The subchondral bone in articular cartilage repair: current problems in the surgical management

As the understanding of interactions between articular cartilage and subchondral bone continues to evolve, increased attention is being directed at treatment options for the entire osteochondral unit, rather than focusing on the articular surface only. It is becoming apparent that without support from an intact subchondral bed, any treatment of the surface chondral lesion is likely to fail. This article reviews issues affecting the entire osteochondral unit, such as subchondral changes after marrow-stimulation techniques and meniscectomy or large osteochondral defects created by prosthetic resurfacing techniques. Also discussed are surgical techniques designed to address these issues, including the use of osteochondral allografts, autologous bone grafting, next generation cell-based implants, as well as strategies after failed subchondral repair and problems specific to the ankle joint. Lastly, since this area remains in constant evolution, the requirements for prospective studies needed to evaluate these emerging technologies will be reviewed

Twelve-month observational study of children with cancer in 41 countries during the COVID-19 pandemic

Introduction Childhood cancer is a leading cause of death. It is unclear whether the COVID-19 pandemic has impacted childhood cancer mortality. In this study, we aimed to establish all-cause mortality rates for childhood cancers during the COVID-19 pandemic and determine the factors associated with mortality. Methods Prospective cohort study in 109 institutions in 41 countries. Inclusion criteria: children <18 years who were newly diagnosed with or undergoing active treatment for acute lymphoblastic leukaemia, non-Hodgkin's lymphoma, Hodgkin lymphoma, retinoblastoma, Wilms tumour, glioma, osteosarcoma, Ewing sarcoma, rhabdomyosarcoma, medulloblastoma and neuroblastoma. Of 2327 cases, 2118 patients were included in the study. The primary outcome measure was all-cause mortality at 30 days, 90 days and 12 months. Results All-cause mortality was 3.4% (n=71/2084) at 30-day follow-up, 5.7% (n=113/1969) at 90-day follow-up and 13.0% (n=206/1581) at 12-month follow-up. The median time from diagnosis to multidisciplinary team (MDT) plan was longest in low-income countries (7 days, IQR 3-11). Multivariable analysis revealed several factors associated with 12-month mortality, including low-income (OR 6.99 (95% CI 2.49 to 19.68); p<0.001), lower middle income (OR 3.32 (95% CI 1.96 to 5.61); p<0.001) and upper middle income (OR 3.49 (95% CI 2.02 to 6.03); p<0.001) country status and chemotherapy (OR 0.55 (95% CI 0.36 to 0.86); p=0.008) and immunotherapy (OR 0.27 (95% CI 0.08 to 0.91); p=0.035) within 30 days from MDT plan. Multivariable analysis revealed laboratory-confirmed SARS-CoV-2 infection (OR 5.33 (95% CI 1.19 to 23.84); p=0.029) was associated with 30-day mortality. Conclusions Children with cancer are more likely to die within 30 days if infected with SARS-CoV-2. However, timely treatment reduced odds of death. This report provides crucial information to balance the benefits of providing anticancer therapy against the risks of SARS-CoV-2 infection in children with cancer

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field

Antibodies against neural, nuclear, cytoskeletal, and streptococcal epitopes in children and adults with Tourette's syndrome, Sydenham's chorea, and autoimmune disorders

Background: Some cases of Tourette's syndrome (TS) are hypothesized to be caused by autoantibodies that develop in response to a preceding group A beta hemolytic streptococcal infection