Search Results (15)

Background/Objectives: Patient-level predictors of treatment response after genicular artery embolization (GAE) for knee osteoarthritis (OA) are poorly understood. We evaluated clinical, serum, and imaging biomarkers for their ability to predict achievement of the minimally clinically important difference (MCID) for WOMAC pain and stiffness subscales following GAE. Methods: Data from a prospective single-arm clinical trial of 25 patients who underwent GAE for symptomatic knee OA was retrospectively analyzed. Candidate predictors included sex, age, BMI, contralateral Kellgren–Lawrence (KL) scores, and baseline values for serum IL-1Ra, serum VEGF, and total bone marrow edema scores on MRI using the MOAKS methodology. The primary outcomes were the frequency of achieving the MCID in WOMAC pain and WOMAC stiffness at 1, 3, and 12 months, modeled as an ordinal outcome (0–3). Ordinal logistic regression models were constructed. Variance inflation factors (VIFs) were assessed to detect multicollinearity, and leave-one-out cross-validation was performed to evaluate model robustness. Results: All candidate predictors were successfully incorporated into regression models, with no evidence of multicollinearity by VIF analysis. Lower contralateral KL scores (OR: 0.087 [0.012–0.618], p = 0.0146) and higher BMI (OR: 1.383 [1.001–1.910], p = 0.049) were significantly associated with achievement of the MCID for WOMAC pain, although significance for BMI was borderline. Lower baseline serum IL-1Ra levels (OR: 0.122 [0.018–0.816], p = 0.030) were significantly associated with achievement of the MCID for WOMAC stiffness. The remaining clinical, serum, and imaging biomarkers were not significantly associated with MCID achievement. Conclusions: In this exploratory analysis, specific baseline clinical and serum factors were associated with achievement of clinically meaningful improvements in pain and stiffness. Analysis of larger cohorts will help clarify ideal demographic-, biomarker- and imaging-based patient selection strategies that can improve prediction of treatment response and guide clinical decision-making in GAE for knee OA. Full article

Background and Clinical Significance: Tyrosine kinase inhibitors (TKIs) have transformed Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) into a largely manageable chronic disease. However, off-target toxicities are increasingly recognized; rarer complications such as bone marrow edema (BME) remain underreported. BME is a radiological syndrome characterized by excess intramedullary fluid on fat-suppressed T2/STIR magnetic resonance imaging sequences and may progress to irreversible osteochondral damage if unrecognized. We report a case series of TKI-associated BME and propose a practical diagnostic-therapeutic framework. Case Presentation: We describe three patients with Ph+ CML who developed acute, MRI-confirmed BME of the lower limb during TKI therapy. Case 1 developed unilateral then bilateral knee BME, temporally associated first with dasatinib and subsequently with imatinib; symptoms improved after TKI interruption, bisphosphonate therapy, and supportive measures, and did not recur after switching to bosutinib. Case 2 presented with proximal femoral BME during long-term imatinib; imatinib was stopped, intravenous neridronate administered, and bosutinib initiated with clinical recovery and later near-complete radiological resolution. Case 3 experienced multifocal foot and ankle BME during imatinib; symptoms resolved after drug discontinuation and bisphosphonate therapy, and disease control was re-established with bosutinib without recurrence of BME. All patients underwent molecular monitoring and mutational analysis to guide safe therapeutic switching. Discussion: Temporal association across cases and the differential kinase profiles of implicated drugs suggest PDGFR (and to a lesser extent, c-KIT) inhibition as a plausible mechanistic driver of TKI-associated BME. PDGFR-β blockade may impair pericyte-mediated microvascular integrity, increase interstitial fluid extravasation, and alter osteoblast/osteoclast coupling, promoting intramedullary edema. Management combining MRI confirmation, temporary TKI suspension, bone-directed therapy (bisphosphonates, vitamin D/calcium), symptomatic care, and, when required, therapeutic switching to a PDGFR-sparing agent (bosutinib) led to clinical recovery and preservation of leukemia control in our series. Conclusions: BME is an underrecognized, potentially disabling, TKI-related adverse event in CML. Prompt recognition with targeted MRI and a multidisciplinary, stepwise approach that includes temporary TKI adjustment, bone-directed therapy, and consideration of PDGFR-sparing alternatives can mitigate morbidity while maintaining disease control. Prospective studies are needed to define incidence, risk factors, optimal prevention, and management strategies. Full article

Background/Objectives: Although MRI with fat-suppression sequences is the gold standard for diagnosis of bone marrow edema (BME), Dual-Layer Spectral CT (DL-SCT) with electron density (ED) provides a viable alternative, particularly in situations where an MRI is not accessible. Using MRI as the reference standard, this study analyzed how DL-SCT with ED reconstructions may be a valid alternative in the detection of BME. Methods: This retrospective study included 28 patients with a suspected diagnosis of BME via MRI conducted between March and September 2024. Patients underwent DL-SCT using ED reconstructions obtained through IntelliSpace software v. 12.1. Images were evaluated by two experienced radiologists and one young radiologist in a blinded way, giving a grade from 0 to 3 to classify BME (0 absence; 1 mild; 2 moderate; 3 severe). To reduce the recall bias effect, the order of image evaluations was set differently for each reader. p-Values were considered significant when <0.05. Fleiss’ Kappa was used to assess inter-rater reliability: agreement was considered poor for k < 0; slight for k 0.01–0.20; fair for 0.21–0.40; moderate for 0.41–0.60; substantial for 0.61–0.80; and almost perfect for 0.81–1.00. Results: All the readers detected the presence or absence of BME using DL-SCT. Inter-rater reliability for grade 0 resulted in 1 (p-value < 0.001); for grade 1: 0.21 (p-value < 0.001); for grade 2: 0.197 (p-value < 0.001); and for grade 3: 0.515 (p-value < 0.001). Conclusions: ED reconstructions allowed the identification of BME presence or absence in all analyzed cases, thus suggesting DL-SCT as a potentially effective method for its detection. Full article

Background: Some evidence suggests that combining hyaluronic acid (HA) with platelet-rich-plasma (PRP) may offer synergistic benefits by enhancing the biological and mechanical properties of joints. However, data on the combination of HA+PRP vs. HA alone in the management of knee osteoarthritis (OA) remain limited. Methods: A double-blinded randomized controlled trial was conducted at an outpatient clinic and enrolled 58 patients with Kellgren–Lawrence grade 2–3 knee OA. They were randomly allocated to receive either intra-articular PRP combined with HA (n = 29 knees) or HA alone (n = 29 knees). The primary outcome was pain, assessed using a visual analog scale (VAS). Secondary outcomes included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), health-related quality of life (EQ-5D-5L), and structural changes on MRI, measured by the Whole-Organ MRI Score (WORMS). The VAS, WOMAC, and EQ-5D-5L were evaluated at baseline and at months 1, 3, 6, and 12. MRI WORMS was assessed at baseline and 12 months. Results: The baseline characteristics were comparable between the HA+PRP and HA groups. Both interventions showed improvements in pain and function at 12 months. However, the between-group difference in VAS at 12 months—the primary outcome—was not statistically significant (p = 0.102) and did not exceed the minimal clinically important difference (MCID) of 20 mm. The HA group demonstrated significantly greater VAS score reductions at 1 month (−31.1 [95% CI: −38.9 to −23.2] vs. −14.3 [95% CI: −22.2 to −6.4], p = 0.003) and at 6 months (−32.1 [95% CI: −40.1 to −24.1] vs. −19.2 [95% CI: −27.1 to −11.3], p = 0.024), compared to the HA+PRP group, although these differences did not reach clinical significance. No significant between-group differences were observed in the WOMAC scores, EQ-5D-5L, or total WORMS scores at all time points (p > 0.05). At 12 months, MRI assessment revealed a significant decrease in bone marrow edema in the HA+PRP group (−0.7 [95% CI: −1.6 to 0.2]) compared to the HA group (0.7 [95% CI: −0.2 to 1.6], p = 0.030). Conclusions: Both HA+PRP and HA treatments were effective in reducing pain and improving function in patients with knee OA over 12 months. While HA demonstrated greater early pain relief, the addition of PRP was associated with a significant reduction in bone marrow edema at 12 months. These findings suggest potential structural benefits of HA+PRP, although clinical superiority over HA alone was not established. Full article

Background: Surgical treatment for Freiberg disease (also known as avascular necrosis of the metatarsal head) has not been completely defined. This retrospective study evaluated short-term outcomes after arthroscopic treatment of Freiberg disease. Methods: From 2015 to 2019, 13 patients (15 feet) diagnosed as having Freiberg disease were enrolled for arthroscopic surgery. Feet were divided based on the Smillie classification system (two with stage I, eight with stage II, three with stage III, one with stage IV, and one with stage V). Arthroscopic interventions, including synovectomy, debridement, chondroplasty, microfracture, and loose body removal, were performed without considering the Smillie classification stage. Radiologic outcomes were evaluated by radiography (preoperatively and 3, 6, and 12 months postoperatively) and magnetic resonance imaging (preoperatively and 12 months postoperatively). Clinical outcomes were evaluated using the American Orthopaedic Foot and Ankle Society (AOFAS) lesser metatarsophalangeal (MTP)–interphalangeal score and the visual analog scale (VAS) score. The MTP joint range of motion was measured using a goniometer preoperatively and postoperatively. Results: Radiologic studies showed no evidence of osteonecrosis progression in postoperative 12-month radiographs of any patients. Postoperative 12-month magnetic resonance images showed reduction of bone marrow edema, irregularity of subchondral bone, and cartilage defects in all patients. Significant improvements in AOFAS and VAS scores occurred at all postoperative time points compared with preoperative scores (P = .001). The MTP joint range of motion also showed improvement at last follow-up (P = .001). Conclusions: Arthroscopic surgery for Freiberg disease showed excellent clinical outcomes, MTP joint range of motion, and short-term outcomes regardless of stage (Smillie classification) in radiologic evaluation. Full article

(1) Background: Type 2 diabetes is a major cause of incidences and the progression of peripheral artery disease (PAD). Bone marrow edema (BME) is an important finding suggestive of underlying bone inflammation in non-traumatic diabetic patients with PAD. Our aim was to evaluate the presence, severity, and clinical implications of BME detected by virtual non-calcium application (VNCa) of dual-energy CT angiography (DE-CTA). (2) Methods: A consecutive series of 76 diabetic patients (55 men; mean age 71.6 ± 11.2 yrs) submitted to lower limb DE-CTA for PAD evaluation and revascularization planning, which were retrospectively analyzed. VNCa images were independently and blindly revised for the presence, location, and severity of BME by two radiologists with 10 years of experience. BME and non-BME groups were evaluated in terms of PAD clinical severity and 6-month secondary major amputation rate. (3) Results: BME was present in 17 (22%) cases, while 59 (78%) patients were non-BME. The BME group showed a significantly higher incidence of major amputation (p < 0.001) and a significantly higher number of patients with advanced clinical stages of PAD compared to the non-BME group (p = 0.024). (4) Conclusions: Lower limb DE-CTA with VNCa application is a useful tool in the detection of BME in diabetic patients with PAD, simultaneously enabling the evaluation of the severity and location of the arterial disease for revascularization planning. BME presence could be a marker of clinically severe PAD and a possible risk factor for revascularization failure. Full article

(1) Background: Whole-body magnetic resonance imaging (WB-MRI) is central to defining total inflammatory burden in juveniles with arthritis. Our aim was to determine and compare the initial distribution of lesions in the WB-MRI in patients with chronic recurrent multifocal osteomyelitis (CRMO), juvenile idiopathic arthritis (JIA), their overlapping syndrome (OS), and with Non-specific Arthropathy (NA). (2) Methods: This retrospective single center study was performed on an Avanto 1.5-T MRI scanner with a dedicated multichannel surface coil system. A total of 173 pediatric patients were included with the following final diagnoses: CRMO (15.0%), JIA (29.5%), OS (4.6%), and NA (50.9%). (3) Results: Bone marrow edema (BME) was the most common abnormality, being seen in 100% patients with CRMO, 88% with OS, 55% with JIA, and 11% with NA. The bones of the lower extremities were the most affected in all compared entities. Effusion was seen in 62.5% children with OS, and in 52.9% with JIA, and in CRMO and NA, the exudate was sporadic. Enthesitis was found in 7.8% of patients with JIA and 3.8% with CRMO, and myositis was seen in 12.5% of patients with OS and in 3.9% with JIA. (4) Conclusions: The most frequent indication for WB-MRI in our center was JIA. The most common pathology in all rheumatic entities was BME, followed by effusion mainly seen in in OS and JIA. Enthesitis and myositis were less common; no case was observed in NA. Full article

Extracorporeal shock waves are high-intensity mechanical waves (500–1000 bar) of a microsecond duration with a morphology characterized by a rapid positive phase followed by a negative phase. Background: Extracorporeal shock waves have been used for pain treatment for various sub-acute and chronic musculoskeletal (MSK) problems since 2000. The aim of this article is to update information on the role of extracorporeal shock wave therapy (ESWT) in the treatment of various pathologies that cause MSK pain. Methods: Given that in the last two years, articles of interest (including systematic reviews and meta-analyses) have been published on less known indications, such as low back pain, nerve entrapments, osteoarthritis and bone vascular diseases, a literature search was conducted in PubMed, the Cochrane Database, EMBASE, CINAHL and PEDro, with the aim of developing a narrative review of the current literature on this topic. The purposes of the review were to review possible new mechanisms of action, update the level of evidence for known indications and assess possible new indications that have emerged in recent years. Results: Although extracorporeal shock waves have mechanical effects, their main mechanism of action is biological, through a phenomenon called mechanotransduction. There is solid evidence that supports their use to improve pain in many MSK pathologies, such as different tendinopathies (epicondylar, trochanteric, patellar, Achilles or calcific shoulder), plantar fasciitis, axial pain (myofascial, lumbar or coccygodynia), osteoarthritis and bone lesions (delayed union, osteonecrosis of the femoral head, Kienbock’s disease, bone marrow edema syndrome of the hip, pubis osteitis or carpal tunnel syndrome). Of the clinical indications mentioned in this review, five have a level of evidence of 1+, eight have a level of evidence of 1−, one indication has a level of evidence of 2− and two indications have a level of evidence of 3. Conclusions: The current literature shows that ESWT is a safe treatment, with hardly any adverse effects reported. Furthermore, it can be used alone or in conjunction with other physical therapies such as eccentric strengthening exercises or static stretching, which can enhance its therapeutic effect. Full article

The effects of the administration of mesenchymal stromal cells (MSC) may vary according to the source. We hypothesized that MSC-derived extracellular vesicles (EVs) obtained from bone marrow (BM), adipose (AD), or lung (L) tissues may also lead to different effects in sepsis. We profiled the proteome from EVs as a first step toward understanding their mechanisms of action. Polymicrobial sepsis was induced in C57BL/6 mice by cecal ligation and puncture (SEPSIS) and SHAM (control) animals only underwent laparotomy. Twenty-four hours after surgery, animals in the SEPSIS group were randomized to receive saline or 3 × 10⁶ MSC-derived EVs from BM, AD, or L. The diffuse alveolar damage was decreased with EVs from all three sources. In kidneys, BM-, AD-, and L-EVs reduced edema and expression of interleukin-18. Kidney injury molecule-1 expression decreased only in BM- and L-EVs groups. In the liver, only BM-EVs reduced congestion and cell infiltration. The size and number of EVs from different sources were not different, but the proteome of the EVs differed. BM-EVs were enriched for anti-inflammatory proteins compared with AD-EVs and L-EVs. In conclusion, BM-EVs were associated with less organ damage compared with the other sources of EVs, which may be related to differences detected in their proteome. Full article

We evaluated the therapeutic effects of bone-marrow-derived mesenchymal stem cells (BMSCs) on behavioral and cognitive function in a mouse model of mild subarachnoid hemorrhage (SAH) and explored the underlying mechanisms in conjunction with the HMGB1–RAGE axis. The SAH models were generated in a total of 126 male C57BL/6J mice via endovascular perforation and evaluated 24 h and 72 h after the intravenous administration of BMSCs (3 × 10⁵ cells). The BMSCs were administered once, at 3 h, or twice, at 3 h and 48 h after the model induction. The therapeutic effects of the BMSCs were compared to those of the saline administration. Compared to saline-treated SAH-model mice, at 3 h, the mice with mild SAH treated with the BMSCs showed significant improvements in their neurological scores and cerebral edema. The administration of the BMSCs decreased the mRNA expression of HMGB1, RAGE, TLR4, and MyD88, as well as the protein expression of HMGB1 and phosphorylated NF-kB p65. Furthermore, the numbers of slips per walking time, impairments in short-term memory, and the recognition of novel objects were improved. There was some improvement in inflammatory-marker levels and cognitive function according to the BMSCs’ administration times, but no large differences were seen. The administration of BMSCs improved behavioral and cognitive dysfunction by ameliorating HMGB1–RAGE axis-mediated neuroinflammation after SAH. Full article

The aim of this study was to evaluate if magnetic resonance imaging allows hip arthritis in JIA to be differentiated from hip arthralgia of unknown etiology in juveniles clinically suspected for hip arthritis. This was a retrospective observational study which included 97 children with clinically suspected hip arthritis. Each hip was assessed and scored in MRI for signs of active and destructive inflammatory lesions and developmental lesions. MRI findings between JIA-confirmed patients and without final diagnosis of JIA were compared and the MRI summarized score was calculated, as the sum of scorings of all 24 hip lesions in an individual patient (i.a., effusion, synovitis, bone marrow edema, enthesitis). MRI showed at least one lesion in the majority of patients (95 patients; 98%). Effusion was the most common feature, followed by bone marrow oedema and synovitis. All lesions were more common in patients with a final diagnosis of JIA, especially synovitis and enthesitis (p = 0.037 and p = 0.047). The MRI summarized score was significantly higher in the JIA group than the non-JIA group: 3 (2–5) vs. 2 (2–2), respectively, p = 0.002. Using a cut-off score of 6, the MRI summarized score showed 25% sensitivity and 100% specificity indicating a good ability in discriminating hip arthritis during JIA from non-JIA patients. MRI allows hip arthritis in JIA to be differentiated from hip arthralgia of unknown etiology with good specificity, thus, may be helpful in confirming the diagnosis of JIA. Full article

The aim of this study is to assess whether perifocal bone marrow edema (BME) in patients with osteoid osteoma (OO) can be accurately detected on dual-layer spectral CT (DLCT) with three-material decomposition. To that end, 18 patients with OO (25.33 ± 12.44 years; 7 females) were pairwise-matched with 18 patients (26.72 ± 9.65 years; 9 females) admitted for suspected pathologies other than OO in the same anatomic location but negative imaging findings. All patients were examined with DLCT and MRI. DLCT data was decomposed into hydroxyapatite and water- and fat-equivalent volume fraction maps. Two radiologists assessed DLCT-based volume fraction maps for the presence of perifocal BME, using a Likert scale (1 = no edema; 2 = likely no edema; 3 = likely edema; 4 = edema). Accuracy, sensitivity, and specificity for the detection of BME on DLCT were analyzed using MR findings as standard of reference. For the detection of BME in patients with OO, DLCT showed a sensitivity of 0.92, a specificity of 0.94, and an accuracy of 0.92 for both radiologists. Interreader agreement for the assessment of BME with DLCT was substantial (weighted κ = 0.78; 95% CI, 0.59, 0.94). DLCT with material-specific volume fraction maps allowed accurate detection of BME in patients with OO. This may spare patients additional examinations and facilitate the diagnosis of OO. Full article

Background: Extracorporeal shockwave therapy (ESWT) has recently been used as a new treatment modality for plantar fasciitis. We aimed to determine the efficacy of ESWT by magnetic resonance imaging (MRI) findings. Methods: Thirty patients with plantar fasciitis who had received no treatment for 6 months were included. Extracorporeal shockwave therapy was applied once a week for a total of three sessions (frequency of 12–15 Hz, 2–3 bars, and 2,500 pulses). All of the patients were assessed with the visual analog scale, a 6-point evaluation scale, the Foot and Ankle Outcome Score (FAOS), and MRI findings before and 3 months after ESWT. Visual analog scale scores were used in determining the pain level of patients in the morning, during activity, and at rest. Foot and ankle–related problems were evaluated with the FAOS. Results: The duration of painless walking according to the 6-point rating scale, the FAOS, and pain showed significant improvements after ESWT (P < .05). Significant decreases in MRI findings, including thickening of the plantar fascia, soft-tissue edema, and bone marrow edema, were observed after treatment (P < .05). Conclusions: Extracorporeal shockwave therapy is a safe and effective treatment that yields favorable results in improvement of pain and function for plantar fasciitis. An MRI is useful for determining response to ESWT for these patients. Full article

The propolis produced by bees are used in alternative medicine for treating inflammation, and infections, presumably due to its antioxidant properties. In this context, five propolis from México were investigated to determine their inhibitory lipid peroxidation properties. The ethyl acetate extract from a red propolis from Chiapas State (4-EAEP) was the most potent (IC₅₀ = 1.42 ± 0.07 μg/mL) in the TBARS assay, and selected for further studies. This extract afforded two new compounds, epoxypinocembrin chalcone (6), and an ε-caprolactone derivative (10), as well as pinostrobin (1), izalpinin (2), cinnamic acid (3), pinocembrin (4), kaempherol (5), 3,3-dimethylallyl caffeate in mixture with isopent-3-enyl caffeate (7a + 7b), 3,4-dimethoxycinnamic acid (8), rhamnetin (9) and caffeic acid (11). The HPLC profile, anti-mycobacterial, and antioxidant properties of this extract was also determined. Most of the isolated compounds were also tested by inhibition of reactive oxygen species (ROS) in challenged mouse bone marrow-derived mast cells (BMMCs), and DPPH. Their anti-inflammatory activity was evaluated by TPA, and MPO (myeloperoxidase) activity by ear edema test in mice. The most potent compounds were 7a + 7b in the TBARS assay (IC₅₀ = 0.49 ± 0.06 μM), and 2 which restored the ROS baseline (3.5 μM). Our results indicate that 4-EAEP has anti-oxidant, and anti-inflammatory properties due to its active compounds, suggesting it has anti-allergy and anti-asthma potential. Full article

Background: Bone marrow edema (BME) of the talus is a rare, mostly self-limiting cause of foot and ankle pain. We sought to investigate in patients with idiopathic BME of the talus the effectiveness of pulsed electromagnetic fields and to determine the effect of this therapy on magnetic resonance imaging findings. Methods: Six patients with BME of the talus confirmed by magnetic resonance imaging were enrolled. Pain was quantified with a visual analog scale from 0 (no pain) to 10 (the worst pain imaginable). The clinical outcome was assessed using the American Orthopaedic Foot and Ankle Society scoring system. Treatment consisted of pulsed electromagnetic field stimulation 8 h/d for 30 days. The device used generated pulses 1.3 milliseconds in duration, with a frequency of 75 Hz and a mean ± SD induced electric field of 3.5 ± 0.5 mV. Results: The mean American Orthopaedic Foot and Ankle Society score improved from 59.4 (range, 40–66) before treatment to 94 (range, 80–100) at the last follow-up. The visual analog scale score decreased significantly from 5.6 (range, 4–7) before treatment to 1 (range, 0–2) at the last follow-up. Magnetic resonance imaging showed that BME improved after 1 month of treatment and resolved completely within 3 months in 5 patients, with normal signal intensity and no signs of progression to avascular necrosis. Conclusions: A significant reduction in BME area was associated with a significant decrease in pain within 3 months of beginning treatment. (J Am Podiatr Med Assoc 105(1): 27-32, 2015) Full article