Variants in ALDH1A2 reveal an anti-inflammatory role for retinoic acid and a new class of disease-modifying drugs in osteoarthritis.

More than 40% of individuals will develop osteoarthritis (OA) during their lifetime, yet there are currently no licensed disease-modifying treatments for this disabling condition. Common polymorphic variants in ALDH1A2, which encodes the key enzyme for synthesis of all-trans retinoic acid (atRA), are associated with severe hand OA. Here, we sought to elucidate the biological significance of this association. We first confirmed that ALDH1A2 risk variants were associated with hand OA in the U.K. Biobank. Articular cartilage was acquired from 33 individuals with hand OA at the time of routine hand OA surgery. After stratification by genotype, RNA sequencing was performed. A reciprocal relationship between ALDH1A2 mRNA and inflammatory genes was observed. Articular cartilage injury up-regulated similar inflammatory genes by a process that we have previously termed mechanoflammation, which we believe is a primary driver of OA. Cartilage injury was also associated with a concomitant drop in atRA-inducible genes, which were used as a surrogate measure of cellular atRA concentration. Both responses to injury were reversed using talarozole, a retinoic acid metabolism blocking agent (RAMBA). Suppression of mechanoflammation by talarozole was mediated by a peroxisome proliferator-activated receptor gamma (PPARγ)-dependent mechanism. Talarozole was able to suppress mechano-inflammatory genes in articular cartilage in vivo 6 hours after mouse knee joint destabilization and reduced cartilage degradation and osteophyte formation after 26 days. These data show that boosting atRA suppresses mechanoflammation in the articular cartilage in vitro and in vivo and identifies RAMBAs as potential disease-modifying drugs for OA.

Population Study of Hand and Wrist Manifestations of Congenital Insensitivity to Pain.

Background: Congenital insensitivity to pain is a rare autosomal recessive condition characterized by insensitivity to painful stimuli due to absence of sensory and sympathetic post ganglionic neurons in the skin and skeletal system leading to lack of protective sensation and altered joint propioception. This study was performed to assess hand and wrist manifestations of patients with congenital insensitivity to pain in the Maltese Islands. Methods: Records of public and private hospitals were reviewed to identify patients suffering from this condition. A review of notes, patients, and imaging was performed. A Disabilities of the Arm, Shoulder, and Hand score was obtained to assess level of function. Results: Nine patients were identified. Mean age of diagnosis was 8.9 years. Interphalangeal joints were most commonly affected. Multiple spontaneous or posttraumatic fingertip ulceration occurred in 5 patients. Anhidrosis resulted in more protracted ulcers and infections, requiring amputation of distal and middle phalanges due to osteomyelitis. The wrist joint was less commonly involved and showed more complex joint involvement. Conclusion: The hand and wrist are involved in different ways, with fingertip ulceration leading to potential infection and osteomyelitis in the hand, whereas the wrist joint is involved in cases of increased axial loading and load transfer, such as following prolonged use of walking and mobility aids. The latter should be borne in mind during management of lower limb conditions. Hand care and hygiene is important in all patients, especially in cases of anhidrosis due to the increased rate of ulceration and osteomyelitis requiring surgical intervention. Despite the severity of the condition, patients report good overall function.

Systematic Review of Thumb Carpometacarpal Joint Hemiresection Interposition Arthroplasty Materials.

BACKGROUND: Osteoarthritis of the first carpometacarpal joint is a common condition. Various management options and surgical procedures have been described to treat symptomatic cases. Many systematic reviews examine aspects of thumb carpometacarpal joint osteoarthritis treatment, although none solely examines the outcomes of trapezial partial resection and interposition arthroplasty in stage II to III patients in detail, yet this technique is of growing interest as surgeons seek more nuanced, tailored approaches for osteoarthritis of the first carpometacarpal joint. METHODS: A systematic review of the thumb carpometacarpal joint hemiresection and interposition arthroplasty was performed with pain assessment as a primary outcome measure and patient-reported outcome measures (PROMs) and reoperation rate as secondary outcome measures. A search was performed between 2004 and 2019 using MEDLINE, Embase, and PubMed. Preferred Reporting Items and Systematic Reviews and Meta-Analyses guidelines were used. RESULTS: Twenty-nine articles met the inclusion criteria and were included in the final review. Pain relief and improved PROMs were described in all the articles using this technique with all the interposition materials. Materials such as polyurethane urea matrix and poly-l/d-lactide scaffold had higher complication rates. Revision rates varied and were highest with the polyurethane urea matrix. CONCLUSIONS: This review shows that hemiresection interposition arthroplasty is a useful technique and provides symptomatic benefit in patients with Eaton-Littler stage II and III osteoarthritis. Revision surgery rates due to persistent pain and instability were higher with the use of implants. Larger and long-term studies of this technique using autologous or more bioinert materials and implants are required to assess duration of symptomatic benefit.

Low rate of subsequent surgery and serious complications following intra-articular steroid injection for base of thumb osteoarthritis: national cohort analysis.

OBJECTIVES: Intra-articular steroid injection is commonly used to treat base of thumb osteoarthritis (BTOA), despite a lack of large-scale data on safety and effectiveness. We estimate the incidence of serious complications and further procedures following BTOA injection, including the risk of post-operative serious surgical site infection for subsequent operative intervention. METHODS: Hospital Episode Statistics data linked to mortality records from 1 April 1998 to 31 March 2017 were used to identify all BTOA injections undertaken in adults in the National Health Service secondary care in England. Patients were followed up longitudinally until death or 31 March 2017. A multivariable regression with a Fine and Gray model adjusting for the competing risk of mortality in addition to age, sex and socioeconomic deprivation was used to identify factors associated with progression to further procedure. Secondary outcomes included serious complications after injection and subsequent surgical site infection. RESULTS: A total of 19 120 primary injections were performed during the 19-year period in 18 356 patients. Of these 76.5% were female; mean age 62 years (s.d. 10.6); 50.48% underwent further procedure; 22.40% underwent surgery. Median time to further intervention was 412 days (IQR 110-1945). Female sex was associated with increased risk of proceeding to surgery. Serious complication rate following injection was 0.04% (0.01-0.08) within 90 days. Of those proceeding to surgery 0.16% (0.06-0.34) presented with a wound infection within 30 days and 90 days, compared with an overall post-operative wound infection rate of 0.03% (0.02-0.05). CONCLUSIONS: Very low rates of serious complications were identified following BTOA injections performed in secondary care; only one in five patients proceeded to subsequent surgery. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov, https://www.clinicaltrials.gov, NCT03573765.

Outcome of arthrodesis for severe recurrent proximal interphalangeal joint contractures in Dupuytren's disease.

We report long-term outcomes of proximal interphalangeal joint arthrodesis for treatment of severe recurrent joint contractures secondary to Dupuytren's disease. The patients had at least two previous procedures for Dupuytren's contracture that involved the same joint, before undergoing joint fusion. Patient demographics, satisfaction, functional outcome, complications, revision and re-operation rates are reported. Eleven patients were included with a mean age of 64 years (range 53-73). The mean proximal interphalangeal joint contracture at presentation was 102° (range 80°-120°). None required revision surgery at a mean of 8 years and 9 months (range 9-199 months). All patients were able to perform their activities of daily living and would recommend this operation to family and friends. This series shows that proximal interphalangeal joint arthrodesis combined with needle fasciotomy or segmental fasciectomy provides a satisfactory salvage procedure in cases of severe recurrent Dupuytren's disease.Level of evidence: IV.

Salvage of the Failed Total Wrist Arthroplasty: A Systematic Review.

Background Although the performance of total wrist arthroplasty systems has improved, failure is encountered and is a major challenge to manage. Questions Does physical function improve with surgical management of the failed wrist arthroplasty? Is there an improvement in secondary outcome measures including pain, grip strength, and range of motion? What are the reasons for failure in primary total wrist arthroplasty? What are the complications associated with revision of the failed total wrist arthroplasty? What are the survival profiles of the different revision strategies? Methods A systematic review of available literature was performed. Studies were systematically assessed, and data extracted from suitable studies for review. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines were adhered to. The study protocol was modified from a previous protocol published on the PROSPERO database. Results Fourteen studies were identified considering 218 patients/214 index operations with a follow-up duration following revision surgery of 2 months to 21 years (silicone wrist arthroplasty-42 cases; nonsilicone wrist arthroplasty-172 cases). The functional outcome of revision surgery was infrequently recorded and documented with only short-term assessments undertaken. Complications were seen in 1:2 revision procedures, with re-revision surgeries required in 21.6% of revised primary nonsilicone arthroplasties. Re-revision rate following a revision arthrodesis was 21.4% (15/70 cases) compared with revision arthroplasty of 34.8% (32/92 cases). Revision arthrodesis nonunion rate was 17.5% (22 cases). Conclusion This review has confirmed the high level of surgical complexity and the likelihood of a complicated postoperative outcome when salvaging a failed wrist replacement. Level of Evidence This is a Level 3, systematic review study.

The Orthopedic Manifestations of Congenital Insensitivity to Pain: A Population-based Study.

BACKGROUND: Congenital insensitivity to pain (CIP) is an extremely rare condition in which there is a failure of the development of the afferent sensory nerves in the dorsal root ganglia resulting in indifference to painful stimuli. The associated orthopedic manifestations are various and often present a diagnostic quandary for the treating surgeon. PURPOSE: This population study provides insight into the orthopedic manifestations and functional scores in patients with CIP, to guide prognosis and management. PATIENTS AND METHODS: We retrospectively review and describe the orthopedic manifestations of all cases of CIP in Malta. All patients were then scored for upper and lower limb function using the abridged version of the Disability of Arm, Shoulder, and Hand score (QuickDASH) and the Lower Extremity Functional Score (LEFS). RESULTS: Nine patients were recruited in total. Mean age at the time of recruitment into this study was of 33.7 years (range 15-58). All patients were Caucasian of Maltese heritage. None had consanguineous parents. All patients had been diagnosed with the condition in childhood (mean age 8.9 years). In total, these patients had 6 long bone fractures, 1 vertebral fracture, 39 upper limb surgical procedures, 88 lower limb surgical procedures, and 7 major lower limb amputations. These are discussed in detail. The main QuickDASH score was 23.97. The main LEFS was 42.22. CONCLUSIONS: This paper is the first population-based study of this condition and one of the largest series with functional scores. A multidisciplinary approach is essential in managing these patients. The surgical treatment of these conditions is often difficult and protracted, and judicious and careful consideration to both the bony and soft tissues aspects of the management need to be taken into account, with functional limb amputation not necessarily being considered as a last resort.

Three Year Review of Dorsal Plating for Complex Intra-Articular Fractures of the Distal Radius.

BACKGROUND: The volar approach is commonly used for plating intra-articular fractures of the distal radius. Despite this, certain fracture configurations are more suitable for dorsal plate fixation. This technique has not gained favour due to the reported high incidence of extensor tendon irritation and attrition ruptures. With the advent of lower profile plates this risk has decreased. METHODS: We report on forty-six cases performed in a tertiary hand centre between January 2011 and May 2014. Patients were identified from a database of distal radius fractures treated with open reduction and internal fixation. Pre-operative radiographs and computed tomogram (CT) scans were reviewed to classify fractures and evaluate fracture configurations. Dorsal displacement of fracture fragments was present in all cases. Records and imaging were reviewed to assess bony union and complications including tendon irritation, rupture and need for further surgery. RESULTS: Plate placement was dependent on the degree of comminution in each fracture component. The combination of a dorsal and radial styloid plate was used in 52% of cases. There were no cases of tendon rupture and one case of post-operative loss of reduction. Removal of metal was performed in ten patients, mainly to improve motion and for tendon irritation (four cases each). CONCLUSIONS: Even though technically challenging, dorsal plating is useful in cases of dorsal fragment displacement and comminution, as well as complex AO-23C3 fractures with involvement of the lunate fossa. It allows stable reduction of the dorso-ulnar fragment which is important to restore DRUJ anatomy. The rate of tendon irritation and rupture is lower when compared to earlier plate designs, and removal of metal is only necessary in a few cases.

Distal radius volar rim plate: Technical and radiographic considerations.

AIM: To determine technical considerations and radiographic outcomes of the Synthes volar rim distal radius plate to treat complex intra-articular fractures. METHODS: This review highlights technical considerations learnt using this implant since it was introduced in a major trauma unit in November 2011, including anatomical reduction and whether this was maintained radiographically. RESULTS: Twenty-six of the 382 internally fixed distal radial fractures at our unit (6.8%) were deemed to require this plate in order to achieve optimal fracture fixation between November 2011 and May 2014. A further dorsal and/or radial plate was necessary in 35% and variable angle screws were used in 54% of cases. Post-operatively, mean radial height, inclination, volar tilt and ulnar variance restored were 11.7 mm, 21º, 4.3º and -1.2 mm respectively. There were no cases of non-union or flexor/extensor tendon rupture; one case of loss of fracture reduction. Overall incidence of plate removal was 15% with one plate removed for flexor and one for extensor tendon irritation. CONCLUSION: The use of a rim plate enables control of challenging far distal fracture patterns. However, additional plates were required to improve and maintain reduction. Variable angle screws were necessary in half the cases to avoid intra-articular screw penetration. If used judiciously, this implant can achieve stable fixation despite the complexity of the fracture pattern.

Four corner fusion using a multidirectional angular stable locking plate.

AIM: To review the results of our experience with the Medartis Aptus plating system for four corner arthrodesis of the wrist, which uses a combination of compression screws and variable angle locking screws. METHODS: We reviewed the results of 17 procedures in 16 patients that underwent scaphoid excision and four corner fusion using the Medartis Aptus system between May 2010 and June 2014. The primary outcome measure was radiographic and clinical union. RESULTS: The mean clinical follow up time was 20.6 mo. The mean union time was 6 mo. Two non-unions required revision procedures. The mean disabilities of the arm, shoulder and hand score taken after union was 36. The mean final grip strength was 27 kg. The mean final range of movement was 30° flexion and 31° of extension. All patients had a restored scapholunate angle on postoperative radiographs. There were no incidences of dorsal impingement. CONCLUSION: Overall our experience with the Aptus plating system shows comparable results to other methods of fixation for four corner fusion, in the short to medium term.