Aspirin may prevent cholangiocarcinoma: a case-control study from the United kingdom.

BACKGROUND: The proliferation of cholangiocarcinoma cells is suppressed in cell culture by nonsteroidal antiinflammatory drugs (NSAIDs) through the inhibition of cyclo-oxygenase-2 enzyme and also by statins which decrease the production of mediators of the cell cycle. AIMS: To investigate whether there is an inverse association between NSAIDs, including aspirin, and the development of cholangiocarcinoma and, for the first time in a Western population, between statin use and the development of cholangiocarcinoma. METHODS: This epidemiological study had a case-control design in which cases of cholangiocarcinoma diagnosed in Norwich between 2004 and 2010 and in Leicester in 2007 were identified from clinical databases. Controls were patients with basal cell carcinomas treated in the respective dermatology departments. The case notes of all subjects were reviewed to confirm diagnoses and obtain information on medication use. The data were analyzed using unconditional logistic regression to calculate odds ratios (OR) with 95 % confidence intervals (CI). RESULTS: In total, 81 cases of cholangiocarcinoma and 275 controls were identified. For all cases there was radiological evidence of cancer and 86 % of the cases involved the extrahepatic biliary system. Aspirin use was inversely associated with the development of cholangiocarcinoma (OR 0.45, 95 % CI 0.22-0.92), but there were no significant associations between the development of cholangiocarcinoma and NSAIDs (OR 0.39; 95 % CI 0.11-1.42) or statins (OR 0.58; 95 % CI 0.28-1.19). CONCLUSIONS: The epidemiological data from this study support the biological evidence for aspirin having a protective effect against the development of cholangiocarcinoma. Aspirin use should be measured in future etiological studies and assessed as a chemoprevention agent in those at high risk of developing this type of cancer.

Operative outcomes for wide awake local anesthesia versus regional and general anesthesia for flexor tendon repair.

Operative repair of flexor tendons after traumatic injury may be performed under general anesthesia (GA), regional blocks, or a wide-awake local anesthesia no tourniquet (WALANT) technique. To our knowledge there are currently no large-scale reports evaluating outcomes of flexor tendon repair in patients where wide-awake anesthesia was utilized in comparison to regional anesthesia (RA) and general anesthesia. We performed a retrospective analysis of patients who underwent treatment for flexor tendon injuries at a tertiary referral center for hand surgery over a two-year period. A total of 151 patients were included (53 WALANT, 57 RA, and 41 GA) and a total of 251 tendons were repaired (63 WALANT, 104 RA and 84 GA). No statistically significant difference was observed in rates of tendon rupture, adhesions, infection, or hand function. Flexor tendon repair under WALANT is found to be safe and presents comparable operative and functional outcomes to more traditional anesthetic techniques. Additional advantages, including the ability to test the repair intraoperatively, patient education, and the potential for boosting theatre efficiency. Further studies, preferably utilizing a randomized trial methodology, may further elucidate the benefits and risks of WALANT versus regional and general anesthesia.

Conservative management of mallet injuries: A national survey of current practice in the UK.

INTRODUCTION: Mallet injuries are common and usually treated conservatively. Various systematic reviews have found a lack of evidence regarding the best management, and it is unclear whether this uncertainty is reflected in current UK practice. METHODS: An online survey was developed to determine the current practice for the conservative treatment of mallet injury among specialist hand clinicians in the UK, including physiotherapists, occupational therapists and surgeons. Clinician's views of study outcome selection were also explored to improve future trials. RESULTS: In total, 336 professionals completed the survey. Inconsistency in overall practice was observed in splint type choice, time to discharge to GP, and assessment of adherence. Greater consistency was observed for recommended duration of continuous immobilisation. Bony injuries were most commonly splinted for 6 weeks (n = 228, 78%) and soft tissue injuries for either 8 weeks (n = 172, 56%) or 6 weeks (n = 119, 39%). Post-immobilisation splinting was frequently recommended, but duration varied between 2 and 10 weeks. The outcome rated as most important by all clinicians was patient satisfaction. DISCUSSION: There is overall variation in the current UK conservative management of mallet injuries, and the development of a standardised, evidence-based protocol is required. Clinicians' opinions may be used to develop a core set of outcome measures, which will improve standardisation and comparability of future trials.

Protective T Cell and Antibody Immune Responses against Hepatitis C Virus Achieved Using a Biopolyester-Bead-Based Vaccine Delivery System.

Hepatitis C virus (HCV) infection is a major worldwide problem. Chronic hepatitis C is recognized as one of the major causes of cirrhosis, hepatocellular carcinoma, and liver failure. Although new, directly acting antiviral therapies are suggested to overcome the low efficacy and adverse effects observed for the current standard of treatment, an effective vaccine would be the only way to certainly eradicate HCV infection. Recently, polyhydroxybutyrate beads produced by engineered Escherichia coli showed efficacy as a vaccine delivery system. Here, an endotoxin-free E. coli strain (ClearColi) was engineered to produce polyhydroxybutyrate beads displaying the core antigen on their surface (Beads-Core) and their immunogenicity was evaluated in BALB/c mice. Immunization with Beads-Core induced gamma interferon (IFN-γ) secretion and a functional T cell immune response against the HCV Core protein. With the aim to target broad T and B cell determinants described for HCV, Beads-Core mixed with HCV E1, E2, and NS3 recombinant proteins was also evaluated in BALB/c mice. Remarkably, only three immunization with Beads-Core+CoE1E2NS3/Alum (a mixture of 0.1 µg Co.120, 16.7 µg E1.340, 16.7 µg E2.680, and 10 µg NS3 adjuvanted in aluminum hydroxide [Alum]) induced a potent antibody response against E1 and E2 and a broad IFN-γ secretion and T cell response against Core and all coadministered antigens. This immunological response mediated protective immunity to viremia as assessed in a viral surrogate challenge model. Overall, it was shown that engineered biopolyester beads displaying foreign antigens are immunogenic and might present a particulate delivery system suitable for vaccination against HCV.

Extensor tendon rehabilitation a prospective trial comparing three rehabilitation regimes.

Forty-two patients with 46 complete extensor tendon injuries were prospectively allocated to one of three rehabilitation regimes: static splintage; interphalangeal joint mobilization with metacarpophalangeal joint immobilization or; the "Norwich" regime. All 42 patients were operated on by one surgeon and assessed by one hand therapist. At 4 weeks the total active motion in the static splintage group was significantly reduced but by 12 weeks there was no difference between the regimes. There was no difference in total active motion between the repaired and uninjured hand at 12 weeks, with all patients achieving good or excellent results. However, grip strength at 12 weeks was significantly reduced compared to the uninjured hand after static splintage. There was no difference in hand therapy input between the regimes.

Flexor tendon repairs in children: Outcomes from a specialist tertiary centre.

We evaluate the functional outcomes of early active mobilization (EAM) after paediatric flexor tendon repair at one centre from 2006 to 2013. A generic rehabilitation protocol was used for the first four to six weeks: boxing glove immobilization (<5 years), dorsal blocking splint and cage (5-10 years) or dorsal blocking splint ± cage (10-16 years). Outcomes were assessed using the Total Active Mobilization (TAM) method of the American Society for Surgery of the Hand and original Strickland criteria (OSC). Sixty-three fingers and 99 tendons were identified, in 57 children. Thirty-five per cent (n = 20) were in zone 2, 23% in zone 1, 18% in zone 5, 14% in zone 3 and 2% in zone 4. Good/excellent results were obtained in 82% by the TAM method and 79% by the OSC of those suitable for analysis (56 tendons in 44 children). The surgical approaches used varied in technique and material; a modified Kessler stitch (n = 42) using prolene (n = 60) represented the majority of core sutures. Epitendinous repair was employed in 76% of repairs (n = 75). The median length of hand therapy follow-up was 83.5 days (IQR 43.5-143.75 days). Complications included: one rupture, one post-operative infection requiring washout and three contractures, two requiring re-operation. EAM is a practical and safe way to rehabilitate children after flexor tendon repair, without increasing ruptures or adhesions. Most children under five are managed effectively in a bulky bandage.

Miniplate fixation for avulsion injuries of the flexor digitorum profundus insertion.

This article describes the use of a miniplate and cortical screws in the treatment of five cases of flexor digitorum profundus (FDP) tendon avulsion. One case was type II, three cases were type III and one case was type IV. Near normal joint congruity was restored together with bony union in all cases. Six months after surgery four cases had near normal range of motion at the distal interphalangeal joint compared with the contralateral uninjured finger. These four patients were to return to their previous activities without restriction by 3 months. One repair of a type III avulsion ruptured but the distal interphalangeal joint was pain free and stable and the patient declined further surgery. Miniplate fixation offers some advantages over existing methods of repair and adds to the range of techniques available for reattachment of the FDP tendon in these injuries.

A prospective review of open central slip laceration repair and rehabilitation.

A prospective review was carried out to evaluate the outcome of surgically repaired open central slip (zone III) injuries which were treated with 3 weeks of proximal interphalangeal joint immobilization within a cylinder splint and then with 3 weeks of controlled mobilization within a Capener coil splint. Thirty-one fingers in 27 patients were assessed by the same independent therapist. All fingers achieved an excellent or good recovery with a mean proximal interphalangeal joint flexion of 94 degrees (range 70-110 degrees) and a mean distal interphalangeal joint flexion of 57 degrees (range 30-81 degrees). Extension deficits of the proximal interphalangeal joint were noted in five fingers (mean 6 degrees, range 3-15 degrees). The results show that a combination of immobilization and controlled mobilization is an effective rehabilitation regime for surgically repaired open central slip injuries.

An alternative splinting and rehabilitation protocol for metacarpophalangeal joint arthroplasty in patients with rheumatoid arthritis.

This prospective study was completed to establish results obtained using a static splinting regimen as an alternative to the dynamic extension splint. Fifteen patients with rheumatoid arthritis, who had undergone metacarpophalangeal (MCP) joint arthroplasties and a postoperative rehabilitation program of alternating MCP joint flexion and extension static splints, were assessed pre-operatively and reviewed postoperatively. Total active arc of MCP joint motion and ulnar deviation were measured, and an activities-of-daily-living questionnaire was completed by each patient at 19 months (mean) postoperatively. Mean total active arc of MCP joint motion showed statistical improvement from 21.6 degrees (range, 5 degrees-60 degrees) pre-operatively to 47.2 degrees (range, 15 degrees-84 degrees) postoperatively. The little finger gained the most improvement, with a 50.2 degree arc, showing that this regimen does not compromise flexion gains at this joint. Ulnar deviation improved from a mean of 30.4 degrees (range, 5 degrees-65 degrees) pre-operatively to 9.7 degrees (range, 0 degrees-30 degrees) postoperatively. These initial results reinforce the clinical impression that this alternating static splint regimen can be used as an effective alternative to the dynamic extension splint.