In this study, we observed the fate of the inverted limbus after closed reduction for the treatment of developmental dysplasia of the hip (DDH) and its impact on acetabular development. Clinical data were reviewed for 26 DDH patients with an inverted or overriding limbus after closed reduction for hip dysplasia. Patients were divided into a residual inversion group (19 cases, 22 hips) and a spontaneous resolution group (7 cases, 7 hips) according to the limbus status at the last follow‐up. Differences in the osseous acetabular index (AI) and cartilaginous AI (CAI), the magnitude of limbus inversion, center‐edge angle (CEA), height‐to‐width index (HWI) of the femoral head epiphysis, and avascular necrosis (AVN) at last follow‐up were compared. There were no statistically significant differences in the preoperative AI and CAI between groups. The magnitude of limbus inversion after reduction and the AI at the final follow‐up in the residual inversion group were both larger than those in the spontaneous resolution group. The CAI, CEA, and HWI were not significantly different between groups. The magnitude of limbus inversion in the residual inversion group did not significantly decrease over time. AVN occurred in five hips in the residual inversion group. No cases of AVN occurred in the spontaneous resolution group. After closed reduction, the inverted limbus was not absorbed in the majority of cases; instead, it evolved into a thin layer of fibrous tissue embedded between the femoral head and acetabulum. This may delay the endochondral ossification of the acetabulum.

Using an animal model, we aimed to investigate the effects of an inverted limbus on acetabular development following closed reduction of developmental dysplasia of the hip (DDH). We interpositioned the menisci of 5-week-old rabbits (n = 40) into the hip joints to simulate limbus inversion following closed reduction for DDH. The acetabular index (AI) on anteroposterior pelvic radiographs and magnetic resonance imaging were used to evaluate acetabular development. Animals were euthanized at 4 and 8 weeks after surgery. Histological sections of the acetabular cartilage were stained and scored in accordance with the modified Mankin system. Scanning electron microscopy and transmission electron microscopy were used to examine the ultrastructure of the acetabular cartilage. Terminal deoxynucleotidyl transferase dUTP nick end-labeling staining was used to evaluate chondrocyte apoptosis.Immunohistochemistry and Western blot analyses were used to examine the expression of type X collagen (Col-X) and matrix metalloproteinase 13 (MMP-13) in the acetabular cartilage. AI values increased over a period and were higher in the experimental group than in the sham group. In the experimental group, the acetabular surface had become rough and had split in some cases. Chondrocytes within the acetabular cartilage had become hypertrophic, gradually forming clusters, and taking on an apoptotic appearance. Col-X and MMP-13 expression also increased with time. Our findings suggest that residual limbus inversion following closed reduction for DDH can cause progressive dysplasia of the acetabulum, apoptosis of acetabular chondrocytes, accelerated cartilage degeneration, and even early-stage osteoarthritis.

<p>Univariate analyses of PFS and OS in 407 transplant-eligible myeloma patients</p>

<p>The prognostic impact of ASCT and early MRD status by molecular risk groups</p>

<div>Abstract<p>Attaining undetectable minimal residual disease (MRD) is the current therapeutic goal for multiple myeloma (MM). But there is a current lack of data regarding the clinical benefit of autologous stem cell transplantation (ASCT) for myeloma patients achieving early MRD-negative status after induction treatment, in addition to the interaction of longitudinal MRD status with ASCT. The present study included 407 transplant-eligible MM patients with available MRD status from the National Longitudinal Cohort of Hematological Diseases in China (NCT04645199), of whom 147 (34.4%) achieved early undetectable MRD and 182 (44.7%) received ASCT. Early MRD-negative status was associated with a lower risk of disease progression (HR=0.447; 95%CI, 0.333-0.600; P<0.001) and death (HR=0.473; 95%CI, 0.320-0.700; P<0.001). Of note, patients who achieved undetectable MRD early still benefitted from ASCT, with a remarkable improvement in the median MRD-negative duration (33.5 to 58.0 months, P<0.001), progression-free survival (PFS; 46.0 to 88.3 months, P<0.001), and overall survival (OS; 76.4 months to not reached, P=0.003). These clinical benefits were more pronounced in patients with aggressive features (high-risk cytogenetic abnormalities or high tumor burden) compared to standard-risk patients. Similar results were observed in patients with detectable MRD after induction treatment. Additionally, we identified four MRD-status transformation patterns following ASCT, which were strongly correlated with diverse survival outcomes (P<0.001). Our study revealed the enhanced clinical significance of ASCT in transplant-eligible myeloma patients, regardless of early MRD status, particularly for high-risk patients. Subsequent prospective trials are essential to validate these observations.</p></div>