Single versus multi-dose intra-articular injection of platelet rich plasma in early stages of osteoarthritis of the knee: A single-blind, randomized, superiority trial.

OBJECTIVES: This study aims to compare the effectiveness of single, double, and triple doses of intra-articular (IA) platelet rich plasma (PRP) in early stages of osteoarthritis (OA) of the knee. PATIENTS AND METHODS: This single-blind, randomized, superiority trial included a total of 180 knees of 90 patients (22 males, 68 females; mean age: 47.9 years; range, 36 to 60 years) with bilateral OA knee of Kellgren-Lawrence Grade 1-2 between May 2017 and December 2018. The patients were randomized (30 in each group) to receive single, double, or triple doses of IA PRP (two weeks apart in repeat injections). The outcome measures were Visual Analog Scale, International Knee Documentation Committee Score, Knee Injury and Osteoarthritis Outcome Score, and Tegner Lysholm Knee Score. The assessor of outcome was blinded. The scores were collected before intervention and at six weeks, three months, six months, and one year after the intervention. RESULTS: All patients completed the study. All three groups were comparable with respect to demographic and disease characteristics. All four scores were comparable among the three groups before intervention and at six weeks, three months, and six months. However, at one-year follow-up, the three-dose group showed superiority to others in terms of all four scores. All three groups showed improvement until six months and deterioration thereafter, which was only marginal in the three-dose group. All groups showed a statistically significant improvement of scores compared to baseline scores at one year. There were no major complications. CONCLUSION: The IA administration of three doses of PRP yields superior outcome to single and double doses at the end of one year. Repeat doses are probably needed to sustain the benefit achieved at one year.

Adenosine deaminase modulates metabolic remodeling and orchestrates joint destruction in rheumatoid arthritis.

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, TGFß 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.

Displaced midshaft clavicle fractures in adults - is non-operative management enough?

INTRODUCTION: Displaced fractures of middle third of clavicle are traditionally managed non-operatively. Recently, the trend is towards surgical management considering functional deficits in some of the non-operatively managed patients. The purpose of the study was to examine the functional outcome of non-operative treatment in these injuries, while identifying the factors responsible for less than ideal outcome and determine the guidelines for patient counselling. PATIENTS AND METHODS: One hundred patients with displaced fractures of middle third of clavicle were prospectively evaluated clinico-radiologically for one year from injury. Risk factors for non-union were determined using Fisher's exact test. Logistic regression was used to identify factors contributing to functional outcome. Threshold values for the radiological displacements were estimated with the smooth threshold regression using the logistic transition function. RESULTS: Ninety-four out of 100 fractures united. The factors associated with non-union were: smoking, diabetes and poor soft tissue condition over the fracture. Ninety-two out of 94 patients who had their fractures united achieved "good" (Constant Score above 70) or "very good" (Constant Score above 85) functional outcome at one year, out of which only 49 belonged to "very good" category. The most important factors influencing functional outcome were fracture angulation and clavicular shortening. From the model, it was estimated that with one unit increase in degree of angulation or 1 mm increase in shortening, the odds of scoring above 85 reduces by around 14%. Based on this, an equation and a probability calculator were developed from which the probability of achieving a Constant Score above 85 can be calculated. Threshold analysis yielded 22.8° for angulation and 16.8 mm for shortening at which the probability of achieving "very good" function is only 0.23. CONCLUSION: Displaced midshaft clavicular fractures with the intent of achieving "good" outcome must be managed non-operatively. If the patient expectation is not to accept even minor functional deficits, the treatment objective must be raised to achieve a minimum Constant score of 86. Substituting the radiological displacements in the equation, the probability of the patient achieving this objective can be calculated. Non-operative management is offered if this probability figure is acceptable to the patient, otherwise counselled for surgery. Non-operatively managed patients with coexisting diabetes, smoking or poor soft tissue condition must be watched for the possibility of going for non-union.

Systems analysis of avascular necrosis of femoral head using integrative data analysis and literature mining delineates pathways associated with disease.

Avascular necrosis of femoral head (AVNFH) is a debilitating disease, which affects the middle aged population. Though the disease is managed using bisphosphonate, it eventually leads to total hip replacement due to collapse of femoral head. Studies regarding the association of single nucleotide polymorphisms with AVNFH, transcriptomics, proteomics, metabolomics, biophysical, ultrastructural and histopathology have been carried out. Functional validation of SNPs was carried out using literature. An integrated systems analysis using the available datasets might help to gain further insights into the disease process. We have carried out an analysis of transcriptomic data from GEO-database, SNPs associated with AVNFH, proteomic and metabolomic data collected from literature. Based on deficiency of vitamins in AVNFH, an enzyme-cofactor network was generated. The datasets are analyzed using ClueGO and the genes are binned into pathways. Metabolomic datasets are analyzed using MetaboAnalyst. Centrality analysis using CytoNCA on the data sets showed cystathionine beta synthase and methylmalonyl-CoA-mutase to be common to 3 out of 4 datasets. Further, the genes common to at least two data sets were analyzed using DisGeNET, which showed their involvement with various diseases, most of which were risk factors associated with AVNFH. Our analysis shows elevated homocysteine, hypoxia, coagulation, Osteoclast differentiation and endochondral ossification as the major pathways associated with disease which correlated with histopathology, IHC, MRI, Micro-Raman spectroscopy etc. The analysis shows AVNFH to be a multi-systemic disease and provides molecular signatures that are characteristic to the disease process.

No role for antiseptics in routine pin site care in Ilizarov fixators: A randomised prospective single blinded control study.

INTRODUCTION: Pin site infection is the commonest complication of Ilizarov external fixation. The aim of the study was to examine if use of antiseptics was superior over control and further if daily dressing was superior to weekly dressing in regular pin site care in reducing the burden of pin site infection in Ilizarov fixators. PATIENTS AND METHODS: A total of 114 patients (2363 pin sites) were randomised to receive regular pin site care alone (30 patients, 638 pin sites) or with additional application of povidone iodine (27 patients, 561 pin sites), silver sulfadiazine (27 patients, 570 pin sites) and chlorhexidine (30 patients, 594 pin sites). The pin tracts were sub-randomised to receive daily (1212 pin sites) or weekly (1151 pin sites) dressings. The primary outcome was pin site infection days rate across all four groups. The secondary outcomes were - mean duration to first episode of infection, differences between daily and weekly dressing groups, mean duration of antibiotic therapy and incidence of re-interventions and sequelae. We also recorded frequency of bacterial pathogens in all microbiological samples submitted. Block randomization using computer-generated random numbers was used. The assessor of outcome was blinded. RESULTS: All patients completed the study. Pin site infection rate days per 1000 pin site days observed was marginally less in chlorhexidine group, but was not statistically significant compared to other antiseptics and control group (Absolute value in control, povidone iodine, silver sulphadiazine and chlorhexidine groups were respectively 2.04 ± 4.27, 2.04 ± 3.65, 1.85 ± 3.37, 1.37 ± 2.35, p value 0.92). Daily dressing category showed slightly less pin site infection days rate within each group and overall, but this was also not statistically significant (1.56 ± 3.99 versus 2.10 ± 5.1, p value 0.35). There was no statistically significant difference among the groups with regard to other secondary outcomes. Methicillin Sensitive Staphylococcus aureus was the most common bacterial pathogen isolated. CONCLUSION: Use of antiseptics does not offer any advantage in regular pin site care in Ilizarov external fixation and daily pin site care is not superior to weekly pin site care. Empirical therapy in early and low grade pin site infections must be targeted against Staphylococcus.

A novel loss-of-function mutation in HACE1 is linked to a genetic disorder in a patient from India.

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.

Avascular Necrosis of Femoral Head: A Metabolomic, Biophysical, Biochemical, Electron Microscopic and Histopathological Characterization.

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.

Functional outcome of arthroscopic assisted fixation of distal radius fractures.

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.

Elbow arthroscopy: review of the literature and case reports.

Elbow arthroscopy, though described first in 1930s, gained popularity only in the last 3 decades. There has been a steady expansion in the clinical applications of elbow arthroscopy owing to the significant improvements in instrumentation and arthroscopic skills. The procedure which was mainly used for diagnostic purpose, loose body removals, and synovial biopsy has now become an important tool for managing elbow arthritis, stiff elbow, and trauma. However, this procedure has a higher incidence of neurological complications and hence case selection and surgeon's expertise are of utmost importance.

Anatomical bases of the free posterior brachial fascial flap.

PURPOSE: Fascias can be used for reconstruction of gliding surfaces of upper and lower extremities or when thin, pliable coverage is required. Free large and well-vascularised fascial flaps are not very many and harvesting is seldom onto upper limb. The aim of this work was to study blood supply of the posterior brachial fascia in order to define the anatomical bases of a new free fascial flap. METHODS: Our study included dissection on 18 anatomic specimens from 10 cadavers. Measures of the flap and blood supply were studied. Histological study was performed to analyse vessels location and measures into flap thickness. RESULTS: The posterior brachial fascia was thin, with a broad surface area and easily separable from the subcutaneous and muscular plane. Its average surface size is 115-mm length and 54-mm width. It was richly vascularised by two major pedicles: the cutaneous posterior brachial pedicule and the fascial branch of the superior ulnar collateral artery. Satellite venous elements were always present. A rich vascular network exists within the thickness of the fascia. Surgical procedure of flap harvesting is described. CONCLUSION: Harvesting of the flap can be carried out by a posteromedial approach into upper limb, without significant donor-site morbidity. This flap is adapted to cover and reconstruct gliding tendinous surfaces onto hand or fingers.

The floating lunate: arthroscopic treatment of simultaneous complete tears of the scapholunate and lunotriquetral ligaments.

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 degrees of flexion, 54 degrees of extension, 77 degrees of pronation, 80 degrees of supination, 25 degrees of ulnar deviation, and 15 degrees 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 follow-up, ten patients had no pain, one had mild pain, and two experienced moderate pain.

Arthroscopically assisted Sauvé-Kapandji procedure: an advanced technique for distal radioulnar joint arthritis.

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.

Treatment of early basal joint arthritis using a combined arthroscopic debridement and metacarpal osteotomy.

Osteoarthritis of the thumb basal joint is a common and disabling condition, and early stages of which are often seen in middle-aged women. Arthroscopic assessment of the first carpometacarpal joint allows easy identification and classification of joint pathology with minimal morbidity. This allows the condition to be managed either arthroscopically or converted to an open procedure as indicated. Different procedures have been described to treat different stages of this disease. The senior author has recently described an arthroscopic staging system to determine treatment for basal joint osteoarthritis. We now present our surgical technique and early clinical experience with arthroscopic synovectomy, debridement, and corrective osteotomy for arthroscopic stage II of thumb basal joint arthritis. Forty-three patients (38 women and 5 men) were arthroscopically diagnosed as having stage II basal joint osteoarthritis of the thumb between 1998 and 2001, and they were the focus of the present study. In all the patients, there was no improvement after a period of 6 to 12 weeks of conservative treatment. All the procedures were performed by the senior author. The surgical procedure included arthroscopic synovectomy, debridement, and occasional thermal capsulorraphy, followed by an extension-abduction closing wedge osteotomy in all the cases. A 0.045-in Kirschner wire provided stability to the osteotomy. By performing an osteotomy that redirects the axial loads in this joint, we have obtained satisfactory results in terms of pain relief, stability, and pinch strength. Arthroscopy allows us to not only determine the optimum indication for this osteotomy, but also to debride the joint and minimize the inflammatory response. Hence, we recommend arthroscopic synovectomy, debridement with or without a thermal capsulorraphy, and a dorsoradial closing wedge osteotomy for the treatment of arthroscopic stage II of thumb carpometacarpal joint osteoarthritis.

Suture welding for arthroscopic repair of peripheral triangular fibrocartilage complex tears.

This report presents a method of arthroscopic repair of the peripheral triangular fibrocartilage tears by using ultrasonic suture welding technique, thus avoiding the need for traditional suture knots. This technique eliminates the potential causes of ulnar-sided wrist discomfort especially during the postoperative period. Twenty-three patients (9 women and 14 men; mean age, 35 years; range, 18-52 years) were operated during a 1-year period in 2001 for Palmer grade 1B triangular fibrocartilage complex tear and followed up for 17 months. At the final follow-up, the average wrist arc of motion was as follows: extension, 65 degrees; flexion, 56 degrees; supination, 80 degrees; pronation, 78 degrees; radial deviation, 12 degrees; and ulnar deviation, 25 degrees. Grip strength measured with a dynamometer (Jamar) averaged 81% of the contralateral side at the final evaluation (range, 53%-105%).

Intercondylar fractures of the distal humerus in adults: a critical analysis of 55 cases.

Intercondylar fractures of the distal humerus in adults are difficult management problems on account of the complex anatomy of the elbow, small sized fracture fragments and the limited amount of sub-chondral bone, which is often osteopenic. The results of managing these fractures non-operatively are compromised by the failure to get anatomical reduction and early mobilization. This often results in a painful stiff elbow and/or pseudarthrosis, thereby making an operative approach for these fractures, desirable. Fifty-five such fractures, operated on by the author during the last 9 years, were reviewed. All the fractures were managed by open reduction and internal fixation followed by early mobilization. The outcome in 51 of these cases was graded as excellent or good using the evaluation criteria of Aitken and Rorabeck. Thirty-three of these cases achieved a range of flexion of more than 130 degrees. There was minimal incidence of complications like ulnar nerve neuropraxia or heterotopic bone formation. Anterior transposition of the ulnar nerve was performed in only one of the patients. Dorsal application of both the plates instead of the commonly advocated supracondylar crest placement resulted in a stable configuration requiring less extensive dissection and retraction of the ulnar nerve and resulting in a low incidence of complications.