Citations

OBJECT While extent of resection has been shown to correlate with outcomes after myxopapillary ependymoma (MPE) resection, the effect of capsular violation has not been well studied. The role of adjuvant radiation also remains controversial. In this paper the authors' goals were to evaluate outcomes following resection of MPE based on intraoperative capsular violation and to explore the role of adjuvant radiotherapy in cases of capsular violation. METHODS A retrospective review of patients undergoing resection of MPE at 2 academic institutions between 1990 and 2013 was performed. Cases with dissemination at presentation, less than 12 months of follow-up, or incomplete records were excluded. Extent of resection was defined as en bloc if all visible tumor was removed without capsular violation, gross-total resection (GTR) if all visible tumor was removed, but with capsular violation, and subtotal resection (STR) if a known residual was left at the time of surgery. Postoperative MR images were reviewed to confirm the extent of resection. Primary outcomes were progression-free survival (PFS) and overall recurrence rates. The effects of extent of resection, capsular violation, and adjuvant radiotherapy on recurrence rates and PFS were analyzed using Kaplan-Meier statistics. Associations between recurrence and preoperative variables were evaluated using Fisher exact methods and t-tests where appropriate. RESULTS Of the 107 patients reviewed, 58 patients (53% were male) met inclusion criteria. The mean age at surgery was 40.8 years (range 7–68 years). The median follow-up was 51.5 months (range 12–243 months). Extent of resection was defined as en bloc in 46.5% (n = 27), GTR in 34.5% (n = 20), and STR in 18.9% (n = 11). No recurrences were noted in the en bloc group, compared with 15% (n = 3) and 45% (n = 5) in the GTR and STR groups. En bloc resection was achieved most frequently in tumors involving the conus. Twelve patients (20%) underwent adjuvant radiotherapy following either STR or GTR. The overall recurrence rate was 13.8% (n = 8), and the 5-year PFS was 81%. Capsular violation was associated with a higher recurrence rate (p = 0.005). Adjuvant radiotherapy showed a nonsignificant trend of lower recurrence rates (16.7% vs 31.6%, p = 0.43) and longer PFS at 5 years (83.3% vs 49.9%, p = 0.16) in cases of capsular violation. CONCLUSIONS A strong correlation between capsular violation and recurrence was found following removal of MPE and should be assessed when defining extent of resection in future studies. Although the use of adjuvant radiotherapy in cases of capsular violation showed a trend toward improved PFS, further investigation is needed to establish its role as salvage therapy also appears to be effective at halting disease progression.

Aims Prognostication and treatment selection for cardiac amyloidosis requires accurate amyloid typing. The aim of this study was to investigate the utility of histomorphology for predicting type. Methods and results Autopsy cases with cardiac amyloidosis (1998–2010) were typed by the use of mass spectrometry‐based proteomics. Deposition patterns were correlated with amyloid type. Among 108 decedents (mean age 75 years; 69% men), 107 had a single type, including transthyretin (ATTR) (60 cases), amyloid light chain (AL) (32 λ; 12 κ), amyloid A (AA) (two), and apolipoprotein AIV (AApoAIV) (one). Interstitial deposition was more extensive in AL amyloidosis cases than in ATTR cases [odds ratio (OR) 6.8, P = 0.0004]. Histomorphological patterns of interstitial deposition were mixed in 61% of AL amyloidosis cases and in 61% of ATTR cases, but diffuse pericellular deposits favoured AL amyloidosis (OR 10.7, P = 0.0001), nodular deposits favoured ATTR (OR 3.1, P = 0.0229), and discrete pericellular deposits tended to partially favour ATTR (OR 1.7, P = 0.1970). Arterial and venous deposits each favoured AL amyloidosis (OR ranging from 9.3 to 192.0, P‐value ranging from 0.0022 to <0.0001), and were severe in AL amyloidosis. Endocardial deposits favoured AL amyloidosis (OR 46.3, P < 0.0001) and were also more severe in AL amyloidosis. Conclusions The extent and distribution of cardiac amyloidosis strongly correlate with amyloid type, suggesting fundamental differences in the pathobiology of deposition. The tendency for mixed patterns to occur limits the practicality and accuracy of using histopathology for amyloid typing.

Trafficking from bedside to bench Typically in translational research, a discovery in cell or molecular biology is later exploited to improve patient care. Occasionally, information flows in the opposite direction. Lo et al. found that patients with an autoimmune disorder caused by deficiency of a protein called LRBA responded dramatically to the drug abatacept (see the Perspective by Sansom). Abatacept contains a segment of a potent inhibitory immune receptor, CTLA4. Experiments prompted by this observation revealed the relationship between the two proteins: LRBA controls the intracellular trafficking and degradation of CTLA4. This information may further improve patient care, because other clinically approved drugs have the desired mechanism of action with potentially fewer side effects. Science , this issue p. 436 ; see also p. 377

Significance During branching morphogenesis of the developing lung, it is generally thought that a spatial template of biochemical cues determines the airway branching pattern. Here, however, we demonstrate that physical mechanisms can control the pattern of airway branching. Using a combination of 3D culture experiments and theoretical modeling, we show that a growth-induced physical instability initiates the formation of new epithelial branches. Tuning epithelial growth rate controls the dominant wavelength of the instability, and thereby the branching pattern. These findings emphasize the role of mechanical forces during morphogenesis and indicate that lung development is not a closed genetic system. Physical cues also regulate the spatially patterned cell behaviors that underlie organ assembly in the embryo.

Background: The medial collateral (MCL) and anterior cruciate ligaments (ACL) are, respectively, the primary and secondary ligamentous restraints against knee abduction, which is a component of the valgus collapse often associated with ACL rupture during athletic tasks. Despite this correlation in function, MCL ruptures occur concomitantly in only 20% to 40% of ACL injuries. Hypothesis/Purpose: The purpose of this investigation was to determine how athletic tasks load the knee joint in a manner that could lead to ACL failure without concomitant MCL failure. It was hypothesized that (1) the ACL would provide greater overall contribution to intact knee forces than the MCL during simulated motion tasks and (2) the ACL would show greater relative peak strain compared with the MCL during simulated motion tasks. Study Design: Controlled laboratory study. Methods: A 6-degrees-of-freedom robotic manipulator articulated 18 cadaveric knees through simulations of kinematics recorded from in vivo drop vertical jump and sidestep cutting tasks. Specimens were articulated in the intact-knee and isolated-ligament conditions. After simulation, each ACL and MCL was failed in uniaxial tension along its fiber orientations. Results: During a drop vertical jump simulation, the ACL experienced greater peak strain than the MCL (6.1% vs 0.4%; P < .01). The isolated ACL expressed greater peak anterior force (4.8% vs 0.3% body weight; P < .01), medial force (1.6% vs 0.4% body weight; P < .01), flexion torque (8.4 vs 0.4 N·m; P < .01), abduction torque (2.6 vs 0.3 N·m; P < .01), and adduction torque (0.5 vs 0.0 N·m; P = .03) than the isolated MCL. During failure testing, ACL specimens preferentially loaded in the anteromedial bundle failed at 637 N, while MCL failure occurred at 776 N. Conclusion: During controlled physiologic athletic tasks, the ACL provides greater contributions to knee restraint than the MCL, which is generally unstrained and minimally loaded. Clinical Relevance: Current findings support that multiplanar loading during athletic tasks preferentially loads the ACL over the MCL, leaving the ACL more susceptible to injury. An enhanced understanding of joint loading during in vivo tasks may provide insight that enhances the efficacy of injury prevention protocols.

AbstractThis analysis was performed to create a scoring system to estimate the survival of patients with non‐small cell lung cancer (NSCLC). Data from 1274NSCLCpatients were analyzed to create and validate a scoring system. Univariate (UV) and multivariate (MV) Cox models were used to evaluate the prognostic importance of each baseline factor. Prognostic factors that were significant on bothUVandMVanalyses were used to develop the score. These included quality of life, age, performance status, primary tumor diameter, nodal status, distant metastases, and smoking cessation. The score for each factor was determined by dividing the 5‐year survival rate (%) by 10 and summing these scores to form a total score.MVmodels and the score were validated using bootstrapping with 1000 iterations from the original samples. The score for each prognostic factor ranged from 1 to 7 points with higher scores reflective of better survival. Total scores (sum of the scores from each independent prognostic factor) of 32–37 correlated with a 5‐year survival of 8.3% (95%CI = 0–17.1%), 38–43 correlated with a 5‐year survival of 20% (95%CI = 13–27%), 44–47 correlated with a 5‐year survival of 48.3% (95%CI = 41.5–55.2%), 48–49 correlated to a 5‐year survival of 72.1% (95%CI = 65.6–78.6%), and 50–52 correlated to a 5‐year survival of 84.7% (95%CI = 79.6–89.8%). The bootstrap method confirmed the reliability of the score. Prognostic factors significantly associated with survival on bothUVandMVanalyses were used to construct a valid scoring system that can be used to predict survival ofNSCLCpatients. Optimally, this score could be used when counseling patients, and designing future trials.

Endogenous female sex hormones influence muscle sympathetic nerve activity (MSNA), a regulator of arterial blood pressure and important factor in hypertension development. Although ≈80% of American women report using hormonal contraceptives sometime during their life, the influence of combined oral contraceptives (OCs) on MSNA and systemic hemodynamics remains equivocal. The goal of this study was to determine whether women taking OCs have altered MSNA and hemodynamics (cardiac output and total peripheral resistance) at rest during the placebo phase of OC use compared with women with natural menstrual cycles during the early follicular phase. We retrospectively analyzed data from studies in which healthy, premenopausal women (aged 18–35 years) participated. We collected MSNA values at rest and hemodynamic measurements in women taking OCs (n=53; 25±4 years) and women with natural menstrual cycles (n=74; 25±4 years). Blood pressure was higher in women taking OCs versus those with natural menstrual cycles (mean arterial pressure, 89±1 versus 85±1 mm Hg, respectively; P =0.01), although MSNA was similar in both groups (MSNA burst incidence, 16±1 versus 18±1 bursts/100 heartbeats, respectively; P =0.19). In a subset of women in which detailed hemodynamic data were available, those taking OCs (n=33) had similar cardiac output (4.9±0.2 versus 4.7±0.2 L/min, respectively; P =0.47) and total peripheral resistance (19.2±0.8 versus 20.0±0.9 U, respectively; P =0.51) as women with natural menstrual cycles (n=22). In conclusion, women taking OCs have higher resting blood pressure and similar MSNA and hemodynamics during the placebo phase of OC use when compared with naturally menstruating women in the early follicular phase.