Citations

Abstract Checkpoint inhibitors targeted at programmed cell death-1 receptor (PD-1) and its ligand (PD-L1) can result in significant benefit to a small proportion of patients with cancer, including those with tumors of the stomach and gastroesophageal junction. These drugs are now approved for several solid tumors, including the recent accelerated approval of pembrolizumab for gastroesophageal adenocarcinomas in the third-line setting and beyond based on the KEYNOTE-059 phase II trial. Data are lacking on the efficacy of chemotherapy after progression on PD-1 blockade in metastatic gastroesophageal adenocarcinoma. This report describes the exceptional response of two patients who received ramucirumab plus paclitaxel after progressive disease on pembrolizumab. This early clinical observation suggests that the sequence of administration of PD-1 blockade and chemotherapy may be important in this disease.

ObjectiveDue to an aging population, increasing prevalence of rheumatic disease, and a growing supply and demand gap of rheumatology providers, innovative solutions are needed to meet the needs of persons with rheumatic conditions. Nurse practitioners (NPs) and physician assistants (PAs) have been identified as a group of health professionals who could help address the workforce shortage. The Executive Committee of the Association of Rheumatology Health Professionals (ARHP), a division of the American College of Rheumatology (ACR), charged a task force to facilitate the preparation of NPs/PAs to work in a rheumatology practice setting.MethodsThe task force, consisting of private practice and academic rheumatologists, and NPs and PAs, from both adult and pediatric settings, conducted a needs assessment survey of current NPs and PAs to identify mechanisms for acquiring rheumatology knowledge. Through face‐to‐face and webinar meetings, and incorporating stakeholder feedback, the task force designed a rheumatology curriculum outline to enrich the training of new NPs and PAs joining rheumatology practice.ResultsInformed by the needs assessment data and stakeholders, an NP/PA rheumatology curriculum outline was developed and endorsed by the ACR Board of Directors for use by community‐based and academic rheumatology practices, whether pediatric or adult, who desire to add NPs and PAs to their practice setting.ConclusionAs rheumatology is facing workforce shortages, the ACR/ARHP rheumatology curriculum outline can be utilized to train NPs and PAs and create more efficient integration of NPs and PAs into rheumatology practice.

BACKGROUNDEarly treatment failure (ETF) in follicular lymphoma (FL), defined as relapse or progression within 2 years of frontline chemoimmunotherapy, is a newly recognized marker of poor survival and identifies a high‐risk group of patients with an expected 5‐year overall survival (OS) rate of approximately 50%. Transplantation is an established option for relapsed FL, but its efficacy in this specific ETF FL population has not been previously evaluated.METHODSThis study compared autologous hematopoietic stem cell transplantation (auto‐HCT) with either matched sibling donor (MSD) or matched unrelated donor (MUD) allogeneic hematopoietic cell transplantation (allo‐HCT) as the first transplantation approach for patients with ETF FL (age ≥ 18 years) undergoing auto‐HCT or allo‐HCT between 2002 and 2014. The primary endpoint was OS. The secondary endpoints were progression‐free survival, relapse, and nonrelapse mortality (NRM).RESULTSFour hundred forty FL patients had ETF (auto‐HCT, 240; MSD hematopoietic stem cell transplantation [HCT], 105; and MUD HCT, 95). With a median follow‐up of 69 to 73 months, the adjusted probability of 5‐year OS was significantly higher after auto‐HCT (70%) or MSD HCT (73%) versus MUD HCT (49%; P = .0008). The 5‐year adjusted probability of NRM was significantly lower for auto‐HCT (5%) versus MSD (17%) or MUD HCT (33%; P < .0001). The 5‐year adjusted probability of disease relapse was lower with MSD (31%) or MUD HCT (23%) versus auto‐HCT (58%; P < .0001).CONCLUSIONSPatients with high‐risk FL, as defined by ETF, undergoing auto‐HCT for FL have low NRM and a promising 5‐year OS rate (70%). MSD HCT has lower relapse rates than auto‐HCT but similar OS. Cancer 2018;124:2541‐51. © 2018 American Cancer Society.

OBJECTIVEAneurysm growth is considered predictive of future rupture of intracranial aneurysms. However, how accurately neuroradiologists can reliably detect incremental aneurysm growth using clinical MRI is still unknown. The purpose of this study was to assess the agreement rate of detecting aneurysm enlargement employing generally used MRI modalities.METHODSThree silicone flow phantom models, each with 8 aneurysms of various sizes at different sites, were used in this study. The aneurysm models were identical except for an incremental increase in the sizes of the 8 aneurysms, which ranged from 0.4 mm to 2 mm. The phantoms were imaged on 1.5-T and 3-T MRI units with both time-of-flight (TOF) and contrast-enhanced MR angiography. Three independent expert neuroradiologists measured the aneurysms in a blinded manner using different measurement approaches. The individual and agreement detection rates of aneurysm enlargement among the 3 experts were calculated.RESULTSThe mean detection rate of any increase in any aneurysmal dimension was 95.7%. The detection rates of the 3 observers (observers A, B, and C) were 98.0%, 96.6%, and 92.7%, respectively (p = 0.22). The detection rates of each MRI modality were 91.3% using 1.5-T TOF, 97.2% using 1.5-T with Gd, 95.8% using 3.0-T TOF, and 97.2% using 3.0-T with Gd (p = 0.31). On the other hand, the mean detection rate for aneurysm enlargement was 54.8%. Specifically, the detection rates of observers A, B, and C were 49.0%, 46.1%, and 66.7%, respectively (p = 0.009). As the incremental enlargement value increased, the detection rate for aneurysm enlargement increased. The use of 1.5-T Gd improved the detection rate for small incremental enlargement (e.g., 0.4–1 mm) of the aneurysm (p = 0.04). The location of the aneurysm also affected the detection rate for aneurysm enlargement (p < 0.0001).CONCLUSIONSThe detection rate and interobserver agreement were very high for aneurysm enlargement of 0.4–2 mm. The detection rate for at least 1 increase in any aneurysm dimension did not depend on the choice of MRI modality or measurement protocol. Use of Gd improved the accuracy of measurement. Aneurysm location may influence the accuracy of detecting enlargement.

Key Points RP2D of PEV 20 mg/m2 in PEV/AZA combo did not alter toxicity profile of AZA; dose-limiting toxicities were transiently elevated AST/ALT. In treatment-naive older AML patients, the intent-to-treat ORR was 50%.

The source and fate of sulfoconjugated catecholamines present in plasma are not known. Sulfated norepinephrine has been shown to overflow together with free norepinephrine from a typical peripheral neuroeffector junction. Some released free norepinephrine is removed via the lymphatic system, but it is not known whether sulfated catecholamines are removed similarly. Serotonin, another biogenic amine, is released from the enterochromaffin cells into portal blood. The aims of the present study were to determine whether conjugated catecholamines and serotonin could be detected in thoracic duct lymph of dogs and to compare concentrations in lymph with those in samples of portal blood collected before and after the dogs were fed. A method is described for the extraction and purification of free and conjugated catecholamines and serotonin from lymph. In lymph and in plasma, there were similar concentrations of free (0.2-0.4 ng/ml) and conjugated (0.1-0.2 ng/ml) norepinephrine and of conjugated dopamine (0.2-1.0 ng/ml). The concentrations of free serotonin were much lower in lymph (0.1-0.2 ng/ml) than in portal blood (100-200 ng/ml). Small amounts of conjugated serotonin (0.1-0.4 ng/ml) were detected in lymph but were not detected in plasma. Feeding caused increases in concentration of conjugated dopamine in lymph and in plasma and small increases in the output of free norepinephrine and free and conjugated serotonin in lymph.