Biomechanical evaluation of the modified lasso technique.

BACKGROUND: The Terrible Triad of the elbow is a constellation of elbow dislocation, radial head fracture and coronoid process fracture. A common type of coronoid fracture documented with this triad is type II Regan-Morrey coronoid fractures. The preferred fixation method for this fracture type is the lasso technique, medial-lateral tunnel orientation being the traditional approach. Considering elbow anatomy, we saw an opportunity to potentially improve fixation by altering the suture lasso tunnel orientation to a proximal-distal orientation. HYPOTHESIS: Two tunnels in the proximal-distal direction would result in greater biomechanical stability as compared to the traditional lasso technique. MATERIAL AND METHODS: A type 2 Regan-Morrey fracture was created in 12 fresh frozen cadaveric elbows at 50% of the coronoid height using an oscillating saw. The humero-ulnar joint was placed in 0 degrees flexion then loaded at a rate of 10mm/min to failure. RESULTS: The control technique (medio-lateral tunnels) showed failure load of 150±81N that was not significantly different (p=0.825) than the 134±116N measured for the modified technique (distal-proximal tunnels). The portion of the load-displacement curve used to calculate stiffness was linear (R^2=0.94±0.04) with determination coefficients that did not differ between the two groups (p=0.351). For stiffness, we measured 17±13N/mm and 14±12N/mm respectively for control and modified techniques that did not result in a significant difference (p=0.674). CONCLUSION: In this attempt to improve the shortcomings of the lasso technique, we found that changing from medio-lateral to proximal-distal drilling directions did not result in an appreciable biomechanical benefit. LEVEL OF EVIDENCE: Basic science study; Biomechanics.

Increasing Hearing Readiness Using Boothless Audiometry.

INTRODUCTION: U.S. Army regulations require all soldiers to undergo annual audiometric testing to maintain hearing readiness. The standard method of monitoring hearing in the DoD is via multi-person testing in sound-treated booths using the Defense Occupational and Environmental Health Readiness System-Hearing Conservation. COVID-19 significantly hindered the standard method, resulting in alarming declines in hearing readiness. In response, the Army Hearing Program initiated a pilot program to use boothless audiometers to supplement standard methods to increase hearing readiness. MATERIALS AND METHODS: Funding from the Coronavirus Aid, Relief, and Economic Security Act was used to purchase 169 boothless audiometers and increase staffing at dozens of Army Hearing Program clinics. Standard operating procedures were established for audiometric testing outside the booth using a process matching standard test parameters (i.e., test frequencies, tone characteristics, and interstimulus intervals). Additional capabilities developed to leverage this new technology during the annual hearing exam include the administration of automated contralateral masking, enhanced tinnitus screening, and hearing health education and training. RESULTS: Monitoring audiometry using boothless audiometers has been conducted for nearly 12,000 service members worldwide. Thresholds obtained via boothless audiometers are comparable to follow-up thresholds obtained from the standard test methods in the booth (mean difference 95% CI, -1.2, 0.9), and hearing readiness has returned to pre-pandemic levels at installations where this novel technology is being used regularly. CONCLUSIONS: Significant reductions in patient encounters as a direct result of the COVID-19 pandemic have led to innovative solutions leveraging boothless audiometers. While this has aided the primary mission to maintain a medically ready force, innovations from this endeavor highlight several additional improvements relative to current standards of care that should be considered for permanent inclusion in DoD Hearing Conservation Programs.

The Ideal Cortical Button Location on the Lateral Femur for Anterior Cruciate Ligament Suspensory Fixation is 30 mm Proximal to the Lateral Epicondyle.

PURPOSE: To determine the ideal location for anterior cruciate ligament (ACL) suspensory cortical button placement on the lateral femur with the highest failure load and to establish the relationship of tunnel diameter and cortical thickness on load to failure. METHODS: Computed tomography (CT) data were obtained from 45 cadaveric distal femurs. A Cartesian coordinate system was established along the lateral femur with the lateral epicondyle (LE) as a reference point. Locations 0, 20 and 30 mm from the LE along lines 0°, 25°, 50°, and 75° posterioproximal from the axial plane were created. Tunnels connecting from each location to the center of the ACL footprint were simulated. Cortical thickness and long axis diameter of the oval cortical holes were determined for each location. Based on the CT data, custom drill guides were created and used to drill 4.5 mm tunnels at each lateral femur location to the ACL footprint on the cadaver femurs. Cortical buttons were placed at each location and pulled using a servohydraulic testing system. The correlation of tunnel diameter and cortical thickness to button failure load were analyzed using a regression analysis. RESULTS: Significant differences were found for failure load (P<.0001) and cortical thickness between the locations tested (P<.0001). The location 30 mm proximal from the LE and 75° from the axial plane had the highest failure load of 573 N. A regression analysis (R2 = .15) indicated that the cortical thickness was significantly correlated with load to failure (P <.0001), whereas the long-axis diameter was not (P = .33). CONCLUSION: The ideal cortical button location on the lateral femur for ACL suspensory fixation was located 30 mm proximal from the lateral epicondyle, based on this area's high failure load. Oblique tunnel drilling of this proximal location may cause a larger long-axis diameter cortical hole, but the cortex is also thicker, which is more closely correlated with failure load. CLINICAL RELEVANCE: Different ACL suspensory cortical button locations on the lateral femur have different failure loads based on the cortical thickness of the bone supporting the button. It is important for surgeons to understand which drilling techniques place the button in a proximal and posterior location, especially if the bone quality of the patient is of concern.

Sustainable development education, practice, and research: an indigenous model of sustainable development at the College of Menominee Nation, Keshena, WI, USA.

The College of Menominee Nation Sustainable Development Institute's theoretical model (SDI model) conceptualizes sustainable development as the process of maintaining the balance and reconciling the inherent tensions among six dimensions of sustainability: land and sovereignty; natural environment (including human beings); institutions; technology; economy; and human perception, activity, and behavior. Each dimension is understood to be dynamic, both internally and in relationship to each of the other five dimensions. Change within one dimension will impact other dimensions in a continual process of change. Change can be externally driven or inherent to the dynamic nature of any of the six dimensions. Sustainable development is a continual and iterative process. A central concept of the model is based on the experience of the Menominee Indian Tribe of Wisconsin and their profound sense of place and relationship with the land that has allowed their community to recognize and balance the tensions among model dimensions through time. This paper provides a detailed description of the SDI model and its development and concludes with short examples illustrating how the model has been used for course design and delivery in higher education, interdisciplinary community planning, and participatory research.

Multivariate analysis of prognostic factors for survival following doxorubicin-eluting bead transarterial chemoembolization for hepatocellular carcinoma.

PURPOSE: To identify prognostic factors for survival in patients with hepatocellular carcinoma (HCC) treated with transarterial chemoembolization with doxorubicin-eluting beads (DEBs). MATERIALS AND METHODS: In a retrospective, single-center analysis, tumor- and patient-related factors were recorded for univariate and multivariate analyses via Kaplan-Meier and Cox regression. Infiltrative HCC phenotype and portal vein invasion (PVI) were correlated, and patients with either or both were classified as having radiographically advanced (RAdv) HCC. The primary endpoint was overall survival, which was calculated from the time of first DEB chemoembolization procedure. RESULTS: A total of 168 patients underwent 248 procedures, of which 215 (86.7%) were outpatient procedures. Mean length of stay was 0.33 days, and 25 patients (10.1%) were readmitted within 30 days. A total of 33 patients underwent liver transplantation and were excluded from survival analyses. A total of 130 had cirrhosis; 62, 50, and 18 had Child class A, B, and C disease, respectively. Forty-one patients had infiltrative HCC phenotype, 28 of whom also had PVI. Multivariate analysis of survival in all patients showed α-fetoprotein (AFP), performance status (PS), RAdv HCC, Child classification, albumin level, and ascites to predict survival. In patients without RAdv HCC, AFP, PS, Child classification, albumin level, and International Normalized Ratio were independent predictors. Increased bilirubin level was not an independent risk factor for death. CONCLUSIONS: Independent prognostic factors in patients with HCC undergoing DEB chemoembolization have been identified. Increased bilirubin level was not an independent risk factor. These data can be used in HCC patient selection and counseling for DEB chemoembolization.

Imidazolopiperazines: lead optimization of the second-generation antimalarial agents.

On the basis of the initial success of optimization of a novel series of imidazolopiperazines, a second generation of compounds involving changes in the core piperazine ring was synthesized to improve antimalarial properties. These changes were carried out to further improve the potency and metabolic stability of the compounds by leveraging the outcome of a set of in vitro metabolic identification studies. The optimized 8,8-dimethyl imidazolopiperazine analogues exhibited improved potency, in vitro metabolic stability profile and, as a result, enhanced oral exposure in vivo in mice. The optimized compounds were found to be more efficacious than the current antimalarials in a malaria mouse model. They exhibit moderate oral exposure in rat pharmacokinetic studies to achieve sufficient multiples of the oral exposure at the efficacious dose in toxicology studies.

Imidazolopiperazines: hit to lead optimization of new antimalarial agents.

Starting from a hit series from a GNF compound library collection and based on a cell-based proliferation assay of Plasmodium falciparum, a novel imidazolopiperazine scaffold was optimized. SAR for this series of compounds is discussed, focusing on optimization of cellular potency against wild-type and drug resistant parasites and improvement of physiochemical and pharmacokinetic properties. The lead compounds in this series showed good potencies in vitro and decent oral exposure levels in vivo. In a Plasmodium berghei mouse infection model, one lead compound lowered the parasitemia level by 99.4% after administration of 100 mg/kg single oral dose and prolonged mice survival by an average of 17.0 days. The lead compounds were also well-tolerated in the preliminary in vitro toxicity studies and represents an interesting lead for drug development.

The use of selected genotoxicity assays in green-lipped mussels (Perna viridis): a validation study in Hong Kong coastal waters.

In Hong Kong, discharges of domestic and industrial wastewaters and disposal of contaminated muds into coastal waters have resulted in high levels of persistent organic contaminants in the water column, biota and bottom sediments. Although the acute toxicity of effluents has been tested by government regulators using mortality-based bioassays, the sublethal effects of many of the pollutants, including environmental carcinogens, have not been well studied. The objective of the present work was to examine the efficiency and efficacy of using: (1) DNA strand breaks (comet assay and alkaline agarose gel electrophoresis assay); (2) oxidative DNA damage (levels of 8-hydroxy-2-deoxyguanosine in cellular DNA) and (3) micronuclei (MN) formation as early warning toxicological indicators of potential environmental carcinogen exposure. Green-lipped mussels (Perna viridis) were transplanted to study sites and retrieved after 4, 8, 12, 16 and 30 days. The bioaccumulation of organic pollutants, including the polycyclic aromatic hydrocarbons (PAHs), organochlorine pesticides (OC pesticides) and polychlorinated biphenyls (PCBs) was observed, and compared with biomarker assays. Some significant dose- and time-dependent inductions of the genotoxic biomarkers, including 8-OHdG, DNA strand breaks and micronuclei were observed. In particular, several very strong (r>0.9) and significantly positive relationships were found at all sites during days 0-12. In addition, significant strong relationships between certain organic contaminants (carcinogenic PAHs and 4 common OC pesticides) and micronuclei were detected at the polluted sites, Tsim Sha Tsui and Sai Wan Ho. The results suggest that the use of micronuclei as a biomarker is potentially effective, especially at the more polluted sites. Nonetheless, further research is required to validate their effectiveness under varying field conditions, especially to elucidate responses under lower contaminant loads, interactions between the environmental and physiological factors affecting organisms in differing coastal environments, and changes in biotransformation and DNA repair enzymes in test organisms.

Sentinel node biopsy after neoadjuvant chemotherapy in breast cancer: results from National Surgical Adjuvant Breast and Bowel Project Protocol B-27.

PURPOSE: Experience with sentinel node biopsy (SNB) after neoadjuvant chemotherapy is limited. We examined the feasibility and accuracy of this procedure within a randomized trial in patients treated with neoadjuvant chemotherapy. PATIENTS AND METHODS: During the conduct of National Surgical Adjuvant Breast and Bowel Project trial B-27, several participating surgeons attempted SNB before the required axillary dissection in 428 patients. All underwent lymphatic mapping and an attempt to identify and remove a sentinel node. Lymphatic mapping was performed with radioactive colloid (14.7%), with lymphazurin blue dye alone (29.9%), or with both (54.7%). RESULTS: Success rate for the identification and removal of a sentinel node was 84.8%. Success rate increased significantly with the use of radioisotope (87.6% to 88.9%) versus with the use of lymphazurin alone (78.1%, P = .03). There were no significant differences in success rate according to clinical tumor size, clinical nodal status, age, or calendar year of random assignment. Of 343 patients who had SNB and axillary dissection, the sentinel nodes were positive in 125 patients and were the only positive nodes in 70 patients (56.0%). Of the 218 patients with negative sentinel nodes, nonsentinel nodes were positive in 15 (false-negative rate, 10.7%; 15 of 140 patients). There were no significant differences in false-negative rate according to clinical patient and tumor characteristics, method of lymphatic mapping, or breast tumor response to chemotherapy. CONCLUSION: These results are comparable to those obtained from multicenter studies evaluating SNB before systemic therapy and suggest that the sentinel node concept is applicable following neoadjuvant chemotherapy.