Avascular necrosis of the femur head (AVNFH) is a debilitating disease caused due to the use of alcohol, steroids, following trauma or unclear (idiopathic) etiology, affecting mostly the middle aged population. Clinically AVNFH is associated with impaired blood supply to the femoral head resulting in bone necrosis and collapse. Although Homocysteine (HC) has been implicated in AVNFH, levels of homocysteine and its associated pathway metabolites have not been characterized. We demonstrate elevated levels of homocysteine and concomitantly reduced levels of vitamins B6 and B12, in plasma of AVNFH patients. AVNFH patients also had elevated blood levels of sodium and creatinine, and reduced levels of random glucose and haemoglobin. Biophysical and ultrastructural analysis of AVNFH bone revealed increased remodelling and reduced bone mineral density portrayed by increased carbonate to phosphate ratio and decreased Phosphate to amide ratio together with disrupted trabeculae, loss of osteocytes, presence of calcified marrow, and elevated expression of osteocalcin in the osteoblasts localized in necrotic regions. Taken together, our studies for the first time characterize the metabolomic, pathophysiological and morphometric changes associated with AVNFH providing insights for development of new markers and therapeutic strategies for this debilitating disorder.
Carpal instabilities continue to be a controversial topic in hand surgery. Accurate diagnosis of the ligament injuries is usually difficult without an arthroscopic evaluation. Few studies have focused on the diagnosis and proper management of simultaneous scapholunate (SL) and lunotriquetral (LT) ligament tears. This is an uncommon injury that leads to marked disability and chronic wrist pain. This is essentially a "floating lunate" and indicates a severe ligamentous lesion. Thirteen patients (six female and seven male) with complete SL and LT tears and with gross arthroscopic dynamic carpal instability were included in the present study. None of the patients showed radiographic evidence of lunate dislocation. One patient presented acutely and was operated on 3 days after the injury. The average time from the initial injury to the arthroscopy for the other 12 patients was 13.5 months (range 1.5-84 months). All patients underwent arthroscopic debridement of the SL and LT ligaments coupled with percutaneous pinning (two 0.045-in. Kirschner wires) in both joints. At the final follow-up, the average range of motion was 50°o f flexion, 54°of extension, 77°of pronation, 80°of supination, 25°of ulnar deviation, and 15°of radial deviation. The average final grip strength was 67% from the non-affected side. All patients had negative shifting tests at final follow-up. Furthermore, there was no evidence of any static or dynamic instability in all the patients except for one patient who developed a volar intercalated segment instability 8 months after the surgery. At the final followup, ten patients had no pain, one had mild pain, and two experienced moderate pain.
A large number of congenital disorders are very rare and localized to rural areas in India, a country that practices both endogamy and consanguinity. Recent advances in genomics can aid in the identification of causative genomic elements when exploring therapeutic interventions and developing neonatal screening to assign novel functions. Here, we report a novel loss-of-function mutation (p.Trp370*) in the HACE1 gene that is associated with a rare congenital neurodevelopmental disorder in a boy from a remote village in southern India.
Background:Many studies in literature have supported the role of wrist arthroscopy as an adjunct to the stable fixation of unstable intraarticular distal radial fractures. This article focuses on the surgical technique, indications, advantages, and results using wrist arthroscopy to assess articular reduction and evaluates the treatment of carpal ligament injuries and triangular fibrocartilage complex (TFCC) injuries in conjunction with the stable fixation of distal radial fractures.Materials and Methods:We retrospectively evaluated 27 patients (16 males and 11 females), who underwent stable fixation of intraarticular distal radial fractures with arthroscopic evaluation of the articular reduction and repair of associated carpal injuries. As per the AO classification, they were 9 C 1, 12 C2, 2 C3, 3 B 1, and 1 B2 fractures. The final results were evaluated by modified Mayo wrist scoring system. The average age was 41 years (range: 18-68 years). The average followup was of 26 months (range 24-52 months).Results:Five patients needed modification of the reduction and fixation after arthroscopic joint evaluation. Associated ligament lesions found during the wrist arthroscopy were TFCC tears (n=17), scapholunate ligament injury (n=8), and luno-triquetral ligament injury (n=1). Five patients had combined injuries i.e. included TFCC tear, scapholunate and/or lunotriquetral ligament tear. There were 20 excellent, 3 good, and 4 fair results using this score.Conclusion:The radiocarpal and mid carpal arthroscopy is a useful adjunct to stable fixation of distal radial fractures.
Rheumatoid Arthritis (RA) is a chronic autoimmune disease associated with inflammation and joint remodeling. Adenosine deaminase (ADA), a risk factor in RA, degrades adenosine, an anti-inflammatory molecule, resulting in an inflammatory bias. We present an integrative analysis of clinical data, cytokines, serum metabolomics in RA patients and mechanistic studies on ADA-mediated effects on in vitro cell culture models. ADA activity differentiated patients into low and high ADA sets. The levels of the cytokines TNFα, IFNγ, IL-10, TGFβ and sRANKL were elevated in RA and more pronounced in high ADA sets. Serum metabolomic analysis shows altered metabolic pathways in RA which were distinct between low and high ADA sets. Comparative analysis with previous studies shows similar pathways are modulated by DMARDs and biologics. Random forest analysis distinguished RA from control by methyl-histidine and hydroxyisocaproic acid, while hexose-phosphate and fructose-6-phosphate distinguished high ADA from low ADA. The deregulated metabolic pathways of High ADA datasets significantly overlapped with high ADA expressing PBMCs GEO transcriptomics dataset. ADA induced the death of chondrocytes, synoviocyte proliferation, both inflammation in macrophages and their differentiation into osteoclasts and impaired differentiation of mesenchymal stem cells to osteoblasts and mineralization. PBMCs expressing elevated ADA had increased expression of cytokines and P2 receptors compared to synovial macrophages which has low expression of ADA. Our data demonstrates increased cytokine levels and distinct metabolic signatures of RA based on the ADA activity, suggests an important role for ADA in the pathophysiology of RA joints and as a potential marker and therapeutic target in RA patients.
Osteoarthritis of distal radioulnar joint (DRUJ) leads to chronic wrist pain, weakness of grip strength, and limitation of motion, all of which affect the quality of life of the patient. Over the years, several procedures have been used for the treatment of this condition; however, this condition still remains a therapeutic challenge for the hand surgeons. Many procedures such as Darrach procedure, Bower procedure, Sauvé-Kapandji procedure, and ulnar head replacement have been used. Despite many advances in wrist arthroscopy, arthroscopy has not been used for the treatment of arthritis of the DRUJ. We describe a novel technique of arthroscopically assisted Sauvé-Kapandji procedure for the arthritis of the DRUJ. The advantages of this technique are its less invasive nature, preservation of the extensor retinaculum, more anatomical position of the DRUJ, faster rehabilitation, and a better cosmesis.
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