The Adverse Event Landscape of Stem Cell Transplant: Evidence for aGVHD Driving Early Transplant Associated Toxicities.

Although unrelated-donor (URD) hematopoietic cell transplantation (HCT) is associated with many toxicities, a detailed analysis of adverse events, as defined by the Common Terminology Criteria for Adverse Events (CTCAE), has not previously been curated. This represents a major unmet need, especially as it relates to assessing the safety of novel agents. We analyzed a detailed AE database from the "ABA2" randomized, double-blind, placebo-controlled clinical trial of abatacept for acute graft-versus-host disease (aGVHD) prevention, for which the FDA mandated a detailed AE assessment through Day +180, and weekly neutrophil and platelet counts through Day +100. These were analyzed for their relationship to key transplant outcomes, with a major focus on the impact of aGVHD on the development/severity of AEs. A total of 2102 AEs and 1816 neutrophil/platelet counts were analyzed from 142 8/8-HLA-matched URD HCT recipients on ABA2 (placebo cohort, n = 69, abatacept cohort, n = 73). This analysis resulted in 2 major observations. (1) Among graft source, conditioning intensity, age, and Grade 2 to 4 aGVHD, only aGVHD impacted Grade 3 to 5 AE acquisition after the first month post-transplant. (2) The development of Grade 3 to 4 aGVHD was associated with thrombocytopenia. We have created a detailed resource for the transplant community by which to contextualize clinical toxicities after transplant. It has identified aGVHD as a major driver of post-HCT Grade 3 to 5 AEs, and underscored a link between aGVHD and thrombocytopenia. This establishes a critical safety framework upon which the impact of novel post-transplant aGVHD therapeutics should be evaluated. This trial was registered at www.clinicaltrials.gov (#NCT01743131).

Persistent or new cytopenias predict relapse better than routine bone marrow aspirate evaluations after hematopoietic cell transplantation for acute leukemia or myelodysplastic syndrome in children and young adult patients.

BACKGROUND: The clinical value of serial routine bone marrow aspirates (rBMAs) in the first year after allogeneic hematopoietic cell transplantation (alloHCT) to detect or predict relapse of acute leukemia (AL) and myelodysplastic syndrome (MDS) in pediatric and young adult patients is unclear. OBJECTIVE: The purpose of this analysis was to determine if assessment of minimal residual disease (MRD) by multiparameter flow cytometry (MFC, MFC-MRD) or donor chimerism (DC) in rBMAs or serial CBCs done in the year after alloHCT predicted relapse of AL or MDS in pediatric and young adult patients. STUDY DESIGN: We completed a retrospective analysis of patients with AL or MDS who had rBMAs performed after alloHCT between January 2012- June 2018. Bone marrow (BM) was evaluated at approximately 3, 6 and 12 months for disease recurrence by morphology, MFC-MRD and percent DC by short tandem repeat (STR) molecular testing. CBCs were performed at every clinic visit. The main outcome of interest was assessment of whether MFC-MRD or DC in rBMAs or serial CBCs done in the year after alloHCT predicted relapse in AL or MDS pediatric and young adult patients. RESULTS: 121 recipients with median age of 13 years (range 1-31) were included: 108 with AL and, 13 with MDS. A total of 423 rBMAs (median 3; 0 - 13) were performed. Relapse at 2 years was 23% (95%CI:16 - 31%) and at 5 years 25% (95%CI 18-33%). 154 of 157 (98%) rBMAs evaluated for MRD by MFC were negative and did not preclude subsequent relapse. Additionally, low DC (< 95%) did not predict relapse and high DC (≥ 95%) did not preclude relapse. For patients alive without relapse at 1 year, BM DC (p = 0.74) and peripheral T-cell DC (p = 0.93) did not predict relapse. Six patients with low level T-cell and/or BM DC had a total of 8-20 BM evaluations, none of these patients relapsed. However, CBC results were informative for relapse; 28 of 31 (90%) relapse patients presented with an abnormal CBC with peripheral blood (PB) blasts (16 patients), cytopenias (9 patients), or extramedullary disease (EMD, 3 patients). Two patients with BM blasts >5% on rBMA had circulating blasts within 5 weeks of rBMA. Neutropenia (ANC <1.5 K/mcl) at 1 year was predictive of relapse (p= 0.01). Neutropenia and thrombocytopenia (<160K/mcl) were predictive of diseases free survival (DFS) with inferior DFS for ANC<1.5 K/mcl; p = 0.001, or platelet count <160K/mcl (p = 0.04). CONCLUSION: These results demonstrate rBMAs after alloHCT assessed for MRD by MFC and/or for level of DC are poor predictors for relapse in pediatric and young adult patients with AL or MDS. Relapse in these patients presents with PB blasts, cytopenias or EMD. ANC and platelet count at 1-year were highly predictive for DFS.

Cemented Stem Design in Total Hip Arthroplasty: Fixation Philosophies, Biomechanics, and an Updated Classification System.

There is renewed interest in cemented femoral fixation in total hip arthroplasty in the United States, and to fully appreciate the evolution of cemented femoral stem designs, an understanding of their history and design rationale is essential. To adequately study the outcomes of modern-day designs, a comprehensive classification system is also necessary. The biomechanical principles, failure mechanisms, and clinical outcomes associated with various cemented femoral stems are described in this comprehensive review. In addition, an updated version of an existing classification system is described that incorporates the primary design characteristics which differentiate implants currently in use. In this classification, implants are categorized as taper-slip (Type I), which are subdivided by Anatomic (IA), Double-Taper (IB), and Triple-Taper (IC) with subclassification for Traditional and Line-to-Line implants. Composite beam (Type II) implants are similarly divided into Anatomic (IIA), Straight (IIB), and Wedge (IIC) with subclassification for Polished, Satin, or Roughened finish. This classification system provides a basis for comparing cemented femoral stems, thereby improving our understanding of the effect of design characteristics on survivorship to guide future advancements and improve clinical outcomes.

The Association between Race and Extended Length of Stay in Low-energy Proximal Humerus Fractures in Elderly Patients.

INTRODUCTION: Proximal humerus fractures (PHFs) are one of the most common fractures among patients aged 65 years and older, commonly due to low-energy mechanisms. It is essential to identify drivers of increased healthcare utilization in geriatric PHF patients and bring awareness to any disparities in care. Here, we identify factors associated with the likelihood of inpatient admission and prolonged hospital stay among patients aged 65 years and older who sustain PHF due to falls. METHODS: A national database was used to identify patients aged 65 years and older who suffered proximal humeral fractures due to a fall. Patient factors were analyzed for association with the likelihood of admission and odds of prolonged stay (≥5 days). RESULTS: In the study period, 75,385 PHF patients who met our inclusion criteria presented to the emergency department and 14,118 (18.7%) were admitted. Black race was significantly associated with decreased odds of admission (P < 0.001) and increased likelihood of prolonged stay (P = 0.007) compared with White patients. Patients aged 75 to 84 and 85+ were both more likely to be admitted (P < 0.001) and experienced a prolonged hospital stay (P = 0.015). Patients undergoing surgical intervention with reverse total shoulder arthroplasty were associated with admission and prolonged length of stay (P < 0.001). Hospitals in Midwestern (P < 0.001) and Western (P < 0.001) regions exhibited lower rates of admission and Northeastern hospitals were associated with prolonged stays (P = 0.001). Finally, trauma and nonmetropolitan (P < 0.001) centers were associated with admission. CONCLUSION: Our study highlights the notable influence of age and race on the likelihood of hospital admission and prolonged hospital stay. Specifically, Black patients exhibited prolonged hospital stay, which has been associated with lower-quality care, warranting additional exploration. Understanding these demographic and hospital-related factors is essential for optimizing resource allocation and reducing healthcare disparities in the care of PHF patients, especially as the population ages and the incidence of PHF continues to rise.

Burnout in Urological Education: An In-Depth Study of Residents and Fellows in the 2021 AUA Census.

PURPOSE: Our goal was to explore the current trends in burnout, career choice regret, and well-being needs among urology residents and fellows, with specific emphasis on identifying key factors associated with burnout. MATERIALS AND METHODS: The AUA Workforce Workgroup collaborated with the AUA Data Team to analyze data from the 2021 AUA Census, comprising a total of 243 residents and fellows. Key demographics, benefits and resources, career choice and debt, and burnout levels were analyzed, focusing on variables like gender, PGY (postgraduate year) level, debt burden, and personal health appointments. RESULTS: Overall, 48% of residents and 33% of fellows met criteria for professional burnout, with a higher incidence among PGY-2 residents (70%). Depersonalization was particularly notable, with 74% of residents reporting medium to high levels. Burnout was significantly associated with difficulty attending personal health appointments (52% vs 34%) and lack of access to on-call rooms (54% vs 36%). In contrast, having children during residency was associated with lower burnout levels (30.8% vs 49.1%). Meal plans were ranked as the most desired benefit (32%), followed by ability to attend health appointments during work hours (17%) and paid family leave (16%). Educational debt over $150,000 was carried by 53% of residents and 48% of fellows. Interestingly, burnout rates showed no statistically significant difference in response rates across genders, relationship status, amount of educational debt, presence of paid maternity or paternity leave, and type of childcare arrangements. CONCLUSIONS: Burnout remains a significant issue among urology trainees, with a complex interplay of factors like lack of personal time and provision of call rooms. The alarming rates of depersonalization and exhaustion highlight the urgency of implementing targeted interventions. Enhanced support systems, improved access to health care appointments, provision of call rooms, and debt management programs are recommended to alleviate the growing problem of professional burnout in the field of urology.

Two novel assays demonstrate persistent daratumumab exposure in a pediatric patient with delayed engraftment following allogeneic hematopoietic stem cell transplantation.

BACKGROUND AIMS: Daratumumab, a human IgG monoclonal antibody targeting CD38, is a promising treatment for pediatric patients with relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL). We describe a case of delayed engraftment following a mismatched, unrelated donor hematopoietic stem cell transplant (HSCT) in a 14-year-old female with relapsed T-ALL, treated with daratumumab and chemotherapy. By Day 28 post-HSCT, the patient had no neutrophil engraftment but full donor myeloid chimerism. METHODS: We developed two novel, semi-quantitative, antibody-based assays to measure the patient's bound and plasma daratumumab levels to determine if prolonged drug exposure may have contributed to her slow engraftment. RESULTS: Daratumumab levels were significantly elevated more than 30 days after the patient's final infusion, and levels inversely correlated with her white blood cell counts. To clear daratumumab, the patient underwent several rounds of plasmapheresis and subsequently engrafted. CONCLUSIONS: This is the first report of both delayed daratumumab clearance and delayed stem cell engraftment following daratumumab treatment in a pediatric patient. Further investigation is needed to elucidate the optimal dosing of daratumumab for treatment of acute leukemias in pediatric populations as well as daratumumab's potential effects on hematopoietic stem cells and stem cell engraftment following allogenic HSCT.

AM-PAC Mobility Score <13 Predicts Development of Ileus Following Adult Spinal Deformity Surgery.

STUDY DESIGN: Retrospective review. OBJECTIVE: To determine whether the Activity Measure for Post-Acute Care (AM-PAC) "6-Clicks" score is associated with the development of postoperative ileus. SUMMARY OF BACKGROUND DATA: Adult spinal deformity (ASD) surgery has a high complication rate. One common complication is postoperative ileus, and poor postoperative mobility has been implicated as a modifiable risk factor for this condition. METHODS: Eighty-five ASD surgeries in which ≥5 levels were fused were identified in a single institution database. A physical therapist/physiatrist collected patients' daily postoperative AM-PAC scores, for which we assessed first, last, and daily changes. We used multivariable linear regression to determine the marginal effect of ileus on continuous AM-PAC scores; threshold linear regression with Bayesian information criterion to identify a threshold AM-PAC score associated with ileus; and multivariable logistic regression to determine the utility of the score thresholds when controlling for confounding variables. RESULTS: Ten of 85 patients (12%) developed ileus. The mean day of developing ileus was postoperative day 3.3±2.35. The mean first and last AM-PAC scores were 16 and 18, respectively. On bivariate analysis, the mean first AM-PAC score was lower in patients with ileus than in those without (13 vs. 16; P<0.01). Ileus was associated with a first AM-PAC score of 3 points lower (Coef. -2.96; P<0.01) than that of patients without ileus. Patients with an AM-PAC score<13 had 8 times greater odds of developing ileus (P=0.023). Neither the last AM-PAC score nor the daily change in AM-PAC score was associated with ileus. CONCLUSIONS: In our institutional cohort, a first AM-PAC score of <13, corresponding to an inability to walk or stand for more than 1 minute, was associated with the development of ileus. Early identification of patients who cannot walk or stand after surgery can help determine which patients would benefit from prophylactic management. LEVEL OF EVIDENCE: Level-III.

Exploring the Demands of Urology: On-Call Compensation, Frequency, and Variability.

INTRODUCTION: We investigate and analyze the available information regarding on-call patterns among urologists in the US. METHODS: The AUA Workforce Workgroup collaborated with the AUA Data Team to analyze information from the 2022 AUA Census. Extracted data were analyzed to identify variability across gender, subspecialty, hours worked per week, AUA section, salary, and practice setting. We used χ2 tests to compare the groups with respect to each factor and defined statistical significance as a P value less than .05. RESULTS: There were significant differences by gender and several other on-call factors including being required to take call to maintain hospital privileges (reported by 76% of female urologists vs 67% of male urologists; P = .026), getting paid for weekend call (28% of females vs 38% of males; P = .030), and making over $500 per day when taking weekend call (18% of females vs 32% of males; P < .001). Other differences existed between AUA sections in percentage of physicians receiving over $500 for weekday or weekend calls (P < .001). Lastly, practice setting differed in likelihood of being paid over $500 for weekday call (44% reported by private practice urologists, 7% reported by academic urologists, 14% reported by institutional urologists; P < .001). CONCLUSIONS: These results underscore the substantial variability in on-call responsibilities and structure within the AUA workforce. Further research and regular participation in future censuses are recommended to continue to characterize these trends.

The Association Between Oral Bone Mineral Density-Reducing Medications and the Risk of 2-Year Implant-Related Complications Following Total Knee Arthroplasty.

BACKGROUND: Certain medications interfere with the bone remodeling process and may potentially increase the risk of complications after total knee arthroplasty (TKA). As patients undergoing TKA may be taking these bone mineral density (BMD)-reducing medications, it is unclear as to whether and which medications impact TKA outcomes. Therefore, the purpose of this study was to observe the impact of various BMD-reducing medications on 2-year implant-related complications following TKA. METHODS: A retrospective analysis of patients undergoing primary TKA was conducted using a national administrative claims database. Patients were identified if they were taking any known BMD-reducing medication and were compared to control patients. To control for confounders associated with taking multiple agents, multivariable logistic regression analyses were conducted for each 2-year outcome (all-cause revision, loosening-indicated revision, and periprosthetic fracture--indicated revision), with the output recorded as odds ratios (ORs). RESULTS: In our study, 502,927 of 1,276,209 TKA patients (39.4%) were taking at least one BMD-reducing medication perioperatively. On multivariable analysis, medications associated with a higher likelihood of 2-year all-cause revision included first- and second-generation antipsychotics (SGAs) (OR: 1.42 and 1.26, respectively), selective serotonin reuptake inhibitors (SSRIs) (OR: 1.14), glucocorticoids (1.13), and proton pump inhibitors (PPIs) (OR: 1.23) (P < .05 for all). Medications associated with a higher likelihood of 2-year periprosthetic fracture included SGAs (OR: 1.51), SSRIs (OR: 1.27), aromatase inhibitors (OR: 1.29), and PPIs (OR: 1.42) (P < .05 for all). CONCLUSIONS: Of the drug classes observed, the utilization of perioperative PPIs, SSRIs, glucocorticoids, first-generation antipsychotics, and SGAs was associated with the highest odds of all-cause revision. Our findings suggest a relationship between these medications and BMD-related complications; however, further studies should seek to determine the causality of these relationships.

Genoprotective role of pembrolizumab liposome in isolated lymphocytes from head and neck squamous cell carcinoma patients compared to those from healthy individuals in vitro.

Pembrolizumab has shown significant anticancer effects against various human cancers. The present study investigated the effects of pembrolizumab liposome and nano (naked) forms in treated lymphocytes from head and neck squamous cell carcinoma (HNSCC) patients compared to healthy individuals. The level of oxidative DNA damage induced by hydrogen peroxide (H2O2) was also investigated. A concentration of 10 µg/ml of pembrolizumab liposome was used to treat the lymphocytes in the Comet and micronucleus assays based on the preliminary dosage optimization tests. To determine the cellular pathways involved in the protective role of pembrolizumab against H2O2, several proteins involved in apoptosis (P53, P21 and Bcl-2) were assessed. Pembrolizumab significantly reduced DNA damage and decreased the number of micronuclei in lymphocytes from HNSCC patients (p < 0.01) compared with healthy individuals. The 10 µg/ml of pembrolizumab liposome significantly reduced the oxidative stress induced by H2O2 and was effective in healthy and HNSCC groups using the Comet and micronucleus assays (p < 0.001). To our knowledge, this is the first report of pembrolizumab in liposome and naked forms exhibiting a protective effect on DNA damage in the treatment of HNSCC patients.

Flexible nailing: Pushing the indications for diametaphyseal lower-extremity fractures.

Elastic stable intramedullary nailing (ESIN) has been shown to be an effective form of surgical management for lower-extremity diametaphyseal fractures in pediatric patients, but studies are limited because ESIN treatment for these fractures is relatively uncommon. We sought to determine whether ESIN can be used effectively in the most distal or proximal short-segment forms of these fractures. We queried the electronic medical record system at Johns Hopkins Hospital using Current Procedural Terminology codes for femur and tibia fractures treated with ESIN in patients under 18 years old between January 2015 and October 2022. Preoperative and postoperative radiographs were subsequently reviewed to identify patients with a proximal or distal third femoral or tibial shaft fracture treated with ESIN and to define criteria for short-segment diametaphyseal fractures. We used Beaty radiological criteria to evaluate radiographic outcomes and Flynn titanium elastic nails (TENs) outcome scale to assess clinical recovery after radiographic evidence of union. There were 43 children who met the inclusion criteria. Among them, 10 patients had short-segment diametaphyseal fractures. There were 22 (51.2%) who sustained femur fractures and 21 (48.8%) who sustained tibia fractures. Using Beaty radiologic criteria, ESIN was associated with more satisfactory outcomes in patients with distal or proximal third shaft fractures (32/33) than in patients with short-segment diametaphyseal fractures (7/10) (P = .03). Using the TENs outcome scale, 21 (63.4%) patients with distal or proximal third shaft fractures had excellent results, 11 (33.3%) had satisfactory results, and 1 (3%) had a poor result. Among patients with short-segment diametaphyseal fractures, 4 (40%) had excellent results, 5 (50%) had satisfactory results, and 1 (10%) had a poor result. There were no differences in TENs outcomes between the groups (P = .24). Patients with short-segment lower-extremity diametaphyseal fractures treated with ESIN had worse radiographic outcomes but did no worse clinically than patients with distal or proximal third shaft fractures. Consequently, ESIN should be considered a safe and effective surgical management option for pediatric patients with even the most distal or proximal forms of these fractures.

The weight of complications: high and low BMI have disparate modes of failure in total hip arthroplasty.

BACKGROUND: Body mass index (BMI) has been shown to influence risk for revision total hip arthroplasty (rTHA), but few studies have specifically examined which causes of rTHA are most likely in different BMI classes. We hypothesized that patients in different BMI classes would undergo rTHA for disparate reasons. METHODS: Ninety-eight thousand six hundred seventy patients undergoing rTHA over 2006-2020 were identified in the National Inpatient Sample. Patients were classified as underweight, normal-weight, overweight/obese, or morbidly obese. Multivariable logistic regression was used to analyze the impact of BMI on rTHA for periprosthetic joint infection (PJI), dislocation, periprosthetic fracture (PPF), aseptic loosening, or mechanical complications. Analyses were adjusted for age, sex, race/ethnicity, socioeconomic status, insurance, geographic region, and comorbidities. RESULTS: Compared to normal-weight patients, underweight patients were 131% more likely to have a revision due to dislocation and 63% more likely due to PPF. Overweight/obese patients were 19% less likely to have a revision due to dislocation and 10% more likely due to PJI. Cause for revision in morbidly obese patients was 4s1% less likely to be due to dislocation, 8% less likely due to mechanical complications, and 90% more likely due to PJI. CONCLUSIONS: Overweight/obese and morbidly obese patients were more likely to undergo rTHA for PJI and less likely for mechanical reasons compared to normal weight patients. Underweight patients were more likely to undergo rTHA for dislocation or PPF. Understanding the differences in cause for rTHA among the BMI classes can aid in patient-specific optimization and management to reduce postoperative complications. LEVEL OF EVIDENCE: III.

Structural Allograft Versus Mechanical Interbody Devices Augmented With Osteobiologics in Anterior Cervical Discectomy and Fusion: A Systematic Review.

STUDY DESIGN: Systematic Literature Review. OBJECTIVE: Perform a systematic review evaluating postoperative fusion rates for anterior cervical discectomy and fusion (ACDF) using structural allograft vs various interbody devices augmented with different osteobiologic materials. METHODS: Comprehensive literature search using PubMed, Embase, The Cochrane Library, and Web of Science was performed. Included studies were those that reported results of 1-4 levels ACDF using pure structural allograft compared with a mechanical interbody device augmented with an osteobiologic. Excluded studies were those that reported on ACDF with cervical corpectomy; anterior and posterior cervical fusions; circumferential (360° or 540°) fusion or revision ACDF for nonunion or other conditions. Risk of bias was determined using the Cochrane review guidelines. RESULTS: 8 articles reporting fusion rates of structural allograft and an interbody device/osteobiologic pair were included. All included studies compared fusion rates following ACDF among structural allograft vs non-allograft interbody device/osteobiologic pairs. Fusion rates were reported between 84% and 100% for structural allograft, while fusion rates for various interbody device/osteobiologic combinations ranged from 26% to 100%. Among non-allograft cage groups fusion rates varied from 73-100%. One study found PEEK cages filled with combinations of autograft, allograft, and demineralized bone matrix (DBM) to have an overall fusion rate of 26%. In one study comparing plate and zero-profile constructs, there was no difference in fusion rates for two-level fusions. CONCLUSION: There was limited data comparing fusion outcomes of patients undergoing ACDF using structural allograft vs interbody devices augmented with osteobiologic materials to support superiority of one method.

Evaluation of Potential Urologic Prescription Drug Savings With Mark Cuban Cost Plus Drug Company.

INTRODUCTION: Mark Cuban Cost Plus Drug Company (MCCPDC) launched in 2022 with a goal to decrease prescription drug costs. Thus far, research has focused on possible savings if Medicare purchased its annual volume of drugs at MCCPDC prices. The aim of this study is to analyze if MCCPDC can offer savings directly to urologic patients compared with other mail-order pharmacies, local pharmacies, and with patients using health insurance. METHODS: Twelve drugs used to treat urological diseases available on MCCPDC were analyzed. Pricing data of 30-tab and 90-tab prescriptions from MCCPDC, other mail-order pharmacies, and local in-person pharmacies near our zip code 40508 (Lexington, Kentucky) were compiled. To compare if MCCPDC could offer savings to patients using health insurance to fill their prescriptions, out-of-pocket drug costs for patients from the 2020 and 2021 Medical Expenditure Panel Survey and the 2021 Medicare Part D spending data were extracted. RESULTS: Greater savings at MCCPDC were found at 90-tab prescriptions, but overall variability in prices existed. When comparing without health insurance, 9 of 12 drugs at MCCPDC were cheaper at 90 tabs with solifenacin and tadalafil saving $20 and $12 per prescription. When considering patients using insurance, abiraterone, sildenafil, and tadalafil offered savings on out-of-pocket costs at 30- and 90-tab prescriptions. CONCLUSIONS: MCCPDC may offer cheaper prices for patients filling urologic medications, especially at 90-tab prescriptions. This study is the first to show patients could save money using MCCPDC and has implications for physician counseling when prescribing common urologic drugs.

Impact of rabbit anti-thymocyte globulin (ATG) exposure on outcomes after ex vivo T-cell-depleted hematopoietic cell transplantation in pediatric and young adult patients.

BACKGROUND AIMS: Traditional weight-based dosing of rabbit anti-thymocyte globulin (rATG) used in allogeneic hematopoietic cell transplantation (HCT) to prevent graft-versus-host disease (GVHD) and graft rejection leads to variable exposures. High exposures induce delayed CD4+immune reconstitution (CD4+IR) and greater mortality. We sought to determine the impact of rATG exposure in children and young adults receiving various types of EX-VIVO T-cell-depleted (EX-VIVO-TCD) HCT. METHODS: Patients receiving their first EX-VIVO-TCD HCT (CliniMACS CD34+, Isolex or soybean lectin agglutination), with removal of residual T cells by E-rosette depletion (E-) between 2008 and 2018 at Memorial Sloan Kettering Cancer Center were retrospectively analyzed. rATG exposure post-HCT was estimated (AU*d/L) using a validated population pharmacokinetic model. Previously defined rATG-exposures, <30, 30-55, ≥55 AU*d/L, were related with outcomes of interest. Cox proportional hazard and cause-specific models were used for analyses. RESULTS: In total, 180 patients (median age 11 years; range 0.1-44 years) were included, malignant 124 (69%) and nonmalignant 56 (31%). Median post-HCT rATG exposure was 32 (0-104) AU*d/L. Exposure <30 AU*d/L was associated with a 3-fold greater probability of CD4+IR (P < 0.001); 2- to 4-fold lower risk of death (P = 0.002); and 3- to 4-fold lower risk of non-relapse mortality (NRM) (P = 0.02). Cumulative incidence of NRM was 8-fold lower in patients who attained CD4+IR compared with those who did not (P < 0.0001). There was no relation between rATG exposure and aGVHD (P = 0.33) or relapse (P = 0.23). Effect of rATG exposure on outcomes was similar in three EX-VIVO-TCD methods. CONCLUSIONS: Individualizing rATG dosing to target a low rATG exposure post-HCT while maintaining total cumulative exposure may better predict CD4+IR, reduce NRM and increase overall survival, independent of the EX-VIVO-TCD method.

Risk Factors Associated With Quadriceps Tendon Extensor Mechanism Disruption Following Total Knee Arthroplasty.

BACKGROUND: Quadriceps tendon extensor mechanism disruption is an infrequent but devastating complication after total knee arthroplasty (TKA). Our knowledge of specific risk factors for this complication is limited by the current literature. Thus, this study aimed to identify potential risk factors for quadriceps tendon extensor mechanism disruption following TKA. METHODS: A retrospective cohort analysis was performed using the PearlDiver Administrative Claims Database. Patients undergoing TKA without a prior history of quadriceps tendon extensor mechanism disruption were identified. Quadriceps tendon extensor mechanism disruption included rupture of the quadriceps tendon, patellar tendon, or fracture of the patella. Patients who had a minimum of 5 years of follow-up after TKA were included. A total of 126,819 patients were included. Among them, 517 cases of quadriceps tendon extensor mechanism disruption occurred (incidence 0.41%). Hypothesized risk factors were compared between those who had postoperative quadriceps tendon extensor mechanism disruption and those who did not. RESULTS: On multivariate analysis, increased Charlson Comorbidity Index (odds ratio (OR): 1.10, 95% confidence interval (CI) [1.07 to 1.13]; P < .001), obesity (OR: 1.49, 95% CI [1.24 to 1.79]; P < .001), and fluoroquinolone use any time after TKA (OR: 1.24, 95% CI [1.01 to 1.52]; P = .036) were significantly associated with quadriceps tendon extensor mechanism disruption. CONCLUSIONS: Our study identified the incidence of quadriceps tendon extensor mechanism disruption following TKA as 0.41%. Identified risk factors for quadriceps tendon extensor mechanism disruption after TKA include an increased Charlson Comorbidity Index, obesity, and use of fluoroquinolones postoperatively.

Overlap chronic GVHD is associated with adverse survival outcomes compared to classic chronic GVHD.

Chronic graft-versus-host-disease (cGVHD) is divided into two subtypes: classic (absence of acute GVHD features) and overlap cGVHD ('ocGVHD'), in which both chronic and acute GVHD clinical features are present simultaneously. While worse outcomes with ocGVHD have been reported, there are few recent analyses. We performed a secondary analysis of data from the ABA2 trial (N = 185), in which detailed GVHD data were collected prospectively and systematically adjudicated. Analyses included cumulative incidence of classic versus ocGVHD, their specific organ manifestations, global disease severity scores, non-relapse mortality (NRM), disease-free survival (DFS) and overall survival (OS) in these two cGVHD subtypes. Of 92 patients who developed cGVHD, 35 were classified as ocGVHD. The 1-year cumulative incidence, organ involvement, and global severity of classic and ocGVHD were similar between ABA2 patients receiving CNI/MTX+placebo and CNI/MTX+abatacept; thus, cohorts were combined for ocGVHD evaluation. This analysis identified ocGVHD as having significantly higher severity at presentation and at maximum global severity compared to classic cGVHD. OS and DFS were significantly lower for ocGVHD versus classic cGVHD. OcGVHD is associated with increased cGVHD severity scores, and is associated with decreased OS and DFS compared to classic cGVHD, underscoring the high risks with this cGVHD subtype.

Can You Pay Your Way to Readership? Free to Publish Open Access Formats Receive Greater Readership and Citations Than Paid Open Access Formats in Total Knee Arthroplasty Literature.

BACKGROUND: As publishing with open access is becoming increasingly popular within orthopaedics, understanding the types of publishing options available and what each may deliver is critically important. Hybrid articles require a high article processing charge. Open journal articles have a lower fee, while closed license articles are freely accessible at no charge. Open repository articles are peer-reviewed manuscripts posted freely online. The purpose of this study was to determine the relationship between article type and resulting citations, social media attention, and readership in total knee arthroplasty (TKA) literature. METHODS: Open access TKA journal articles published since 2016 were found using the Altmetric Explorer Database. Data gathered included the Altmetric Attention Score (attention), Mendeley Readership Score (readership), and citations per article. Articles were grouped by type: open journal, hybrid, closed license, and open repository. Results were analyzed using descriptive statistics and Tukey's analysis; α = 0.05. RESULTS: A total of 9,606 publications were included. The open repository had the greatest mean citations (14.40), while open journal (9.55) had fewer than all other categories (P < .001). Hybrid had the greatest mean attention (10.35), and open journal (6.16) had a lower mean attention than all other categories (P ≤ .002). Open repository had the greatest mean readership (44.68), and open journal (34.00) had a lower mean readership than all other categories (P ≤ .012). The mean publication fee for paid publication options was $1,792 United States dollars. CONCLUSIONS: In open access TKA literature, free-to-publish open repositories had the greatest mean citations and readership. Free publication options, open repositories and closed licenses, had greater readership compared to paid publication options.

Trends in Extended Oral Antibiotic Prophylaxis Utilization Following Primary and Revision Total Hip Arthroplasty From 2010 to 2022.

BACKGROUND: In patients considered high-risk for infection, extended oral antibiotic (EOA) prophylaxis has been demonstrated to reduce rates of prosthetic joint infection following total hip arthroplasty (THA). Although national guidelines regarding their use have not yet been created, the increase in literature surrounding EOA prophylaxis suggests a potential change in practice patterns. The purpose of this study was to investigate the trends in utilization of EOA prophylaxis following THA from 2010 to 2022 and identify prescription patterns. METHODS: A total of 646,059 primary THA and 51,879 aseptic revision THA patients were included in this study. Patients who underwent primary or aseptic revision THA between 2010 and 2022 were identified in a national administrative claims database. Rates and duration of EOA prescriptions were calculated. A secondary analysis examined rates of utilization across demographics, including patients considered high risk for infection. RESULTS: From 2010 to 2022, utilization of EOA increased by 366% and 298% following primary and revision THA, respectively. Of patients prescribed postoperative antibiotics, 30% and 59% were prescribed antibiotics for more than 7 days following primary and revision THA, respectively. Rates of utilization were similar between high-risk individuals and the general population. CONCLUSIONS: Rates of utilization of EOA prophylaxis after THA have increased significantly since 2010. As current trends demonstrate a wide variation in prescription patterns, including in length of antibiotic duration and in patient population prescribed, guidelines surrounding the use of EOA prophylaxis after THA are necessary to promote antibiotic stewardship while preventing rates of periprosthetic joint infection.