Search

Osteoarthritis (OA) is a leading cause of morbidity among aging populations, yet symptom and/or disease-modification remains elusive. Adipose-derived mesenchymal stromal cells (adMSCs) have demonstrated immunomodulatory and anti-inflammatory properties that may alleviate clinical signs and interrupt disease onset and progression. Indeed, multiple manuscripts have evaluated intra-articular administration of adMSCs as a therapeutic; however, comparatively few evaluations of systemic delivery methods have been published. Therefore, the aim of this study was to evaluate the short-term impact of intravenous (IV) delivery of allogeneic adMSCs in an established model of spontaneous OA, the Hartley guinea pig. Animals with moderate OA received once weekly injections of 2 × 10 6 adMSCs or vehicle control for 4 weeks in peripheral veins; harvest occurred 2 weeks after the final injection. Systemic administration of adMSCs resulted in no adverse effects and was efficacious in reducing clinical signs of OA (as assessed by computer-aided gait analysis) compared to control injected animals. Further, there were significant decreases in key inflammatory mediators (including monocyte chemoattractant protein-1, tumor necrosis factor, and prostaglandin E 2 ) both systemically (liver, kidney, and serum) and locally in the knee (joint tissues and synovial fluid) in animals treated with IV adMSCs relative to controls (as per enzyme-linked immunosorbent assay and/or immunohistochemistry, dictated by tissue sample). Thus, systemic administration of adMSCs by IV injection significantly improved gait parameters and reduced both systemic and intra-articular inflammatory mediators in animals with OA. These findings demonstrate the potential utility of alternative delivery approaches for cellular therapy of OA, particularly for patients with multiple affected joints., (© 2022 The Authors. Journal of Orthopaedic Research® published by Wiley Periodicals LLC on behalf of Orthopaedic Research Society.)

Background: IQ·SPECT is a recently introduced collimator design for myocardial perfusion imaging (MPI). Little data exist on use of this collimator type in obese patients, particularly Class 2 or 3 [body mass index (BMI) > 35 kg/m 2 ]., Methods: Two consecutive rest-stress MPI scans were prospectively acquired using a conventional collimator and IQ·SPECT (acquisition times of 20 and 7 minutes, respectively) in 20 patients with a BMI of >30 kg/m 2 . Assigned by two blinded, independent readers, image quality (on a 5-point scale) and metrics of myocardial perfusion [summed stress score (SSS), summed rest score (SRS) and summed difference score (SDS)] were compared. Software-based left ventricular ejection fraction (EF) was also correlated., Results: Mean BMI was 39.6 ± 7.6 kg/m 2 . Class 2 or 3 obesity was present in 12 patients (BMI, 44.1 ± 6.8 kg/m 2 ). Gated/non-gated images from IQ·SPECT revealed fair to good quality scores (median ≥ 3.25), which were inferior to the conventional collimator (median ≥ 4.0; P ≤ 0.01). Significant correlative indices were achieved when comparing IQ·SPECT and conventional collimators for EF values (r = 0.86, P < 0.01), SSS (r = 0.75, P < 0.0001) and SRS (r = 0.60, P < 0.005), but not for SDS (r = 0.15)., Conclusion: IQ·SPECT was comparable to conventional SPECT in obese patients. The reduced acquisition time of IQ·SPECT may allow for improved throughput with no loss in diagnostic accuracy., (© 2022. The Author(s) under exclusive licence to American Society of Nuclear Cardiology.)

Objective: The purpose of our work is to assess the role of tumour-to-normal tissue (T/N) dosimetry ratios for predicting response in patients undergoing locoregional therapy to the liver with 90 Y microspheres., Methods: A total of 39 patients (7 female:32 male, mean age 68.3 ± 7.6 years), underwent positron emission tomography (PET)/CT imaging after treatment with 90 Y microspheres. For attenuation correction and localization of the 90 Y microspheres, the low-dose, non-diagnostic CT images from PET/CT were used. The acquisition took 15 min and the reconstruction matrix size was 200 × 200 × 75 mm and voxel size of 4.07 × 4.07 × 3.00 mm. For dosimetry calculations, the local deposition method with known activity of 90 Y was used. For each patient, regions of interest for tumour(s) and whole liver were manually created; the normal tissue region of interest was created automatically. mRECIST criteria on MRI done at 1 month post-treatment and subsequently every 3 months after 90 Y treatment, were used to assess response., Results: For 39 patients, the mean liver, tumour and normal tissue doses (mean ± SD) were, 55.17 ± 26.04 Gy, 911.87 ± 866.54 Gy and 47.79 ± 20.47 Gy, respectively. Among these patients, 31 (79%) showed complete response (CR) and 8 (21%) showed progression of disease (PD). For patients with CR, the mean T/N dose ratio obtained was 24.91 (range 3.09-80.12) and for patients with PD, the mean T/N dose ratio was significantly lower, at 6.69 (range 0.36-14.75)., Conclusion: Our data show that patients with CR have a statistically higher T/N dose ratio than those with PD. Because, the number of PD cases was limited and partial volume effect was not considered, further investigation is warranted., Advances in Knowledge: T/N dosimetry ratios can be used for assessing response in patients undergoing locoregional therapy to the liver with 90 Y microspheres.

Objective: Faced with the frustration of chronic discomfort and restricted mobility due to osteoarthritis (OA), many individuals have turned to acupuncture for relief. However, the efficacy of acupuncture for OA is uncertain, as much of the evidence is inconclusive. The purpose of this study was to evaluate electroacupuncture (EA) in a rodent model of OA such that conclusions regarding its effectiveness for symptom or disease modification could be drawn., Methods: Ten 12-month-old male Hartley guinea pigs-which characteristically have moderate to advanced OA at this age-were randomly assigned to receive EA for knee OA (n = 5) or anesthesia only (control group, n = 5). Treatments were performed three times weekly for 3 weeks, followed by euthanasia 2 weeks later. Gait analysis and enclosure monitoring were performed weekly to evaluate changes in movement. Serum was collected for inflammatory biomarker testing. Knee joints were collected for histology and gene expression., Results: Animals receiving EA had significantly greater changes in movement parameters compared to those receiving anesthesia only. There was a tendency toward decreased serum protein concentrations of complement component 3 (C3) in the EA group compared to the control group. Structural and antioxidant gene transcripts in articular cartilage were increased by EA. There was no significant difference in total joint histology scores between groups., Conclusion: This study provides evidence that EA has a positive effect on symptom, but not disease, modification in a rodent model of OA. Further investigations into mechanistic pathways that may explain the efficacy of EA in this animal model are needed.

We investigated the prognostic impact and clinical utility of serum free light chains (sFLC) and serum heavy-light chains (sHLC) in patients with multiple myeloma treated according to the GEM2005MENOS65, GEM2005MAS65, and GEM2010MAS65 PETHEMA/GEM phase III clinical trials. Serum samples collected at diagnosis were retrospectively analyzed for sFLC (n = 623) and sHLC (n = 183). After induction or autologous transplantation, 309 and 89 samples respectively were available for sFLC and sHLC assays. At diagnosis, a highly abnormal (HA) sFLC ratio (sFLCr) (<0.03 or >32) was not associated with higher risk of progression. After therapy, persistence of involved-sFLC levels >100 mg/L implied worse survival (overall survival [OS], P = 0.03; progression-free survival [PFS], P = 0.007). Among patients that achieved a complete response, sFLCr normalization did not necessarily indicate a higher quality response. We conducted sHLC investigations for IgG and IgA MM. Absolute sHLC values were correlated with monoclonal protein levels measured with serum protein electrophoresis. At diagnosis, HA-sHLCrs (<0.29 or >73) showed a higher risk of progression (P = 0.006). Additionally, involved-sHLC levels >5 g/L after treatment were associated with shorter survival (OS, P = 0.001; PFS, P = 0.018). The HA-sHLCr could have prognostic value at diagnosis; absolute values of involved-sFLC >100 mg/L and involved-sHLC >5 g/L could have prognostic value after treatment., Competing Interests: The authors have declared that no competing interests exist.