Equine Polyclonal Antibodies Prevent Acute Chikungunya Virus Infection in Mice.

Chikungunya virus (CHIKV) is a mosquito-transmitted pathogen that causes chikungunya disease (CHIK); the disease is characterized by fever, muscle ache, rash, and arthralgia. This arthralgia can be debilitating and long-lasting, seriously impacting quality of life for years. Currently, there is no specific therapy available for CHIKV infection. We have developed a despeciated equine polyclonal antibody (CHIKV-EIG) treatment against CHIKV and evaluated its protective efficacy in mouse models of CHIKV infection. In immunocompromised (IFNAR-/-) mice infected with CHIKV, daily treatment for five consecutive days with CHIKV-EIG administered at 100 mg/kg starting on the day of infection prevented mortality, reduced viremia, and improved clinical condition as measured by body weight loss. These beneficial effects were seen even when treatment was delayed to 1 day after infection. In immunocompetent mice, CHIKV-EIG treatment reduced virus induced arthritis (including footpad swelling), arthralgia-associated cytokines, viremia, and tissue virus loads in a dose-dependent fashion. Collectively, these results suggest that CHIKV-EIG is effective at preventing CHIK and could be a viable candidate for further development as a treatment for human disease.

Oral administration of berberine limits post-traumatic osteoarthritis development and associated pain via AMP-activated protein kinase (AMPK) in mice.

OBJECTIVE: We investigated the effect of berberine, a natural plant product that can activate AMP-activated protein kinase (AMPK), on Osteoarthritis (OA) development and associated pain in mice. DESIGN: Human primary knee chondrocytes were utilized to investigate how AMPK is activated by berberine. Both global knockout (KO) of AMPKα1 and congenic wild type (WT) mice were subjected to the post-traumatic OA through destabilization of medial meniscus (DMM) surgery. Two weeks after surgery, the mice were randomly divided into two groups with one group receiving berberine chloride daily via drinking water and were sacrificed at 6 and 12 weeks after surgery. OA severity was assessed by histological and histomorphometric analyses of cartilage degradation, synovitis, and osteophyte formation. OA-associated pain behavior was also determined. Immunohistochemistry (IHC) analyses were carried out to examine changes in AMPK signaling. RESULTS: Berberine induced phosphorylation of AMPKα (Thr172) via liver kinase B1 (LKB1), the major upstream kinase of AMPK, in chondrocytes in vitro. Both WT and AMPKα1KO developed OA and associated pain post DMM surgery. However, treatment with berberine significantly reduced severity of OA and associated pain in WT but not AMPKα1KO mice. IHC analysis of WT DMM knee cartilage further revealed that berberine inhibited concomitant loss of expression and phosphorylation of AMPKα and expression of SIRT1 and SIRT3, suggesting an important role of activation of AMPK signaling in mediating beneficial effect of berberine. CONCLUSIONS: Berberine acts through AMPK to reduce joint structural damage and pain associated with post-traumatic OA in mice in vivo.

Effect of Tart Cherry on Aromatase Inhibitor-Induced Arthralgia (AIA) in Nonmetastatic Hormone-Positive Breast Cancer Patients: A Randomized Double-Blind Placebo-Controlled Trial.

BACKGROUND: Aromatase Inhibitor induced Arthralgia (AIA) can cause noncompliance leading to decreased breast-cancer survival. Effective interventions for AIA are limited. Tart cherry (TC) showed beneficial effect on musculoskeletal pain. 48 patients (Pts) randomized to TC versus placebo over 6 weeks, TC (23pts) had 34.7% mean pain decrease versus 1.4% in Placebo (25pts). TC can improve AIA in nonmetastatic breast-cancer patients. METHODS: Randomized, placebo-controlled, double-blind trial. Eligible patients with NMHPBC on AI for at least 4 weeks were randomized to TC concentrate [50 tart cherries] vs. placebo (P) [syrup] in 1:1 model. Patients instructed to consume 1 Oz of concentrate in 8 Oz water daily for 6 weeks, and document their pain intensity at baseline, weekly and at study completion in a diary using Visual Analog Scale (VAS), with 0 mm indicating no pain, and 100 mm indicating highest pain. RESULTS: Sixty patients were enrolled. Two patients did not complete the study due to diarrhea, and 10 patients were noncompliant. Forty-eight patients were included in the final analysis. TC group (23 pts) had 34.7% mean decrease in pain compared to 1.4% in P group (25 pts). This difference was statistically significant (Mann-Whitney U Test, P = .034). CONCLUSIONS: Tart cherry can significantly improve AIA in nonmetastatic breast cancer patient.

Effects of myofascial release on frequency of joint bleedings, joint status, and joint pain in patients with hemophilic elbow arthropathy: A randomized, single-blind clinical trial.

BACKGROUND: Chronic joint injury of the elbow joint is common in patients with hemophilia. Myofascial release is used for the management of pain and functionality in patients with chronic restrictions. OBJECTIVE: To evaluate the effectiveness of myofascial release in patients with hemophilic elbow arthropathy. METHODS: Sixty-nine patients with hemophilia took part in this randomized controlled trial. They were recruited from 10 hemophilia patient Associations. They were randomly allocated to experimental (n = 35) or control group (n = 34). The intervention consisted of three 50-min sessions of fascial therapy over a 3-week period. The intervention included 11 bilaterally administered maneuvers in both upper limbs (from shoulder girdle to forearm). The study variables were frequency of elbow bleeding (self-report), joint status (Hemophilia Joint Health Score), and joint pain (visual analog scale) at baseline, after the intervention, and at the 3-month follow-up. RESULTS: There were significant changes (P < .001) in the repeated measures factor in the frequency of hemarthrosis (F = 20.64), joint status (F = 31.45), and perceived joint pain (F = 30.08). We found group interaction with the (P < .001) in the frequency of hemarthrosis (F = 21.57), joint status (F = 99.98), and perceived joint pain (F = 44.26). There were changes (P < .01) in the pairwise comparison analysis between the pretreatment assessment and the posttreatment and follow-up assessments. CONCLUSIONS: Myofascial release decreases frequency of elbow bleedings, and improved joint status and perception of elbow pain in patients with hemophilic elbow arthropathy. Myofascial release may be recommended to improve joint status and joint pain in patients with hemophilic elbow arthropathy.

Factors associated with pain resolution in those with knee pain: the MOST study.

OBJECTIVES: To determine how many persons with knee pain have subsequent pain resolution and what factors are associated with resolution, focusing especially on types of physical activity. METHODS: Using data from MOST, an NIH funded longitudinal cohort study of persons with or at risk of knee osteoarthritis, we studied participants who at baseline reported knee pain on most days at both a telephone interview and clinic visit. We defined pain resolution if at 30 and 60 month exams, they reported no knee pain on most days and compared these participants to those who reported persistent pain later. In logistic regression analyses, we examined the association of baseline risk factors including demographic factors, BMI, depressive symptoms, isokinetic quadriceps strength and both overall physical activity (using the PASE survey) and specific activities including walking, gardening, and different intensities of recreational activities with pain resolution. RESULTS: Of 1,304 participants with knee pain on most days at baseline, 265 (20.3%) reported no knee pain at 30 and 60 months. Lower BMI and stronger quadriceps were associated with higher odds of pain resolution while overall physical activity was not. Of activities, walking decreased the odds of pain resolution (adjOR = 0.86 (95% CI 0.76, 0.98)), but gardening (adjOR = 1.59 (1.16, 2.18)) and moderate intensity recreational activities ((adjOR = 1.24 (1.05, 1.46)) increased it. CONCLUSION: Pain resolution is common in those with knee pain. Factors increasing the odds of pain resolution include lower BMI, greater quadriceps strength and gardening and moderately intensive recreational activities.

Medial femoral trochlea flap reconstruction: Clinical outcomes and perspectives.

INTRODUCTION: We report our experience with use of the medial femoral trochlea (MFT) osteochondral flap for carpal applications. METHODS: Outcomes of all patients treated with MFT flaps were reviewed. Healing, range of motion, grip strength, carpal alignment, pain, and complication data were collected. RESULTS: MFT flaps were performed on seven patients with a mean age of 26.1 (range, 17-42) years. Indications included scaphoid proximal pole nonunion (n = 3), Kienböck's disease (n = 3), and Preiser's disease (n = 1). The mean follow-up was 32.3 (range, 5-70) months. Union was achieved in five patients at a mean of 12 (range 6-22) weeks. All five patients had increased grip strength and absence of pain at follow-up. There were two failures due to graft resorption. CONCLUSIONS: The MFT osteochondral flap is a technically challenging yet powerful tool to replace the loss of both carpal articular cartilage and adjacent bone.

CB2 agonism controls pain and subchondral bone degeneration induced by mono-iodoacetate: Implications GPCR functional bias and tolerance development.

BACKGROUND AND PURPOSE: The endocannabinoid system became a promising target for osteoarthritis (OA) treatment. Functional selectivity of cannabinoids may increase their beneficial properties while reducing side effects. The aim of the present study was to evaluate the analgesic potential of two functionally biased CB2 agonists in different treatment regimens to propose the best pharmacological approach for OA management. EXPERIMENTAL APPROACH: Two functionally selective CB2 agonists were administered i.p. - JWH133 (cAMP biased) and GW833972A (ß-arrestin biased), in a chemically induced model of OA in rats. The drugs were tested in acute and chronic treatment regimens. Analgesic effects were assessed by pressure application measurement and kinetic weight bearing. X-ray microtomography was used for the morphometric analysis of the femur's subchondral bone tissue. Underlying biochemical changes were analysed via RT-qPCR. KEY RESULTS: Dose-response studies established the effective dose for both JWH133 and GW833972A. In chronic treatment paradigms, JWH133 was able to elicit analgesia throughout the course of the experiment, whereas GW833972A lost its efficacy after 2 days of treatment. Later studies revealed improvement in subchondral bone architecture and decrement of matrix metalloproteinases and proinflammatory factors expression following JWH133 chronic treatment. CONCLUSION AND IMPLICATIONS: Data presents analgesic and disease-modifying potential of CB2 agonists in OA treatment. Moreover, the study revealed more pronounced tolerance development for analgesic effects of the ß-arrestin biased CB2 agonist GW833972A. These results provide a better understanding of the molecular underpinnings of the anti-nociceptive potential of CB2 agonists and may improve drug development processes for any cannabinoid-based chronic pain therapy.

No Clinically Important Differences in Thigh Pain or Bone Loss Between Short Stems and Conventional-length Stems in THA: A Randomized Clinical Trial.

BACKGROUND: Short-length stems were developed to reduce bone loss of the proximal femur and potentially decrease the incidence of thigh pain after cementless THA. However, it remains unknown whether short stems indeed reduce bone loss or the frequency of thigh pain. QUESTIONS/PURPOSES: Is there a difference between short- and standard-length stems in terms of: (1) the frequency or severity of thigh pain, (2) modified Harris hip scores, (3) implant loosening, or (4) bone mineral density as measured by dual-energy x-ray absorptiometry? METHODS: Between March 2013 and January 2014, three surgeons performed 205 primary THAs. To be eligible, patients needed to be at least 20 years of age, have not undergone previous history of hip surgery, and have no metabolic bone disease. A total of 100 patients were randomized to receive THA either with a short stem (n = 56) or with a standard-length stem (n = 44). Both stems were proximally coated, tapered, cementless stems. Compared with standard stems, short stems typically were 30- to 35-mm shorter. A total of 73% (41 of 56) and 77% (34 of 44) of those groups, respectively, were accounted for at a minimum of 5 years and were analyzed. The presence of thigh pain during activity was evaluated using a 10-point VAS, and the modified Harris hip score was calculated by research assistants who were blinded to the treatment groups. Plain radiographs were taken at 6 weeks, 6 months, and 12 months postoperatively, and every 1 year thereafter; loosening was defined as subsidence > 3 mm or a position change > 3° on serial radiographs. Radiological assessment was performed by two researchers who did not participate in the surgery and follow-up evaluations. Bone mineral density of the proximal femur was measured using dual-energy x-ray absorptiometry at 4 days, 1 year, 2 years, and 5 years postoperatively. The primary endpoint of our study was the incidence of thigh pain during 5-year follow-up. Our study was powered at 80% to detect a 10% difference in the proportion of patients reporting thigh pain at the level of 0.05. RESULTS: With the numbers available, we found no difference between the groups in the proportion of patients with thigh pain; 16% (9 of 56) of patients in the short-stem group and 14% (6 of 44) of patients in the standard-stem group experienced thigh pain during the follow-up period (p = 0.79). In all patients, the pain was mild or moderate (VAS score of 4 or 6 points). Among the 15 available patients who reported thigh pain, there was no difference between the implant groups in mean severity of thigh pain (4.3 ± 0.8 versus 4.2 ± 0.7; p = 0.78). There were no between-group differences in the short versus standard-length stem groups in terms of mean modified Harris hip score by 5 years after surgery (89 ± 13 versus 95 ± 7 points; p = 0.06). No implant was loose and no hip underwent revision in either group. Patients in the short-stem group showed a slightly smaller decrease in bone mineral density in Gruen Zones 2, 3, and 5 than those in the standard-stem group did; the magnitude of the difference seems unlikely to be clinically important. CONCLUSION: We found no clinically important differences (and few differences overall) between short and standard-length THA stems 5 years after surgery in a randomized trial. Consequently, we recommend that clinicians use standard-length stems in general practice because standard-length stems have a much longer published track record in other studies, and short stems can expose patients to the uncertainty associated with novelty, without any apparent offsetting benefit. LEVEL OF EVIDENCE: Level I, therapeutic study.

Defining Pain That Does Not Interfere With Activities Among Rheumatoid Arthritis Patients.

OBJECTIVE: The objectives of this study were to: 1) characterize the distribution of noninterfering pain (defined as the pain intensity level at which individuals can function without interference) across different aspects of life among patients with rheumatoid arthritis (RA), and 2) identify clinical characteristics associated with differing levels of noninterfering pain. METHODS: Patients with RA in FORWARD, The National Databank for Rheumatic Diseases completed 8 items from the Patient-Reported Outcomes Measurement Information System (PROMIS) pain interference item bank that asked about interference with activities. If subjects reported pain interference, they were asked, "At what level would pain no longer interfere with this activity?" on a scale of 0 to 10. Subjects were also asked, "At what level of pain would you be able to do everything you want to do?" Multiple linear regression analyses examined associations between clinical characteristics and noninterfering pain. RESULTS: A total of 3,949 patients with RA completed the questionnaires. Pain interference was most common for daily activities and least common for ability to concentrate. The mean ± SD level at which pain no longer interfered with activities ranged from 2.7 ± 2.1 for ability to fall/stay asleep to 3.1 ± 2.0 for social activities. Overall, the mean ± SD threshold for noninterfering pain was 2.8 ± 1.9. The mean ± SD level of pain at which patients could do everything they wanted to do was 2.3 ± 1.9. More severe pain intensity was associated with higher noninterfering pain. CONCLUSION: The mean pain level that did not interfere with activities was 3. High pain intensity was associated with high self-reported noninterfering pain.

PTH1-34 inhibited TNF-α expression and antagonized TNF-α-induced MMP13 expression in MIO mice.

This study aims to investigate the effects and mechanisms of parathyroid hormone [1-34] (PTH1-34) on TNF-α-stimulated mice chondrocytes, as well as cartilage from a meniscus injury induced osteoarthritis (MIO) mice model. The C57BL/6J mice received medial meniscectomy, and then administrated with PTH1-34. The results showed that PTH1-34 administration decreased secondary allodynia and the pain-related transcripts. The IHC, ELISA, Micro-CT imaging and histopathology analysis revealed the significantly improved subchondral plate thickness and bone porosity, the reduced pro-inflammatory cytokines in serum and joint fluid. In vitro, mice chondrocyte was treated with TNF-α or co-cultured with synovial cells. The results showed that TNF-α markedly upregulated the MMP13 expression, and the ERK1/2, NF-κB or PI3K signaling pathway inhibitors could reverse the induction effect of TNF-α on expression of MMP13 in chondrocytes. PTH1-34 alone has no effect on the expression of MMP13 and NF-κB signaling pathways, but the PTH1-34 could reverse the induction effect of TNF-α on MMP13 expression and NF-κB signaling pathway activation in chondrocytes. In addition, PTH1-34 administration inhibited the expression of TNF-α and MMP13, and chondrocyte viability, while the PKA repressor reversed the effect of PTH1-34 in chondrocytes co-cultured with synovial cells. In conclusion, PTH1-34 has an obvious analgesic and anti-inflammatory effect, inhibits the matrix synthesis and alleviates the progression of osteoarthritis. In vitro, PTH1-34 inhibited TNF-α expression and antagonized TNF-α-induced MMP13 expression via the PKA pathway and the NF-κB signaling pathways, respectively.

Effectiveness of supervised resistance training for patients with hip osteoarthritis - a systematic review.

INTRODUCTION: The overall effectiveness of supervised progressive resistance training among patients with hip osteoarthritis is only scarcely investigated. The objective of this study was to estimate the effectiveness of supervised progressive resistance training compared with common treatment for patients with hip osteoarthritis, focusing on patient-reported function, pain, health-related quality of life, performance-based function at end of treatment and patient-reported function at 6-12 months. METHODS: This was a systematic review and meta-analysis. A systematic search was performed on 30 January 2019 in eight electronic databases (Medline, Embase, Cochrane, Pedro, AMED, Scopus, SPORTDiscus and Cinahl). The methodology of the included studies and the overall quality of evidence was assessed using the Cochrane Risk of Bias tool and the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS: A total of 189 participants with hip osteoarthritis > 50 years of age were included in the three studies. A significant difference in favour of the supervised progressive resistance groups was found in patient-reported function (weighted mean difference (MD) = 9.13 (95% confidence interval (CI): 4.45-13.80)), hip-related pain (weighted MD = 7.83 (95% CI: 2.64-13.02)) and health-related quality of life (weighted MD = 6.80 (95% CI: 1.96-11.63)) at end of treatment. The overall quality of evidence was downgraded to low due to a lack of blinding in the included studies and due to imprecision. CONCLUSIONS: Supervised progressive resistance training might be of clinical relevance for patients with hip osteoarthritis and was effective in improving patient-reported function, hip-related pain and health-related quality of life. The level of evidence is low and future studies may therefore affect the findings reported herein.

Conventional and Complementary Health Care Approaches Used by American Adults Reporting Joint Pain: Patterns from the National Health Interview Survey 2012.

Objective: To describe patterns of conventional health care (CH) and complementary and alternative medicine (CAM) use among U.S. adults reporting recent joint symptoms in a nationally representative sample. Design: This study uses the adult alternative medicine supplement from the 2012 National Health Interview Survey (NHIS). Location: United States. Subjects: Nationally representative cross-sectional sample of non-institutionalized U.S. residents. Of 34,525 respondents who answered the alternative medicine supplement, approximately 30% (n = 10,964) reported recent pain symptoms (pain, aching, stiffness). Outcome measures: Among adults reporting joint symptoms, we examine reported use of CH, CAM, both CH and CAM, or neither specifically for joint symptoms or joint condition. Results: Among adults reporting joint symptoms in the past 30 days, 64% reported using only CH for their joint pain, whereas ∼10% reported using CAM. Among those using CAM for their joint symptoms, 83% also sought help from a CH practitioner. CAM-only users comprised only 1.6% of the sample of joint pain sufferers. Those who reported using both CH and CAM for joint pain were more likely to report a diagnosis of a joint condition compared with CAM-only users, but also reported higher comorbidities and worse self-reported health. Conclusion: Most U.S. adults reporting recent joint pain seek care only from a CH practitioner, although among the 10% who report CAM use for joint conditions, a strong majority also report seeking care from a CH practitioner. CH and CAM providers should consistently inquire about other forms of treatment their patients are using for specific symptoms to provide effective integrative health care management.

Poloxamer micellar system for intra-articular injection of 15-deoxy-Δ12,14-prostaglandin J2 with improved bioavailability and anti-inflammatory properties in the temporomandibular joint of rats.

Painful conditions of the temporomandibular joint (TMJ) are challenging to manage and most attempts often result in unsatisfactory outcomes. In such context, nanocarrier systems, such as polymeric micelles, have been showing encouraging results in solving therapeutic limitations. Poloxamers are widely used, especially PL 407, because of their high biocompatibility and approval by the Food and Drug Administration (FDA) for clinical use. 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) has shown important antinociceptive and anti-inflammatory activity. The present study evaluated the efficacy and viability of the micellar system of PL-15dPGJ2 in a formalin-induced acute pain model in the temporomandibular joint of rats. The PL-15dPGJ2 was prepared and characterized. The animals were pretreated with an intra-articular injection of PL-15dPGJ2 followed by the formalin challenge. The nociceptive response was evaluated at different time-periods and the periarticular tissue and articular wash were collected for analysis. We found that intra-articular injection of PL-15d-PGJ2 produced pain relief at lower concentrations and in a sustained manner compared with free 15d-PGJ2. Moreover, a strong anti-inflammatory effect was observed with decreased levels of key pro-inflammatory cytokines and modulation of the leukocyte migration process. Our findings suggest that 15d-PGJ2 combined with a poloxamer micellar system provided clinical relevance in terms of bioavailability, long-lasting effect, and safe dosage. The formulation investigated herein is a promising micellar carrier system for managing pain conditions of the TMJ.

Oral treatments with a flavonoid-enriched fraction from Cecropia hololeuca and with rutin reduce articular pain and inflammation in murine zymosan-induced arthritis.

ETHNOPHARMACOLOGICAL RELEVANCE: Cecropia Loefl. species (Urticaceae) are widely spread across the rainforest in tropical and subtropical regions of Central and South America. Inhabitants of different regions of Brazil employ leaves, fruits and sprouts of Cecropia hololeuca Miq. mainly as anti-inflammatory, anti-asthmatic, expectorant, fever suppressant, and against cough. AIM OF THE STUDY: To evaluate the antinociceptive and anti-inflammatory activities of an aqueous leaf extract of C. hololeuca in a murine model of zymosan-induced arthritis (ZIA) and characterize compounds contributing to these effects. MATERIALS AND METHODS: The crude aqueous extract of C. hololeuca (CAE) was obtained by infusion, screened for antinociceptive and anti-inflammatory activities, and fractionated (solvent partition; RP-2 and Sephadex G-25 column chromatography), yielding fractions that were chemically and pharmacologically investigated. TLC, HPLC-DAD, HPLC-DAD-ESI-MS/MS and NMR analyses were peformed. The antinociceptive activity was assessed by means of acetic acid-induced writhing, hot-plate and rota-rod tests. ZIA was used to evaluate the anti-arthritic activity of oral treatment with CAE, butanolic (BF) and aqueous fraction (AF), as well as the fractions obtained from BF (F2, F2-A and F2-B). Rutin, a flavonoid found in C. hololeuca, was also tested. Mechanical hypernociception, joint edema, local neutrophil recruitment and articular TNF-α quantification were performed to measure the severity of arthritis and identify the anti-inflammatory potential of C. hololeuca. RESULTS: CAE (0.03-1 g/kg, p.o.) showed a dose-related inhibitory effect on acetic acid-induced writhing test, but did not change the pain latency in the hotplate test, nor the first fall time on the rota-rod test. In addition, CAE (1 g/kg, p.o.) inhibited by 65% the mechanical hypernociception, 46% the joint edema, 54% the neutrophil recruitment and 53% the articular TNF-α concentration levels in ZIA. BF (0.4 g/kg, p.o.), AF (0.6 g/kg), F2 (0.1 g/kg) and F2-A (0.045 g/kg), but not F2-B (0.055 g/kg), inhibited the mechanical hypernociception, joint edema and neutrophil recruitment in ZIA. Rutin (0.001-0.03 g/kg, p.o.) produced dose-related inhibitory effects in the mechanical hypernociception, joint edema and neutrophil recruitment, and at 0.03 g/kg also inhibited articular TNF-α synthesis after intra-articular zymosan injection. Isoorientin, isovitexin, rutin and isoquercitrin were identified in the most active fraction (F2-A), along with luteolin and apigenin derivatives, tentatively identified as isoorientin-2″-O-glucoside and isovitexin-2″-O-glucoside. CONCLUSION: This study corroborates the popular use by oral route of aqueous preparations of C. hololeuca against joint inflammatory disorders, such as rheumatoid arthritis. Our results demonstrated for the first time that oral administration of rutin shows antinociceptive and anti-inflammatory effects in ZIA, indicating that this flavonoid is one of the immunomodulatory compounds involved in the anti-arthritic activity of C. hololeuca.

Does Circumferential Patellar Denervation Result in Decreased Knee Pain and Improved Patient-reported Outcomes in Patients Undergoing Nonresurfaced, Simultaneous Bilateral TKA?

BACKGROUND: Anterior knee pain, which has a prevalence of 4% to 49% after TKA, may be a cause of patient dissatisfaction after TKA. To limit the occurrence of anterior knee pain, patellar denervation with electrocautery has been proposed. However, studies have disagreed as to the efficacy of this procedure.Questions/purposes We evaluated patients undergoing bilateral, simultaneous TKA procedures without patellar resurfacing to ask: (1) Does circumferential patellar cauterization decrease anterior knee pain (Kujala score) postoperatively compared with non-cauterization of the patella? (2) Does circumferential patellar cauterization result in better functional outcomes based on patient report (VAS score, Oxford knee score, and Knee Injury and Osteoarthritis Outcome Score) than non-cauterization of the patella? (3) Is there any difference in the complication rate (infection, patellar maltracking, fracture, venous thromboembolism, or reoperation rate) between cauterized patellae and non-cauterized patellae? METHODS: Seventy-eight patients (156 knees) were included in this prospective, quasi-randomized study, with each patient serving as his or her own control. Patellar cauterization was always performed on the right knee during simultaneous, bilateral TKA. Five patients (6%) were lost to follow-up before the 2-year minimum follow-up interval. A single surgeon performed all TKAs using the same type of implant, and osteophyte excision was performed in all patellae, which were left unresurfaced. Patellar cauterization was performed at 2 mm to 3 mm deep and approximately 5 mm circumferentially away from the patellar rim. The preoperative femorotibial angle and degree of osteoarthritis (according to the Kellgren-Lawrence grading system) were measured. Restoration of the patellofemoral joint was assessed using the anterior condylar ratio. Clinical outcomes, consisting of clinician-reported outcomes (ROM and Kujala score) and patient-reported outcomes (VAS pain score, Oxford knee score, and Knee Injury and Osteoarthritis Outcome Score), were evaluated preoperatively and at 1 month and 2 years postoperatively. Preoperatively, the radiologic severity of osteoarthritis, based on the Kellgren-Lawrence classification, was not different between the two groups, nor were the baseline pain and knee scores. The mean femorotibial angle of the two groups was also comparable: 189° ± 4.9° and 191° ± 6.3° preoperatively (p = 0.051) and 177° ± 2.9° and 178° ± 2.1° postoperatively (p = 0.751) for cauterized and non-cauterized knees, respectively. The preoperative (0.3 ± 0.06 versus 0.3 ± 0.07; p = 0.744) and postoperative (0.3 ± 0.06 versus 0.2 ± 0.07; p = 0.192) anterior condylar ratios were also not different between the cauterized and non-cauterized groups. RESULTS: At the 2-year follow-up interval, no difference was observed in the mean Kujala score (82 ± 2.9 and 83 ± 2.6 for cauterized and non-cauterized knees, respectively; mean difference 0.3; 95% confidence interval, -0.599 to 1.202; p = 0.509). The mean VAS pain score was 3 ± 0.9 in the cauterized knee and 3 ± 0.7 in the non-cauterized knee (p = 0.920). The mean ROM was 123° ± 10.8° in the cauterized knee and 123° ± 10.2° in the non-cauterized knee (p = 0.783). There was no difference between cauterized and non-cauterized patellae in the mean Knee Injury and Osteoarthritis Outcome Score for symptoms (86 ± 4.5 versus 86 ± 3.9; p = 0.884), pain (86 ± 3.8 versus 86 ± 3.6; p = 0.905), activities (83 ± 3.2 versus 83 ± 2.8; p = 0.967), sports (42 ± 11.3 versus 43 ± 11.4; p = 0.942), and quality of life (83 ± 4.9 versus 83 ± 4.7; p = 0.916), as well as in the Oxford knee score (40 ± 2.1 versus 41 ± 1.9; p = 0.771). Complications were uncommon and there were no differences between the groups (one deep venous thromboembolism in the cauterized group and two in the control group; odds ratio 0.49, 95% CI, 0.04-5.56; p = 0.57). CONCLUSIONS: Patellar cauterization results in no difference in anterior knee pain, functional outcomes, and complication rates compared with non-cauterization of the patella in patients who undergo non-resurfaced, simultaneous, bilateral, primary TKA with a minimum of 2 years of follow-up. We do not recommend circumferential patellar cauterization in non-resurfaced patellae in patients who undergo TKA. LEVEL OF EVIDENCE: Level II, therapeutic study.

Effects of Modified Posterior Shoulder Stretching Exercises on Shoulder Mobility, Pain, and Dysfunction in Patients With Subacromial Impingement Syndrome.

BACKGROUND: Posterior shoulder stretching exercises (PSSEs) aim to reduce posterior shoulder tightness (PST). Position modification of traditional PSSEs has been suggested to minimize inadequate control of scapular and glenohumeral rotation, possibly leading to increased subacromial impingement. HYPOTHESIS: Modified PSSEs will have positive effects on shoulder mobility, pain, and dysfunction. STUDY DESIGN: Randomized controlled trial. LEVEL OF EVIDENCE: Level 1. METHODS: A total of 67 symptomatic patients with subacromial impingement syndrome (SIS) and shoulder internal rotation asymmetry were randomly assigned to 3 groups: modified cross-body stretch (MCS) (n = 22; treatment program + MCS), modified sleeper stretch (MSS) (n = 22; treatment program + MSS), and a control group (n = 23; treatment program consisting of only modalities, range of motion [ROM], and strength training but no PSSEs) for 4 weeks. Pain, PST, shoulder rotation ROM, and dysfunction were evaluated. RESULTS: Pain, PST, shoulder rotation ROM, function, and disability improved in all groups (P < 0.05). The MCS and MSS groups had better results compared with the control group with regard to pain with activity, internal rotation ROM, function, and disability (P < 0.05). There was no significant difference between the stretching groups (P > 0.05). CONCLUSION: All treatments improved pain, shoulder mobility, function, and disability in patients with SIS. However, modified PSSEs in addition to a treatment program was superior to the treatment program alone (without PSSEs) in improving pain with activity, internal rotation ROM, and dysfunction. Moreover, stretching provided clinically significant improvements. CLINICAL RELEVANCE: Modified PSSEs, in addition to a treatment program, are beneficial for patients with SIS. Both modified cross-body and sleeper stretches are safe and efficacious for improving shoulder mobility, pain, and dysfunction.

Zoledronic acid is more efficient than ibandronic acid in the treatment of symptomatic bone marrow lesions of the knee.

PURPOSE: The purpose of this study was to determine the efficacy and tolerability of different antiresorptive therapeutic regimens for treating symptomatic bone marrow lesions (BML) of the knee. METHODS: Patient records of 34 patients with radiologically diagnosed, painful BML of the knee treated with either a bisphosphonate (zoledronic, ibandronic, or alendronic acid) or with a human monoclonal antibody (denosumab) were retrospectively evaluated. Response to treatment was assessed, as change in patient-reported pain, by evaluation of BML expansion on MRI using the Whole-Organ Magnetic Resonance Imaging Score (WORMS), and by laboratory analysis of bone turnover markers: C-terminal cross-linking telopeptide (CTx) and procollagen type 1 amino-terminal propeptide (P1NP). Tolerability was evaluated by documentation of adverse reactions. RESULTS: Zoledronic acid was more or at least equally effective as the other treatment regimens with response to treatment in 11 of 12 patients (92%). The highest rate of adverse events was noted in 4 of 12 patients (33%) treated with zoledronic acid. CTx and WORMS differentiated well between responders and non-responders, whereas P1NP failed to do so. Changes in pain correlated moderately with change in WORMS (r = - 0.32), weakly with change in CTx (r = - 0.07), and not at all with change in P1NP. CONCLUSION: Zoledronic acid appeared to be more effective than other antiresorptive medications-at the cost of more frequent adverse events. While radiological and laboratory evaluation methods may allow for objective treatment monitoring, they appear to capture different dimensions than patient-reported pain. LEVEL OF EVIDENCE: III.

Osgood-Schlatter disease: a 2020 update of a common knee condition in children.

PURPOSE OF REVIEW: Osgood-Schlatter disease (OSD) is one of the most common causes for anterior knee pain in children and adolescents resulting from a traction apophysitis of the tibial tubercle. While a peak in boys aged 12-15 years old was well documented, there seems to be no difference in sex distribution nowadays. This may result from increased participation of young females in high-impact sports. This review provides an up-to-date account on contemporary prophylaxis as well as diagnostic and therapeutic approaches. RECENT FINDINGS: Numerous studies have examined risk factors for OSD. These include body weight, muscle tightness, muscle weakness during knee extension and flexibility of hamstring muscles. In particular, shortening of the rectus femoris may substantially alter biomechanical functions of the knee. Conservative management remains successful in over 90% of patients. However, if disabling symptoms and pain persistent after physeal closure, operative treatment may be necessary. SUMMARY: OSD is a mostly self-limiting apophysitis of the tibial tubercle and the adjacent patella tendon in young active patients with open physis. Prevention strategies include quadriceps and hamstring stretching and therefore should be implemented in everyday practice routines for children who partake in regular sports activities.

I Would Never Take Preventive Medication! Perspectives and Information Needs of People Who Underwent Predictive Tests for Rheumatoid Arthritis.

OBJECTIVE: Little is known about the experiences, values, and needs of people without arthritis who undergo predictive biomarker testing for the development of rheumatoid arthritis (RA). Our study aimed to explore the perspectives of these individuals and describe their information needs. METHODS: A qualitative, multicenter interview study with a thematic analysis was conducted in Austria, Germany and the UK. Individuals were interviewed who underwent predictive biomarker testing for RA and had a positive test result but no diagnosis of any inflammatory joint disease. Participants included patients with arthralgia and asymptomatic individuals. Information and education needs were developed from the qualitative codes and themes using the Arthritis Educational Needs Assessment Tool as a frame of reference. RESULTS: Thematic saturation was reached in 34 individuals (76% female, 24 [71%] with arthralgia, and 10 [29%] asymptomatic individuals). Thirty-seven codes were summarized into 4 themes: 1) decision-making around whether to undergo initial predictive testing, 2) willingness to consider further predictive tests, and/or 3) preventive interventions, including medication, and 4) varying reactions after receiving a positive test result. Individuals with arthralgia were more likely to be willing to take preventive action, undergo further testing, and experience psychological distress than asymptomatic individuals. All participants expressed the need for tailored, patient-understandable information. CONCLUSION: Individuals at risk of RA are currently the subjects of research aimed at developing better predictive strategies and preventive approaches. Their perceptions and needs should be addressed to inform the future development of interventions combined with education.

Wrist pain in gymnasts: Efficacy of a wrist brace to decrease wrist pain while performing gymnastics.

STUDY DESIGN: This was a clinical trial of prospective cohort. INTRODUCTION: Wrist pain in gymnasts is a global phenomenon. Compression forces acting on wrists while performing gymnastics is a predisposing factor in the development of wrist pain and consequential injury of the distal radial physis in skeletally immature gymnasts. One approach to mitigate these forces is wrist bracing; however, studies on the efficacy of wrist braces to reduce wrist pain experienced by gymnasts are limited. PURPOSE OF THE STUDY: The purpose of this study was to investigate the efficacy of an innovative design of a wrist brace to decrease gymnasts' wrist pain while performing gymnastics. METHODS: A wrist brace was designed and trialled over 3 weeks by 48 male gymnasts (aged 8-22 years, levels 4-7) with wrist pain. Wrist pain was recorded on a visual analog scale of 1 to 10 before and after trial. Data analysis was performed using SPSS-22 (IBM Inc). Paired t-tests were performed to compare variables before and after trial, with effect size analyses used to quantify the relative magnitude of any differences. RESULTS: Paired t-tests indicated the gymnasts reported significantly reduced pain (P = .002; 53.5%) while wearing the braces for training on the pommel, floor, and parallel bars. The overall large effect size value was practically significant (d = 0.902). DISCUSSION: For any wrist brace to be effective, it needs to be implemented when the gymnast experiences wrist pain before an injury occurs. This would minimize the development of pain-provoked adaptive movement patterns that perpetuate dysfunction. CONCLUSIONS: The brace with the volar gel pad is recommended to be worn as an adjunct to current strategies in management of gymnasts' wrist pain or as an injury prevention device in skeletally immature gymnasts.