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Background: Increased posterior tibial slope (PTS) leads to a relative anterior translation of the tibia on the femur. This is thought to decrease the stress on posterior cruciate ligament (PCL) reconstruction (PCLR) grafts. Purpose/Hypothesis: The purpose of this study was to analyze the effect of PTS on knee laxity, graft failure, and patient-reported outcome (PRO) scores after PCLR without concomitant anterior cruciate ligament reconstruction (ACLR). It was hypothesized that patients with higher PTS would have less knee laxity, fewer graft failures, and better PROs compared with patients with lower PTS. Study Design: Case-control study; Level of evidence, 3. Methods: All patients who underwent PCLR between 2001 and 2020 at a single institution were identified. Patients were excluded if they underwent concomitant or prior ACLR or proximal tibial osteotomy, were younger than 18 years, had <2 years of in-person clinical follow-up, and did not have documented PRO scores (Lysholm score and International Knee Documentation Committee [IKDC] score). Data were collected retrospectively from a prospectively gathered database. PTS measurements were recorded from perioperative lateral knee radiographs. A linear regression model was created to analyze PTS in relation to PRO scores. Patients with a grade 1 (1-5 mm) or higher posterior drawer were compared with those who had a negative posterior drawer. Results: A total of 37 knees met inclusion criterion; the mean age was 30.7 years at the time of surgery. The mean clinical follow-up was 5.8 years. No significant correlation was found between either the Lysholm score or the IKDC score and the PTS. Twelve knees (32.4%) had a positive posterior drawer at final follow-up. The mean PTS in knees with a positive posterior drawer was 6.2°, whereas that for knees with a negative posterior drawer was 8.3° ( P = .08). No significant differences in PRO scores were identified for knees with versus knees without a positive posterior drawer. No documented graft failures or revisions were found. Conclusion: No significant differences were found in PROs or graft failure rates based on PTS at a mean of 5.8 years after PCLR. Increased tibial slope trended toward being protective against a positive posterior drawer, although this did not reach statistical significance.

Background: Osteochondral allograft transplantation (OCAT) is an accepted knee joint–preserving treatment strategy for focal osteochondral lesions that is often conducted in combination with meniscal allograft transplantation (MAT). Despite its frequent and simultaneous utilization, there remains a lack in the literature reporting on outcomes and failure rates after concomitant procedures. Purpose: To determine (1) the midterm clinical success rate after OCAT+MAT in comparison with a matched-pair cohort undergoing isolated OCAT, (2) whether patient-specific and procedural variables influence the risk of failure, and (3) patient-reported outcome measures over time. Study Design: Cohort study; Level of evidence, 3. Methods: A single-center matched-pair cohort study was conducted investigating outcomes in patients who underwent OCAT of the medial or lateral femoral condyle with and without MAT between 2004 and 2020. Patients were matched 1:1 by age (±5 years), sex (male or female), body mass index (±5), and grouped Kellgren and Lawrence grade (grades 0-1 or 2-4). 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 (Lysholm score, Knee injury and Osteoarthritis Outcome Score [KOOS] including subscores, International Knee Documentation Committee [IKDC] score, and visual analog scale score) were collected preoperatively and at follow-up. Clinical failure was defined as revision surgery for graft failure or conversion to total knee arthroplasty. Patient-reported, clinical, and radiographic outcomes were compared between groups. Results: In total, 66 patients (33 treated with isolated OCAT, 33 treated with OCAT+MAT; 57.6% male) with a mean age of 26.3 years (range, 18-62 years) were followed for a mean of 5.6 years (minimum, 2 years; range, 24-218 months). The 2 cohorts showed no difference in Kellgren and Lawrence grade postoperatively ( P = .59). There was a significantly higher ICRS grade detected at follow-up in the OCAT+MAT group (2.81 ± 1.10) compared with the OCAT group (2.04 ± 0.96) ( P < .05). There were no statistically significant differences between the groups regarding reoperation rate (OCAT: n = 6; OCAT+MAT: n = 13; P = .116), time to reoperation (OCAT: 46.67 ± 47.27 months vs OCAT+MAT: 28.08 ± 30.16 months; P = .061), and failure rate (OCAT: n = 4 [12.1%] vs OCAT+MAT: n = 5 [15.2%]; P = .66). In the OCAT+MAT group, an increase of tibial slope by 1° conferred a 1.65-fold increase in the hazard for failure over decreased slope (hazard ratio, 1.65; 95% CI, 1.10-2.50; P < .05). The overall survival rate was 86% at a mean follow-up of 5.6 years. Patient-reported outcome scores were significantly improved at the final follow-up compared with preoperative status. No significant differences were seen between groups with respect to subjective IKDC, Lysholm, Tegner, and KOOS results, except for the KOOS Symptoms subscale score, which was significantly higher in the OCAT+MAT group than in the OCAT group (mean difference, 14.6; P < .05) and did exceed the minimal clinically important difference threshold of 10.7. Conclusion: Midterm results after isolated OCAT and OCAT+MAT show high rates of healing and sustainable subjective improvement of knee function and quality of life. However, it should be noted that the difference in reoperation rate and time to reoperation between the groups is arguably clinically important and that lack of statistical significance may be because of low power. These results imply that isolated OCAT is an efficient joint-preserving treatment that can be combined with MAT in well-selected patients with meniscal insufficiency without negative influence on global clinical outcomes.

ImportanceFinding a reliable diagnostic biomarker for the disorders collectively known as synucleinopathies (Parkinson disease [PD], dementia with Lewy bodies [DLB], multiple system atrophy [MSA], and pure autonomic failure [PAF]) is an urgent unmet need. Immunohistochemical detection of cutaneous phosphorylated α-synuclein may be a sensitive and specific clinical test for the diagnosis of synucleinopathies.ObjectiveTo evaluate the positivity rate of cutaneous α-synuclein deposition in patients with PD, DLB, MSA, and PAF.Design, Setting, and ParticipantsThis blinded, 30-site, cross-sectional study of academic and community-based neurology practices conducted from February 2021 through March 2023 included patients aged 40 to 99 years with a clinical diagnosis of PD, DLB, MSA, or PAF based on clinical consensus criteria and confirmed by an expert review panel and control participants aged 40 to 99 years with no history of examination findings or symptoms suggestive of a synucleinopathy or neurodegenerative disease. All participants completed detailed neurologic examinations and disease-specific questionnaires and underwent skin biopsy for detection of phosphorylated α-synuclein. An expert review panel blinded to pathologic data determined the final participant diagnosis.ExposureSkin biopsy for detection of phosphorylated α-synuclein.Main OutcomesRates of detection of cutaneous α-synuclein in patients with PD, MSA, DLB, and PAF and controls without synucleinopathy.ResultsOf 428 enrolled participants, 343 were included in the primary analysis (mean [SD] age, 69.5 [9.1] years; 175 [51.0%] male); 223 met the consensus criteria for a synucleinopathy and 120 met criteria as controls after expert panel review. The proportions of individuals with cutaneous phosphorylated α-synuclein detected by skin biopsy were 92.7% (89 of 96) with PD, 98.2% (54 of 55) with MSA, 96.0% (48 of 50) with DLB, and 100% (22 of 22) with PAF; 3.3% (4 of 120) of controls had cutaneous phosphorylated α-synuclein detected.Conclusions and RelevanceIn this cross-sectional study, a high proportion of individuals meeting clinical consensus criteria for PD, DLB, MSA, and PAF had phosphorylated α-synuclein detected by skin biopsy. Further research is needed in unselected clinical populations to externally validate the findings and fully characterize the potential role of skin biopsy detection of phosphorylated α-synuclein in clinical care.

Since the UK commenced newborn screening for isovaleric acidemia in 2015, changes in prescribing have increased the incidence of false positive (FP) results due to pivaloylcarnitine. A review of screening results between 2015 and 2022 identified 24 true positive (TP) and 84 FP cases, with pivalate interference confirmed in 76/84. Initial C5 carnitine (C5C) did not discriminate between FP and TP with median (range) C5C of 2.9 (2.0–9.6) and 4.0 (1.8–>70) µmol/L, respectively, and neither did Precision Newborn Screening via Collaborative Laboratory Integrated Reports (CLIR), which identified only 1/47 FP cases. However, among the TP cases, disease severity showed a correlation with initial C5C in ‘asymptomatic’ individuals (n = 17), demonstrating a median (range) C5C of 3.0 (1.8–7.1) whilst ‘clinically affected’ patients (n = 7), showed a median (range) C5C of 13.9 (7.7–70) µmol/L. These findings allowed the introduction of dual cut-off values into the screening algorithm to reduce the incidence of FPs, with initial C5C results ≥ 5 µmol/L triggering urgent referral, and those >2.0 and <5.0 µmol/L prompting second-tier C5-isobar testing. This will avoid delayed referral in babies at particular risk whilst reducing the FP rate for the remainder.

PURPOSE Allogeneic hematopoietic cell transplantation (HCT) improves outcomes for patients with AML harboring an internal tandem duplication mutation of FLT3 ( FLT3-ITD) AML. These patients are routinely treated with a FLT3 inhibitor after HCT, but there is limited evidence to support this. Accordingly, we conducted a randomized trial of post-HCT maintenance with the FLT3 inhibitor gilteritinib (ClinicalTrials.gov identifier: NCT02997202 ) to determine if all such patients benefit or if detection of measurable residual disease (MRD) could identify those who might benefit. METHODS Adults with FLT3-ITD AML in first remission underwent HCT and were randomly assigned to placebo or 120 mg once daily gilteritinib for 24 months after HCT. The primary end point was relapse-free survival (RFS). Secondary end points included overall survival (OS) and the effect of MRD pre- and post-HCT on RFS and OS. RESULTS Three hundred fifty-six participants were randomly assigned post-HCT to receive gilteritinib or placebo. Although RFS was higher in the gilteritinib arm, the difference was not statistically significant (hazard ratio [HR], 0.679 [95% CI, 0.459 to 1.005]; two-sided P = .0518). However, 50.5% of participants had MRD detectable pre- or post-HCT, and, in a prespecified subgroup analysis, gilteritinib was beneficial in this population (HR, 0.515 [95% CI, 0.316 to 0.838]; P = .0065). Those without detectable MRD showed no benefit (HR, 1.213 [95% CI, 0.616 to 2.387]; P = .575). CONCLUSION Although the overall improvement in RFS was not statistically significant, RFS was higher for participants with detectable FLT3-ITD MRD pre- or post-HCT who received gilteritinib treatment. To our knowledge, these data are among the first to support the effectiveness of MRD-based post-HCT therapy.

ImportanceRedirection of care refers to withdrawal, withholding, or limiting escalation of treatment. Whether maternal social determinants of health are associated with redirection of care discussions merits understanding.ObjectiveTo examine associations between maternal social determinants of health and redirection of care discussions for infants born extremely preterm.Design, Setting, and ParticipantsThis is a retrospective analysis of a prospective cohort of infants born at less than 29 weeks’ gestation between April 2011 and December 2020 at 19 National Institute of Child Health and Human Development Neonatal Research Network centers in the US. Follow-up occurred between January 2013 and October 2023. Included infants received active treatment at birth and had mothers who identified as Black or White. Race was limited to Black and White based on service disparities between these groups and limited sample size for other races. Maternal social determinant of health exposures were education level (high school nongraduate or graduate), insurance type (public/none or private), race (Black or White), and ethnicity (Hispanic or non-Hispanic).Main Outcomes and MeasuresThe primary outcome was documented discussion about redirection of infant care. Secondary outcomes included subsequent redirection of care occurrence and, for those born at less than 27 weeks’ gestation, death and neurodevelopmental impairment at 22 to 26 months’ corrected age.ResultsOf the 15 629 infants (mean [SD] gestational age, 26 [2] weeks; 7961 [51%] male) from 13 643 mothers, 2324 (15%) had documented redirection of care discussions. In unadjusted comparisons, there was no significant difference in the percentage of infants with redirection of care discussions by race (Black, 1004/6793 [15%]; White, 1320/8836 [15%]) or ethnicity (Hispanic, 291/2105 [14%]; non-Hispanic, 2020/13 408 [15%]). However, after controlling for maternal and neonatal factors, infants whose mothers identified as Black or as Hispanic were less likely to have documented redirection of care discussions than infants whose mothers identified as White (Black vs White adjusted odds ratio [aOR], 0.84; 95% CI, 0.75-0.96) or as non-Hispanic (Hispanic vs non-Hispanic aOR, 0.72; 95% CI, 0.60-0.87). Redirection of care discussion occurrence did not differ by maternal education level or insurance type.Conclusions and RelevanceFor infants born extremely preterm, redirection of care discussions occurred less often for Black and Hispanic infants than for White and non-Hispanic infants. It is important to explore the possible reasons underlying these differences.

Abstract Defining prognostic variables in T-lymphoblastic lymphoma (T-LL) remains a challenge. AALL1231 was a Children’s Oncology Group phase 3 clinical trial for newly diagnosed patients with T acute lymphoblastic leukemia or T-LL, randomizing children and young adults to a modified augmented Berlin-Frankfurt-Münster backbone to receive standard therapy (arm A) or with addition of bortezomib (arm B). Optional bone marrow samples to assess minimal residual disease (MRD) at the end of induction (EOI) were collected in T-LL analyzed to assess the correlation of MRD at the EOI to event-free survival (EFS). Eighty-six (41%) of the 209 patients with T-LL accrued to this trial submitted samples for MRD assessment. Patients with MRD &lt;0.1% (n = 75) at EOI had a superior 4-year EFS vs those with MRD ≥0.1% (n = 11) (89.0% ± 4.4% vs 63.6% ± 17.2%; P = .025). Overall survival did not significantly differ between the 2 groups. Cox regression for EFS using arm A as a reference demonstrated that MRD EOI ≥0.1% was associated with a greater risk of inferior outcome (hazard ratio, 3.73; 95% confidence interval, 1.12-12.40; P = .032), which was independent of treatment arm assignment. Consideration to incorporate MRD at EOI into future trials will help establish its value in defining risk groups. CT# NCT02112916.

Summary Background Stricturing Crohn's disease (CD) occurs most commonly in the terminal ileum and poses a clinical problem. Cross‐sectional imaging modalities such as intestinal ultrasound (IUS), computed tomography enterography (CTE), and magnetic resonance enterography (MRE) allow for assessment of the entire bowel wall and associated peri‐enteric findings. Radiologic definitions of strictures have been developed for CTE and MRE; their reliability and responsiveness are being evaluated in index development programs. A comprehensive assessment strategy for strictures using IUS is needed. Aims To provide a detailed summary of definitions, diagnosis and monitoring of strictures on IUS as well as technical aspects of image acquisition. Methods We searched four databases up to 6 January 2024. Two‐stage screening was done in duplicate. We assessed risk of bias using QUADAS‐2. Results There were 56 studies eligible for inclusion. Definitions for strictures on IUS are heterogeneous, but the overall accuracy for diagnosis of strictures is high. The capability of IUS for characterising inflammation versus fibrosis in strictures is not accurate enough to be used in clinical practice or trials. We summarise definitions for improvement of strictures on IUS, and discuss parameters for image acquisition and standardisation. Conclusions This systematic review is the first step for a structured program to develop a stricture IUS index for CD.

AbstractBackgroundClot based assays used for lupus anticoagulant (LAC) detection are typically interpreted in a qualitative fashion and may not reflect LAC potency. In this cross‐sectional study, we describe a method for quantifying the LAC titer using serial (dependent) two‐fold dilutions in normal pooled plasma.MethodsSerial dilutions of 51 residual plasma samples from 50 patients were tested using the Russell's viper venom screening time (DRVVT) and activated partial thromboplastin screening time (APTT) methodologies. The measured clotting times and the corresponding dilution factors were then used to derive a four‐parameter logistic model. The LAC titer for each patient was interpolated as the sample dilution that corresponds to the upper reference interval limit of the corresponding assay.ResultsCalculated APTT and DRVVT LAC titers displayed a strong linear correlation (R2 = 0.84) between each other, but not with the degree of prolongation of the APTT/DRVVT screening time in the neat undiluted samples. Using data driven partitioning, patients could be grouped into low (<10) or high (≥10) DRVVT LAC titer. There were no significant differences in anticardiolipin (aCL) or anti‐beta 2 glycoprotein 1 (aB2GPI) antibody levels or prevalence of thromboembolic events between low and high LAC titer groups. In contrast, antiphosphatidylserine/prothrombin (aPS/PT) IgM antibody levels, but not IgG, were significantly higher in the high LAC titer group.ConclusionsThe degree of prolongation of the APTT/DRVVT screening time is not correlated with the LAC titer. Only aPS/PT IgM antibodies levels were strongly correlated with the LAC titers. Additional studies are warranted to determine clinical implications of high LAC titers.