Can we predict the clinical outcome of arthroscopic partial meniscectomy? A systematic review

NHS-Prospero registration number 42016048592 Objective In order to make a more evidence-based selection of patients who would benefit the most from arthroscopic partial meniscectomy (APM), knowledge of prognostic factors is essential. We conducted a systematic review of predictors for the clinical outcome following APM. Design Systematic review Data sources Medline, Embase, Cochrane Central Register, Web of Science, SPORTDiscus, PubMed Publisher, Google Scholar Inclusion criteria Report an association between factor(s) and clinical outcome; validated questionnaire; follow-up >1 year. Exclusion criteria 1 year) are associated with worse clinical outcome following APM. In addition, resecting >50% of meniscal tissue and leaving a non-intact meniscal rim after meniscectomy are intra-articular predictive factors for worse clinical outcome. Moderate evidence was found that sex, onset of symptoms (acute or chronic), tear type or preoperative sport level are not predictors for clinical outcome. Conflicting evidence was found for the prognostic value of age, perioperative chondral damage, body mass index and leg alignment. Summary/conclusion Long duration of symptoms (>1 year), radiological knee osteoarthritis and resecting >50% of meniscus are associated with a worse clinical outcome following APM. These prognostic factors should be considered in clinical decision making for patients with meniscal tears

Development and assessment of a digital X-ray software tool to determine vertebral rotation in adolescent idiopathic scoliosis

BACKGROUND CONTEXT: The amount of vertebral rotation in the axial plane is of key importance in the prognosis and treatment of adolescent idiopathic scoliosis (AIS). Current methods to determine vertebral rotation are either designed for use in analogue plain radiographs and not useful in digital images, or lack measurement precision and are therefore less suitable for the follow-up of rotation in AIS patients.PURPOSE: This study aimed to develop a digital X-ray software tool with high measurement precision to determine vertebral rotation in AIS, and to assess its (concurrent) validity and reliability.STUDY DESIGN/SETTING: In this study a combination of basic science and reliability methodology applied in both laboratory and clinical settings was used.METHODS: Software was developed using the algorithm of the Perdriolle torsion meter for analogue AP plain radiographs of the spine. Software was then assessed for (1) concurrent validity and (2) intra-and interobserver reliability. Plain radiographs of both human cadaver vertebrae and outpatient AIS patients were used. Concurrent validity was measured by two independent observers, both experienced in the assessment of plain radiographs. Reliability-measurements were performed by three independent spine surgeons.RESULTS: Pearson correlation of the software compared with the analogue Perdriolle torsion meter for mid-thoracic vertebrae was 0.98, for low-thoracic vertebrae 0.97 and for lumbar vertebrae 0.97. Measurement exactness of the software was within 5 degrees in 62% of cases and within 10 degrees in 97% of cases. Intraclass correlation coefficient (ICC) for inter-observer reliability was 0.92 (0.91-0.95), ICC for intra-observer reliability was 0.96 (0.94-0.97).CONCLUSIONS: We developed a digital X-ray software tool to determine vertebral rotation in AIS with a substantial concurrent validity and reliability, which may be useful for the follow-up of vertebral rotation in AIS patients. (C) 2015 Elsevier Inc. All rights reserved.</p

Traumatic Meniscal Tears Are Associated With Meniscal Degeneration

Background: Meniscal tears are traditionally classified into traumatic versus degenerative tears. Although this classification plays a major role in clinical decision making, no consensus exists on the exact definition of a traumatic or degenerative tear, and the histopathological basis for thi

T2mapping of healthy knee cartilage: Multicenter multivendor reproducibility

Background: T2 mapping is increasingly used to quantify cartilage degeneration in knee osteoarthritis (OA), yet reproducibility studies in a multicenter setting are limited. The purpose of this study was to determine the longitudinal reproducibility and multicenter variation of cartilage T2 mapping, using various MRI equipment and acquisition protocols. Methods: In this prospective multicenter study, four traveling, healthy human subjects underwent T2 mapping twice at five different centers with a 6-month-interval. Centers had various MRI scanners, field strengths, and T2 mapping acquisition protocols. Mean T2 values were calculated in six cartilage regions of interest (ROIs) as well as an average value per patient. A phantom was scanned once at each center. To evaluate longitudinal reproducibility, intraclass correlation coefficients (ICC), root-mean-square coefficient of variation (RMS-CV), and a Bland-Altman plot were used. To assess the variation of in vivo and phantom T2 values across centers, ANOVA was performed. Results: ICCs of the T2 mapping measurements per ROI and the ROI's combined ranged from 0.73 to 0.91, indicating good to excellent longitudinal reproducibility. RMS-CVs ranged from 1.1% to 1.5% (per ROI) and 0.6% to 1.6% (ROIs combined) across the centers. A Bland-Altman plot did not reveal a systematic error. Evident, but consistent, discrepancies in T2values were observed across centers, both in vivo and in the phantom. Conclusions: The results of this study suggest that T2mapping can be used to longitudinal assess cartilage degeneration in multicenter studies. Given the differences in absolute cartila

T-2 mapping of the meniscus is a biomarker for early osteoarthritis

Purpose To evaluate in vivo T2 mapping as quantitative, imaging-based biomarker for meniscal degeneration in humans, by studying the correlation between T2 relaxation time and degree of histological degeneration as reference standard. Methods In this prospective validation study, 13 menisci from seven patients with radiographic knee osteoarthritis (median age 67 years, three males) were included. Menisci were obtained during total knee replacement surgery. All patients underwent preoperative magnetic resonance imaging using a 3-T MR scanner which included a T2 mapping pulse sequence with multiple echoes. Histological analysis of the collected menisci was performed using the Pauli score, involving surface integrity, cellularity, matrix organization, and staining intensity. Mean T2 relaxation times were calculated in meniscal regions of interest corresponding with the areas scored histologically, using a multi-slice multi-echo postprocessing algorithm. Correlation between T2 mapping and histology was assessed using a generalized least squares model fit by maximum likelihood. Results The mean T2 relaxation time was 22.4 ± 2.7 ms (range 18.5–27). The median histological score was 10, IQR 7–11 (range 4–13). A strong correlation between T2 relaxation time and histological score was found (rs = 0.84, CI 95% 0.64–0.93). Conclusion In vivo T2 mapping of the human meniscus correlates strongly with histological degeneration, suggesting that T2 mapping enables the detection and quantification of early compositional changes of the meniscus in knee OA

Phospholamban antisense oligonucleotides improve cardiac function in murine cardiomyopathy

Heart failure (HF) is a major cause of morbidity and mortality worldwide, highlighting an urgent need for novel treatment options, despite recent improvements. Aberrant Ca(2+) handling is a key feature of HF pathophysiology. Restoring the Ca(2+) regulating machinery is an attractive therapeutic strategy supported by genetic and pharmacological proof of concept studies. Here, we study antisense oligonucleotides (ASOs) as a therapeutic modality, interfering with the PLN/SERCA2a interaction by targeting Pln mRNA for downregulation in the heart of murine HF models. Mice harboring the PLN R14del pathogenic variant recapitulate the human dilated cardiomyopathy (DCM) phenotype; subcutaneous administration of PLN-ASO prevents PLN protein aggregation, cardiac dysfunction, and leads to a 3-fold increase in survival rate. In another genetic DCM mouse model, unrelated to PLN (Cspr3/Mlp(−/−)), PLN-ASO also reverses the HF phenotype. Finally, in rats with myocardial infarction, PLN-ASO treatment prevents progression of left ventricular dilatation and improves left ventricular contractility. Thus, our data establish that antisense inhibition of PLN is an effective strategy in preclinical models of genetic cardiomyopathy as well as ischemia driven HF

Associations between depressive symptoms and disease progression in older patients with chronic kidney disease: results of the EQUAL study

Background Depressive symptoms are associated with adverse clinical outcomes in patients with end-stage kidney disease; however, few small studies have examined this association in patients with earlier phases of chronic kidney disease (CKD). We studied associations between baseline depressive symptoms and clinical outcomes in older patients with advanced CKD and examined whether these associations differed depending on sex. Methods CKD patients (&gt;= 65 years; estimated glomerular filtration rate &lt;= 20 mL/min/1.73 m(2)) were included from a European multicentre prospective cohort between 2012 and 2019. Depressive symptoms were measured by the five-item Mental Health Inventory (cut-off &lt;= 70; 0-100 scale). Cox proportional hazard analysis was used to study associations between depressive symptoms and time to dialysis initiation, all-cause mortality and these outcomes combined. A joint model was used to study the association between depressive symptoms and kidney function over time. Analyses were adjusted for potential baseline confounders. Results Overall kidney function decline in 1326 patients was -0.12 mL/min/1.73 m(2)/month. A total of 515 patients showed depressive symptoms. No significant association was found between depressive symptoms and kidney function over time (P = 0.08). Unlike women, men with depressive symptoms had an increased mortality rate compared with those without symptoms [adjusted hazard ratio 1.41 (95% confidence interval 1.03-1.93)]. Depressive symptoms were not significantly associated with a higher hazard of dialysis initiation, or with the combined outcome (i.e. dialysis initiation and all-cause mortality). Conclusions There was no significant association between depressive symptoms at baseline and decline in kidney function over time in older patients with advanced CKD. Depressive symptoms at baseline were associated with a higher mortality rate in men

3D MRI in Osteoarthritis

Osteoarthritis (OA) is among the top 10 burdensome diseases, with the knee the most affected joint. Magnetic resonance imaging (MRI) allows whole-knee assessment, making it ideally suited for imaging OA, considered a multitissue disease. Three-dimensional (3D) MRI enables the comprehensive assessment of OA, including quantitative morphometry of various joint tissues. Manual tissue segmentation on 3D MRI is challenging but may be overcome by advanced automated image analysis methods including artificial intelligence (AI). This review presents examples of the utility of 3D MRI for knee OA, focusing on the articular cartilage, bone, meniscus, synovium, and infrapatellar fat pad, and it highlights several applications of AI that facilitate segmentation, lesion detection, and disease classification

Immuno-histological analysis of dendritic cells in nasal biopsies of IgA nephropathy patients

BACKGROUND: IgA nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. Intranasal vaccination of patients with IgAN has shown mucosal and systemic IgA hyporesponsiveness. Here, we investigated whether this IgA hyporesponse in IgAN patients can be explained by reduced numbers or altered subset distribution of dendritic cells (DCs) in nasal mucosa. METHODS: Eighteen IgAN patients and 18 healthy volunteers were recruited for this study. Nasal biopsies were taken, after local anaesthesia, from the lower edge of the inferior turbinate. Staining for different subsets of DCs was performed using specific monoclonal antibodies. To detect myeloid DCs, we used CD1a, DC-SIGN and blood dendritic cell antigen-1 (BDCA-1) as a marker and for plasmacytoid DCs we used BDCA-2. DC-cell numbers in the epithelium and in lamina propria were counted separately and expressed as positively stained cells per mm(2). RESULTS: Both myeloid and plasmacytoid DC could be demonstrated in nasal biopsies. Quantification showed that IgAN patients contained significantly more DC-SIGN-positive cells in the lamina propria compared to controls. In addition, in IgAN patients, we observed more CD1a-positive cells in the epithelium. No differences in BDCA-1 and BDCA-2-positive cells were found between patients and controls. The number of positively stained cells in the epithelial layer correlated strongly with the number of positively stained cells in the lamina propria. CONCLUSIONS: Patients with IgAN have higher numbers of CD1a-positive cells in the epithelial layer and more DC-SIGN-positive cells in the lamina propria. Therefore, the earlier observed IgA hyporesponsiveness in IgAN patients after mucosal vaccination cannot be explained by lower numbers of nasal DC