Purpose/Hypothesis: The purpose of this study was to compare the clinical and radiologic outcomes of remnant-preserving PCL reconstruction using anatomic versus low tibial tunnels. We hypothesized that the outcomes of low tibial tunnel placement would be superior to those of anatomic tibial tunnel placement at the 2-year follow-up after remnant-preserving PCL reconstruction.
Study Design: Cohort study; Level of evidence, 3.
Methods: We retrospectively reviewed the data for patients who underwent remnant-preserving PCL reconstruction between March 2011 and January 2018 with a minimum follow-up of 2 years (N = 63). On the basis of the tibial tunnel position on postoperative computed tomography, the patients were divided into those with anatomic placement (group A; n = 31) and those with low tunnel placement (group L; n = 32). Clinical scores (International Knee Documentation Committee subjective score, Lysholm score, and Tegner activity level), range of motion, complications, and stability test outcomes at follow-up were compared between the 2 groups. Graft signal on 1-year follow-up magnetic resonance imaging scans was compared between 22 patients in group A and 17 patients in group L.
Results: There were no significant differences between groups regarding clinical scores or incidence of complications, no between-group differences in posterior drawer test results, and no side-to-side difference on Telos stress radiographs (5.2 ± 2.9 mm in group A vs 5.1 ± 2.8 mm in group L; P = .900). Postoperative 1-year follow-up magnetic resonance imaging scans showed excellent graft healing in both groups, with no significant difference between them.
Conclusion: The clinical and radiologic outcomes and complication rate were comparable between anatomic tunnel placement and low tibial tunnel placement at 2-year follow-up after remnant-preserving PCL reconstruction. The findings of this study suggest that both tibial tunnel positions are clinically feasible for remnant-preserving PCL reconstruction.
HYPOTHESIS: Medial MAT would improve anteroposterior stability, and lateral MAT would improve rotational stability.
STUDY DESIGN: Cohort study; Level of evidence, 3.
METHOD: We retrospectively investigated 31 cases of MAT after a previous total or nearly total meniscectomy and ACL reconstruction between November 2008 and June 2017. Cases were divided into medial (16 cases) and lateral (15 cases) MAT groups. The patients were assessed preoperatively and at the 2-year follow-up.
RESULTS: In the medial MAT group, the International Knee Documentation Committee, Lysholm, Lysholm instability, and Tegner scores improved significantly at the 2-year follow-up, and there were also significant improvements in the anterior drawer, Lachman, and pivot-shift tests. In the lateral MAT group, the Lysholm and Tegner scores improved significantly at the 2-year follow-up, as had the anterior drawer and Lachman tests but not the pivot-shift test. The medial MAT group showed significant improvement in side-to-side difference on Telos stress radiographs, from 6.5 mm (preoperatively) to 3.6 mm (2-year follow-up) (P = .001), while the lateral MAT group showed no significant change. There was no progression of arthritis in either group.
CONCLUSION: Medial MAT improved not only anteroposterior stability but also rotational stability in the meniscus-deficient ACL-reconstructed knee. Lateral MAT showed improvements in the anterior drawer and Lachman tests but not in the pivot-shift test or side-to-side difference on Telos stress radiographs in meniscus-deficient ACL-reconstructed knees. Instability and pain are indications for MAT in meniscus-deficient ACL-reconstructed knees.
METHODS: 63 patients who underwent remnant-preserving single-bundle PCL reconstruction between 2011 and 2018 with a minimum 2-year follow-up were retrospectively reviewed. Patients were divided into two groups according to the femoral tunnel position: group A (33 patients with anatomical femoral tunnel) and group H (30 patients with high femoral tunnels). The femoral tunnel was positioned at the center (group A) or upper margin (group H) of the remnant anterolateral bundle. The position of the femoral tunnel was evaluated using the grid method on three-dimensional computed tomography. Clinical and radiological outcomes and failure rates were compared between the groups at the 2-year follow-up.
RESULTS: The position of the femoral tunnel was significantly high in group H than in group A (87.4% ± 4.2% versus 76.1% ± 3.7%, p
METHODS: ALPHA is an ongoing, international, phase 3, randomised, double-blind, placebo-controlled trial evaluating danicopan as add-on therapy to ravulizumab or eculizumab. Eligible patients were adults (age ≥18 years) with PNH and clinically significant extravascular haemolysis (haemoglobin ≤9·5 g/dL; absolute reticulocyte count ≥120 × 109/L) on ravulizumab or eculizumab for at least 6 months. Patients were randomly assigned (2:1) to danicopan or placebo added to ravulizumab or eculizumab for 12 weeks using an interactive response technology system. Randomisation was stratified based on transfusion history, haemoglobin, and patients enrolled from Japan. The initial oral danicopan dose was 150 mg three times a day; escalation to 200 mg three times a day was permitted based on clinical response. The infusion dose level of eculizumab (every 2 weeks) ranged from 900 mg to 1500 mg, and for ravulizumab (monthly or every 8 weeks) ranged from 3000 mg to 3600 mg. The primary endpoint was change in haemoglobin concentration from baseline to week 12. Here we present the protocol-prespecified interim analysis, planned when approximately 75% of participants were randomly assigned to treatment and completed or discontinued at 12 weeks. This trial is registered with ClinicalTrials.gov (NCT04469465).
FINDINGS: Individuals were randomly assigned between Dec 16, 2020, and Aug 29, 2022. At data cutoff (June 28, 2022), 73 individuals were randomly assigned, received treatment, and were analysed for safety (danicopan, n=49; placebo, n=24). The protocol-prespecified interim efficacy analysis set included the first 63 participants (danicopan, n=42; placebo, n=21). At week 12, danicopan plus ravulizumab or eculizumab increased haemoglobin versus placebo plus ravulizumab or eculizumab (least squares mean [LSM] change from baseline: danicopan, 2·94 g/dL [95% CI 2·52 to 3·36]; placebo, 0·50 g/dL [-0·13 to 1·12]; LSM difference, 2·44 g/dL [1·69 to 3·20]; p<0·0001). Grade 3 adverse events in the danicopan group were increased alanine aminotransferase (two [4%] of 49 patients), leukopenia (one [2%]), neutropenia (two [4%]), cholecystitis (one [2%]), COVID-19 (one [2%]), increased aspartate aminotransferase (one [2%]), and increased blood pressure (one [2%]), and in the placebo group were anaemia (one [4%] of 24 patients), thrombocytopenia (one [4%]), and asthenia (one [4%]). The serious adverse events reported in the danicopan group were cholecystitis (one [2%] patient) and COVID-19 (one [2%]) and in the placebo group were anaemia and abdominal pain, both in one (4%) patient. There were no serious adverse events related to study drug or deaths reported in the study.
INTERPRETATION: These primary efficacy and safety results show that danicopan as add-on treatment to ravulizumab or eculizumab significantly improved haemoglobin concentrations at week 12 with no new safety concerns, suggesting an improved benefit-risk profile in patients with PNH and clinically significant extravascular haemolysis.
FUNDING: Alexion, AstraZeneca Rare Disease.
METHODS: We did a retrospective study of patients with newly diagnosed ENKTL without any previous treatment history for the disease who were given non-anthracycline-based chemotherapies with or without upfront concurrent chemoradiotherapy or radiotherapy with curative intent. A prognostic model to predict overall survival and progression-free survival on the basis of pretreatment clinical and laboratory characteristics was developed by filling a multivariable model on the basis of the dataset with complete data for the selected risk factors for an unbiased prediction model. The final model was applied to the patients who had complete data for the selected risk factors. We did a validation analysis of the prognostic model in an independent cohort.
FINDINGS: We did multivariate analyses of 527 patients who were included from 38 hospitals in 11 countries in the training cohort. Analyses showed that age greater than 60 years, stage III or IV disease, distant lymph-node involvement, and non-nasal type disease were significantly associated with overall survival and progression-free survival. We used these data as the basis for the prognostic index of natural killer lymphoma (PINK), in which patients are stratified into low-risk (no risk factors), intermediate-risk (one risk factor), or high-risk (two or more risk factors) groups, which were associated with 3-year overall survival of 81% (95% CI 75-86), 62% (55-70), and 25% (20-34), respectively. In the 328 patients with data for Epstein-Barr virus DNA, a detectable viral DNA titre was an independent prognostic factor for overall survival. When these data were added to PINK as the basis for another prognostic index (PINK-E)-which had similar low-risk (zero or one risk factor), intermediate-risk (two risk factors), and high-risk (three or more risk factors) categories-significant associations with overall survival were noted (81% [95% CI 75-87%], 55% (44-66), and 28% (18-40%), respectively). These results were validated and confirmed in an independent cohort, although the PINK-E model was only significantly associated with the high-risk group compared with the low-risk group.
INTERPRETATION: PINK and PINK-E are new prognostic models that can be used to develop risk-adapted treatment approaches for patients with ENKTL being treated in the contemporary era of non-anthracycline-based therapy.
FUNDING: Samsung Biomedical Research Institute.
METHODS: We followed up 240 participants (112 cognitively unimpaired [CU], 78 amnestic mild cognitive impairment [aMCI], and 50 Alzheimer's disease (AD) dementia [ADD]) for 2 years from 9 referral centers in South Korea. Participants were assessed with neuropsychological tests and 18F-flutemetamol (FMM) positron emission tomography (PET). Ten regions (frontal, precuneus/posterior cingulate (PPC), lateral temporal, parietal, and striatum of each hemisphere) were visually examined in the FMM scan, and participants were divided into three groups: No-FMM, Focal-FMM (FMM uptake in 1-9 regions), and Diffuse-FMM. We used mixed-effects model to investigate the speed of cognitive decline in the Focal-FMM group according to the cognitive level, extent, and location of Aß involvement, in comparison with the No- or Diffuse-FMM group.
RESULTS: Forty-five of 240 (18.8%) individuals were categorized as Focal-FMM. The rate of cognitive decline in the Focal-FMM group was faster than the No-FMM group (especially in the CU and aMCI stage) and slower than the Diffuse-FMM group (in particular in the CU stage). Within the Focal-FMM group, participants with FMM uptake to a larger extent (7-9 regions) showed faster cognitive decline compared to those with uptake to a smaller extent (1-3 or 4-6 regions). The Focal-FMM group was found to have faster cognitive decline in comparison with the No-FMM when there was uptake in the PPC, striatum, and frontal cortex.
CONCLUSIONS: When predicting cognitive decline of patients with focal Aß deposition, the patients' cognitive level, extent, and location of the focal involvement are important.
METHODS: Records of patients with thrombotic microangiopathy (TMA) were reviewed. Patients' ADAMTS13 activity levels were obtained, along with clinical/laboratory findings relevant to the PLASMIC score. Both PLASMIC scores and PLASMIC-LDH scores, in which LDH replaced traditional lysis markers, were calculated. We generated a receiver operator characteristics (ROC) curve and compared the area under the curve values (AUC) to determine the predictive ability of each score.
RESULTS: 46 patients fulfilled the inclusion criteria, of which 34 had ADAMTS13 activity levels of <10%. When the patients were divided into intermediate-to-high risk (scores 5‒7) and low risk (scores 0‒4), the PLASMIC score showed a sensitivity of 97.1% and specificity of 58.3%, with a positive predictive value (PPV) of 86.8% and negative predictive value (NPV) of 87.5%. The PLASMIC-LDH score had a sensitivity of 97.1% and specificity of 33.3%, with a PPV of 80.5% and NPV of 80.0%.
CONCLUSION: Our study validated the utility of the PLASMIC score, and demonstrated PLASMIC-LDH as a reasonable alternative in the absence of traditional lysis markers, to help identify high-risk patients for treatment via plasma exchange.