Citations

ObjectiveDisease relapses are frequent in antineutrophil cytoplasmic antibody–associated vasculitis (AAV). This study was undertaken to evaluate outcomes in patients with AAV who are re‐treated with rituximab (RTX) and prednisone for severe disease relapses.MethodsThe Rituximab in AAV trial was a randomized, double‐blind, placebo‐controlled trial comparing the rates of remission induction among patients treated with RTX (n = 99) and patients treated with cyclophosphamide (CYC) followed by azathioprine (AZA) (n = 98). Prednisone was tapered to discontinuation after 5.5 months. After remission was achieved, patients who experienced a severe disease relapse between months 6 and 18 were eligible to receive RTX and prednisone on an open‐label basis according to a prespecified protocol. Investigators remained blinded with regard to the original treatment assignment.ResultsTwenty‐six patients received RTX for disease relapse after remission had initially been achieved with their originally assigned treatment. Fifteen of these patients were initially randomized to receive RTX and 11 to receive CYC/AZA. Thirteen (87%) of the patients originally assigned to receive RTX and 10 (91%) originally assigned to receive CYC/AZA achieved remission again with open‐label RTX (an overall percentage of 88%). In half of the patients treated with open‐label RTX, prednisone could be discontinued entirely. Patients in this cohort experienced fewer adverse events compared to the overall study population (4.7 adverse events per patient‐year versus 11.8 adverse events per patient‐year).ConclusionRe‐treatment of AAV relapses with RTX and glucocorticoids appears to be a safe and effective strategy, regardless of previous treatment.

Background— Exercise intolerance is a hallmark of heart failure, but factors associated with impaired exercise capacity in heart failure with preserved ejection fraction are unclear. We hypothesized that in heart failure with preserved ejection fraction, the severity of resting ventricular and vascular dysfunction are associated with impairment in exercise tolerance as assessed by peak oxygen consumption. Methods and Results— Subjects with heart failure with preserved ejection fraction enrolled in the PhosphodiesteRasE-5 Inhibition to Improve CLinical Status And EXercise Capacity in Diastolic Heart Failure (RELAX) clinical trial (n=216) underwent baseline Doppler echocardiography, cardiopulmonary exercise testing, and cardiac MRI. RELAX participants were elderly (median age 69 years) and 48% were women. Ejection fraction (60%) and stroke volume (77 mL) were normal, while diastolic dysfunction (medial E / e ′, 16; deceleration time, 185 ms; left atrial volume, 44 mL/m 2 ) and increased arterial load (arterial elastance, 1.51 mm Hg/mL) were evident. Peak oxygen consumption was reduced (11.7 mLkg −1 min −1 , 1141 mL/min) and age, sex, body mass index, hemoglobin, and chronotropic response collectively explained 64% of the variance in raw peak oxygen consumption (mL/min). After adjustment for these variables, left ventricular structure (diastolic dimension [1.5%, P =0.008] and left ventricular mass [1.6%, P =0.008]), resting stroke volume (2.0%, P =0.002), left ventricular diastolic dysfunction (deceleration time [0.9%, P =0.03] and E / e ′ [1.4%, P =0.009]), and arterial function (arterial elastance [2.1%, P =0.002] and systemic arterial compliance [1.5%, P =0.007]), each explained only a small additional portion of the variance in peak oxygen consumption. Conclusions— In heart failure with preserved ejection fraction, potentially modifiable factors (obesity, anemia, and chronotropic incompetence) are strongly associated with exercise capacity, whereas resting measures of ventricular and vascular structure and function are not. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00763867

ABSTRACTIntroduction: The primary aim of this investigation was to determine whether use of write‐zoom magnification affects sonographically determined cross‐sectional area (CSA) of peripheral nerves. Methods: CSAs of the median (MN) and posterior interosseous (PIN) nerves were measured in 22 limbs from 11 asymptomatic volunteers using both standard imaging and write‐zoom magnification. CSA measurements were repeated on the same images 1 week later. Results: The average CSA of write‐zoomed images for the MN was significantly larger at both measurement sessions (week 1: 11.1 mm2 write‐zoom vs. 10.0 mm2 standard, P = 0.019; week 2: 11.8 mm2 vs. 10.4 mm2, P = 0.023). Similar differences were noted for the PIN (week 1: 2.3 mm2 vs. 1.9 mm2, P = 0.002; week 2: 2.5 mm2 vs. 1.9 mm2, P = 0.001). Conclusions: Write‐zoom magnification may significantly increase the measured CSA of peripheral nerves. These changes appear to be more substantial when smaller nerves are measured. Muscle Nerve 51: 30–34, 2015

Abstract Androgen has been implicated as a negative regulator of host immune function and a factor contributing to the gender dimorphism of autoimmunity. Conversely, androgen deprivation has been suggested to potentiate male host immunity. Studies have shown that removal of androgen in postpubertal male mice produces an increase in size and cellularity of primary and peripheral lymphoid organs, and enhances a variety of immune responses. Yet, few details are known about the effect of androgen removal on T cell-mediated immunity. In this study, we demonstrate two pronounced and independent alterations in T cell immunity that occur in response to androgen deprivation, provided by castration, in postpubertal male mice. First, we show that levels of T cells in peripheral lymphoid tissues of mice are increased by androgen deprivation. Second, T cells from these mice transiently proliferate more vigorously to TCR- and CD28-mediated costimulation as well as to Ag-specific activation. In addition, androgen deprivation accelerates normalization of host T and B cell levels following chemotherapy-induced lymphocyte depletion. Such alterations induced by androgen deprivation may have implications for enhancing immune responses to immunotherapy and for accelerating the recovery of the immune system following chemotherapy.

Abstract Adoptive γδ T cell immunotherapy has moved briskly into clinical trials prompted by several small studies suggesting abundant accumulation of γδ T cells within renal cell carcinoma (RCC). In this study, we re-examined levels of γδ T cells within RCC tumors and correlated levels of these cells with pathologic features and outcome associated with this form of cancer. Tissues from 248 consecutive clear cell RCC tumors obtained from 2000 to 2003 were stained and quantified for total CD3+ and γδ T cells per mm2. Wilcoxon rank sum and Kruskal-Wallis tests were used to evaluate associations between T cell amounts and prognostic factors (age, gender, tumor size, stage, grade, tumor necrosis). Cox models were used to assess associations with RCC-specific death. Median numbers of total CD3+ and γδ T cells were 281/mm2 (interquartile range (IQR): 149–536) and 2.6/mm2 (IQR: 1.3–4.6), respectively. The median percentage of CD3+ T cells that were γδ T cells was 1.0% (IQR: 0.4–1.9). This low percentage of intratumoral γδ T cells was diluted even further with rising CD3+ T cell infiltration. Percentages of γδ T cells were not associated with even one single clinicopathologic feature examined. Median follow-up for this study was 3.1 years (48 patients died of RCC) and Cox analysis failed to demonstrate that γδ T cells (hazard ratio = 1.02, p = 0.25) were predictive of RCC-specific death. γδ T cells are rare and not recruited nor expanded within RCC tumors. Percentages of γδ T cells fail to correlate with any prognostic features of RCC nor specific death. As such, the role of γδ T cells in RCC immunobiology remains questionable.

Object The clinical success rates of anterior cervical discectomy and fusion (ACDF) procedures are substantially reduced as more cervical levels are included in the fusion procedure. One method that has been proposed as an adjunctive technique for multilevel ACDF is the placement of screws across the facet joints (“transfacet screws”). However, the biomechanical stability imparted by transfacet screw placement (either unilaterally or bilaterally) has not been reported. Therefore, the purpose of this study was to determine the acute stability conferred by implementation of unilateral and bilateral transfacet screws to an ACDF construct. Methods Eight C2–T1 fresh-frozen human cadaveric spines (3 female and 5 male; mean age 50 years) were tested. Three different instrumentation variants were performed on cadaveric cervical spines across C4–7: 1) ACDF with an intervertebral spacer and standard plate/screw instrumentation; 2) ACDF with an intervertebral spacer and standard plate/screw instrumentation with unilateral facet screw placement; and 3) ACDF with an intervertebral spacer and standard plate/screw instrumentation with bilateral facet screw placement. Kinetic ranges of motion in flexion-extension, lateral bending, and axial rotation at 1.5 Nm were captured after each of these procedures and were statistically analyzed for significance. Results All 3 fixation scenarios produced statistically significant reductions (p < 0.05) in all 3 bending planes compared with the intact condition. The addition of a unilateral facet screw to the ACDF construct produced significant reductions at the C4–5 and C6–7 levels in lateral bending and axial rotation but not in flexion-extension motion. Bilateral facet screw fixation did not produce any statistically significant decreases in flexion-extension motion compared with unilateral facet screw fixation. However, in lateral bending, significant reductions at the C4–5 and C5–6 levels were observed with the addition of a second facet screw. The untreated, adjacent levels (C2–3, C3–4, and C7–1) did not demonstrate significant differences in range of motion. Conclusions The data demonstrated that adjunctive unilateral facet screw fixation to an ACDF construct provides significant gains in stability and should be considered a potential option for increasing the likelihood for obtaining a successful arthrodesis for multilevel ACDF procedures.

Objective To evaluate the horizontal and vertical stability of the quadrangular Le Fort I in patients with congenital cleft lip and palate. Design Prospective longitudinal study. Patients A total of 15 congenital cleft lip and palate patients treated with the maxillary quadrangular Le Fort I were enrolled. Intervention Lateral cephalometric radiographic examinations were obtained preoperatively, early postoperatively, and late postoperatively for four dental and skeletal landmarks. A questionnaire regarding patients' satisfaction with treatment and functional/cosmetic outcomes (airway, speech, mastication) was administered. Main Outcome Measures Surgical horizontal and vertical movement, late postsurgical horizontal and vertical movement, and surgical and postsurgical movement in relation to age and cleft type were evaluated using Spearman correlation coefficients, Wilcoxon signed rank tests, and Mann-Whitney tests. Results Surgical horizontal movements of all measured points showed significant changes. Significant differences of postsurgical horizontal movement were observed in younger patients versus adult patients. Significant differences of postsurgical horizontal movement were observed in unilateral cleft patients versus bilateral cleft patients. A high percentage of patients showed significant functional improvement in nasal airflow, speech, mastication, temporomandibular joint function, and mouth versus nose breathing. Conclusions The quadrangular Le Fort I is a functionally stable and a surgically predictable procedure for cleft lip and palate patients who present with midface deficiency. Patients under the age of 18 at the time of the osteotomy had a higher relapse rate than patients over 18 years of age. Younger patients who need surgery should be advised regarding the increased risk of skeletal relapse. Patients' satisfaction was high in all aesthetic- and function-related items on the questionnaire.