A contact binary satellite of the asteroid (152830) Dinkinesh.

Asteroids with diameters less than about 5 km have complex histories because they are small enough for radiative torques (that is, YORP, short for the Yarkovsky-O'Keefe-Radzievskii-Paddack effect)1 to be a notable factor in their evolution2. (152830) Dinkinesh is a small asteroid orbiting the Sun near the inner edge of the main asteroid belt with a heliocentric semimajor axis of 2.19 AU; its S-type spectrum3,4 is typical of bodies in this part of the main belt5. Here we report observations by the Lucy spacecraft6,7 as it passed within 431 km of Dinkinesh. Lucy revealed Dinkinesh, which has an effective diameter of only 720 m, to be unexpectedly complex. Of particular note is the presence of a prominent longitudinal trough overlain by a substantial equatorial ridge and the discovery of the first confirmed contact binary satellite, now named (152830) Dinkinesh I Selam. Selam consists of two near-equal-sized lobes with diameters of 210 m and 230 m. It orbits Dinkinesh at a distance of 3.1 km with an orbital period of about 52.7 h and is tidally locked. The dynamical state, angular momentum and geomorphologic observations of the system lead us to infer that the ridge and trough of Dinkinesh are probably the result of mass failure resulting from spin-up by YORP followed by the partial reaccretion of the shed material. Selam probably accreted from material shed by this event.

Estrogenic control of reward prediction errors and reinforcement learning.

Gonadal hormones act throughout the brain 1 , and nearly all neuropsychiatric disorders vary in symptom severity with hormonal fluctuations over the reproductive cycle, gestation, and perimenopause 2-4 . Yet the mechanisms by which hormones influence mental and cognitive processes are unclear. Exogenous estrogenic hormones modulate dopamine signaling in the nucleus accumbens core (NAcc) 5,6 , which instantiates reward prediction errors (RPEs) for reinforcement learning 7-16 . Here we show that endogenous estrogenic hormones enhance RPEs and sensitivity to previous rewards by regulating expression of dopamine reuptake proteins in the NAcc. We trained rats to perform a temporal wagering task with different reward states; rats adjusted how quickly they initiated trials across states, balancing effort against expected rewards. Dopamine release in the NAcc reflected RPEs that predicted and causally in-fluenced subsequent initiation times. When fertile, females more quickly adjusted their initiation times to match reward states due to enhanced dopaminergic RPEs in the NAcc. Proteomics revealed reduced expression of dopamine transporters in fertile stages of the reproductive cycle. Finally, genetic suppression of midbrain estrogen receptors eliminated hormonal modulation of behavior. Estrogenic hormones therefore control the rate of reinforcement learning by regulating RPEs via dopamine reuptake, providing a mechanism by which hormones influence neural dynamics for motivation and learning.

Balanced Nonopioid General Anesthesia With Lidocaine Is Associated With Lower Postoperative Complications Compared With Balanced Opioid General Anesthesia With Sufentanil for Cardiac Surgery With Cardiopulmonary Bypass: A Propensity Matched Cohort Study.

BACKGROUND: There are no data on the effect of balanced nonopioid general anesthesia with lidocaine in cardiac surgery with cardiopulmonary bypass. The main study objective was to evaluate the association between nonopioid general balanced anesthesia and the postoperative complications in relation to opioid side effects. METHODS: Patients undergoing cardiac surgery with cardiopulmonary bypass between 2019 and 2021 were identified. After exclusion of patients for heart transplantation, left ventricular assistance device, and off-pump surgery, we classified patients according to an opioid general balanced anesthesia or a nonopioid balanced anesthesia with lidocaine. The primary outcome was a collapsed composite of postoperative complications that comprise respiratory failure and confusion, whereas secondary outcomes were acute renal injury, pneumoniae, death, intensive care unit (ICU), and hospital length of stay. RESULTS: We identified 859 patients exposed to opioid-balanced general anesthesia with lidocaine and 913 patients exposed to nonopioid-balanced general anesthesia. Propensity score matching yielded 772 individuals in each group with balanced baseline covariates. Two hundred thirty-six patients (30.5%) of the nonopioid-balanced general anesthesia versus 186 patients (24.1%) presented postoperative composite complications. The balanced lidocaine nonopioid general anesthesia group was associated with a lower proportion with the postoperative complication composite outcome OR, 0.72 (95% CI, 0.58-0.92; P = .027). The number of patients with acute renal injury, death, and hospital length of stay did not differ between the 2 groups. CONCLUSIONS: A balanced nonopioid general anesthesia protocol with lidocaine was associated with lower odds of postoperative complication composite outcome based on respiratory failure and confusion.

Unravelling the genetics of non-random fertilization associated with gametic incompatibility.

In the dairy industry, mate allocation is dependent on the producer's breeding goals and the parents' breeding values. The probability of pregnancy differs among sire-dam combinations, and the compatibility of a pair may vary due to the combination of gametic haplotypes. Under the hypothesis that incomplete incompatibility would reduce the odds of fertilization, and complete incompatibility would lead to a non-fertilizing or lethal combination, deviation from Mendelian inheritance expectations would be observed for incompatible pairs. By adding an interaction to a transmission ratio distortion (TRD) model, which detects departure from the Mendelian expectations, genomic regions linked to gametic incompatibility can be identified. This study aimed to determine the genetic background of gametic incompatibility in Holstein cattle. A total of 283,817 genotyped Holstein trios were used in a TRD analysis, resulting in 422 significant regions, which contained 2075 positional genes further investigated for network, overrepresentation, and guilt-by-association analyses. The identified biological pathways were associated with immunology and cellular communication and a total of 16 functional candidate genes were identified. Further investigation of gametic incompatibility will provide opportunities to improve mate allocation for the dairy cattle industry.

Reproductive tract size and position score: Estimation of genetic parameters for a novel fertility trait in dairy cows.

The dairy industry is moving toward selecting animals with better fertility to decrease the economic losses linked to reproductive issues. The reproductive tract size and position score (SPS) was recently developed in physiological studies as an indicator of pregnancy rate and the number of services to conception. Cows are scored as SPS 1, 2, or 3 based on the size of their reproductive tract and its position in the pelvis, as determined by transrectal palpation. The objective of this study was to estimate genetic parameters for SPS to assess its potential as a novel fertility trait. Phenotypes were collected at the University of British Columbia's research herd from 2017 to 2020, consisting of 3,247 within- and across-lactation SPS records from 490 Holstein cows. A univariate animal model was used to estimate the variance components for SPS. Both threshold and linear models were fit under a Bayesian approach and the results were compared using the Spearman rank correlation (r) between the estimated breeding values. The 2 models ranked the animals very similarly (r = 0.99), and the linear model was selected for further analysis. Genetic correlations with other currently evaluated traits were estimated using a bivariate animal model. The posterior means (± posterior standard deviation) for heritability and repeatability within- and across-lactation were 0.113 (± 0.013), 0.242 (± 0.012), and 0.134 (± 0.014), respectively. The SPS showed null correlations with production traits and favorable correlations with traditional fertility traits, varying from -0.730 (nonreturn rate) to 0.931 (number of services). Although preliminary, these results are encouraging because SPS seems to be more heritable than and strongly genetically correlated with number of services, nonreturn rate, and first service to conception, indicating potential for effective indirect selection response on these traits from SPS genetic selection. Therefore, further studies with larger data sets to validate these findings are warranted.

Rational development and evaluation of novel formulations for urinary health.

OBJECTIVE: Urinary tract infections (UTI) among women form a substantial part of medical practice and both patients and medical professionals have an interest in non-antibiotic treatments and preventative measures. This research provides preliminary data on a multi-functional composition, DAPAD, which explored several biologic activities of relevance to UTI. STUDY DESIGN: This formulation included D-mannose, citric acid, three prebiotic compounds, and extracts of dandelion and astragalus. Studies performed employed 4 bacterial strains that have relevance to UTI including E. coli, Proteus mirabilis, Streptococcus agalactiae and Enterococcus faecalis. RESULTS: Key findings from in vitro studies included: DAPAD at full- and half-strength inhibited growth of all UTI bacteria. Evidence for D-mannose agglutination of E. coli was demonstrated. D-mannose also showed unexpected effects on bacterial membrane integrity with vital staining and modest growth restriction. We did not demonstrate growth inhibition by dandelion or astragalus extracts but the latter showed diminished cytokine elaboration by bladder epithelial cells. CONCLUSION: DAPAD is a multifunctional composition that may warrant further development as a UTI treatment or preventive if supported by clinical evaluation.

Vasopressor-Sparing Strategies in Patients with Shock: A Scoping-Review and an Evidence-Based Strategy Proposition.

Despite the abundant literature on vasopressor therapy, few studies have focused on vasopressor-sparing strategies in patients with shock. We performed a scoping-review of the published studies evaluating vasopressor-sparing strategies by analyzing the results from randomized controlled trials conducted in patients with shock, with a focus on vasopressor doses and/or duration reduction. We analyzed 143 studies, mainly performed in septic shock. Our analysis demonstrated that several pharmacological and non-pharmacological strategies are associated with a decrease in the duration of vasopressor therapy. These strategies are as follows: implementing a weaning strategy, vasopressin use, systemic glucocorticoid administration, beta-blockers, and normothermia. On the contrary, early goal directed therapies, including fluid therapy, oral vasopressors, vitamin C, and renal replacement therapy, are not associated with an increase in vasopressor-free days. Based on these results, we proposed an evidence-based vasopressor management strategy.

Pupillometry pain index decreases intraoperative sufentanyl administration in cardiac surgery: a prospective randomized study.

Pupillometry has proven effective for the monitoring of intraoperative analgesia in non-cardiac surgery. We performed a prospective randomized study to evaluate the impact of an analgesia-guided pupillometry algorithm on the consumption of sufentanyl during cardiac surgery. Fifty patients were included prior to surgery. General anesthesia was standardized with propofol and target-controlled infusions of sufentanyl. The standard group consisted of sufentanyl target infusion left to the discretion of the anesthesiologist. The intervention group consisted of sufentanyl target infusion based on the pupillary pain index. The primary outcome was the total intraoperative sufentanyl dose. The total dose of sufentanyl was lower in the intervention group than in the control group and (55.8 µg [39.7-95.2] vs 83.9 µg [64.1-107.0], p = 0.04). During the postoperative course, the cumulative doses of morphine (mg) were not significantly different between groups (23 mg [15-53] vs 24 mg [17-46]; p = 0.95). We found no significant differences in chronic pain at 3 months between the 2 groups (0 (0%) vs 2 (9.5%) p = 0.49). Overall, the algorithm based on the pupillometry pain index decreased the dose of sufentanyl infused during cardiac surgery.Clinical trial number: NCT03864016.

Agreement between different non-invasive methods of ventricular elastance assessment for the monitoring of ventricular-arterial coupling in intensive care.

Ventricular-arterial coupling is calculated as the arterial elastance to end systolic elastance ratio (EA/Ees). Although the gold standard is invasive pressure volume loop analysis, Chen method is the clinical reference non-invasive method for estimating end systolic elastance (Ees). Several simplified methods calculate Ees from the end systolic pressure to volume ratio (ESP/ESV). The objective of the present study was to determine whether ESP/ESV simplification can be used instead of the Chen formula to measure ventricular-arterial coupling and to monitor changes following therapeutic intervention. In this retrospective, single-center study, 3 non-invasive EA/Ees calculation methods were applied to 86 cardiac ICU patients. The Chen method was used as the reference method. Ees was also calculated according to method 1: Ees1 = 0.9 × SAP/ESV and method 2: Ees2= EA/(1/LVEF) - 1. EA was estimated as 0.9 × SAP/SV (mmHg ml-1). After simplification: EA/Ees1 = EA/Ees2 = (1/LVEF) - 1, with the stroke volume estimated as the product of the aortic velocity-time integral (VTIAo) and the aortic area or as the difference between the end diastolic volume (EDV) and the ESV. All patients received fluid infusion, norepinephrine, or dobutamine. At baseline, the concordance correlation coefficient with EA/EesChen was 0.13 [- 0.07; 0.31] for EA/Ees1 and 0.32 [0.19; 0.44] for EA/Ees2. Bias and limit of agreement were 0.28 [- 0.02; 0.36] and [- 5.8; 2.6] for EA/Ees1 and of 0.44 [0.31; 0.53] and [- 3.2; 2.6] for EA/Ees2. When used to follow variations in EA/Ees following therapeutic interventions, only 65% (for EA/Ees1) and 70% (for EA/Ees2) of measures followed the same trend as EA/EesChen. Our results do not support the use of ESP/ESV based method as substitute for Chen method to measure and assess changes in ventriculo-arterial coupling (EA/Ees) in cardiac intensive care patients. Further investigations are needed to establish the most reliable non-invasive method.

Complications in patients with intramedullary nails: a case series from a single Cambodian surgical clinic.

PURPOSE: Since its development in 1999, the SIGN nail has been used in over 190,000 surgeries spanning 55 countries. To date, however, evaluation of SIGN nail outcomes has been limited to small prospective studies or large retrospective studies using SIGN's online database. This study uses the experience of a single, independent Cambodian surgical clinic to characterize common complications, provide commentary on ways to reduce the risk of those complications, and determine whether several observed nail fractures were due to metallurgic defects. METHODS: Clinic medical records were queried to identify complications in patients with SIGN nails. Data was abstracted including age, sex, mechanism of injury, and latency between injury, primary implantation, and presentation with a complication. Two nails that fractured in vivo were analyzed by light microscopy, scanning electron microscopy, and polarized light microscopy after chemical etching. RESULTS: Fifty-four complications in 51 patients were identified. The most common complications were non-union (n = 26, 48%), infection (n = 16, 30%), flexion limitation (n = 11, 20%), nail fracture (n = 4, 7%), delayed union (n = 4, 7%), and malunion (n = 4, 7%). Other complications included broken or floating screws. Fractography revealed that two of the fractured nails most likely failed by fatigue followed by fast fracture at the site of non-union. We found no evidence of intrinsic nail defects. We identified multiple inconsistencies between SIGN's database and independent clinic records. CONCLUSIONS: Non-union and infection were common relative to all complications. Based on radiographic review, risk for non-union and malunion can be minimized by selecting an appropriate nail diameter, using multiple interlocking screws, and employing the correct implant and approach for fracture morphology when using SIGN nails. Nail fractures were unlikely to be caused by metallurgical flaws. Further study is necessary to determine the appropriate management of non-unions based on radiographic and clinical factors.

Role of corrosion in taper failure and head disassociation in total hip arthroplasty of a single design.

Modular junctions have been associated with corrosion in total hip arthroplasty. In a small number of cases, disassociation of the femoral head from the stem following gross wear of the taper has been reported. The purpose of this study was to investigate the role of corrosion in the development of mechanical changes leading to disassociation. Twenty-one retrieved stems and heads of one design previously reported with head disassociation were identified in an IRB-approved database. Components were scored for corrosion and measured for material loss. Stem alloy hardness was measured. Parametric and non-parametric statistics were performed (α < 0.05). Seven of twenty-one stems demonstrated gross material loss of the stem taper and head disassociation. The maximum linear depth (MLD) of material loss on stem tapers without dissociation and all head bores was 7.63 ± 6.04 and 63.76 ± 60.83 µm, respectively. Hardness of the stem material was statistically distinct, but similar to other stem materials. Results suggest material loss via corrosion at the head bore loosens the taper lock, allowing relative motion leading to abrasive wear of the stem taper. All cases of disassociation occurred at greater than 65 months with a minimum of 50 µm of loss at on the head bore. It may be warranted to survey patients with systems reporting head disassociation; for this system, including recalled heads, risk appears to begin after 6 years in vivo. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2996-3003, 2018.

The ABC transporter Rv1272c of Mycobacterium tuberculosis enhances the import of long-chain fatty acids in Escherichia coli.

Mycobacterium tuberculosis (Mtb), which causes tuberculosis, is capable of accumulating triacylglycerol (TAG) by utilizing fatty acids from host cells. ATP-binding cassette (ABC) transporters are involved in transport processes in all organisms. Among the classical ABC transporters in Mtb none have been implicated in fatty acid import. Since the transport of fatty acids from the host cell is important for dormancy-associated TAG synthesis in the pathogen, mycobacterial ABC transporter(s) could potentially be involved in this process. Based on sequence identities with a bacterial ABC transporter that mediates fatty acid import for TAG synthesis, we identified Rv1272c, a hitherto uncharacterized ABC-transporter in Mtb that also shows sequence identities with a plant ABC transporter involved in fatty acid transport. We expressed Rv1272c in E. coli and show that it enhances the import of radiolabeled fatty acids. We also show that Rv1272c causes a significant increase in the metabolic incorporation of radiolabeled long-chain fatty acids into cardiolipin, a tetra-acylated phospholipid, and phosphatidylglycerol in E. coli. This is the first report on the function of Rv1272c showing that it displays a long-chain fatty acid transport function.

The Pedicles Are Not the Densest Regions of the Lumbar Vertebrae: Implications for Bone Quality Assessment and Surgical Treatment Strategy.

STUDY DESIGN: Cadaver study. OBJECTIVE: To determine the bone density of lumbar vertebral anatomic subregions. Bone mineral density (BMD) is a major factor in osseous fixation construct strength. The standard region for implant fixation of the spine is the pedicle; however, other regions may be more viable options with higher bone quality. METHODS: Using computed tomography images, the spine was digitally isolated by applying a filter for adult bone. The spine model was separated into 5 lumbar vertebrae, followed by segmentation of each vertebra into 7 regions and determination of average Hounsfield units (HU). HU was converted to BMD with calibration phantoms of known BMD. RESULTS: Overall mean BMD in vertebral regions ranged from 172 to 393 mg/cm3 with the highest and lowest BMD in the lamina and vertebral body, respectively. Vertebral regions formed 3 distinct groups (P < .03). The vertebral body and transverse processes represent one group with significantly lower BMD than other regions. Spinous process, pedicles, and superior articular processes represent a second group with moderate BMD. Finally, inferior articular process (IAP) and lamina represent a third group with significantly higher BMD than other regions. CONCLUSIONS: Standard lumbar fusion currently uses the vertebral body and pedicles as primary locations for fixation despite their relatively low BMD. Utilization of posterior elements, especially the lamina and IAP, may be advantageous as a supplement to modern constructs or the primary site for fixation, possibly mitigating construct failures due to loosening or pullout.

Assessment of Corrosion, Fretting, and Material Loss of Retrieved Modular Total Knee Arthroplasties.

BACKGROUND: Modular junctions in total hip arthroplasties have been associated with fretting, corrosion, and debris release. The purpose of this study is to analyze damage severity in total knee arthroplasties of a single design by qualitative visual assessment and quantitative material loss measurements to evaluate implant performance and patient impact via material loss. METHODS: Twenty-two modular knee retrievals of the same manufacturer were identified from an institutional review board-approved database. Junction designs included tapers with an axial screw and tapers with a radial screw. Constructs consisted of 2 metal alloys: CoCr and Ti6Al4V. Components were qualitatively scored and quantitatively measured for corrosion and fretting. Negative values represent adhered material. Statistical differences were analyzed using sign tests. Correlations were tested with a Spearman rank order test (P < .05). RESULTS: The median volumetric material loss and the maximum linear depth for the total population were -0.23 mm3 and 5.84 µm, respectively. CoCr components in mixed metal junctions had higher maximum linear depth (P = .007) than corresponding Ti components. Fretting scores of Ti6Al4V alloy components in mixed metal junctions were statistically higher than the remaining groups. Taper angle did not correlate with material loss. CONCLUSION: Results suggest that CoCr components in mixed metal junctions are more vulnerable to corrosion than other components, suggesting preferential corrosion when interfacing with Ti6Al4V. Overall, although corrosion was noted in this series, material loss was low, and none were revised for clinical metal-related reaction. This suggests the clinical impact from corrosion in total knee arthroplasty is low.

Biomechanical demands on posterior fusion instrumentation during lordosis restoration procedures.

OBJECTIVE The goal of this study was to investigate the forces placed on posterior fusion instrumentation by 3 commonly used intraoperative techniques to restore lumbar lordosis: 1) cantilever bending; 2) in situ bending; and 3) compression and/or distraction of screws along posterior fusion rods. METHODS Five cadaveric torsos were instrumented with pedicle screws at the L1-5 levels. Specimens underwent each of the 3 lordosis restoration procedures. The pedicle screw pullout force was monitored in real time via strain gauges that were mounted unilaterally at each level. The degree of correction was noted through fluoroscopic imaging. The peak loads experienced on the screws during surgery, total demand on instrumentation, and resting loads after corrective maneuvers were measured. RESULTS A mean overall lordotic correction of 10.9 ± 4.7° was achieved. No statistically significant difference in lordotic correction was observed between restoration procedures. In situ bending imparted the largest loads intraoperatively with an average of 1060 ± 599.9 N, followed by compression/distraction (971 ± 534.1 N) and cantilever bending (705 ± 413.0 N). In situ bending produced the largest total demand and postoperative loads at L-1 (1879 ± 1064.1 and 487 ± 118.8 N, respectively), which were statistically higher than cantilever bending and compression/distraction (786 ± 272.1 and 138 ± 99.2 N, respectively). CONCLUSIONS In situ bending resulted in the highest mechanical demand on posterior lumbar instrumentation, as well as the largest postoperative loads at L-1. These results suggest that the forces generated with in situ bending indicate a greater chance of intraoperative instrumentation failure and postoperative proximal pedicle screw pullout when compared with cantilever bending and/or compression/distraction options. The results are aimed at optimizing correction and fusion strategies in lordosis restoration cases.

Fatigue failure of reverse shoulder humeral tray components of a single design.

BACKGROUND: Modularity in shoulder arthroplasty provides surgical flexibility and facilitates less-complex revision surgery. Modular designs must fit in the glenohumeral joint space, necessitating minimal thickness and careful material selection. The potential for fatigue fracture is higher, and fatigue fracture has been experienced by patients. The purpose of this study was to determine the impact of geometry and materials used for modular humeral trays from a single manufacturer. METHODS: We consecutively retrieved 8 humeral trays of nearly identical designs: 4 Ti-6Al-4V (Ti) and 4 CoCrMo (CoCr). Optical microscopy and scanning electron microscopy were used, along with metallurgical techniques. Finite element and fatigue analyses of the stresses at the humeral tray taper informed observation interpretation. RESULTS: Two Ti devices were revised for in vivo fracture. Scanning electron microscopy showed cracking in the other 2 Ti trays and no evidence of cracking in the CoCr components. A geometric difference in the CoCr devices resulted in a 25% decreased stress under simulated activities of daily living. Accounting for the tray material properties, the fatigue failure envelope ranged from 1000 to 1 million cycles for Ti and from 30,000 to >10 million cycles for CoCr. CONCLUSIONS: All Ti humeral tray retrievals fractured in vivo or were cracked at the taper fillet. No CoCr retrievals showed signs of cracking. Finite element and fatigue analyses predict a 10-fold lifetime increase for the CoCr devices compared with the Ti devices. This study shows that fatigue failure is possible for some reverse shoulder components and is likely exacerbated by fillet radius, tray thickness, and material choice.

Analysis of severely fractured glenoid components: clinical consequences of biomechanics, design, and materials selection on implant performance.

BACKGROUND: The longevity of total shoulder replacement is primarily limited by the performance of the ultrahigh-molecular-weight polyethylene (UHMWPE) glenoid component in vivo. Variations in glenoid design (conformity, thickness), biomechanics (joint kinematics), and UHMWPE material selection (sterilization, cross-linking) distinguish total shoulder replacements from hip and knee arthroplasty devices. These variables can lead to severe mechanical failures, including gross fracture. METHODS: Sixteen retrieved glenoids with severe fracture were analyzed. The explant cohort included 3 material groups (gamma-sterilized Hylamer; gamma-sterilized UHMWPE; and gas plasma-sterilized, remelted, highly cross-linked UHMWPE [HXL]) and a range of conformities (0- to 10-mm radial mismatch). Analysis included fractography (optical and scanning electron microscopy) and Fourier transform infrared spectroscopy for oxidative analysis. RESULTS: Fracture primarily occurred along the exterior rim for all 16 explants. Fourier transform infrared analysis and fractography revealed significant oxidative embrittlement for all gamma-sterilized glenoids. Fatigue striations and internal flaws were evident on the fracture surface of the HXL glenoid, with little oxidation detected. CONCLUSIONS: Fracture initiated at the external rim of all devices. Elevated oxidation levels and visible material distortion for representative gamma-sterilized conventional and Hylamer devices suggest oxidative embrittlement as a driving force for crack inception and subsequent fracture. Brittle fracture of theHXL glenoid resulted from a combination of elevated contact stress due to a nonconforming surface, an internal flaw, and reduced resistance to fatigue crack growth. This demonstrates that glenoid fracture associated with oxidation has not been eliminated with the advent of modern materials (HXL) in the shoulder domain. LEVEL OF EVIDENCE: Basic Science Study; Implant Retrieval Study.

Lenalidomide is safe and active in Waldenström macroglobulinemia.

Lenalidomide is manageable and effective in multiple myeloma, particularly in elderly patients. Surprisingly, the combination of lenalidomide with rituximab produced clinically significant anemia at 25 mg/day for 21/28 days, the highest possible dose, in Waldenström's Macroglobulinemia (WM). We aimed to determine the maximum tolerated dose (MTD) of single agent lenalidomide and determine its impact on WM. RV-WM-0426 is a multicenter dose escalation open label phase 1/2 study of lenalidomide in relapsed/refractory WM (RRWM). Lenalidomide was given orally 21/28 days per cycle for 1 year, at escalated dose of 15 to 20 mg during phase 1 to determine the MTD; the phase 2 part was conducted at the MTD. Seventeen RRWM patients were included. The MTD was established at 15 mg/day 21/28. By ITT analysis, the overall response rate was 29%. With a median follow-up of 36 months, median TTP was 16 months (95% CI 5.5-26), the 5-year OS was 91%. The most frequent adverse events ≥ grade 3 at 15 mg were 14% anemia and 43% neutropenia. The MTD of lenalidomide is 15 mg/day 21/28 days in RRWM. Lenalidomide is active in the treatment of RRWM and the safety profile appears manageable. Future studies may look into combinations of lenalidomide and continuous dosing.

Gender-specific associations between functional autonomy and physical capacities in independent older adults: results from the NuAge study.

BACKGROUND: Even with healthy and active aging, many older adults will experience a decrease in physical capacities. This decrease might be associated with diminished functional autonomy. However, little is known about the physical capacities associated with functional autonomy in older women and men. OBJECTIVE: This study aimed to examine gender-specific associations between functional autonomy and physical capacities in independent older women and men. METHODS: Secondary analyses were carried out using cross-sectional data from 652 women and 613 men who participated in the NuAge longitudinal study. The "functional autonomy measurement system" (SMAF) was used to evaluate functional autonomy. The physical capacities measured (tests used) were: biceps and quadriceps strength (Microfet dynamometer), grip strength (Martin vigorimeter), unipodal balance, changing position & walking (timed up and go), normal & fast walking (four-meter walking speed) and changing position (chair stand). Correlation and multiple linear regression analyses adjusted for age, depressive symptoms and body composition were performed. RESULTS: On average, participants were aged 73 years and had mild to moderate functional autonomy loss. In women, after controlling for age, depressive symptoms and body composition, greater functional autonomy was best explained by faster changing position & walking skills and superior biceps strength (R(2)=0.46; p<0.001). After controlling for depressive symptoms, faster changing position & walking skills and better unipodal balance best explained greater functional autonomy in men (R(2)=0.21; p<0.001). CONCLUSION: According to these results, physical capacities are moderately associated with functional autonomy among independent older adults, especially women.