Emergent Management of Severe Hypothermia, Acidemia, and Coagulopathy in Operative Penetrating Ballistic Cranial Trauma.

Hypothermia in a trauma patient has been associated with increased morbidity and mortality and is more frequently seen in those sustaining traumatic brain injuries (TBIs). Acidosis is an important consequence of hypothermia that leads to derangements across the spectrum of the coagulation cascade. Here, we present a case of a 31-year-old male presented after suffering a right parietal penetrating ballistic injury with an associated subdural hematoma and 7 mm midline shift requiring decompressive craniectomy and external ventricular drain (EVD) placement in the setting of severe hypothermia (28°C) and acidosis (pH 7.12). With aggressive rewarming intraoperatively, the use of full-body forced-air warming, warmed IV fluids, and increasing the ambient room temperature, the patient's acidosis and hypothermia improved to pH 7.20 and 34°C. Despite these aggressive attempts to rewarm the patient, he developed coagulopathy in the setting of concurrent hypothermia and acidosis. This case highlights the importance of prompt reversal of hypothermia due to its potentially fatal effects, particularly in the setting of severe TBIs. We discuss the critical aspects of surgical management of the injury and anesthetic management of hypothermia, acidosis, and coagulopathy perioperatively.

A weak subducting slab at intermediate depths below northeast Japan.

Knowledge of the state of stress in subducting slabs is essential for understanding their mechanical behavior and the physical processes that generate earthquakes. Here, we develop a framework which uses a high-resolution focal mechanism catalog to determine the change in the position of the neutral plane before and after the M9 Tohoku-oki earthquake to determine that the deviatoric stress within the slab at intermediate depths must be very low (∼1 MPa). We show that by combining the static stress calculated from coseismic slip distributions with the stress orientations before and after the mainshock, we can determine the full deviatoric stress tensor within the subducting slab at intermediate depths. These results preclude earthquake source mechanisms that require large background driving stresses, favoring a mechanically weak subducting slab, thus providing quantitative constraints on the physical processes that generate intermediate-depth earthquakes.

A field-validated equilibrium passive sampler for the monitoring of per- and polyfluoroalkyl substances (PFAS) in sediment pore water and surface water.

A simple equilibrium passive sampler, consisting of water in an inert container capped with a rate-limiting barrier, for the monitoring of per- and polyfluoroalkyl substances (PFAS) in sediment pore water and surface water was developed and tested through a series of laboratory and field experiments. The objectives of the laboratory experiments were to determine (1) the membrane type that could serve as the sampler's rate-limiting barrier, (2) the mass transfer coefficient of environmentally relevant PFAS through the selected membrane, and (3) the performance reference compounds (PRCs) that could be used to infer the kinetics of PFAS diffusing into the sampler. Of the membranes tested, the polycarbonate (PC) membrane was deemed the most suitable rate-limiting barrier, given that it did not appreciably adsorb the studied PFAS (which have ≤8 carbons), and that the migration of these compounds through this membrane could be described by Fick's law of diffusion. When employed as the PRC, the isotopically labelled PFAS M2PFOA and M4PFOS were able to predict the mass transfer coefficients of the studied PFAS analytes. In contrast, the mass transfer coefficients were underpredicted by Br- and M3PFPeA. For validation, the PC-based passive samplers consisting of these four PRCs, as well as two other PRCs (i.e., M8PFOA and C8H17SO3-), were deployed in the sediment and water at a PFAS-impacted field site. The concentration-time profiles of the PRCs indicated that the samplers deployed in the sediment required at least 6 to 7 weeks to reach 90% equilibrium. If the deployment times are shorter (e.g., 2 to 4 weeks), PFAS concentrations at equilibrium could be estimated based on the concentrations of the PRCs remaining in the sampler at retrieval. All PFAS concentrations determined via this approach were within a factor of two compared to those measured in the mechanically extracted sediment pore water and surface water samples obtained adjacent to the sampler deployment locations. Neither biofouling of the rate-limiting barrier nor any physical change to it was observed on the sampler after retrieval. The passive sampler developed in this study could be a promising tool for the monitoring of PFAS in pore water and surface water.

A review of peeper passive sampling approaches to measure the availability of inorganics in sediment porewater.

Sediment porewater dialysis passive samplers, also known as "peepers," are inert containers with a small volume of water (usually 1-100 mL) capped with a semi-permeable membrane. When exposed to sediment over a period of days to weeks, chemicals (typically inorganics) in sediment porewater diffuse through the membrane into the water. Subsequent analysis of chemicals in the peeper water sample can provide a value that represents the concentrations of freely-dissolved chemicals in sediment, a useful measurement for understanding fate and risk. Despite more than 45 years of peeper uses in peer-reviewed research, there are no standardized methods available, which limits the application of peepers for more routine regulatory-driven decision making at sediment sites. In hopes of taking a step towards standardizing peeper methods for measuring inorganics in sediment porewater, over 85 research documents on peepers were reviewed to identify example applications, key methodological aspects, and potential uncertainties. The review found that peepers could be improved by optimizing volume and membrane geometry to decrease the necessary deployment time, decrease detection limits, and provide sufficient sample volumes needed for commercial analytical laboratories using standardized analytical methods. Several methodological uncertainties related to the potential impact of oxygen presence in peeper water prior to deployment and oxygen accumulation in peepers after retrieval from sediment were noted, especially for redox-sensitive metals. Additional areas that need further development include establishing the impact of deionized water in peeper cells when used in marine sediment and use of pre-equilibration sampling methods with reverse tracers allowing shorter deployment periods. Overall, it is expected that highlighting these technical aspects and research needs will encourage work to address critical methodological challenges, aiding in the standardization of peeper methods for measuring porewater concentrations at contaminated regulatory-driven sediment sites.

DNA methylation-based biomarkers for ageing long-lived cetaceans.

Epigenetic approaches for estimating the age of living organisms are revolutionizing studies of long-lived species. Molecular biomarkers that allow age estimates from small tissue biopsies promise to enhance studies of long-lived whales, addressing a fundamental and challenging parameter in wildlife management. DNA methylation (DNAm) can affect gene expression, and strong correlations between DNAm patterns and age have been documented in humans and nonhuman vertebrates and used to construct "epigenetic clocks". We present several epigenetic clocks for skin samples from two of the longest-lived cetaceans, killer whales and bowhead whales. Applying the mammalian methylation array to genomic DNA from skin samples we validate four different clocks with median errors of 2.3-3.7 years. These epigenetic clocks demonstrate the validity of using cytosine methylation data to estimate the age of long-lived cetaceans and have broad applications supporting the conservation and management of long-lived cetaceans using genomic DNA from remote tissue biopsies.

Analysis of Local Control Outcomes and Clinical Prognostic Factors in Localized Pelvic Ewing Sarcoma Patients Treated With Radiation Therapy: A Report From the Children's Oncology Group.

PURPOSE: To identify potential clinical prognostic factors associated with a higher risk of local recurrence in patients with localized pelvic Ewing sarcoma treated with radiation therapy. METHODS AND MATERIALS: Data for 101 patients treated with definitive radiation therapy (RT) or both surgery and radiation (S + RT) to primary pelvic tumors on INT-0091, INT-0154, and AEWS0031 were analyzed. Imaging data for patients who did not receive radiation were not available for central review; therefore, patients with surgery alone were not included. Cumulative incidence rates for local failure at 5 years from time of local control were calculated accounting for competing risks. RESULTS: The most common pelvic subsite was sacrum (44.6%). RT was used in 68% of patients and S + RT in 32%. The local failure rate was 25.0% for RT and 6.3% for S + RT (P = .046). There was no statistically significant difference in local control modality by tumor characteristics. Tumors originating in the ischiopubic-acetabulum region were associated with the highest local failure incidence, 37.5% (P = .02, vs sacrum and iliac/buttock tumors), particularly those treated with RT (50.0%, P = .06). A higher incidence of local failure was seen with each additional 100 mL of tumor at diagnosis (P = .04). Multivariable analysis demonstrated RT alone (hazard ratio [HR], 5.1; P = .04), tumor subsite (particularly ischiopubic-acetabulum tumors; HR 4.6; P = .02), and increasing volume per 100 mL (HR, 1.2; P = .01) were associated with a higher incidence of local recurrence. CONCLUSIONS: Combination surgery and RT is associated with improved local control in patients with pelvic Ewing sarcoma compared with definitive RT. Tumors involving the ischiopubic-acetabulum region and increasing tumor volume at diagnosis are associated with inferior local control. Tumor characteristics did not correlate with choice of local therapy modality suggesting an opportunity to develop best local therapy practices guidelines for future studies based on tumor features.

Development of a hardened THz energy meter for use on the kilojoule-scale, short-pulse OMEGA EP laser.

A highly adaptable and robust terahertz (THz) energy meter is designed and implemented to detect energetic THz pulses from high-intensity (>1018 W/cm2) laser-plasma interactions on the OMEGA EP. THz radiation from the laser driven target is detected by a shielded pyrometer. A second identical pyrometer is used for background subtraction. The detector can be configured to detect THz pulses in the 1 mm to 30 µm (0.3- to 10-THz) range and pulse energies from joules to microjoules via changes in filtration, aperture size, and position. Additional polarization selective filtration can also be used to determine the THz pulse polarization. The design incorporates significant radiation and electromagnetic pulse shielding to survive and operate within the OMEGA EP radiation environment. We describe the design, operational principle, calibration, and testing of the THz energy meter. The pyrometers were calibrated using a benchtop laser and show linear sensitivity to up to 1000 nJ of absorbed energy. The initial results from four OMEGA EP THz experiments detected up to ∼15µJ at the detector, which can correspond to hundreds of mJ depending on THz emission and reflection models.

The Posterior Femoral Cutaneous Nerve and Branches are in Proximity to the Surgical Approach During Proximal Hamstring Repair.

Purpose: The purpose of our study is to identify the location of the posterior femoral cutaneous nerve (PFCN) and its branches in relation to the proximal hamstring tendon. Methods: Fifteen lower torso human cadaveric specimens were dissected in prone position. Skin and subcutaneous tissues were reflected to expose the gluteal and hamstring musculature. The distance between the ischial tuberosity and lateral border of the hamstring, PFCN, perineal branch of the PFCN, and descending femoral branch of the PFCN was measured with digital calipers. Measurements were repeated three times and averaged. Results: The PFCN was 30.5 ± 11.4 mm lateral to the central tip of the ischial tuberosity (range: 15.7 to 52.0 mm). The average longitudinal distance from the tip of the ischial tuberosity to the point where the perineal branch crossed the hamstrings was 24.1 ± 15.0 mm (range: 9.9 to 52.2 mm). The average longitudinal distance to the point where the descending cutaneous branch crossed the hamstrings was 83.3 ± 21.3 mm (range: 41.3 to 110.3 mm). The PFCN was nearest to the inferior border of the gluteus maximus 45.8 ± 13.6 mm lateral to the ischial tuberosity (range: 13.6 to 62.1 mm). Eleven specimens (73%) had one identifiable perineal branch; four (27%) had two distinct perineal branches. Conclusions: The PFCN was in close proximity to the surgical approach used during proximal hamstring repair, with the perineal branch consistently crossing the surgical field transversely. The location of these nerves varied substantially among the specimens tested, with some nerves less than 1 cm from the ischial tuberosity and 27% of specimens with two perineal branches.

Maternal Exercise-Induced SOD3 Reverses the Deleterious Effects of Maternal High-Fat Diet on Offspring Metabolism Through Stabilization of H3K4me3 and Protection Against WDR82 Carbonylation.

Preclinical studies reveal maternal exercise as a promising intervention to reduce the transmission of multigenerational metabolic dysfunction caused by maternal obesity. The benefits of maternal exercise on offspring health may arise from multiple factors and have recently been shown to involve DNA demethylation of critical hepatic genes leading to enhanced glucose metabolism in offspring. Histone modification is another epigenetic regulator, yet the effects of maternal obesity and exercise on histone methylation in offspring are not known. Here, we find that maternal high-fat diet (HFD; 60% kcal from fat) induced dysregulation of offspring liver glucose metabolism in C57BL/6 mice through a mechanism involving increased reactive oxygen species, WD repeat-containing 82 (WDR82) carbonylation, and inactivation of histone H3 lysine 4 (H3K4) methyltransferase leading to decreased H3K4me3 at the promoters of glucose metabolic genes. Remarkably, the entire signal was restored if the HFD-fed dams had exercised during pregnancy. WDR82 overexpression in hepatoblasts mimicked the effects of maternal exercise on H3K4me3 levels. Placental superoxide dismutase 3 (SOD3), but not antioxidant treatment with N-acetylcysteine was necessary for the regulation of H3K4me3, gene expression, and glucose metabolism. Maternal exercise regulates a multicomponent epigenetic system in the fetal liver resulting in the transmission of the benefits of exercise to offspring.

An Ecological Accounting System for Integrated Aquatic Planning and Habitat Banking with Case Study on the Toronto Waterfront, Ontario, Canada.

A key aspect of contemporary fish habitat management is the need to account for losses and gains associated with development and offsetting measures while protecting high quality features. We propose an ecological accounting framework for aquatic ecosystems using habitat equivalents scaled to aquatic productivity, and using fish-to-habitat associations by life stage, based on local fish community needs. The framework uses both landscape-scale and site-level evaluations of pre- and post-project habitat changes to assign and track habitat parcels, using ecological baselines and fish-habitat target setting. Concepts of natural capital reserves and productivity-based ecotypes are used for trading losses and gains between impacts from development projects and offsets, including restoration actions, while maintaining ecologically important areas intact. Traditional accounting terms such as deposits, withdrawals, and transfers are defined using scaled habitat-equivalents as the currency. Other key features of the framework include setting a service area that is ecologically meaningful, and conducting habitat transactions guided by habitat conservation, protection, and restoration (habitat CPR) principles. The nearshore area of the Toronto and Region is used as a case study to illustrate the eco-accounting framework and how habitat banking could be incorporated along with planned restoration to remediate this degraded but continually developed area. The framework represents significant advances in managing cumulative habitat effects in an integrated way, moving away from a focus on only project- or site-level assessments. We feel this approach could be adapted to other ecosystem types in addition to the lake, nearshore area example provided here.

Weightbearing after combined medial and lateral plate fixation of AO/OTA 41-C2 bicondylar tibial plateau fractures: a biomechanical study.

BACKGROUND: Combined medial and lateral plate fixation is recommended for complex tibial plateau fractures with medial fragments or no cortical bone contact. Although such fixation is adequate to resist forces during range of motion, it may be insufficient to support immediate postoperative weightbearing. Here, we analyzed displacement, stiffness, and fixation failure during simulated full weightbearing of bicondylar tibial plateau fractures treated with combined medial and lateral locking plate fixation. METHODS: We used 10 fresh-frozen adult human cadaveric tibias and mated femurs. Osteotomies were performed with an oscillating saw and cutting template to simulate an AO Foundation and Orthopaedic Trauma Association (AO/OTA) 41-C2 fracture (simple articular, multifragmentary metaphyseal fracture). Specimens were anatomically reduced and stabilized with combined medial and lateral locking plates (AxSOS, Stryker, Mahwah, NJ). Specimens were loaded axially to simulate 4 weeks of walking in a person weighing 70 kg. The specimens were cyclically loaded from 200 N to a maximum of 2800 N. Then, if no failure, loading continued for 200,000 cycles. We measured displacement of each bone fragment and defined fixation failure as ≥5 mm of displacement. Construct stiffness and load at failure were calculated. Categorical and continuous data were analyzed using Chi-squared and unpaired t-tests, respectively. RESULTS: Mean total displacement values after 10,000 loading cycles were as follows: lateral, 0.4 ± 0.8 mm; proximal medial, 0.3 ± 0.7 mm; distal medial, 0.3 ± 0.6 mm; and central 0.4 ± 0.5 mm. Mean stiffness of the construct was 562 ± 164 N/mm. Fixation failure occurred in 6 of 10 specimens that reached 5 mm of plastic deformation before test completion. In the failure group, the mean load at failure was 2467 ± 532 N, and the mean number of cycles before failure was 53,155. After test completion, the greatest displacement was found at the distal medial fracture site (2.3 ± 1.4 mm) and lateral fracture site (2.2 ± 1.7 mm). CONCLUSIONS: Although combined medial and lateral plate fixation of complex tibial plateau fractures provides adequate stability to allow early range of motion, immediate full weightbearing is not recommended.

The APB study: apixaban pharmacokinetics in bariatric patients before to 1 year after vertical sleeve gastrectomy or Roux-en-Y gastric bypass.

BACKGROUND: The optimal regimen for prevention and treatment of venous thromboembolism in bariatric surgical patients remains controversial. Direct oral anticoagulants are potentially advantageous over other agents, but inadequate evidence exists regarding their effects in bariatric surgical patients. OBJECTIVES: To investigate single-dose pharmacokinetic (PK) and pharmacodynamic (PD) parameters of apixaban when administered to patients undergoing vertical sleeve gastrectomy (VSG) or Roux-en-Y gastric bypass (RYGB) and to determine whether the PK and PD parameters are affected by type of bariatric surgery and weight loss in the immediate and postoperative period up to 12 months. SETTING: University Hospital and A Bariatric Center of Excellence, Baltimore, Maryland. METHODS: Adults with a body mass index ≥35 kg/m2 approved for bariatric surgery were enrolled in a single-center, open-label, nonrandomized, single-dose clinical study (NCT No. 02406885; www. CLINICALTRIALS: gov). Apixaban PK and PD parameters were measured after a single 5 mg dose of the drug was given preoperatively and at 1, 6, and 12 months postoperatively in patients undergoing VSG and RYGB. Change in PK parameters was assessed as maximum concentration, time to maximum concentration, elimination half-life, and area under the concentration-time curve from 0-72 hours and change in PD parameters were assessed by chromogenic factor X activity. RESULTS: Of 33 patients enrolled, 28 (14 VSG, 14 RYGB) completed all visits and were analyzed. Most patients (89%) were female, with a mean age of 43.8 years and a body mass index of 48.7 kg/m2. Area under the concentration-time curve from 0-72 hours increased from baseline to 1 month (1009.1 to 1232.9 ng/mL/hr, P = .002), returned to baseline at 6 months (1000.9 ng/mL/hr, P = .88), and decreased significantly at 12 months (841.8 ng/mL/hr, P = .001). Maximum concentration did not change significantly. Predose factor X activity dropped significantly from 113% preoperatively to 89.8 % at 12 months postoperatively (P < .0001). Three-hour postdose factor X activity was significantly lower at 1, 6, and 12 months postoperatively versus preoperatively. However, the magnitude of the decrease from predose to 3-hour postdose was not significantly altered by surgery. CONCLUSION: The effect of either VSG or RYGB on apixaban PK and PD parameters is minimal. Factor X activity after 5 mg apixaban was lower in postoperative versus preoperative bariatric patients, but this effect appears to be primarily the result of a decrease in factor X activity from bariatric surgery itself and not a postoperative change in apixaban PK and PD parameters. Future studies should investigate the safety, efficacy, and clinical outcomes of apixaban and other direct oral anticoagulants perioperatively and beyond 12 months following bariatric surgery.

Cannabis Exposure Decreases Need for Blood Pressure Support During General Anesthesia in Orthopedic Trauma Surgery.

Introduction: As cannabis use continues to increase in popularity, it is important to investigate how it impacts public health in all sectors of the population, including patients undergoing anesthetic management. This retrospective study focuses on the orthopedic trauma population presenting through an emergency department (ED) and receiving a urine drug screen (UDS) with subsequent urgent surgical intervention. We aimed to evaluate differences in response to general anesthesia in patients with exposure to THC, a major cannabinoid, compared to controls that screened negative for THC. Materials and Methods: All ED visits at UC Irvine, a level 1 trauma center between November 4, 2017 and January 7, 2020, were evaluated in this study. Only adult patients who received a UDS and underwent urgent orthopedic trauma surgery within 48 h of ED visit were included in this study. Additional inclusion criteria required an anesthesia time greater than 1 h as well as anesthesia induction and intubation while in the operating room. Overall, we analyzed a total of 221 adult patients. Discussion: When adjusting for demographic variability, there were statistically significant differences in response to general anesthesia between these two groups. The THC-positive (THC(+)) group was less likely to receive intraoperative vasopressors, had higher mean arterial blood pressure and mean diastolic blood pressure, needed less total fluid input and had a lower overall fluid balance. Chronic exposure to THC has been shown to downregulate cannabinoid 1 receptors and cause alterations in endocannabinoid tone. These are two potential mechanisms by which the THC(+) group in our study may have become more resistant to the typically observed hypotensive effects of general anesthesia. Conclusion: The present study suggests that prior use of cannabis, objectively assessed by urinalysis, results in a decreased need for blood pressure support during general anesthesia. The physiological basis for this phenomenon is unclear, but possible causes might include the downregulation of vascular cannabinoid receptor 1 and/or altered endocannabinoid levels after exposure to cannabis.

Comparison of Lag Versus Nonlag Screw Fixation for Long Oblique Proximal Phalanx Fractures: A Biomechanical Study.

PURPOSE: To compare lag versus nonlag screw fixation for long oblique proximal phalanx (P1) fractures in a cadaveric model of finger motion via the flexor and extensor tendons. METHODS: We simulated long oblique P1 fractures with a 45° oblique cut in the index, middle, and ring fingers of 4 matched pairs of cadaveric hands for a total of 24 simulated fractures. Fractures were stabilized using 1 of 3 techniques: two 1.5-mm fully threaded bicortical screws using a lag technique, two 1.5-mm fully threaded bicortical nonlag screws, or 2 crossed 1.14-mm K-wires as a separate control. The fixation method was randomized for each of the 3 fractures per matched-pair hand, with each fixation being used in each hand and 8 total P1 fractures per fixation group. Hands were mounted to a custom frame where a computer-controlled, motor-driven, linear actuator powered movement of the flexor and extensor tendons. All fingers underwent 2,000 full flexion and extension cycles. Maximum interfragmentary displacement was continuously measured using a differential variable reluctance transducer. Our primary outcome was the difference in the mean P1 fragment displacement between lag and nonlag screw fixation at 2,000 cycles. RESULTS: The observed differences in mean displacement between lag and nonlag screw fixation were not statistically significant throughout all time points. A two one-sided test procedure for paired samples confirmed statistical equivalence in the fragment displacement between these fixation methods at all time points, including the primary end point of 2,000 cycles. CONCLUSIONS: Nonlag screws provided equivalent biomechanical stability to lag screws for simulated long oblique P1 fractures during cyclic testing in this cadaveric model. CLINICAL RELEVANCE: Fixation of long oblique P1 fractures with nonlag screws has the potential to simplify treatment without sacrificing fracture stability during immediate postoperative range of motion.

High-efficiency, fifth-harmonic generation of a joule-level neodymium laser in a large-aperture ammonium dihydrogen phosphate crystal.

High-energy deep ultraviolet (UV) sources are required for high-density plasma diagnostics. The fifth-harmonic generation of large-aperture neodymium lasers in ammonium dihydrogen phosphate (ADP) can significantly increase UV energies due to the availability of large ADP crystals. Noncritical phase matching in ADP for (ω + 4ω) was achieved by cooling a 65 × 65-mm crystal in a two-chamber cryostat to 200 K. The crystal chamber used helium as the thermally conductive medium between the crystal and the crystal chamber, which was surrounded by a high-vacuum chamber with a liquid nitrogen reservoir. A temperature variation of 0.2 K across the crystal aperture was obtained. The total conversion efficiency from the fundamental to the fifth harmonic at 211 nm was 26%.

Placental superoxide dismutase 3 mediates benefits of maternal exercise on offspring health.

Poor maternal diet increases the risk of obesity and type 2 diabetes in offspring, adding to the ever-increasing prevalence of these diseases. In contrast, we find that maternal exercise improves the metabolic health of offspring, and here, we demonstrate that this occurs through a vitamin D receptor-mediated increase in placental superoxide dismutase 3 (SOD3) expression and secretion. SOD3 activates an AMPK/TET signaling axis in fetal offspring liver, resulting in DNA demethylation at the promoters of glucose metabolic genes, enhancing liver function, and improving glucose tolerance. In humans, SOD3 is upregulated in serum and placenta from physically active pregnant women. The discovery of maternal exercise-induced cross talk between placenta-derived SOD3 and offspring liver provides a central mechanism for improved offspring metabolic health. These findings may lead to novel therapeutic approaches to limit the transmission of metabolic disease to the next generation.

Interference Screw Versus Suture Anchors for Femoral Fixation in Medial Patellofemoral Ligament Reconstruction: A Biomechanical Study.

BACKGROUND: Femoral-sided graft fixation in medial patellofemoral ligament (MPFL) reconstruction is commonly performed using an interference screw (IS). However, the IS method is associated with several clinical disadvantages that may be ameliorated by the use of suture anchors (SAs) for femoral fixation. PURPOSE: To compare the load to failure and stiffness of SAs versus an IS for the femoral fixation of a semitendinosus autograft in MPFL reconstruction. STUDY DESIGN: Controlled laboratory study. METHODS: Based on a priori power analysis, a total of 6 matched pairs of cadaveric knees were included. Specimens in each pair were randomly assigned to receive either SA or IS fixation. After an appropriate reconstruction procedure, the looped end of the MPFL graft was pulled laterally at a rate of 6 mm/s until construct failure. The best-fit slope of the load-displacement curve was then used to calculate the stiffness (N/mm) in a post hoc fashion. A paired t test was used to compare the mean load to failure and the mean stiffness between groups. RESULTS: No significant difference in load to failure was observed between the IS and the SA fixation groups (294.0 ± 61.1 vs 250.0 ± 55.9; P = .352), although the mean stiffness was significantly higher in IS specimens (34.5 ± 9.6 vs 14.7 ± 1.2; P = .004). All IS reconstructions failed by graft pullout from the femoral tunnel, whereas 5 of the 6 SA reconstructions failed by anchor pullout. CONCLUSION: In this biomechanical study using a cadaveric model of MPFL reconstruction, SA femoral fixation was not significantly different from IS fixation in terms of load to failure. The mean load-to-failure values for both reconstruction techniques were greater than the literature-reported values for the native MPFL. CLINICAL RELEVANCE: These results suggest that SAs are a biomechanically viable alternative for femoral-sided graft fixation in MPFL reconstruction.

Tocilizumab for the Treatment of COVID-19 Among Hospitalized Patients: A Matched Retrospective Cohort Analysis.

BACKGROUND: There is currently no single treatment that mitigates all harms caused by severe acute respiratory syndrome coronavirus 2 infection. Tocilizumab, an interleukin-6 antagonist, may have a role as an adjunctive immune-modulating therapy. METHODS: This was an observational retrospective study of hospitalized adult patients with confirmed coronavirus disease 2019 (COVID-19). The intervention group comprised patients who received tocilizumab; the comparator arm was drawn from patients who did not receive tocilizumab. The primary outcome was all-cause mortality censored at 28 days; secondary outcomes were all-cause mortality at discharge, time to clinical improvement, and rates of secondary infections. Marginal structural Cox models via inverse probability treatment weights were applied to estimate the effect of tocilizumab. A time-dependent propensity score-matching method was used to generate a 1:1 match for tocilizumab recipients; infectious diseases experts then manually reviewed these matched charts to identify secondary infections. RESULTS: This analysis included 90 tocilizumab recipients and 1669 controls. Under the marginal structural Cox model, tocilizumab was associated with a 62% reduced hazard of death (adjusted hazard ratio [aHR], 0.38; 95% CI, 0.21 to 0.70) and no change in time to clinical improvement (aHR, 1.13; 95% CI, 0.68 to 1.87). The 1:1 matched data set also showed a lower mortality rate (27.8% vs 34.4%) and reduced hazards of death (aHR, 0.47; 95% CI, 0.25 to 0.88). Elevated inflammatory markers were associated with reduced hazards of death among tocilizumab recipients compared with controls. Secondary infection rates were similar between the 2 groups. CONCLUSIONS: Tocilizumab may provide benefit in a subgroup of patients hospitalized with COVID-19 who have elevated biomarkers of hyperinflammation, without increasing the risk of secondary infection.

Exercise Training Promotes Sex-Specific Adaptations in Mouse Inguinal White Adipose Tissue.

Recent studies demonstrate that adaptations to white adipose tissue (WAT) are important components of the beneficial effects of exercise training on metabolic health. Exercise training favorably alters the phenotype of subcutaneous inguinal WAT (iWAT) in male mice, including decreasing fat mass, improving mitochondrial function, inducing beiging, and stimulating the secretion of adipokines. In this study, we find that despite performing more voluntary wheel running compared with males, these adaptations do not occur in the iWAT of female mice. Consistent with sex-specific adaptations, we report that mRNA expression of androgen receptor coactivators is upregulated in iWAT from trained male mice and that testosterone treatment of primary adipocytes derived from the iWAT of male, but not female mice, phenocopies exercise-induced metabolic adaptations. Sex specificity also occurs in the secretome profile, as we identify cysteine-rich secretory protein 1 (Crisp1) as a novel adipokine that is only secreted from male iWAT in response to exercise. Crisp1 expression is upregulated by testosterone and functions to increase glucose and fatty acid uptake. Our finding that adaptations to iWAT with exercise training are dramatically greater in male mice has potential clinical implications for understanding the different metabolic response to exercise training in males and females and demonstrates the importance of investigating both sexes in studies of adipose tissue biology.