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Abstract Background Professional medical societies recommend that carrier screening for 113 different genetic disorders be offered during pregnancy or preconception to all individuals, regardless of ancestry, in order to provide more equitable opportunities for patients to ascertain their reproductive risks. In our clinical laboratory experience, however, the vast majority of healthcare providers continue to order carrier screening for only cystic fibrosis (CF), which is disproportionately common in white individuals of Northern European descent. Our highest volume CF screening test is performed on >10,500 diverse patients per year and utilizes a targeted genotyping array that detects >500 variants in CFTR and >1200 variants in >150 other pertinent genes. Here we report the inequities in diagnostic yield among our first 8,000 patients for whom only limited testing was ordered and examine the barriers to widespread adoption of more inclusive carrier screening. Methods Three carrier screening options (CF, CF+spinal muscular atrophy [SMA], CF+SMA+fragile X syndrome [FXS]+hemoglobinopathies) were ordered clinically and performed on DNA extracted from 8,000 whole blood samples from unique individuals utilizing a custom SNP array (Thermo Fisher GeneTitanTM platform) designed to detect >1700 pathogenic variants in 218 different genes. Data was retrospectively reviewed to determine overall detection rates for carriers of all recommended conditions vs. only the condition(s) included in the originally ordered service. Finally, reproductive health providers at nine different ordering sites across the U.S. were interviewed regarding their current carrier screening practices. Results Patients were referred for testing by 119 different clinical facilities. 98.1% (7847/8000) had CF-only testing ordered, 1.2% (99/8000) had CF+SMA testing ordered, and 0.68% (54/8000) had testing for CF+SMA+FXS+hemoglobinopathies ordered. 7.1% (568/8000) of patients had reportable variants in CFTR. Had CF+SMA testing been ordered on all 8,000 patients, however, the diagnostic yield would have been 8.9%. Of the patients who had CF-only or CF+SMA testing ordered, 11.9% (943/7946) were found to be carriers of hemoglobinopathies. Finally, had all 8000 patients had testing for all currently recommended targets on the panel, the diagnostic yield would have increased to 55% (4396/8000). Ordering providers at 9/50 different contacted sites agreed to interview requests. 100% (9/9) of respondents indicated that their patients experience significant disparities in access to carrier screening, and that the primary cause of these inequities was insufficient insurance reimbursement. 67% (6/9) of respondents indicated that >50% of their patient population identified as non-white and would have “very strongly” benefitted from “testing for other disorders beyond CF.” Conclusions Despite clinical practice guidelines urging for more population-neutral carrier screening, major gaps exist between what is recommended versus ultimately ordered. This significantly limits the clinical utility of testing, especially in patients from underrepresented backgrounds. Improved insurance coverage for more inclusive carrier screening is needed to help reduce such disparities.

PURPOSE Older patients with relapsed or refractory AML (RR AML) have dismal prognoses without allogeneic hematopoietic cell transplantation (alloHCT). SIERRA compared a targeted pretransplant regimen involving the anti-CD45 radioconjugate 131 I-apamistamab with conventional care. METHODS SIERRA (ClinicalTrials.gov identifier: NCT02665065 ) was a phase III open-label trial. Patients age ≥55 years with active RR AML were randomly assigned 1:1 to either an 131 I-apamistamab–led regimen before alloHCT or conventional care followed by alloHCT if initial complete remission (CR)/CR with incomplete platelet recovery (CRp) occurred. Initial response was assessed 28-56 days after alloHCT in the 131 I-apamistamab group and 28-42 days after salvage chemotherapy initiation; patients without CR/CRp or with AML progression could cross over to receive 131 I-apamistamab followed by alloHCT. The primary end point was durable complete remission (dCR) lasting 180 days after initial CR/CRp. Secondary end points were overall survival (OS) and event-free survival (EFS), assessed hierarchically in the intention-to-treat (ITT) population. RESULTS The ITT population included 153 patients ( 131 I-apamistamab [n = 76]; conventional care [n = 77]). In total, 44/77 conventional care arm patients crossed over and 40/77 (52%) received 131 I-apamistamab and alloHCT, with six patients (13.6%) experiencing a dCR. In the ITT population, the dCR rate was significantly higher with 131 I-apamistamab (17.1% [95% CI, 9.4 to 27.5]) than conventional care (0% [95% CI, 0 to 4.7]; P < .0001). The OS hazard ratio (HR) was 0.99 (95% CI, 0.70 to 1.41; P = .96), and the EFS HR was 0.23 (95% CI, 0.15 to 0.34), with HR <1 favoring 131 I-apamistamab. Grade ≥3 treatment-related adverse events occurred in 59.7% and 59.2% of the 131 I-apamistamab and conventional care groups, respectively. CONCLUSION The 131 I-apamistamab–led regimen was associated with a higher dCR rate than conventional care in older patients with RR AML. 131 I-apamistamab was well tolerated and could address an unmet need in this population.

Multiligament knee injuries (MLKIs) represent a broad spectrum of pathology with potentially devastating consequences. Currently, disagreement in the terminology, diagnosis and treatment of these injuries limits clinical care and research. This study aimed to develop consensus on the nomenclature, diagnosis, treatment and rehabilitation strategies for patients with MLKI, while identifying important research priorities for further study. An international consensus process was conducted using validated Delphi methodology in line with British Journal of Sports Medicine guidelines. A multidisciplinary panel of 39 members from 14 countries, completed 3 rounds of online surveys exploring aspects of nomenclature, diagnosis, treatment, rehabilitation and future research priorities. Levels of agreement (LoA) with each statement were rated anonymously on a 5-point Likert scale, with experts encouraged to suggest modifications or additional statements. LoA for consensus in the final round were defined ‘a priori’ if >75% of respondents agreed and fewer than 10% disagreed, and dissenting viewpoints were recorded and discussed. After three Delphi rounds, 50 items (92.6%) reached consensus. Key statements that reached consensus within nomenclature included a clear definition for MLKI (LoA 97.4%) and the need for an updated MLKI classification system that classifies injury mechanism, extent of non-ligamentous structures injured and the presence or absence of dislocation. Within diagnosis, consensus was reached that there should be a low threshold for assessment with CT angiography for MLKI within a high-energy context and for certain injury patterns including bicruciate and PLC injuries (LoA 89.7%). The value of stress radiography or intraoperative fluoroscopy also reached consensus (LoA 89.7%). Within treatment, it was generally agreed that existing literature generally favours operative management of MLKI, particularly for young patients (LoA 100%), and that single-stage surgery should be performed whenever possible (LoA 92.3%). This consensus statement will facilitate clinical communication in MLKI, the care of these patients and future research within MLKI.

Background: Previous studies have demonstrated that medial meniscus posterior root tear (MMPRT) repair is superior to debridement in terms of patient-reported outcomes, rates of conversion to total knee arthroplasty (TKA), and long-term costs. Despite the known poor midterm outcomes, there is a paucity of long-term results of partial meniscectomy for degenerative MMPRTs. Purpose: To 1) evaluate long-term patient-reported and radiographic outcomes of patients who underwent partial medial meniscectomy (PMM) for MMPRTs, and 2) determine the rate of and risk factors for conversion to total knee TKA. Study Design: Case series; Level of evidence, 4. Methods: A previously identified cohort of 26 patients treated with partial meniscectomy for isolated MMPRTs between 2005 and 2013 was prospectively followed for long-term outcomes at a minimum 10-year follow-up. Patients were evaluated for International Knee Documentation Committee (IKDC) outcome score, reoperation, and conversion to TKA. Failure was defined as conversion to arthroplasty or a severely abnormal IKDC subjective score <75.4. Results: This study included 26 patients (10 men, 16 women; mean age, 54 ± 8.7 years [range, 38-71 years] at diagnosis; body mass index, 32.9 ± 5.5) who were followed for a mean of 14.0 ± 3.6 years (range, 10.1-19.6 years). At the final follow-up, 1 patient was deceased and 18 (72%) of the remaining 25 patients had progressed to TKA, with 1 (4%) patient undergoing repeat meniscectomy. The 6 (24%) patients who had not progressed to TKA or revision surgery reported a mean IKDC score of 57 ± 23. Nineteen patients underwent subsequent surgery and 5 demonstrated severely abnormal IKDC scores resulting in a clinical failure rate of 96% (24 of the 25 living patients) at a mean 14-year follow-up. Conclusion: PMM for medial meniscus posterior horn root tears demonstrated 72% progression to TKA and 96% failure according to subjective clinical outcomes at a minimum 10-year follow-up.

Abstract Patient Initiated Follow-Up (PIFU) is gaining momentum in the NHS, aiming to optimize outpatient care amidst rising service demands. PIFU is valuable in rheumatology, where the increasing demand for ongoing management exacerbates the patient backlog. Importantly, PIFU has demonstrated comparable safety and outcomes to traditional care in numerous studies. PIFU empowers patients, drives personalized care, increases efficiency, and has the potential to reduce waiting lists by allowing services to focus on new and acute cases. Effective PIFU implementation includes careful selection of patients, educating patients and healthcare staff, well defined operational guidelines, and robust remote monitoring. Digital solutions can enhance PIFU through patient education, active remote monitoring and streamlined escalation. Electronic Patient Reported Outcome Measures (ePROMs) provide a suitable and safe metric to monitor patients remotely. Given the potential benefits, outpatient departments should consider investing in PIFU as a solution to current healthcare delivery challenges and as a means for future proofing clinical systems against increasing service demands.

ImportanceTranexamic acid reduces bleeding and blood transfusion in many types of surgery, but its effect in patients undergoing liver resection for a cancer-related indication remains unclear.ObjectiveTo determine whether tranexamic acid reduces red blood cell transfusion within 7 days of liver resection.Design, Setting, and ParticipantsMulticenter randomized clinical trial of tranexamic acid vs placebo conducted from December 1, 2014, to November 8, 2022, at 10 hepatopancreaticobiliary sites in Canada and 1 site in the United States, with 90-day follow-up. Participants, clinicians, and data collectors were blinded to allocation. A volunteer sample of 1384 patients undergoing liver resection for a cancer-related indication met eligibility criteria and consented to randomization.InterventionsTranexamic acid (1-g bolus followed by 1-g infusion over 8 hours; n = 619) or matching placebo (n = 626) beginning at induction of anesthesia.Main Outcomes and MeasuresThe primary outcome was receipt of red blood cell transfusion within 7 days of surgery.ResultsThe primary analysis included 1245 participants (mean age, 63.2 years; 39.8% female; 56.1% with a diagnosis of colorectal liver metastases). Perioperative characteristics were similar between groups. Red blood cell transfusion occurred in 16.3% of participants (n = 101) in the tranexamic acid group and 14.5% (n = 91) in the placebo group (odds ratio, 1.15 [95% CI, 0.84-1.56]; P = .38; absolute difference, 2% [95% CI, −2% to 6%]). Measured intraoperative blood loss (tranexamic acid, 817.3 mL; placebo, 836.7 mL; P = .75) and total estimated blood loss over 7 days (tranexamic acid, 1504.0 mL; placebo, 1551.2 mL; P = .38) were similar between groups. Participants receiving tranexamic acid experienced significantly more complications compared with placebo (odds ratio, 1.28 [95% CI, 1.02-1.60]; P = .03), with no significant difference in venous thromboembolism (odds ratio, 1.68 [95% CI, 0.95-3.07]; P = .08).Conclusions and RelevanceAmong patients undergoing liver resection for a cancer-related indication, tranexamic acid did not reduce bleeding or blood transfusion but increased perioperative complications.Trial RegistrationClinicalTrials.gov Identifier: NCT02261415

Objectives: Radial tears of the meniscus are increasingly treated with repair instead of partial meniscectomy, with satisfactory short-term clinical outcomes. There remains a paucity of mid- and long-term outcomes data for this preservation technique. The purpose of this study was to 1) evaluate the mid- to long-term clinical outcomes and reoperation rate of radial meniscal repair versus bucket-handle meniscal repair and 2) evaluate the outcomes of both surgeries overtime. We hypothesized that radial repair would provide similar outcomes and reoperation rates to that of bucket-handle meniscal repair in this propensity-matched cohort. Methods: A previously identified cohort of radial meniscal tears without concurrent root injuries undergoing surgical repair at a single institution between 2011 and 2015 were reviewed. Inclusion criteria was patients undergoing repair of full-thickness radial tears. Exclusion criteria were patients who had 1) not consented for research follow-up, 2) <2 year of follow-up, 3) high-grade (Outerbridge grade 3 or 4) chondromalacia, 4) knee dislocations or combined anterior cruciate ligament and posterior cruciate ligament injuries, 5) repair of posterior meniscal root tears, and 6) repair of partial radial tears. Propensity matching was performed based on age at surgery, sex, laterality, body mass index (BMI), and concomitant anterior cruciate ligament reconstruction (ACLR) using a comparison pool of 70 bucket-handle meniscal repairs (BHMR). Reoperation-free survival rates, Tegner Activity Score, visual analog scale (VAS) for pain, and International Knee Documentation Committee (IKDC) scores were analyzed. Results: Twenty-four patients (18 males, 6 females, age 22.8 ± 11.9 years, BMI 26.5 ± 5.8) with radial meniscal repair were included in this study. Eighteen of these patients were successfully propensity matched to 18 bucket-handle meniscal tears for an overall mean follow-up of 10.2 ± 1.7 years (range, 7.3-13.5) (Table 1). The 24 radial tear repairs demonstrated significant and durable postoperative improvements at mean 10.2 years across VAS at rest (3.0 ± 2.5 vs 0.5 ± 1.0, p < 0.001), VAS for pain at use (5.8 ± 2.9 vs 1.4 ± 1.9, p < 0.001) Tegner (2.6 ± 1.4 vs 6.8 ± 2.0, p < 0.001) and IKDC (39.8 ± 12.3 vs 84.1 ± 16.5, p < 0.001) (Table 1). Of patients not undergoing reoperation (19), 100% reported being “Satisfied” 4/19 (21%) or “Very Satisfied” 15/19 (79%). When the 18 radial tear repairs were compared to the 18 BHMT repairs, there was no significant difference across VAS for pain at rest (0.6 ± 1.2 vs 0.3 ± 0.7, p = 0.48), VAS for pain at use (1.6 ± 2.1 vs 1.1 ± 1.3, p = 0.48) Tegner (6.9 ± 2.2 vs 6.4 ± 2.1, p = 0.51) and IKDC (83.4 ± 17.4 vs 82.1 ± 14.1, p = 0.83) (Table 2). Importantly, survival without reoperation rates were not statistically different between the 2 groups at 10-year follow-up (14/18 (78%) vs 16/18 (89%), p = 0.37) (Figure 1). There was no significant difference between clinical outcomes (Tegner and IKDC) at final follow-up in the radial repair group as compared to the 4-year mid-term outcomes (p = 0.58 and 0.19 respectively). For the BHMR group, Tegner scores were not significantly different (p = 0.60) compared with their 4-year timepoint; however, IKDC scores at the final timepoint were significantly lower 93.4 ± 3.4 vs 82.1 ± 14.1 (p = 0.01). Notably, both the radial repair and bucket-handle repairs groups reported final follow-up Tegner scores that were not significantly different from their preinjury Tegner scores (p = 0.70 for the radial group and p = 0.62 for the bucket-handle group). Conclusions: At mean 10-year follow-up, significant clinical improvements and high rates of satisfaction were observed for radial meniscal tear repair. When propensity matched, radial and BHMR demonstrated durable improvements in postoperative VAS for pain, IKDC, and Tegner scores, as well as similar, acceptable reoperation rates. [Figure: see text]

Objectives: Medial meniscus posterior root tears (MMPRTs) render the meniscus essentially non-functional, resulting in increased peak contact pressures, reduced forced dissipation, and increased risk of early osteoarthritis. Transtibial root repair has shown promise at restoring meniscus function and improving clinical outcomes; however, a paucity of literature exists evaluating the prognostic clinical and radiographic factors for poor outcomes following isolated meniscus root repair. The purpose of this study was to 1) describe the patient reported clinical outcomes after isolated MMPRT repair at minimum 2-year follow-up, 2) determine the retear and conversion to arthroplasty rates, and 3) identify prognostic factors for clinical outcomes and International Knee Documentation Committee (IKDC) Patient Acceptable Symptom State (PASS) achievement. Methods: Isolated MMPRT repairs from 2010-2020 at three institutions in Rochester, MN; Jacksonville, FL; and Phoenix, AZ were followed prospectively for postoperative Tegner Activity Scale, Visual Analog Scale (VAS) for pain, IKDC, Forgotten Joint Score (FJS), subjective improvement and knee preference, and subsequent surgeries at minimum 2-year follow up. PASS for IKDC was set at 69. Demographics, injury characteristics, and surgical details were collected. Results: Eighty-four patients were included in this study (age: 49.7 ± 11.0 years [range: 13-76]; sex: 75.0% female; BMI: 31.6 ± 6.9 kg/m 2 [MH1] ). Forty-five patients (53.6%) had BMI >30 kg/m 2 , and 14 patients (16.7%) reported a history of active smoking (Table 1). Mean medial compartment Outerbridge grade was 2.0 ± 1.1, with 73.8% of patients having grade ≥2 changes. Mean preinjury Tegner score, preoperative VAS at rest, and preoperative VAS with use were 4.6 ± 2.4, 3.6 ± 2.7, and 6.5 ± 2.5, respectively. At final follow-up (mean 3.9 ± 2.0 years), mean Tegner score was 4.3 ± 1.8, mean VAS at rest was 1.2 ± 2.0, and mean VAS with use was 2.3 ± 2.2. There was no significant difference in preinjury vs. postoperative Tegner scores (p = 0.208), and preinjury Tegner was significantly positively correlated with postoperative Tegner (p < 0.001). Significant (p < 0.001) postoperative improvements in both VAS at rest and with use were observed. Mean postoperative IKDC score was 73.3 ± 17.0, and mean FJS was 59.6 ± 27.9 at final follow-up. When asked to rate their knee at final follow-up compared to before surgery on a scale from 0-5 (0 = “significantly worse”, 1 = “mildly worse”, 3 = “unchanged”, 4 = “mildly improved”, 5 = “significantly improved”), the mean score 4.6 ± 0.8. Forty-one patients (74.5%) reported significant improvement, 8 (14.5%) reported mild improvement, 3 (5.5%) reported no change, and 3 (5.5%) reported mild worsening. No patients reported significant worsening. When asked which knee they preferred, 13 patients (26.0%) reported preferring their operated knee, compared to 18 (36.0%) who preferred their nonoperated knee. The remaining 19 patients (38.0%) had no preference for one knee over the other. A summary of all patient reported outcomes is reported in Table 2. At the time of final follow-up, 16 (19.0%) of patients had reached a clinical endpoint. Twenty-nine patients (34.5%) underwent postoperative MRIs at an average of 1.5 ± 1.7 years (range: 0.3-5.9 years) after surgery[MH1] . Twelve of the MRIs (41.4%) were ordered for evaluation of continued pain, while 7 (24.1%) were ordered for new pain or injury, and 10 (34.5%) were ordered for research purposes. Five patients (6.0%) had MRI-confirmed retears of the MMPRT repair at an average of 1.1 ± 1.3 years (range: 0.3-3.4) after surgery[HMMP2] , one of which was in an asymptomatic patient who received a follow-up MRI for research purposes. No patients underwent revision MMPRT repair surgery, and 7 patients (8.3%) progressed to arthroplasty (6 TKA, 1 UKA) at an average of 3.4 ± 4.3 years (range 0.6-12.6), one of whom also sustained a root retear. Therefore, the surgical failure was noted in 11 patients, corresponding to a surgical failure rate of 13.1% in this cohort. Of note, three of the five patients with MRI-confirmed retears had not received any further surgical intervention[MH3] [BA(M4] at the time of final follow-up 2.7, 3.8, and 8.5 years after surgery. Additionally, there were six non-MMPRT revision, non-arthroplasty subsequent surgeries in five patients, and there were three patients (3.6%) who sustained new medial meniscus tears 2.8-, 3.6-, and 5.9-years postoperatively, respectively. A concise summary of clinical endpoints can be found in Table 3 and Table 4. Significantly more females experienced surgical failures than males (17.5% vs. 0%, p = 0.040), and significantly more patients with medial compartment Outerbridge grades ≥2 experienced surgical failure than those with grades <2 (17.7% vs. 0%, p = 0.034). Additionally, patients who failed did have significantly higher mean KL grades than those who did not (1.4 ± 0.9 vs. 0.7 ± 0.7, p = 0.012). There were no other significant differences in the demographic or pathologic characteristics of patients who experienced surgical failure and those who did not. Of note, 37% of patients failed to achieve IKDC PASS, with smoking status associated with a 15-point reduction in IKDC (p=0.010) Conclusions: Patients undergoing transtibial root repair demonstrate restoration of pre-injury activity levels, significant clinical improvements in pain and function, and low surgical failure rates at minimum 2-year follow-up, with 89% of patients reporting subjective improvement after surgery. However, only 63% of patients were able to achieve PASS thresholds, suggesting that while effective, additional research on root repair technical and clinical optimization is warranted.

Objectives: Meniscal allograft transplantation (MAT) is an accepted and effective treatment option in the context of unsalvageable menisci, particularly in young and active patients. It has been shown to reduce pain and improve knee function in previously symptomatic patients. However, there is still limited knowledge about the long-term survival rates of allografts, the durability of clinical results, and the influence of patient-specific parameters, such as leg alignment, tibial slope, and preoperative International Cartilage Regeneration & Joint Preservation Society (ICRS) grade. The purpose of this study was to determine (1) the long-term clinical success rate after MAT with bony fixation in a large, single-center cohort of consecutive patients, and (2) if patient-specific and procedural variables influence the clinical, anatomic, and subjective outcomes and risk of failure. Methods: Data on 185 consecutive knees undergoing MAT in a single institution were prospectively collected and screened for inclusion in this study. The minimum follow-up time was 2 years. Radiographic variables (International Cartilage Regeneration & Joint Preservation Society [ICRS] grade and Kellgren and Lawrence grade) were assessed preoperatively and at follow-up. Subjective patient-reported outcome measures (PROMs), Lysholm score, Knee Disability and Osteoarthritis Outcome Score (KOOS) including subscores, International Knee Documentation Committee (IKDC) score, and visual analog score (VAS) were collected preoperatively and at follow-up. Clinical failure was defined as revision surgery due to graft failure or conversion to total knee arthroplasty (TKA). Anatomic failure was considered a tear covering >20% of the allograft, any peripheral tear, and unstable peripheral fixation leading to dislocation of the graft. Subjective failure was defined as Lysholm score ≤65. Preoperative tibial slope and leg alignment were assessed. Survival analyses were performed utilizing the Kaplan-Meier estimate. Univariate and multivariate analyses were performed to determine risk factors for clinical and anatomic failure. Results: A total of 157 knees met inclusion criteria (Table 1). After a mean follow-up time of 7 ± 3.5 years, 127 (80.9%) knees were free of clinical, anatomic, and subjective failure. Fourteen (8.9%) knees experienced clinical failure, 26 (16.6%) knees were identified as anatomic failure, and 13 patients (8.3%) suffered from subjective failure with a reported Lysholm score of ≤65 at a mean follow-up of 7 years. Concurrent osteochondral allograft transplantation was identified as a predictor of both clinical (HR 4.55; 95% CI 1.46-14.17; p=0.009) and anatomic failure (HR 3.05; 95% CI 1.34-6.92; p=0.008). Cartilage damage of ICRS grade 3 or 4 of the index compartment conveyed an increased risk for clinical (HR 3.41; 95% CI 1.05-11.01; p=0.04) and anatomic failure (HR 3.04; 95% CI 1.31-7.11; p=0.01) (Table 2). There were no differences in outcomes between medial and lateral MAT. High-grade cartilage damage (defined as ICRS grades 3 and 4) preoperatively (HR 10.67; 95% CI 1.037-109.768; p=0.046), patients age over 25 (HR 5.44; 95% CI 0.120-246.070; p=0.384), and a body mass index >30 (HR 2.24; 95% CI 0.748-6.705; p=0.149) were associated with subjective failure. Considering the entire study population, PROMs including KOOS and IKDC were significantly improved at final follow-up compared to preoperative scores across all measurements (p<0.005). Conclusions: MAT showed good-to-excellent clinical results at a mean follow-up of 7 years. Low ICRS lesion grade was associated with a higher clinical and anatomic survival rate. Patients with concurrent osteochondral allograft transplantation are at higher risk of clinical and anatomic failure, but still report significantly improved PROMs. These results suggest MAT has a lasting beneficial effect both as in isolation and in complex cases with one or more concurrent procedures.