Strategies to Guide Preemptive Waitlisting and Equity in Waittime Accrual by Race/Ethnicity.

BACKGROUND: Use of eGFR to determine preemptive waitlisting eligibility may contribute to racial/ethnic disparities in access to waitlisting, which can only occur when the eGFR falls to ≤20 ml/min per 1.73 m 2 . Use of an alternative risk-based strategy for waitlisting may reduce these inequities ( e.g. , a kidney failure risk equation [KFRE] estimated 2-year risk of kidney failure) rather than the standard eGFR threshold for determining waitlist eligibility. Our objective was to model the amount of preemptive waittime that could be accrued by race and ethnicity, applying two different strategies to determine waitlist eligibility. METHODS: Using electronic health record data, linear mixed models were used to compare racial/ethnic differences in preemptive waittime that could be accrued using two strategies: estimating the time between an eGFR ≤20 and 5 ml/min per 1.73 m 2 versus time between a 25% 2-year predicted risk of kidney failure (using the KFRE, which incorporates age, sex, albuminuria, and eGFR to provide kidney failure risk estimation) and eGFR of 5 ml/min per 1.73 m 2 . RESULTS: Among 1290 adults with CKD stages 4-5, using the Chronic Kidney Disease Epidemiology Collaboration equation yielded shorter preemptive waittime between an eGFR of 20 and 5 ml/min per 1.73 m 2 in Black (-6.8 months; 95% confidence interval [CI], -11.7 to -1.9), Hispanic (-10.2 months; -15.3 to -5.1), and Asian/Pacific Islander (-10.3 months; 95% CI, -15.3 to -5.4) patients compared with non-Hispanic White patients. Use of a KFRE threshold to determine waittime yielded smaller differences by race and ethnicity than observed when using a single eGFR threshold, with shorter time still noted for Black (-2.5 months; 95% CI, -7.8 to 2.7), Hispanic (-4.8 months; 95% CI, -10.3 to 0.6), and Asian/Pacific Islander (-5.4 months; -10.7 to -0.1) individuals compared with non-Hispanic White individuals, but findings only met statistical significance criteria in Asian/Pacific Islander individuals. When we compared potential waittime availability using a KFRE versus eGFR threshold, use of the KFRE yielded more equity in waittime for Black ( P = 0.02), Hispanic ( P = 0.002), and Asian/Pacific Islander ( P = 0.002) patients. CONCLUSIONS: Use of a risk-based strategy was associated with greater racial equity in waittime accrual compared with use of a standard single eGFR threshold to determine eligibility for preemptive waitlisting.

Association Between Dialysis Facility Ownership and Mortality Risk in Children With Kidney Failure.

Importance: In adults, treatment at profit dialysis facilities has been associated with a higher risk of death. Objective: To determine whether profit status of dialysis facilities is associated with the risk of death in children with kidney failure treated with dialysis and whether any such association is mediated by differences in access to transplant. Design, Setting, and Participants: This retrospective cohort study reviewed US Renal Data System records of 15 359 children who began receiving dialysis for kidney failure between January 1, 2000, and December 31, 2019, in US dialysis facilities. The data analysis was performed between May 2, 2022, and June 15, 2023. Exposure: Time-updated profit status of dialysis facilities. Main Outcomes and Measures: Adjusted Fine-Gray models were used to determine the association of time-updated profit status of dialysis facilities with risk of death, treating kidney transplant as a competing risk. Cox proportional hazards regression models were also used to determine time-updated profit status with risk of death regardless of transplant status. Results: The final cohort included 8465 boys (55.3%) and 6832 girls (44.7%) (median [IQR] age, 12 [3-15] years). During a median follow-up of 1.4 (IQR, 0.6-2.7) years, with censoring at transplant, the incidence of death was higher at profit vs nonprofit facilities (7.03 vs 4.06 per 100 person-years, respectively). Children treated at profit facilities had a 2.07-fold (95% CI, 1.83-2.35) higher risk of death compared with children at nonprofit facilities in adjusted analyses accounting for the competing risk of transplant. When follow-up was extended regardless of transplant status, the risk of death remained higher for children treated in profit facilities (hazard ratio, 1.47; 95% CI, 1.35-1.61). Lower access to transplant in profit facilities mediated 67% of the association between facility profit status and risk of death (95% CI, 45%-100%). Conclusions and Relevance: Given the higher risk of death associated with profit dialysis facilities that is partially mediated by lower access to transplant, the study's findings indicate a need to identify root causes and targeted interventions that can improve mortality outcomes for children treated in these facilities.

Assessment of the clinical perception, quality of life and satisfaction of patients with severe congenital haemophilia A without inhibitor after 1 year of emicizumab therapy.

INTRODUCTION: Since the approval by the EMA of emicizumab for the care of severe haemophilia A without inhibitor, most of the patients of our haemophilia treatment centre started this new treatment. Thanks to the setting of a therapeutic patient education program including three pharmaceutical consultations (PC), we could follow patients' lifestyle evolution. AIM: The study aimed to assess the perceived clinical evolution, quality of life and treatment satisfaction of patients after 1 year of emicizumab therapy in real-life settings. METHODS: The study was observational, retrospective and monocentric. Every patient over 18 years old receiving emicizumab from June 2020 and who underwent the 3 PC until March 2022 were included. The clinical evolution was self-estimated by patients with zero-to-six scales before versus 1 year after emicizumab, according to the following parameters: general health state, pain and bleedings (spontaneous or post-traumatic, and patients' identification ability). Patients' quality of life was also estimated with the EQ-5D-3L survey. Their satisfaction, graduated with a zero-to-ten scale, and treatment management were reported during the third PC. RESULTS: Thirty-eight patients were enrolled. Their general health state improved significantly (p = .0023) with an EQ-5D-3L score at 69.6 (±19.4) out of 100. Although chronic pains remained a persistent issue for 33 (86.8%) patients, their intensity was significantly decreasing after 1 year. Perceived frequency of bleedings was significantly reduced too. On average, the satisfaction of emicizumab therapy was 9.1 (± 1.02) out of 10. CONCLUSION: After 1 year of emicizumab therapy, the general health state estimated by patients improved, the pain and the perceived frequency of bleedings diminished. Overall, this treatment received a high patients' satisfaction rate.

Variants of the human RAD52 gene confer defects in ionizing radiation resistance and homologous recombination repair in budding yeast.

RAD52 is a structurally and functionally conserved component of the DNA double-strand break (DSB) repair apparatus from budding yeast to humans. We recently showed that expressing the human gene, HsRAD52 in rad52 mutant budding yeast cells can suppress both their ionizing radiation (IR) sensitivity and homologous recombination repair (HRR) defects. Intriguingly, we observed that HsRAD52 supports DSB repair by a mechanism of HRR that conserves genome structure and is independent of the canonical HR machinery. In this study we report that naturally occurring variants of HsRAD52, one of which suppresses the pathogenicity of BRCA2 mutations, were unable to suppress the IR sensitivity and HRR defects of rad52 mutant yeast cells, but fully suppressed a defect in DSB repair by single-strand annealing (SSA). This failure to suppress both IR sensitivity and the HRR defect correlated with an inability of HsRAD52 protein to associate with and drive an interaction between genomic sequences during DSB repair by HRR. These results suggest that HsRAD52 supports multiple, distinct DSB repair apparatuses in budding yeast cells and help further define its mechanism of action in HRR. They also imply that disruption of HsRAD52-dependent HRR in BRCA2-defective human cells may contribute to protection against tumorigenesis and provide a target for killing BRCA2-defective cancers.

Phase II Study of Pembrolizumab As First-Line, Single-Drug Therapy for Patients With Unresectable Cutaneous Squamous Cell Carcinomas.

PURPOSE: To evaluate first-line pembrolizumab monotherapy efficacy and safety in patients with unresectable cutaneous squamous cell carcinomas (CSCCs). PATIENTS AND METHODS: Patients, predominantly men, with their CSSCs' immunohistochemically determined programmed cell death-ligand 1 (PD-L1) status determined (tumor proportion score threshold, 1%), received pembrolizumab (200 mg every 3 weeks). The primary endpoint was the 39-patient primary cohort's objective response rate at week 15 (ORRW15). Secondary objectives were best ORR, overall survival (OS), progression-free survival (PFS), duration of response (DOR), safety, ORR according to PD-L1 status and health-related quality of life using Functional Assessment of Cancer Therapy-General (FACT-G) score. An 18-patient expansion cohort, recruited to power the study to evaluate the ORRW15 difference between PD-L1+ and PD-L1- patients, was assessed for ORR, disease control rate, and safety, but not survival. RESULTS: Median age of all patients was 79 years. The primary cohort's ORRW15 was 41% (95% CI, 26% to 58%), including 13 partial and 3 complete responses. Best responses were 8 partial and 8 complete responses. At a median follow-up of 22.4 months, respective median PFS, DOR, and OS were 6.7 months, not reached, and 25.3 months, respectively. Pembrolizumab-related adverse events affected 71% of the patients, and 4 (7%) were grade ≥ 3. One death was related to rapid CSCC progression; another resulted from a fatal second aggressive head and neck squamous cell carcinoma diagnosed 15 weeks postinclusion. ORRW15 for the entire population was 42%; it was significantly higher for PD-L1+ patients (55%) versus PD-L1- patients (17%; P = .02). Responders' W15 total FACT-G score had improved (P = .025) compared with nonresponders. CONCLUSION: First-line pembrolizumab monotherapy exhibited promising anti-CSCC activity, with durable responses and manageable safety. PD-L1 positivity appears to be predictive of pembrolizumab efficacy.

Drawing and Hydrophobicity-patterning Long Polydimethylsiloxane Silicone Filaments.

Polydimethylsiloxane (PDMS) silicone is a versatile polymer that cannot readily be formed into long filaments. Traditional spinning methods fail because PDMS does not exhibit long-range fluidity at melting. We introduce an improved method to produce filaments of PDMS by a stepped temperature profile of the polymer as it cross-links from a fluid to an elastomer. By monitoring its warm-temperature viscosity, we estimate a window of time when its material properties are amendable to drawing into long filaments. The filaments pass through a high-temperature tube oven, curing them sufficiently to be harvested. These filaments are on the order of hundreds of micrometers in diameter and tens of centimeters in length, and even longer and thinner filaments are possible. These filaments retain many of the material properties of bulk PDMS, including switchable hydrophobicity. We demonstrate this capability with an automated corona-discharge patterning method. These patternable PDMS silicone filaments have applications in silicone weavings, gas-permeable sensor components, and model microscale foldamers.

Shear bond strength of two 2-step etch-and-rinse adhesives when bonding ceramic brackets to bovine enamel.

AIM: The present study assessed a fracture analysis and compared the shear bond strength (SBS) of two 2-step etch-and-rinse (E&R) adhesives when bonding ceramic orthodontic brackets to bovine enamel. MATERIALS AND METHODS: Thirty healthy bovine mandibular incisors were selected and were equally and randomly assigned to 2 experimental groups. Ceramic brackets (FLI Signature Clear®, RMO) were bonded onto bovine enamel using an adhesive system. In group 1 (n=15), the conventional E&R adhesive (OrthoSolo®+Enlight®, Ormco) was used, and in group 2 (n=15), the new E&R adhesive limited to ceramic bracket bonding (FLI ceramic adhesive®: FLI sealant resin®+FLI adhesive paste®, RMO) was used. In order to obtain appropriate enamel surfaces, the vestibular surfaces of mandibular bovine incisors were flat ground. After bonding, all the samples were stored in distilled water at room temperature for 21 days and subsequently tested for SBS, using the Instron® universal testing machine. The Adhesive Remnant Index (ARI) scores were evaluated. Failure modes were assessed using optical microscopy at magnification ×40. A statistic data analysis was performed using the Mann-Whitney U-test (P<0.05). RESULTS: The test showed a significant difference (P=0.00155) between the two groups for the SBS values. Group 1 had significantly higher SBS values (9.79 to 20.83MPa) than group 2 (8.45 to 13.94MPa). Analysis of the ARI scores revealed that most of the failures occurred at the enamel/adhesive interface. A statistically significant difference was found for the ARI scores between the two groups (P=0.00996). Only two fractured brackets, which remained bonded onto the bovine enamel, were reported. Both occurred in group 1. CONCLUSION: When bonded to ceramic brackets, FLI ceramic adhesive® (RMO) was demonstrated to be very predictable and safe for clinical application in enamel bonding, whereas the results obtained with the conventional adhesive system (OrthoSolo®+Enlight®, Ormco) were less reproducible and revealed slightly excessive shear bond strength values.

Treatment-related knowledge and skills of patients with haemophilia and their informal caregivers.

BACKGROUND: Replacement therapy in haemophilia plays an important role in the effective management of this rare bleeding disorder and requires a high level of knowledge and practical skills. OBJECTIVE: To evaluate and to compare the knowledge and skills about the medicines and their management among people with haemophilia treated with clotting factor concentrates, and their informal caregivers. SETTING: Eight Hospital Pharmacies working closely with Haemophilia Care Centres in France. Method In this cross-sectional and multi-centre study, 26-item questionnaire was specifically developed to assess the knowledge and skills. Face-to-face interviews using a questionnaire were conducted with patients and caregivers. MAIN OUTCOME MEASURE: Level of knowledge and skills about disease, treatment and medication management. Results This study included 80 patients and 55 caregivers. Although most interviewees had basic knowledge of the treatment, only 43.7 % knew the effect of clotting factor concentrates on the haemostasis process. Similarly, only 12.7 % of the patients and 30.9 % of the caregivers referred to inhibitors as adverse effects. Despite intensive training for home treatment, 55.7 % reported difficulties with reconstitution or injection. The knowledge required for the responsible management of their medications had not been totally acquired: only 17 participants were indeed familiar with the medication storage conditions; 29 patients and 9 caregivers had already experienced an emergency which they had to treat with no medicine available at home; and 47.4 % of participants had already thrown away an unused drug vial. CONCLUSION: This study shows the need of a regular update and to renew awareness of haemophilia treatment specificities among these populations. The identified needs suggest that we should more invest in educational techniques or therapeutic education programs more focused on medication management.

A major target for warm immunoglobulin G autoantibodies: the third external loop of Band 3.

BACKGROUND: Rh proteins and the Wr(b) antigen, which results from an interaction between Band 3 and glycophorin A, are the most common targets for warm immunoglobulin (Ig)G autoantibodies. Apart from autoanti-Di(b) , a scarce specificity, IgG warm autoantibodies specific for Band 3 have never been characterized by serologic methods. STUDY DESIGN AND METHODS: Blood samples from 120 patients with autoimmune hemolytic anemia (AIHA) and IgG-coated red blood cells (RBCs) were studied by serologic methods. Some autoantibodies were investigated by immunochemical methods. RESULTS: Autoantibodies against the third external loop of Band 3 have a distinctive pattern of reactivity in that they fail to react after RBC treatment with α-chymotrypsin and pronase, whereas papain, ficin, and trypsin have no effect. Eleven (9%) patients had pure anti-Band 3 autoantibodies. Autoanti-Band 3 antibodies were associated with other specificities in 66 (55%) patients. Immunoprecipitation and rare RBCs from a Wu+ homozygote, known to have an unusual pattern of reactivity after protease treatment, were used to confirm the Band 3 specificity. Treatment with sodium hypochlorite, believed to oxidize the Met residue at Position 559 in the third loop, showed that these autoantibodies were heterogeneous. Most antibodies reacted optimally at 37 °C, but two patients had incomplete cold IgG autoantibodies. Unlike autoantibodies to Rh proteins, warm autoanti-Band 3 activate complement and are almost totally bound to autologous RBCs. CONCLUSION: We describe the first cases of warm IgG autoantibodies specific for the third loop of Band 3. This external loop also appears as a major target in patients with warm antibody AIHA.

[Retroperitoneal sarcomas imaging]. / Imagerie des sarcomes rétropéritonéaux.

Retroperitoneal sarcomas are rare neoplasms. The aim of this article is to expose imaging protocols and useful radiological signs, to show the core biopsy technique for diagnosis, to precise imaging key points before treatment and for survey.