Osteochondritis dissecans of the knee: Epidemiology, etiology, and natural history.

Osteochondritis dissecans of the knee is a disease that typically affects skeletally immature patients. Clinically manifested with knee pain, limping, and joint disfunction, this condition has remained misunderstood and undervalued for a long period. Although being a rare condition, its awareness is of utmost clinical interest because of the possible severe consequences it can bring when misrecognized or inadequately treated. Its etiology remains unclear and is still debated. Many theories have been proposed, including inflammation, local ischemia, subchondral ossification abnormalities, genetic factors, and repetitive mechanical microtrauma, with a likely interplay of the same. This review article aims to deliver and discuss current and up-to-date concepts on epidemiology, etiology, and natural history of this pediatric condition. Level of evidence: level V

Discoid meniscus in human fetuses: A systematic review

Background: Discoid meniscus (DM) is a rare variant of regular knee anatomy. Compared to standard meniscus it is thicker and abnormal in shape; these characteristics make it more prone to tear. It is a congenital defect whose correct etiology is still debated and far from being clarified. The purpose of this systematic review is to evaluate evidences of DM in human fetuses in order to assess whether embryological development may have a role. Methods: A systematic review was performed on PubMed, Scopus, and Embase with different combinations of the keywords \u201cdiscoid meniscus\u201d, \u201cembryology\u201d, \u201cfetus\u201d, \u201cneonatal\u201d. Search yielded 1013 studies, on which we performed a primary evaluation. Results: Seven studies were considered including a total of 1378 fetal menisci specimens, from 396 different fetuses. Discoid shape was not found represented as a normal stage of prenatal development. From 782 lateral menisci analyzed, only 86 (10.86%) were discoid (13 complete, 73 incomplete type). None of medial menisci was found to be discoid. Lateral meniscus was observed to cover a larger surface of tibial plateau than medial one until 28th gestational week. Conclusion: Lateral meniscus seems to be more prone to discoid shape for its natural tendency of covering a larger surface of the tibial plateau during fetal stages. However the fact that a discoid shape was not found in the majority of fetuses suggests that it is not a normal stage of fetal development. To support a single etiological factor it will be appropriate to have further morphological and morphometric studies

Wide-transcriptome analysis and cellularity of bone marrow CD34+/lin- cells of patients with chronic-phase chronic myeloid leukemia at diagnosis vs. 12 months of first-line nilotinib treatment

BACKGROUND: Chronic myeloid leukemia (CML) is a clonal myeloproliferative disorder with heterogeneous biological and clinical features. The biomolecular mechanisms of CML response to tyrosine-kinase inhibitors are not fully defined. OBJECTIVE: We undertook a gene expression profiling (GEP) study of selected bone marrow (BM) CD34+/lin-cells of chronic-phase CML patients at diagnosis and after 12 months of TKI nilotinib to investigate molecular signatures characterizing both conditions. METHODS:We selected and counted BM CD34+/lin- cells of 30 CML patients at diagnosis and during 3, 6 and 12 months of first-line nilotinib treatment. GEP was performed between CD34+/lin- cells of patients at diagnosis and the same patients after 12 months of nilotinib. RESULTS: The number of BM CD34+/lin- cells dramatically decreased after 3, 6 and 12 months of nilotinib. GEP detected 264 statistically significant differentially expressed genes at diagnosis vs. 12 months of nilotinib. Functional enrichment analysis revealed groups of genes belonging to 14 pathways differentially active during nilotinib treatment. CONCLUSIONS: In conclusion, lipid, glucose and sphingolipid metabolism, insulin resistance, complement and coagulation, platelet activation, cytoscheleton, cell adhesion, transport, B cell differentiation, RAS-signaling pathway, proliferation, growth factors, and apoptosis were significantly deregulated between CML patients at diagnosis and after 12 months of nilotinib

A prognostic model to predict survival after 6 months of ruxolitinib in patients with myelofibrosis

Ruxolitinib (RUX) is extensively used in myelofibrosis (MF). Despite its early efficacy, most patients lose response over time and, after discontinuation, have a worse overall survival (OS). Currently, response criteria able to predict OS in RUX-treated patients are lacking, leading to uncertainty regarding the switch to second-line treatments. In this study, we investigated predictors of survival collected after 6 months of RUX in 209 MF patients participating in the real-world ambispective observational RUXOREL-MF study (NCT03959371). Multivariable analysis identified the following risk factors: (1) RUX dose,20 mg twice daily at baseline, months 3 and 6 (hazard ratio [HR], 1.79; 95% confidence interval [CI], 1.07-3.00; P 5.03), (2) palpable spleen length reduction from baseline #30% at months 3 and 6 (HR, 2.26; 95% CI, 1.40-3.65; P 5.0009), (3) red blood cell (RBC) transfusion need at months 3 and/or 6 (HR, 1.66; 95% CI, 0.95-2.88; P 5.07), and (4) RBC transfusion need at all time points (ie, baseline and months 3 and 6; HR, 2.32; 95% CI, 1.19-4.54; P 5.02). Hence, we developed a prognostic model, named Response to Ruxolitinib After 6 Months (RR6), dissecting 3 risk categories: low (median OS, not reached), intermediate (median OS, 61 months; 95% CI, 43-80), and high (median OS, 33 months; 95% CI, 21-50). The RR6 model was validated and confirmed in an external cohort comprised of 40 MF patients. In conclusion, the RR6 prognostic model allows for the early identification of RUX-treated MF patients with impaired survival who might benefit from a prompt treatment shift

Second primary malignancies in ruxolitinib-treated myelofibrosis: Real-world evidence from 219 consecutive patients

We present real-world data on all ruxolitinib-treated myelofibrosis patients in a 10-million-resident region, with a follow-up of 2 years.We found no evidence of an increased risk of developing lymphomas