Citations

PURPOSEPatients with indolent non-Hodgkin lymphoma typically respond well to first-line immunochemotherapy. At relapse, single-agent rituximab is commonly administered. Data suggest the immunomodulatory agent lenalidomide could increase the activity of rituximab.METHODSA phase III, multicenter, randomized trial of lenalidomide plus rituximab versus placebo plus rituximab was conducted in patients with relapsed and/or refractory follicular or marginal zone lymphoma. Patients received lenalidomide or placebo for 12 cycles plus rituximab once per week for 4 weeks in cycle 1 and day 1 of cycles 2 through 5. The primary end point was progression-free survival per independent radiology review.RESULTSA total of 358 patients were randomly assigned to lenalidomide plus rituximab (n = 178) or placebo plus rituximab (n = 180). Infections (63% v 49%), neutropenia (58% v 23%), and cutaneous reactions (32% v 12%) were more common with lenalidomide plus rituximab. Grade 3 or 4 neutropenia (50% v 13%) and leukopenia (7% v 2%) were higher with lenalidomide plus rituximab; no other grade 3 or 4 adverse event differed by 5% or more between groups. Progression-free survival was significantly improved for lenalidomide plus rituximab versus placebo plus rituximab, with a hazard ratio of 0.46 (95% CI, 0.34 to 0.62; P < .001) and median duration of 39.4 months (95% CI, 22.9 months to not reached) versus 14.1 months (95% CI, 11.4 to 16.7 months), respectively.CONCLUSIONLenalidomide improved efficacy of rituximab in patients with recurrent indolent lymphoma, with an acceptable safety profile.

AbstractBackgroundSevere primary graft dysfunction (PGD) is the leading cause of early death after heart transplant.AimTo examine the outcomes of heart transplant recipients who received venoarterial extracorporeal membrane oxygenation (VA‐ECMO) for severe PGD.MethodsWe reviewed electronic health records of adult patients who underwent heart transplant from November 2005 through June 2015. We defined severe PGD according to International Society for Heart and Lung Transplantation consensus statements.ResultsOf 1030 heart transplant patients, 31 (3%) had severe PGD and required VA‐ECMO. The mean (range) age was 59 (43‐69) years. Fifteen patients (48%) underwent prior sternotomy and 10 (32%) received a left ventricular assist device as a bridge to transplant. Severe PGD manifested as failure to wean from cardiopulmonary bypass in 20 patients (65%) and as severe hemodynamic instability in the immediate postoperative period in 10 (32%), including cardiac arrest in 3 (10%). Twenty‐five patients (81%) were successfully weaned from VA‐ECMO, and 19 (61%) were discharged; the other 12 (39%) died.ConclusionsAlthough VA‐ECMO is a common method for providing mechanical circulatory support to patients with PGD, multicenter studies are needed to assess factors associated with successful outcomes and improved survival of these patients.

PURPOSE Evidence-based treatments for metastatic, human epidermal growth factor receptor 2 (HER2)–positive breast cancer to the CNS are limited. We previously reported modest activity of neratinib monotherapy for HER2-positive breast cancer brain metastases. Here we report the results from additional study cohorts. PATIENTS AND METHODS Patients with measurable, progressive, HER2-positive brain metastases (92% after receiving CNS surgery and/or radiotherapy) received neratinib 240 mg orally once per day plus capecitabine 750 mg/m 2 twice per day for 14 days, then 7 days off. Lapatinib-naïve (cohort 3A) and lapatinib-treated (cohort 3B) patients were enrolled. If nine or more of 35 (cohort 3A) or three or more of 25 (cohort 3B) had CNS objective response rates (ORR), the drug combination would be deemed promising. The primary end point was composite CNS ORR in each cohort separately, requiring a reduction of 50% or more in the sum of target CNS lesion volumes without progression of nontarget lesions, new lesions, escalating steroids, progressive neurologic signs or symptoms, or non-CNS progression. RESULTS Forty-nine patients enrolled in cohorts 3A (n = 37) and 3B (n = 12; cohort closed for slow accrual). In cohort 3A, the composite CNS ORR = 49% (95% CI, 32% to 66%), and the CNS ORR in cohort 3B = 33% (95% CI, 10% to 65%). Median progression-free survival was 5.5 and 3.1 months in cohorts 3A and 3B, respectively; median survival was 13.3 and 15.1 months. Diarrhea was the most common grade 3 toxicity (29% in cohorts 3A and 3B). Neratinib plus capecitabine is active against refractory, HER2-positive breast cancer brain metastases, adding additional evidence that the efficacy of HER2-directed therapy in the brain is enhanced by chemotherapy. For optimal tolerance, efforts to minimize diarrhea are warranted.

The ability to regulate behavior in service of long-term goals is a widely studied psychological construct known as self-regulation. This wide interest is in part due to the putative relations between self-regulation and a range of real-world behaviors. Self-regulation is generally viewed as a trait, and individual differences are quantified using a diverse set of measures, including self-report surveys and behavioral tasks. Accurate characterization of individual differences requires measurement reliability, a property frequently characterized in self-report surveys, but rarely assessed in behavioral tasks. We remedy this gap by ( i ) providing a comprehensive literature review on an extensive set of self-regulation measures and ( ii ) empirically evaluating test–retest reliability of this battery in a new sample. We find that dependent variables (DVs) from self-report surveys of self-regulation have high test–retest reliability, while DVs derived from behavioral tasks do not. This holds both in the literature and in our sample, although the test–retest reliability estimates in the literature are highly variable. We confirm that this is due to differences in between-subject variability. We also compare different types of task DVs (e.g., model parameters vs. raw response times) in their suitability as individual difference DVs, finding that certain model parameters are as stable as raw DVs. Our results provide greater psychometric footing for the study of self-regulation and provide guidance for future studies of individual differences in this domain.

A 60-year-old male patient presented to an outside hospital with severe cardiogenic shock. A triple bridge of mechanical circulatory support was utilized to transition him to heart transplantation listing. Initially, coronary artery disease was percutaneously treated and Impella 2.5 was used as mechanical circulatory support for 5 days followed by the second Impella 2.5 for 4 days. Veno-arterial extracorporeal membrane oxygenation support was deployed for 16 days. This was exchanged for HeartWare ventricular assist device support as the third stage of mechanical circulatory support to heart transplantation listing. The patient experienced acute renal failure which was managed by continuous renal replacement therapy then intermittent hemodialysis with eventual complete recovery of the renal function. He was discharged home 56 days after HeartWare ventricular assist device implantation with stable hemodynamic, intact neurologic status and fully recovered renal function. Currently, the patient is listed for heart transplantation.

A true left middle lobe (lingular lobe) is very rare, but accessory fissures can be unexpectedly found at transplant. Pre-transplant knowledge of accessory lobes and accessory fissures aids in preparation, transplantation, postoperative assessment, and long-term care planning; however, fissures and accessory lobes can be overlooked by radiologists during routine evaluation of images. Here, we describe the first left lung with three anatomical lobes that was successfully transplanted into a 63-year-old patient with idiopathic pulmonary fibrosis. This anatomical variation did not change our surgical plan or technique, but surgeons should be aware of this possibility, especially when planning postoperative care.

Background: Two-stage exchange is the most common form of treatment of chronic infection following total hip arthroplasty (THA). We examined the prevalence of, and risk factors associated with, hip instability following 2-stage exchange as well as the fate of reimplanted hip prostheses that dislocated. Methods: Data on 515 2-stage exchange THAs performed between 2000 and 2014 at a single institution were retrospectively reviewed. Risk factors for instability as well as postoperative reoperations and revisions were analyzed. The impact of dislocation on these outcomes was evaluated as well. The mean age at the time of reimplantation was 65 years, and the mean duration of follow-up was 5 years (range, 2 to 15 years). Results: Dislocation occurred in 52 hips following reimplantation (cumulative probability = 8.9% at 1 year). There was a higher risk of instability in women (hazard ratio [HR] = 1.8, p = 0.038) and in those who had a history of dislocation prior to the 2-stage revision (HR = 5.1, p < 0.001). Younger age, body mass index, number of previous operations, spacer type, surgical approach, use of a constrained liner, femoral head diameter, and persistent or recurrent infection were not found to be significant risk factors. Patients with an absent or ununited greater trochanter or abductor deficiency also had a higher rate of dislocation (HR = 30, p < 0.001), as did patients who underwent reimplantation with a megaprosthesis (HR = 6.0, p < 0.001). The risk of additional reoperations (HR = 121, p < 0.001) and revision surgery (HR = 13, p < 0.001) was significantly higher in patients who experienced a dislocation after the 2-stage exchange. Conclusions: Dislocation after 2-stage exchange THA continues to be a major concern, with the 1-year cumulative probability found to be 9% in the present study. Female sex, a history of dislocation, an absent or ununited greater trochanter or abductor deficiency, and reimplantation with a megaprosthesis were identified as risk factors for dislocation. There is a remarkable 121-fold increase in the rate of reoperations and a 13-fold increase in the rate of revisions in hips that dislocated after 2-stage exchange THA. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.