Biomechanical analysis of tendon turnover tenorrhaphy compared to direct repair and Pulvertaft weave.

The aim of the present study was to evaluate biomechanical properties of tendon turnover repair in comparison to direct repair and Pulvertaft weave. A total of 48 sheep flexor tendons were assigned to eight groups comprising single or double tendon turnover repair, tendon turnover segment (without tenorrhaphy), direct repair or Pulvertaft weave. Tensile strength, stiffness and failure mechanisms were evaluated with a 500 N load cell. Turnover repair showed no significant difference in tensile strength to direct repair. Failure in turnover repair occurred largely at the site of tenorrhaphy due to suture pull-through or suture rupture. the increase in cross-sectional area after turnover repair was similar to that after direct repair, but less than after Pulvertaft weave. Tendon turnover offers tensile strength similar to direct repair with no associated increase in bulk. It provides a biomechanically secure and quicker alternative to tendon grafting for reconstructing tendon defects, without secondary donor site morbidity.Level of evidence: V.

Modifiable Risk Factors for Prevention in Dupuytren Disease: A UK Biobank Case-Control Study.

BACKGROUND: Dupuytren disease is associated with significant comorbidity and mortality, and it has no existing prevention strategies. It is unclear which modifiable risk factors are most amenable for prevention. This study aimed to determine the strength of modifiable risk factors for Dupuytren disease, and to investigate associations with other diseases. METHODS: Using UK Biobank data, this case-control study analyzed the association between phenotypic variables and Dupuytren disease through multivariable logistic regression. Exposures assessed were age, sex, body mass index, waist-to-hip ratio, Townsend deprivation index, smoking status, alcohol intake, diabetes mellitus, hypertension, cancer, liver disease, respiratory disease, rheumatoid arthritis, epilepsy, psoriasis, and gout. RESULTS: There were 4148 cases and 397,425 controls. Male sex (OR, 3.23; 95% CI, 2.90 to 3.60; P = 1.07 × 10 -100 ), increasing age (OR, 1.08; 95% CI, 1.07 to 1.08; P = 6.78 × 10 -167 ), material deprivation (OR, 1.01; 95% CI, 1.00 to 1.02; P = 0.0305), high-density lipoprotein cholesterol (OR, 1.76; 95% CI, 1.58 to 1.96; P = 3.35 × 10 -24 ), smoking exposure, and alcohol intake were all associated with increased odds of Dupuytren disease. With increasing obesity class, there was approximately 25% decreased odds (OR, 0.774; 95% CI, 0.734 to 0.816; P = 4.71 × 10 -21 ). Diabetes with microvascular or end-organ complications was associated with more than 2.5 times increased odds of Dupuytren disease (OR, 2.59; 95% CI, 1.92 to 3.44; P = 1.92 × 10 -10 ). Within this group, increasing hemoglobin A1c values by 10 mmol/mol, or 0.9%, increased the odds by 31% (OR, 1.31; 95% CI, 1.13 to 1.51; P = 2.19 × 10 -4 ). CONCLUSION: Diabetes and poor glycemic control are major risk factors for Dupuytren disease, which present an opportunity for prevention. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

A multicentre study of the relationship between abdominal flap and mastectomy weights in immediate unilateral free flap breast reconstruction and the effect of adjuvant radiotherapy.

Abdominal free flaps are considered the gold standard for post-mastectomy autologous breast reconstruction. A key element of outcome assessment is breast symmetry often achieved by approximating the reconstructed breast dimensions such as weight (wt) to those of the mastectomy. However, the ideal relationship between these two entities remains unclear. 525 immediate unilateral abdominal free flap breast reconstruction (FFBR) patients were enrolled in a multicentre study (UK 141; Italy 384) and subdivided into Group A (flap wt < mastectomy wt, n = 163), Group B (flap wt > mastectomy wt, n = 260) and Group C (flap wt = mastectomy wt, n = 102). Their rates of contralateral balancing and ipsilateral revision surgeries were compared using Chi-Square tests. Radiotherapy influence on these adjustment procedures was also assessed. More contralateral balancing procedures (17%) were performed than ipsilateral revisions (10%). Group A rates of contralateral balancing procedures were three times higher than Group B's with a ratio of 37 to 1 versus Group C (37% vs 11% vs 1% respectively, p < 0.001). Similarly, the ipsilateral breast revision surgery rate in Group A was double that of Group B and almost three times that of Group C (17% vs 8% vs 6% respectively, p = 0.01). Adjuvant radiotherapy disproportionately increased ipsilateral revisions versus contralateral balancing surgeries (p = 0.028). A flap-to-mastectomy weight ratio of less than 1 (Group A) significantly increases subsequent adjustments on both contralateral and reconstructed breasts whilst irradiation predisposes to ipsilateral revisions. This is important in patient counselling and intraoperative flap contouring. Flap weight should ideally approximate or exceed mastectomy weight in unilateral FFBR.

Versatility of percutaneous needle fasciotomy for Dupuytren's disease across a spectrum of disease severity: A single-surgeon experience of 118 rays.

BACKGROUND: Percutaneous needle fasciotomy (PNF) represents the only minimally invasive approach for treatment of Dupuytren's disease in Europe since withdrawal of collagenase from European markets. Though well-established, surgeon preference and uncertainty regarding safety and efficacy, results in limited provision in favour of open fasciectomy. METHODS: A retrospective review of 74 patients who self-opted to receive PNF between 2017 and 2020 was conducted. Demographic data, complications and degree of release achieved were compared across three cohorts based on contracture severity as per Tubiana staging (TS): Stage 1, 0-45°; Stage 2, 46-90°; Stage 3, 91-130° with χ2 analysis. RESULTS: One hundred and eighteen rays were treated amongst 74 patients (mean age, 68 years (R, 32-86), males: 74%) with mean follow-up 51 weeks (IQR 28-76 weeks) with no significant difference in baseline characteristics across cohorts. No cases of permanent sensory disturbance, flexor tendon rupture, arterial transection nor infection were observed. Neuropraxia was seen in six patients, resolving with mean recovery of 6 weeks. 86% (n = 166) of joints had satisfactory release (residual passive extension deficit (PED) ≤10°) with full release in 67%. Full release was most likely in metacarpophalangeal joint (MCPJ; 93%) than distal interphalangeal joint (DIPJ; 67%) or proximal interphalangeal joint (PIPJ; 45%; p<0.0001). Mean release was 54° in MCPJ and 56° in PIPJ. All TS1 patients achieved release with ≤10° residual PED versus 75% of TS2 patients and 22% of TS3 patients (p<0.05), the latter of whom had a mean residual PED of 12° Ninety-two percent of patients stated they would undergo PNF again if necessary, in preference to open fasciectomy. CONCLUSION: We find PNF to facilitate a safe, effective yet minimally invasive approach amongst patients of varying disease severity, across different age groups, with recurrent disease, associated comorbidities or concurrent anticoagulation therapy. Patients reported high satisfaction in preference to open procedures. We, therefore, intend to recommend PNF first-line to all patients regardless of disease severity.

ZFYVE21 is a complement-induced Rab5 effector that activates non-canonical NF-κB via phosphoinosotide remodeling of endosomes.

Complement promotes vascular inflammation in transplant organ rejection and connective tissue diseases. Here we identify ZFYVE21 as a complement-induced Rab5 effector that induces non-canonical NF-κB in endothelial cells (EC). In response to membrane attack complexes (MAC), ZFYVE21 is post-translationally stabilized on MAC+Rab5+ endosomes in a Rab5- and PI(3)P-dependent manner. ZFYVE21 promotes SMURF2-mediated polyubiquitinylation and proteasome-dependent degradation of endosome-associated PTEN to induce vesicular enrichment of PI(3,4,5)P3 and sequential recruitment of activated Akt and NF-κB-inducing kinase (NIK). Pharmacologic alteration of cellular phosphoinositide content with miltefosine reduces ZFYVE21 induction, EC activation, and allograft vasculopathy in a humanized mouse model. ZFYVE21 induction distinctly occurs in response to MAC and is detected in human renal and synovial tissues. Our data identifies ZFYVE21 as a Rab5 effector, defines a Rab5-ZFYVE21-SMURF2-pAkt axis by which it mediates EC activation, and demonstrates a role for this pathway in complement-mediated conditions.