Citations

AbstractBackgroundCachexia is a significant problem in patients with cancer. The effect of cancer on interstitial cells of Cajal (ICC) and neurons of the gastrointestinal tract have not been studied previously. Although supplementation with L‐glutamine 2% may have beneficial effects in cancer‐related cachexia, and be protective of ICC in models of oxidative stress such as diabetes, its effects on ICC in cancer have also not been studied.MethodsTwenty‐eight male Wistar rats were divided into four groups: control (C), control supplemented with L‐glutamine (CG), Walker 256 tumor (WT), and Walker 256 tumor supplemented with L‐glutamine (WTG). Rats were implanted with tumor cells or injected with saline in the right flank. After 14 days, the jejunal tissues were collected and processed for immunohistochemical techniques including whole mounts and cryosections and Western blot analysis.Key ResultsTumor‐bearing rats demonstrate reduced numbers of Myenteric ICC and deep muscular plexus ICC and yet increased Ano1 protein expression and enhanced ICC networks. In addition, there is more nNOS protein expressed in tumor‐bearing rats compared to controls. L‐glutamine treatment had a variety of effects on ICC that may be related to the disease state and the interaction of ICC and nNOS neurons. Regardless, L‐glutamine reduced the size of tumors and also tumor‐induced cachexia that was not due to altered food intake.Conclusions & InferencesThere are significant effects on ICC in the Walker 256 tumor model. Although supplementation with L‐glutamine has differential and complex effects of ICC, it reduces tumor size and tumor‐associated cachexia, which supports its beneficial therapeutic role in cancer.

Purpose Autologous hematopoietic cell transplantation, or autotransplantation, is effective in light-chain amyloidosis (AL), but it is associated with a high risk of early mortality (EM). In a multicenter randomized comparison against oral chemotherapy, autotransplantation was associated with 24% EM. We analyzed trends in outcomes after autologous hematopoietic cell transplantation for AL in North America. Patients and Methods Between 1995 and 2012, 1,536 patients with AL who underwent autotransplantation at 134 centers were identified in the Center for International Blood and Marrow Transplant Research database. EM and overall survival (OS) were analyzed in three time cohorts: 1995 to 2000 (n = 140), 2001 to 2006 (n = 596), and 2007 to 2012 (n = 800). Hematologic and renal responses and factors associated with EM, relapse and/or progression, progression-free survival and OS were analyzed in more recent subgroups from 2001 to 2006 (n = 197) and from 2007 to 2012 (n = 157). Results Mortality at 30 and 100 days progressively declined over successive time periods from 11% and 20%, respectively, in 1995 to 2000 to 5% and 11%, respectively, in 2001 to 2006, and to 3% and 5%, respectively, in 2007 to 2012. Correspondingly, 5-year OS improved from 55% in 1995 to 2000 to 61% in 2001 to 2006 and to 77% in 2007 to 2012. Hematologic response to transplantation improved in the latest cohort. Renal response rate was 32%. Centers performing more than four AL transplantations per year had superior survival outcomes. In the multivariable analysis, cardiac AL was associated with high EM and inferior progression-free survival and OS. Autotransplantation in 2007 to 2012 and use of higher dosages of melphalan were associated with a lowered relapse risk. A Karnofsky score less than 80 and creatinine levels 2 mg/m2 or greater were associated with worsened OS. Conclusion Post-transplantation survival in AL has improved, with a dramatic reduction in early post-transplantation mortality and excellent 5-year survival. The risk-benefit ratio for autotransplantation has changed, and randomized comparison with nontransplantation approaches is again warranted.

Abstract Therapy for polymyalgia rheumatica (PMR) varies widely in clinical practice as international recommendations for PMR treatment are not currently available. In this paper, we report the 2015 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) recommendations for the management of PMR. We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology as a framework for the project. Accordingly, the direction and strength of the recommendations are based on the quality of evidence, the balance between desirable and undesirable effects, patients’ and clinicians’ values and preferences, and resource use. Eight overarching principles and nine specific recommendations were developed covering several aspects of PMR, including basic and follow‐up investigations of patients under treatment, risk factor assessment, medical access for patients and specialist referral, treatment strategies such as initial glucocorticoid (GC) doses and subsequent tapering regimens, use of intramuscular GCs and disease modifying anti‐rheumatic drugs (DMARDs), as well as the roles of non‐steroidal anti‐rheumatic drugs and non‐pharmacological interventions. These recommendations will inform primary, secondary and tertiary care physicians about an international consensus on the management of PMR. These recommendations should serve to inform clinicians about best practices in the care of patients with PMR.

FiberNet® is a second generation non-conventional embolization protection device (EPD) that purports to offer several advantages: ability to capture debris as small as 40 μm, more flexibility with placement and positioning in curved segments requiring a small landing zone, ability to conform to asymmetric vessels, and improved deliverability. The design features a low profile with large surface area to capture debris. Legitimate concerns include inducement of obstruction or low flow with debris capture and requirements in the IFU to aspirate during re-capture and device removal. Our goal was to compare the results of carotid artery stenting (CAS) using FiberNet® against a multi-center experience of CAS using other filter devices to identify any differences in technical success or event rates. FiberNet® (n=25) results were compared to all CAS cases performed at the Mayo Clinic in Rochester, MN, St Mary's/Duluth Clinic in MN, and North Central Heart Institute in Sioux Falls, SD (n=250) from March 2001 to December 2008. Chi-square or means were used to compare variables, as appropriate. Bivariate logistic regression was used to identify possible correlates of adverse outcome. Statistical significance was set at < 0.05. FiberNet® patients were more likely to be older (78.1+5.4 vs 73.6+9.4, p=0.019), female (48% vs 29%, p=0.047), and have peripheral vascular disease (84.0% vs 37.2%, p=0.025), and less likely to have diabetes (8.0% vs 29.8%, p=0.012) than patients in the comparison group. FiberNet® patients had more lesion calcification (40.0% vs 18.9%, p=0.014) and increased number of type 2 and 3 arches (44.2% vs 73.9%, p=0.006). Procedural success rate was 100% in both groups. None of the FiberNet® patients showed evidence of stagnant flow. The thirty-day outcome for TIA, CVA, or death was 4% in FiberNet® versus 4.8% in the comparison group (p NS). None of the independent variables – age gender, serum creatinine, arch complexity, lesion length, lesion calcium, lesion thrombus, PVD, diabetes, contralateral carotid occlusion, or ipsilateral carotid endarterectomy – predicted adverse events. Although FiberNet® patients had more lesion calcium and more challenging arch anatomy, procedural success and adverse events were comparable between groups. The advantages of FiberNet® can be applied to CAS with good technical results and may be a promising EPD for certain high-risk situations.

Abstract Purpose: The interaction of programmed death-1 ligand (PD-L1) with its receptor (PD-1) on T cells inactivates antitumor immune responses. PD-L1 expression has been associated with poor outcomes in renal cell carcinoma (RCC) but has not been investigated in advanced RCC patients receiving VEGF-targeted therapy. Experimental Design: Formalin-fixed paraffin-embedded specimens were collected at baseline from patients in the COMPARZ trial. Tumor cell PD-L1 expression by IHC was evaluated using H-score (HS). Dual PD-L1/CD68 staining was used to differentiate PD-L1 tumor expression from tumor-associated macrophages. Intratumor CD8-positive T cells were quantified morphometrically. Associations between biomarkers and survival were investigated using the log-rank test. Results: HS data were available from 453 of 1,110 patients. Sixty-four percent of patients had negative PD-L1 expression (HS = 0). Patients with HS &gt; 55 (n = 59, 13%) had significantly shorter overall survival (OS) than those with HS ≤ 55 in both pazopanib and sunitinib arms (median 15.1 vs. 35.6 and 15.3 vs. 27.8 months, respectively, P = 0.03). In both arms, median OS was shortest in patients with HS &gt; 55 and intratumor CD8-positive T-cell counts &gt; 300 (9.6 and 11.9 months with pazopanib and sunitinib, respectively). Median OS in patients with HS ≤ 55 and CD8-positive T-cell counts ≤ 300 was 36.8 and 28.0 months with pazopanib and sunitinib, respectively. Progression-free survival results were similar to OS results. Conclusions: Increased tumor cell PD-L1, or PD-L1 plus tumor CD8-positive T-cell counts, were associated with shorter survival in patients with metastatic RCC receiving VEGF-targeted agents. These findings may have implications for future design of randomized clinical trials in advanced RCC. Clin Cancer Res; 21(5); 1071–7. ©2014 AACR.

This paper presents commentaries on whether eosinophilic esophagitis is a food allergy; inflammation in the context of eosinophilic esophagitis; whether eosinophilic esophagitis a cause of noncardiac chest pain; the role of endoscopy in the evaluation of eosinophilic esophagitis; and whether response to proton pump inhibitor therapy can distinguish eosinophilic esophagitis from gastroesophageal reflux disease.

The following paper on gastroesophageal reflux disease (GERD) and Barrett's esophagus (BE) includes commentaries on defining esophageal landmarks; new techniques for evaluating upper esophageal sphincter (UES) tone; differential diagnosis of GERD, BE, and hiatal hernia (HH); the use of high‐resolution manometry for evaluation of reflux; the role of fundic relaxation in reflux; the use of 24‐h esophageal pH–impedance testing in differentiating acid from nonacid reflux and its potential inclusion in future Rome criteria; classification of endoscopic findings in GERD; the search for the cell origin that generates BE; and the relationship between BE, Barrett's carcinoma, and obesity.