Citations

Background: Medicaid reimbursement to physicians is often perceived to be lower than Medicare, but little is known about orthopaedic foot and ankle reimbursement. This study sought to compare Medicare and Medicaid reimbursement for the 20 most common foot and ankle procedures. Methods: Medicare reimbursement rates for common foot and ankle codes were obtained from the online Centers for Medicare & Medicaid fee schedule, while Medicaid rates were found from individual state fee schedule websites. Medicaid rates were compared by state and pooled to obtain national differences. The Medicare Wage Index was used to adjust Medicaid rates by state wages to ensure a more accurate comparison. Variability between states was measured using state percentages of Medicare and coefficient of variation values. Results: Medicaid reimbursed physicians higher than Medicare in 31 states overall, with average reimbursement ranging from 37% to 324% of Medicare. Nationally, Medicaid reimbursed 8.8% higher than Medicare, but Medicare reimbursed 3.7% higher when adjusted for the Medicare Wage Index. The Current Procedural Terminology ( CPT ) codes with the highest ratio of Medicaid to Medicare reimbursement were CPT 28002 for incision and drainage of the foot (176.6%) and CPT 28820 for toe amputation (167.6%). Five codes had lower relative Medicaid reimbursement on average: CPT 27687 for repair procedures on the leg and ankle joint, CPT 28810 for amputation procedures on the foot and toes, CPT 28010 for toe tenotomy, CPT 28005 for incision procedures on the foot and toes, and CPT 28470 for closed treatment of a metatarsal fracture. The coefficient of variation values ranged from 0.34 to 0.84 in the Medicaid group and 0.40 to 0.78 in the adjusted group, indicating high variability between states and between procedures. Conclusion: Medicaid reimbursement is highly inconsistent between states, ranging from 37% to 324% of Medicare. Medicaid reimbursed more than Medicare overall, which is in contrast with most published findings that tend to show higher reimbursement for Medicare when compared to Medicaid. When adjusting for wage differences between states, Medicare reimbursed slightly higher than Medicaid. Level of Evidence: Level IV, economic analysis.

Abstract Background The ataxia-telangiectasia mutated (ATM) protein coordinates the cellular response to therapeutic radiation, and ATM inhibitors can potentially enhance the efficacy of radiation in otherwise radiation-resistant tumors. Methods The small molecule ATM kinase inhibitor WSD0628 was specifically designed for enhanced distribution across the blood-brain barrier to more effectively treat glioblastoma (GBM) and brain metastases in combination with radiation therapy (RT). GBM and brain metastasis patient-derived xenograft models were used to understand target inhibition, radiosensitization, inhibition of the DNA damage response, and in vivo efficacy. Results Initial in vitro characterization of WSD0628 demonstrates a high level of selectivity across kinase families, limited aldehyde oxidase liability, and low risk of hERG interactions. Consistent with a central role for ATM in radiation response, WSD0628 blocked radiation-induced signaling and enhanced radiosensitivity in U251 glioma cells and brain tumor PDXs GBM120 and M12. In comparison to control or RT alone in orthotopic PDXs, the combination of WSD0628 with RT markedly prolonged median survival—GBM12 (19, 55, and 408 days, respectively); GBM43 (26, 44, and 143 days, respectively); GBM120 (51, 89, and 231 days, respectively); M12 (17, 39, and 190 days, respectively). Pharmacokinetic and pharmacodynamic testing after treatment in orthotopic GBM43 tumors showed inhibitory levels of WSD0628 and a reduction of γH2AX foci in the combination-treated tumors. Conclusions Collectively, these results suggest a promising role for WSD0628 in combination with RT in brain tumors and provide the rationale for an ongoing Phase 0/1A clinical trial testing this combination in recurrent GBM.

Purpose: To identify reasons for variable intraocular pressure (IOP) responses to latanoprost and timolol in healthy volunteers and to generate the control group as part of Eye Dynamics and Engineering Network. Methods: In this multicenter, randomized, crossover study (NCT01677507), both eyes of 106 healthy subjects (212 eyes) were treated with latanoprost or timolol for 7 days, with a 6-week washout between treatments. Ocular biometrics, tonometry, and aqueous humor dynamics (AHD) were assessed at baseline and day 8 of each treatment. Subjects were divided into responders and nonresponders using cutoffs of >15% or >10% IOP reduction. Treatment effects and correlations were analyzed with paired t-tests. Results: More subjects responded to latanoprost (54%) than timolol (27%) at >15% cutoff ( p < 0.01). Responders had higher mean baseline IOP than nonresponders for both drugs at both cutoffs ( p < 0.01). Among timolol nonresponders ( n = 56), 39% responded to latanoprost in both eyes, 20% in one eye, and 41% in neither. Among latanoprost nonresponders ( n = 31), 13% responded to timolol in both eyes, 13% in one eye, and 74% in neither. Latanoprost increased uveoscleral outflow, while timolol reduced aqueous flow and outflow facility. Low baseline uveoscleral outflow was associated with latanoprost response. Conclusions: Higher baseline IOP predicted better responses to both drugs. Higher baseline uveoscleral outflow predicted nonresponse to latanoprost. No AHD differences were linked to the timolol response. Timolol nonresponders were often responsive to latanoprost, but not vice versa.

Background: Transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) are leading causes of transfusion-related morbidity and mortality. Soluble factors in erythrocyte supernatant may increase risk for these complications. The authors hypothesized that point-of-care allogeneic erythrocyte washing may be an effective intervention to mitigate elevations in soluble factors as well as physiologic responses associated with transfusion-associated respiratory complications in the setting of cardiac surgery. Methods: This is a two-center, nonblinded, randomized clinical trial evaluating point-of-care washed versus standard issue allogeneic erythrocyte transfusions administered during or on the day of cardiac surgery. The primary analysis was performed via modified intention to treat. The primary outcomes assessed were changes in intermediate markers of lung injury as well as cardiopulmonary physiologic responses to erythrocyte transfusion. Secondary outcomes included the duration of intensive care unit and hospital stay, durations of mechanical ventilation and oxygen supplementation, presence of TRALI or TACO, and mortality. Results: Among 154 analyzed patients (81 washed, 73 standard issue), the median age was 66 yr, and 77 (50.0%) were women. The median (interquartile range) number of allogeneic erythrocyte units transfused on the day of surgery was 3.0 (2.0 to 5.0) in the washed erythrocyte group and 3.0 (2.0 to 4.0) in the standard issue group (P = 0.13). No between-group differences were identified in any of the assessed recipient lung injury biomarkers (all P values > adjusted alpha). Durations of intensive care unit stay (median [interquartile range], 3.0 [2.0 to 5.0] vs. 3.0 [2.0 to 4.0] days; P = 0.117) and hospital length of stay (12.0 [9.0 to 17.0] vs. 12.0 [9.0 to 17.0] days; P = 0.801) were similar, as were the number of ventilator-free days at day 28 (27.0 [27.0 to 27.0] vs. 27.0 [26.0 to 27.0]; P = 0.699) and oxygen-free days at day 28 (24.0 [19.0 to 26.0] vs. 24.0 [22.0 to 26.0]; P = 0.400). No significant differences were noted in mortality rate or in incidence rates for TRALI, TACO, and acute kidney injury. Conclusions: Among patients undergoing cardiovascular surgery with high risk of erythrocyte transfusion, point-of-care washing of allogeneic erythrocyte transfusions did not mitigate changes in intermediate markers of lung injury or cardiopulmonary physiologic responses to erythrocyte transfusion and was not associated with improved clinical outcomes.

Key Points In phospholipase A2 receptor-membranous nephropathy, clinical variables and antibody levels over 3 or 6 months of treatment were predictors of remission at 1 year. Prediction models at 3 and 6 months had similar performance predicting remission, with the 3-month model allowing for earlier assessment of response. The 3-month and 6-month prediction models could be applied in those treated with supportive therapy, rituximab, calcineurin inhibitors, or cyclophosphamide. Background In patients with antiphospholipase A2 receptor antibody–associated membranous nephropathy, there is currently no accepted method to predict an individual's probability of remission after treatment with immunosuppression or supportive therapy using changes in antibody levels and clinical variables during the first 3–6 months of therapy. Methods Using a cohort of 187 patients from the Glomérulopathie extramembraneuse rituximab, Membranous Nephropathy Trial of Rituximab, and Sequential Treatment with Tacrolimus and Rituximab Versus Alternating Corticosteroids and Cyclophosphamide in primary Membranous Nephropathy clinical trials with antibody levels at baseline ≥14 RU/ml, we derived logistic regression models to predict proteinuria remission at 12 months that can be used at baseline or after 3 or 6 months of treatment. Treatment exposures in the trials included supportive therapy, rituximab, calcineurin inhibitors, and cyclophosphamide. Predictors in the models included male sex and baseline and changes in serum albumin, proteinuria, and antibody levels, with or without changes in eGFR. Results Proteinuria remission at 12 months was achieved in 107 patients. Compared with the model at baseline, the 3-month and 6-month models had better model fit with lower Akaike information criterion (186/158 versus 225) and higher R 2 (52.7%/62.4% versus 25.8%), better discrimination with higher C-statistic (0.87 and 0.91 versus 0.75, P < 0.001), and better calibration with lower integrated calibration index (0.89%/2.22% versus 2.51%). The 3-month and 6-month models had no consistent difference in prediction performance, and decision curve analysis demonstrated similar net benefit for treatment decisions based on either model up to a threshold probability of 31%. Prediction performance was similar after internal validation using optimism correction. Prediction performance was maintained within subgroups of different treatment regimens, including supportive therapy, rituximab, calcineurin inhibitors, and cyclophosphamide. Conclusions Either the 3-month or 6-month models can be used in patients with antiphospholipase A2 receptor antibody associated membranous nephropathy after 3 or 6 months of treatment with a variety of immunosuppression or supportive therapy to predict remission status at 12 months.

Background: The objective of this study was to describe thrombin generation in children undergoing cardiac surgery with cardiopulmonary bypass. Change in the endogenous thrombin potential (ETP) across three measurements before and after cardiopulmonary bypass (after protamine and at chest closure) was the primary outcome. Secondary analyses explored an association between thrombin generation and transfusion requirements and predictors of the thrombin generation decline. Methods: Blood samples of children (median age, 6.3 months; 68.5% weighed less than 10 kg) were collected intraoperatively three times: before administration of heparin (baseline), shortly after protamine, and at sternal closure. Platelet-poor plasma obtained after centrifugation of these samples was frozen at −80ºC. Thrombin generation and anti-Xa assays were performed in series on batches of thawed samples to evaluate thrombin generation parameters and functional activity of unfractionated heparin, which could have affected thrombin generation assay results. Results: Between August 2022 and May 2024, 162 plasma samples from 54 patients were collected and analyzed. Compared with baseline, mean ETP decreased by 1,911 nM (95% CI, 1,655 to 2,168) after administration of protamine and by 1,865 nM (95% CI, 1,609 to 2,122) at sternal closure (P < 0.001). Similar changes were observed in secondary thrombin generation parameters. Median unfractionated heparin activity was less than 0.1 U/ml at all three time points. Secondary analyses showed a strong negative correlation between ETP after protamine and volume of transfusion after bypass (ρ = −0.52, P < 0.001). Among five examined factors, only total heparin dose was independently associated with ETP decline, with a higher dose being predictive of greater ETP decline (P = 0.002). Conclusions: In children undergoing cardiac surgery, thrombin generation assay revealed significant and persistent decline in endogenous thrombin potential after cardiopulmonary bypass, despite hemostatic interventions. This reduced thrombin potential correlated with a higher volume of transfusions. Additionally, greater intraoperative heparin requirements could be linked to a more pronounced decline in thrombin generation.

This case report discusses a man who tested positive for IgLON5-IgG antibody after intermittent episodes of paresthetic feeling involving the throat and jaw, associated with subtle dysarthria and dysphagia, and upper-extremity paresthesia with piloerection of the forearms.

This Viewpoint discusses clinicians as legal petitioners of extreme risk protection orders to promote the safety and well-being of patients and communities.