicians were engaged in a user-centered design approach to develop BE-Choice. Phase-I included review of evidence on BE-LGD management, observation of usual care (UC), creation, field-testing, and iterative development of BE-Choice in clinical settings. Phase-II: Impact of BE-Choice on patient-important outcomes (patient knowledge, decisional conflict, and patient involvement in decision making) was assessed using a controlled before-after study design (UC vs. BE-Choice). Results: Phase-I: Initial prototype was designed with observation of 8 clinical encounters. With field-testing, 3 successive iterations were made before finalizing BE-Choice. BE-Choice was paper based and fulfilled the qualifying criteria of International patient decision aid standards. Phase II: 29 patients were enrolled, 8 to UC and 21 to BE-Choice. Compared with UC, use of BE-Choice improved patient knowledge (90.4% vs. 70.5%; P =0.03), decisional comfort (89.6 vs. 71.9; P =0.01), and patient involvement (OPTION score: 27.1 vs. 19.2; P =0.01). Conclusions: BE-Choice is a feasible and effective decision aid to promote SDM in the management of BE-LGD. On pilot testing, BE-Choice had promising impact on patient-important outcomes. A larger multicenter trial is needed to confirm our results and promote widespread use of BE-Choice.

In this article we present a case of a patient who received reversal of anticoagulation therapy with factor IX in violation of hospital guidelines. As a direct result, myocardial infarction and ischemic stroke occurred, leaving the patient neurologically debilitated. Factor IX is indicated in the setting of warfarin-induced, life-threatening bleeding. The patient’s care was provided by an intern with attending physician supervision. Delayed charting and questionable shared decision-making were present in the care. We discuss usage of factor IX, liability for supervision of physicians in training, and factors that can lead to plaintiff awards.

404 Background: Concurrent chemoradiation(CRT) followed by esophagectomy is a standard of care for locally advanced esophageal(LA-EAC) and GEJ adenocarcinoma. Approximately 50% of patients(pts) experience disease relapse within the 1st yr after treatment(tx) completion. No adjuvant tx has been shown to improve survival in these pts. Immune checkpoint inhibitors have activity in metastatic PD-L1 positive EAC. Preclinical studies have shown radiation +/- chemotherapy upregulate PD-1/PD-L1 pathway. Methods: We conducted a phase II trial evaluating safety and efficacy of durvalumab(durva) in pts with LA-EAC and GEJ adenocarcinoma who have residual disease in surgical specimen after neoadjuvant CRT and R0 resection. Pts received durva 1500mg IV every 4 weeks for up to 1yr. Results: 24 pts were enrolled from 4/2016-1/2018(median age: 60yrs (range, 43-70). 18 received carbo/paclitaxel and 6 received cis/5-FU concurrently with radiation. Staging at diagnosis: T2N0(n = 3, 12.5%), T2N2(n = 3, 12.5%),T3N0(n = 6, 25%), T3N1(n = 6, 25%), T3N2(n = 4, 17%), T3N3(n = 1, 4%), T3Nx(n = 1, 4%).19 pts(79%) had positive lymph nodes(LNs) at the time of surgery following CRT. 12 pts completed 1yr of tx, 12 came off tx because of relapse(6), AEs(5), and consent withdrawal(1). Most common AEs were fatigue(n = 8, 33.3%) and nausea(n = 6, 25%). 3pts (12.5%) developed grade 3 irAEs: pneumonitis(1), hepatitis(1), colitis(1). At median follow up of 21.9mo(range, 1.7-23.9mo), 11 pts have relapsed: 9 distant and 2 locoregional. Two of 3 pts with grade 3 irAEs are alive and disease free at 17 and 23 mo respectively. 1-yr RFS and OS were 79.2% and 95.5%, respectively. RFS at 26 mo was 20.6%. Overall mOS and mOS after relapse were 28.1mo(range, 22.9-28.1) and 11.1 mo(range, 0.1-11.3mo) respectively. The study was expanded to enroll 14 additional pts who are currently undergoing tx. Conclusions: Adjuvant durvalumab following trimodality therapy for LA-EAC and GEJ adenocarcinoma is safe with improvement in 1-yr RFS to 79.2% compared to historical rate of 50%. RFS was 20.6% at 26 months. Evaluation of predictive biomarkers of RFS with durva is underway. Clinical trial information: NCT02639065.

This case highlights the importance of recognizing any new soft tissue abnormalities in cancer patients with an indwelling pleural catheter (IPC) or who has had an IPC. This report also describes the first case of catheter tract metastasis (CTM) due to renal cell carcinoma (RCC) and the second case of CTM post‐IPC removal.

The automated low‐flow ascites pump (alfapump) is an implantable device that drains ascites directly into the urinary bladder. We studied its safety (absence of serious complications) and efficacy (decreased large‐volume paracentesis [LVP] requirement and improved quality of life [QoL]) in the management of ascites in a cohort of North American patients with cirrhosis and recurrent ascites ineligible for transjugular intrahepatic portosystemic shunt (TIPS). QoL was measured by the Chronic Liver Disease Questionnaire (CLDQ) and Ascites Questionnaire (Ascites Q). Following alfapump implantation, patients were monitored for ascites control, laboratory abnormalities, QoL, adverse events, and survival at 12 months. A total of 30 patients (60.0 ± 9.9 years; 57% male; Model for End‐Stage Liver Disease score, 11.4 ± 2.7) received an alfapump, mostly by an interventional radiology approach (97%), followed by longterm prophylactic antibiotics. The alfapump removed a mean ascites volume of 230.6 ± 148.9 L/patient at 12 months, dramatically reducing the mean LVP frequency from 2.4 ± 1.4/patient/month before pump implantation to 0.2 ± 0.4/patient/month after pump implantation. All surviving patients had improved QoL (baseline versus 3 months; CLDQ, 3.9 ± 1.21 versus 5.0 ± 1.0; Ascites Q, 51.7 ± 21.9 versus 26.7 ± 18.6; P < 0.001 for both) and a better biochemical index of nutritional status (prealbumin 87.8 ± 37.5 versus 102.9 ± 45.3 mg/L at 3 months; P = 0.04). Bacterial infections (15 events in 13 patients), electrolyte abnormalities (11 events in 6 patients), and renal complications (11 events in 9 patients) were the most common severe adverse events. By 12 months, 4 patients died from complications of cirrhosis. Alfapump insertion may be a definitive treatment for refractory ascites in cirrhosis, especially in patients who are not TIPS candidates.

Abstract A chromatographic system for organic acids has been developed, with improved stability, resolution, and sensitivity for measuring organic anions in biological samples. A calibration mixture containing 100 nEq each of 18 organic anions was clearly resolved, with a signal-to-noise ratio greater than 100:1. The baseline was essentially flat throughout the chromatogram. With scale expansion, the sensitivity limit was about 0.2 nEq per constituent. The width of each peak at half its height was 1 to 2% of its retention time. The system could thus resolve 50 or more constituents. In chromatograms of whole blood and urine more than 40 compounds are resolved. The system is basically a liquid-liquid partition between an acidified aqueous phase on silicic acid and a gradient of nonpolar and polar solvents. Eluted organic acids are detected photometrically by mixing the column effluent with a miscible solvent containing a suitable indicator. Samples require about 6 h for complete chromatography at present.