Abstract Background Periprosthetic joint infection (PJI) remains one of the most serious complications after joint arthroplasty, and accurate diagnosis continues to pose significant challenges. A reliable distinction between septic and aseptic failure is essential for appropriate surgical and antibiotic management. This systematic review and meta-analysis evaluate the most recent clinical evidence on the diagnostic accuracy, methodological quality, and standardization potential of established “classical” and emerging serum and synovial biomarkers for PJI diagnosis. Methods This systematic review and meta-analysis were conducted in accordance with PRISMA-DTA guidelines, with PRISMA used as a general reporting framework. Selected items from the STARD checklist were used solely to inform data extraction and were not applied as a reporting guideline. Clinical studies published between January 1, 2020, and October 31, 2025, were identified through PubMed, Scopus, and Web of Science. Eligible studies reported sensitivity, specificity, and/or diagnostic thresholds for serum or synovial biomarkers based on MSIS, ICM, or EBJIS criteria for PJI definition. Study quality was assessed using the QUADAS-C tool, and a meta-analysis of chronic PJI cohorts was performed. Results Twenty-six studies were included (8 serum, 18 synovial). Among serum biomarkers, C-reactive protein and erythrocyte sedimentation rate showed moderate diagnostic accuracy (Area Under the ROC curve [AUC] 0.82–0.90), while fibrinogen demonstrated comparable performance in selected cohorts. D-dimer and other coagulation indices showed variable results. Synovial biomarkers demonstrated superior diagnostic performance. α-defensin, D-lactate, calprotectin (CP), and neutrophil gelatinase-associated lipocalin achieved excellent accuracy (AUC > 0.90; sensitivity and specificity > 90%). Synovial white blood cell count (WBC) and polymorphonuclear percentage (PMN%) remained reliable and cost-effective. Meta-analysis confirmed high pooled diagnostic performance for WBC (0.88/0.97) and PMN% (0.84/0.97). Conclusions Traditional serum biomarkers remain useful first-line diagnostic tools, whereas synovial biomarkers—particularly α-defensin, D-lactate, CP, and WBC indices—demonstrate superior diagnostic accuracy and may be especially valuable in culture-negative PJI. However, substantial heterogeneity and risk of bias identified by QUADAS-C—particularly in patient selection, reference standards, and threshold derivation—suggest that pooled estimates may represent optimistic upper-bound performance, limiting generalizability. Future diagnostic strategies should integrate multimodal biomarker panels with molecular diagnostics and artificial intelligence-based approaches to improve diagnostic precision and clinical applicability.
Abstract Background Muscle lesions are common sport injuries resulting in prolonged absence from sport activity and long rehabilitation periods. The aim of this systematic review and meta-analysis was to quantify the clinical benefits of platelet-rich plasma (PRP) injections in treating acute muscle injuries. Methods The search was conducted on PubMed, Cochrane Library, and Web of Science in January 2026. The PRISMA guidelines were used. Inclusion criteria were: randomized controlled trials (RCTs) published in English comparing PRP injections with control (rehabilitation or placebo) for the treatment of acute muscle injuries. The outcomes analysed were: time to return to sport (RTS), Visual Analogue Scale (VAS) for pain, re-injury and complication rates. Two sub-analyses were performed, one on the double-blind RCTs and one on the RCTs focusing on hamstrings. A fragility analysis was performed using the fragility index (FI) and the continuous FI (CFI). The quality of each article was assessed using the Cochrane RoB 2 and the GRADE tools. Results Among the 4969 articles retrieved, nine RCTs (474 patients) were included. PRP provided faster RTS both in the overall analysis (p < 0.001, mean difference (MD) = 7.5, CFI = 188) and in the two sub-analyses (p < 0.001, MD = 8.8, CFI = 67 and p = 0.001, MD = 7.5, CFI = 97 respectively), as well as superior VAS improvement in the hamstring sub-analysis (p = 0.006, MD = 0.4, CFI = 22). No difference was found in terms of re-injury and complication rates between the two groups (FI = 5 and FI = 7, respectively). The evaluation using the RoB 2 tool showed that four studies had a “low risk” of bias and five had a “high risk” of bias. The GRADE evaluation showed a limited quality of evidence of the analysed outcomes. Conclusion PRP produced a faster RTS compared to controls in acute muscle injury patients, both in the overall analysis and in the sub-analyses. PRP was able to produce a statistically higher pain relief only in the hamstring subgroup, while no difference was found in terms of re-injury and complication rates, suggesting a similar safety profile when compared to rehabilitation alone and placebo. The fragility analysis supported the benefits in terms of RTS, although the high-quality literature addressing this topic remains limited, warranting caution in the interpretation of the current results.
Older men suffer from hip FFx (fragility fracture) at femoral neck T-score approximately 0.6 higher than older women, thus we proposed a new category of low BMD status, osteofrailia, for older Caucasian men with femoral neck T-score ≤ −2.0 (T-score ≤ −2.1 for older East Asian men) who have an increased risk of hip FFx. Around the age of 78 years, mean LS (lumbar spine) QCT BMD is around 68 mg/mL and 100 mg/mL for East Asian men and Caucasian men, respectively. For East Asian men, LS QCT BMD <68 mg/mL offers a sensitivity of 77
STUDY OBJECTIVES:We aim to analyze the microbiota composition in Restless Legs Syndrome (RLS) patients and its relationship with the different RLS phenotypes. METHODS:We recruited idiopathic RLS (RLS) and insomnia (INS) patients and healthy subjects (CTRL). Validated questionnaires (Pittsburg Sleep Quality Index, International Restless Legs Syndrome Study Group Rating Scale, Insomnia Severity Index, Beck Depression Inventory-II) were administered in the RLS and INS. Fecal microbiota was analyzed by 16S rRNA gene sequencing according to Illumina metagenomics standard procedure on MiSeq Platform. Dada2 pipeline was used to process sequencing data, while DESeq2 and Aldex2 tools were used to calculate differential abundance taxa, correcting for age, sex, body mass index, sequencing run, and presence of mood disorders. RESULTS:The sample included 37 RLS (28 females, mean age 64.78 years), 31 INS (22 females, mean age 60.64 years), and 33 CTRL (24 females, mean age 62.54 years). Differential abundance analysis revealed a statistically significant decrease in the abundance of Lachnoclostridium and Flavonifractor genera in RLS compared to CTRL and INS, but not in the INS compared to CTRL. Lachnoclostridium abundance tended to decrease with long disease duration and a predominant motor phenotype. In the RLS group, several genera were identified as significantly associated with International Restless Legs Syndrome Study Group Rating Scale and Pittsburg Sleep Quality Index scores. CONCLUSIONS:Although only a few previous studies have reported the presence of small intestinal bacterial overgrowth in RLS, to the best of our knowledge this is the first study to highlight significant differences in the gut microbiota composition of RLS compared to both CTRL and INS, identifying a specific RLS metagenomic signature. Statement of Significance This is the first study to comprehensively characterize the gut microbiota in patients with Restless Legs Syndrome (RLS), identifying a distinct microbial signature compared to insomnia patients and healthy controls. We observed alterations alpha and beta diversity and specific changes in bacterial families and genera, some of which significantly correlated with RLS clinical features. In particular, Lachnoclostridium genus was significantly reduced in RLS and tended to be less abundant in patients with longer disease duration and without sensory symptoms. This genus is known to modulate systemic inflammation through the production of short-chain fatty acids, suggesting a potential link between gut dysbiosis, inflammation, and dopaminergic dysfunction. These findings support a role for gut microbiota alterations in RLS pathogenesis and open new avenues for microbiota-based diagnostic and therapeutic strategies.
11544 Background: Tenosynovial giant cell tumor (TGCT) is a rare, locally aggressive tumor originating in the synovial lining of the joint, bursa, and tendon sheath. Since TGCT typically impacts individuals 20-50 years of age, pediatric TGCT is ultra-rare. However, pediatric patients are often not included in clinical trials or prospective data. Real-world data are needed to understand the impact of TGCT on pediatric patients’ quality of life and any differences between adults with TGCT. Methods: The TGCT Support Registry is an international, prospective registry initiated in 2022 by TGCT Support, a program of The Life Raft Group. The registry is the largest registry of patients with TGCT and records patient-reported demographic, pathologic, clinical information. This cross-sectional analysis presents data of patients ≤ 18 years of age at time of enrollment with Diffuse (D)-TGCT, Localized (L)-TGCT, or unknown subtype. Results: A total of 122 pediatric patients (9.5%) were included from a 1,278-patient registry (Table). Most patients were female (67.2%), had D-TGCT (73.0%), in the knee (83.6%), and a median age at diagnosis of 14.5 years. Symptoms reported were pain (94.3%), limited joint range of motion (89.3%), and swelling (84.4%). >50% of pediatric patients were initially misdiagnosed and were more likely to be misdiagnosed than adults (62.3% vs 49.9%, p < 0.01). 64.8% of pediatric patients were diagnosed by orthopedic surgeons, and 52.5% were diagnosed ≥1 years after symptom onset. Half of pediatric patients had joint aspirations to manage symptoms (47.5%) and non-steroidal anti-inflammatories were common (76.2%). Surgery was the predominant treatment modality and 61.5% reported that surgery occurred ≤ 3 months of diagnosis. Pediatric patients with D-TGCT underwent an average of 3.4 surgeries, compared to 1.8 surgeries for those with L-TGCT. 66.3% of pediatric patients with D-TGCT had ≥1 post-operative recurrence compared to 15.0% of L-TGCT pediatric patients. Most pediatric patients were referred to general orthopedic surgeons (80.3%), only a third consulted an oncology specialist, and 35.3% were also treated by pediatricians. Systemic therapies (i.e., imatinib, nilotinib, pexidartinib) were prescribed infrequently to pediatric patients with D-TGCT (17.2%). Pediatric patients reported that pain often interfered with daily activities and enjoyment of life. Conclusions: This real-world analysis highlights the significant disease burden of pediatric TGCT, as compared to adults, which severely affecting their quality of life. The reliance on surgical treatment and underuse of multidisciplinary care emphasizes the unmet need for provider education and treatment advancements tailored to this population. Greater efforts to develop systemic therapies specific to pediatrics are warranted to reduce recurrence rates and improve quality of life. Characteristics of patients stratified by subtype (localized, diffuse, or unknown), including sex, age, region, location of disease, misdiagnosis, duration from symptom onset to diagnosis, average surgeries, recurrences, and use of systemic therapies. Diffuse(n=89, 73.0%) Localized(n=20, 16.4%) Unknown(n=13, 10.6%) Total(N=122) Female sex, n (%) 59 (66.3) 14 (70.0) 9 (69.2) 82 (67.2) Median age at Diagnosis, years (range) 14 (3 - 17) 15 (4 - 17) 14.5 (7 - 15) 14.5 (3 - 17) Median age at Enrollment, years (range) 16 (4-18) 17 (6-18) 15 (10-18) 16 (4-18) Located in the US, n (%) 47 (52.8) 11 (55.0) 4 (30.8) 62 (50.8) Location of disease, n (%) Knee 76 (85.4) 16 (80.0) 10 (76.9) 102 (83.6) Hip 8 (9.0) 4 (20.0) 1 (7.7) 13 (10.7) Ankle 5 (5.6) 0 (0.0) 0 (0.0) 5 (4.1) Other a 0 (0.0) 0 (0.0) 2 (15.4) 2 (1.6) Misdiagnosis, n (%) 56 (62.9) 10 (50.0) 10 (76.9) 76 (62.3) Time from Symptom Onset to Diagnosis, n (%) <12 months 42 (47.1) 8 (40.0) 4 (30.8) 54 (44.3) 12–24 months 24 (27.0) 5 (25.0) 3 (23.1) 32 (26.2) 25–60 months 14 (15.7) 4 (20.0) 3 (23.1) 21 (17.2) >60 months 6 (6.7) 3 (15.0) 2 (15.4) 11 (9.0) Diagnosed during Surgery 3 (3.4) 0 (0.0) 1 (7.7) 4 (3.3) Average surgeries, (SD) Median 3.4 (2.8)2 1.8 (1.5)1 1 (1.2)1 2.9 (2.5)2 Systemic Therapy, Check all that apply Pexidartinib Imatinib Nilotinib 20 (22.5)7 (7.9)12 (13.5)1 (1.1) 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) 1 (7.7)1 (7.7)0 (0.0)0 (0.0) 21 (17.2)8 (7.4)12 (9.8)1 (0.8) Local Recurrences, n (%) Yes 1 Recurrence ≥ 2 Recurrences 59 (66.3)19 (21.3)40 (44.9) 3 (15.0)2 (10.0)1 (5.0) 4 (3.8)1 (7.7)3 (23.1) 66 (54.1)22 (18.0)44 (36.1) No I have not had surgery I am unsure 30 (33.7)12 (13.5)8 (9.0) 17 (85.0)2 (10.0)4 (20.0) 9 (69.2)5 (38.5)1 (7.7) 56 (45.9)19 (15.6)13 (10.7)
