Development of a fast curing tissue adhesive for meniscus tear repair

Isocyanate-terminated adhesive amphiphilic block copolymers are attractive materials to treat meniscus tears due to their tuneable mechanical properties and good adhesive characteristics. However, a drawback of this class of materials is their relatively long curing time. In this study, we evaluate the use of an amine cross-linker and addition of catalysts as two strategies to accelerate the curing rates of a recently developed biodegradable reactive isocyanate-terminated hyper-branched adhesive block copolymer prepared from polyethylene glycol (PEG), trimethylene carbonate, citric acid and hexamethylene diisocyanate. The curing kinetics of the hyper-branched adhesive alone and in combination with different concentrations of spermidine solutions, and after addition of 2,2-dimorpholinodiethylether (DMDEE) or 1,4-diazabicyclo [2.2.2] octane (DABCO) were determined using FTIR. Additionally, lap-shear adhesion tests using all compositions at various time points were performed. The two most promising compositions of the fast curing adhesives were evaluated in a meniscus bucket handle lesion model and their performance was compared with that of fibrin glue. The results showed that addition of both spermidine and catalysts to the adhesive copolymer can accelerate the curing rate and that firm adhesion can already be achieved after 2 h. The adhesive strength to meniscus tissue of 3.2–3.7 N was considerably higher for the newly developed compositions than for fibrin glue (0.3 N). The proposed combination of an adhesive component and a cross-linking component or catalyst is a promising way to accelerate curing rates of isocyanate-terminated tissue adhesives

Impregnation of bone chips with alendronate and cefazolin, combined with demineralized bone matrix: a bone chamber study in goats

Contains fulltext : 108265.pdf (publisher's version ) (Open Access)BACKGROUND: Bone grafts from bone banks might be mixed with bisphosphonates to inhibit the osteoclastic response. This inhibition prevents the osteoclasts to resorb the allograft bone before new bone has been formed by the osteoblasts, which might prevent instability. Since bisphosphonates may not only inhibit osteoclasts, but also osteoblasts and thus bone formation, we studied different bisphosphonate concentrations combined with allograft bone. We investigated whether locally applied alendronate has an optimum dose with respect to bone resorption and formation. Further, we questioned whether the addition of demineralized bone matrix (DBM), would stimulate bone formation. Finally, we studied the effect of high levels of antibiotics on bone allograft healing, since mixing allograft bone with antibiotics might reduce the infection risk. METHODS: 25 goats received eight bone conduction chambers in the cortical bone of the proximal medial tibia. Five concentrations of alendronate (0, 0.5 mg/mL, 1 mg/mL, 2 mg/mL, and 10 mg/mL) were tested in combination with allograft bone and supplemented with cefazolin (200 mug/mL). Allograft not supplemented with alendronate and cefazolin served as control. In addition, allograft mixed with demineralized bone matrix, with and without alendronate, was tested. After 12 weeks, graft bone area and new bone area were determined with manual point counting. RESULTS: Graft resorption decreased significantly (p < 0.001) with increasing alendronate concentration. The area of new bone in the 1 mg/mL alendronate group was significantly (p = 0.002) higher when compared to the 10 mg/mL group. No differences could be observed between the group without alendronate, but with demineralized bone, and the control groups. CONCLUSIONS: A dose-response relationship for local application of alendronate has been shown in this study. Most new bone was present at 1 mg/mL alendronate. Local application of cefazolin had no effect on bone remodelling

Severity of oEsophageal Anastomotic Leak in patients after oesophagectomy:the SEAL score

Background Anastomotic leak (AL) is a common but severe complication after oesophagectomy. It is unknown how to determine the severity of AL objectively at diagnosis. Determining leak severity may guide treatment decisions and improve future research. This study aimed to identify leak-related prognostic factors for mortality, and to develop a Severity of oEsophageal Anastomotic Leak (SEAL) score. Methods This international, retrospective cohort study in 71 centres worldwide included patients with AL after oesophagectomy between 2011 and 2019. The primary endpoint was 90-day mortality. Leak-related prognostic factors were identified after adjusting for confounders and were included in multivariable logistic regression to develop the SEAL score. Four classes of leak severity (mild, moderate, severe, and critical) were defined based on the risk of 90-day mortality, and the score was validated internally. Results Some 1509 patients with AL were included and the 90-day mortality rate was 11.7 per cent. Twelve leak-related prognostic factors were included in the SEAL score. The score showed good calibration and discrimination (c-index 0.77, 95 per cent c.i. 0.73 to 0.81). Higher classes of leak severity graded by the SEAL score were associated with a significant increase in duration of ICU stay, healing time, Comprehensive Complication Index score, and Esophagectomy Complications Consensus Group classification. Conclusion The SEAL score grades leak severity into four classes by combining 12 leak-related predictors and can be used to the assess severity of AL after oesophagectomy.The Severity of oEsophageal Anastomotic Leak (SEAL) score was developed using data from the TENTACLE-Esophagus study, an international, multicentre retrospective cohort study including 1509 patients with anastomotic leak after oesophagectomy. The SEAL score was developed to determine anastomotic leak severity at diagnosis, and combines 12 leak-related parameters at diagnosis. The score may be useful in clinical practice and could improve future research.</p

Treatment of anastomotic leak after oesophagectomy for oesophageal cancer:large, collaborative, observational TENTACLE cohort study

Background: Anastomotic leak is a severe complication after oesophagectomy. Anastomotic leak has diverse clinical manifestations and the optimal treatment strategy is unknown. The aim of this study was to assess the efficacy of treatment strategies for different manifestations of anastomotic leak after oesophagectomy. Methods: A retrospective cohort study was performed in 71 centres worldwide and included patients with anastomotic leak after oesophagectomy (2011-2019). Different primary treatment strategies were compared for three different anastomotic leak manifestations: interventional versus supportive-only treatment for local manifestations (that is no intrathoracic collections; well perfused conduit); drainage and defect closure versus drainage only for intrathoracic manifestations; and oesophageal diversion versus continuity-preserving treatment for conduit ischaemia/necrosis. The primary outcome was 90-day mortality. Propensity score matching was performed to adjust for confounders. Results: Of 1508 patients with anastomotic leak, 28.2 per cent (425 patients) had local manifestations, 36.3 per cent (548 patients) had intrathoracic manifestations, 9.6 per cent (145 patients) had conduit ischaemia/necrosis, 17.5 per cent (264 patients) were allocated after multiple imputation, and 8.4 per cent (126 patients) were excluded. After propensity score matching, no statistically significant differences in 90-day mortality were found regarding interventional versus supportive-only treatment for local manifestations (risk difference 3.2 per cent, 95 per cent c.i. -1.8 to 8.2 per cent), drainage and defect closure versus drainage only for intrathoracic manifestations (risk difference 5.8 per cent, 95 per cent c.i. -1.2 to 12.8 per cent), and oesophageal diversion versus continuity-preserving treatment for conduit ischaemia/necrosis (risk difference 0.1 per cent, 95 per cent c.i. -21.4 to 1.6 per cent). In general, less morbidity was found after less extensive primary treatment strategies. Conclusion: Less extensive primary treatment of anastomotic leak was associated with less morbidity. A less extensive primary treatment approach may potentially be considered for anastomotic leak. Future studies are needed to confirm current findings and guide optimal treatment of anastomotic leak after oesophagectomy.</p

Stoma-free survival after anastomotic leak following rectal cancer resection: worldwide cohort of 2470 patients

Background: the optimal treatment of anastomotic leak after rectal cancer resection is unclear. this worldwide cohort study aimed to provide an overview of four treatment strategies applied. Methods: Patients from 216 centres and 45 countries with anastomotic leak after rectal cancer resection between 2014 and 2018 were included. treatment was categorized as salvage surgery, faecal diversion with passive or active (vacuum) drainage, and no primary/secondary faecal diversion. The primary outcome was 1-year stoma-free survival. In addition, passive and active drainage were compared using propensity score matching (2 : 1). results: Of 2470 evaluable patients, 388 (16.0 per cent) underwent salvage surgery, 1524 (62.0 per cent) passive drainage, 278 (11.0 per cent) active drainage, and 280 (11.0 per cent) had no faecal diversion. one-year stoma-free survival rates were 13.7, 48.3, 48.2, and 65.4 per cent respectively. propensity score matching resulted in 556 patients with passive and 278 with active drainage. there was no statistically significant difference between these groups in 1-year stoma-free survival (OR 0.95, 95 per cent c.i. 0.66 to 1.33), with a risk difference of -1.1 (95 per cent c.i. -9.0 to 7.0) per cent. after active drainage, more patients required secondary salvage surgery (OR 2.32, 1.49 to 3.59), prolonged hospital admission (an additional 6 (95 per cent c.i. 2 to 10) days), and ICU admission (OR 1.41, 1.02 to 1.94). Mean duration of leak healing did not differ significantly (an additional 12 (-28 to 52) days). Conclusion: Primary salvage surgery or omission of faecal diversion likely correspond to the most severe and least severe leaks respectively. In patients with diverted leaks, stoma-free survival did not differ statistically between passive and active drainage, although the increased risk of secondary salvage surgery and ICU admission suggests residual confounding

Intrathoracic vs Cervical Anastomosis After Totally or Hybrid Minimally Invasive Esophagectomy for Esophageal Cancer A Randomized Clinical Trial

Background: Transthoracic minimally invasive esophagectomy (MIE) is increasingly performed as part of curative multimodality treatment. There appears to be no robust evidence on the preferred location of the anastomosis after transthoracic MIE. Objective: To compare an intrathoracic with a cervical anastomosis in a randomized clinical trial. Design, Setting, and Participants: This open, multicenter randomized clinical superiority trial was performed at 9 Dutch high-volume hospitals. Patients with midesophageal to distal esophageal or gastroesophageal junction cancer planned for curative resection were included. Data collection occurred from April 2016 through February 2020. Intervention: Patients were randomly assigned (1:1) to transthoracic MIE with intrathoracic or cervical anastomosis. Main Outcomes and Measures: The primary end point was anastomotic leakage requiring endoscopic, radiologic, or surgical intervention. Secondary outcomes were overall anastomotic leak rate, other postoperative complications, length of stay, mortality, and quality of life. Results: Two hundred sixty-two patients were randomized, and 245 were eligible for analysis. Anastomotic leakage necessitating reintervention occurred in 15 of 122 patients with intrathoracic anastomosis (12.3%) and in 39 of 123 patients with cervical anastomosis (31.7%; risk difference, -19.4% [95% CI, -29.5% to -9.3%]). Overall anastomotic leak rate was 12.3% in the intrathoracic anastomosis group and 34.1% in the cervical anastomosis group (risk difference, -21.9% [95% CI, -32.1% to -11.6%]). Intensive care unit length of stay, mortality rates, and overall quality of life were comparable between groups, but intrathoracic anastomosis was associated with fewer severe complications (risk difference, -11.3% [-20.4% to -2.2%]), lower incidence of recurrent laryngeal nerve palsy (risk difference, -7.3% [95% CI, -12.1% to -2.5%]), and better quality of life in 3 subdomains (mean differences: dysphagia, -12.2 [95% CI, -19.6 to -4.7]; problems of choking when swallowing, -10.3 [95% CI, -16.4 to 4.2]; trouble with talking, -15.3 [95% CI, -22.9 to -7.7]). Conclusions and Relevance: In this randomized clinical trial, intrathoracic anastomosis resulted in better outcome for patients treated with transthoracic MIE for midesophageal to distal esophageal or gastroesophageal junction cancer. Trial Registration: Trialregister.nl Identifier: NL4183 (NTR4333)

Stoma-free Survival After Rectal Cancer Resection With Anastomotic Leakage: Development and Validation of a Prediction Model in a Large International Cohort

Objective: This study aimed to develop and validate a prediction model (STOMA-score) for one-year stoma-free survival in rectal cancer (RC) patients with anastomotic leakage (AL). Background: AL after RC resection often results in a permanent stoma. Methods: This international retrospective cohort study (TENTACLE-Rectum) encompassed 216 participating centres, and included patients who developed AL after RC surgery between 2014-2018. Clinically relevant predictors for one-year stoma-free survival were included in uni- and multivariable logistic regression models. The STOMA-score was developed and internally validated in a cohort of patients operated between 2014-2017, with subsequent temporal validation in a 2018 cohort. The discriminative power and calibration of the models' performance were evaluated. Results: This study included 2499 AL patients; 1954 in the development cohort and 545 in the validation cohort. Baseline characteristics were comparable. One-year stoma-free survival was 45.0% in the development cohort and 43.7% in the validation cohort. The following predictors were included in the STOMA-score: sex, age, ASA-classification, body mass index, clinical M-disease, neoadjuvant therapy, abdominal- and transanal approach, primary defunctioning stoma, multivisceral resection, clinical setting in which AL was diagnosed, postoperative day of AL diagnosis, abdominal contamination, anastomotic defect circumference, bowel wall ischemia, anastomotic fistula, retraction and reactivation leakage. The STOMA-score showed good discrimination and calibration (c-index 0.71, 95%CI 0.66-0.76). Conclusion: The STOMA-score consists of eighteen clinically relevant factors and estimates the individual risk for one-year stoma-free survival in patients with AL after RC surgery, which may improve patient counselling and give guidance when analyzing efficacy of different treatment strategies in future studies

Evaluation of subsidence, chondrocyte survival and graft incorporation following autologous osteochondral transplantation

Contains fulltext : 95878.pdf (publisher's version ) (Open Access)PURPOSE: The aim of this study was to evaluate subsidence tendency, surface congruency, chondrocyte survival and plug incorporation after osteochondral transplantation in an animal model. The potential benefit of precise seating of the transplanted osteochondral plug on the recipient subchondral host bone ('bottoming') on these parameters was assessed in particular. METHODS: In 18 goats, two osteochondral autografts were harvested from the trochlea of the ipsilateral knee joint and inserted press-fit in a standardized articular cartilage defect in the medial femoral condyle. In half of the goats, the transplanted plugs were matched exactly to the depth of the recipient hole (bottomed plugs; n = 9), whereas in the other half of the goats, a gap of 2 mm was left between the plugs and the recipient bottom (unbottomed plugs; n = 9). After 6 weeks, all transplants were evaluated on gross morphology, subsidence, histology, and chondrocyte vitality. RESULTS: The macroscopic morphology scored significantly higher for surface congruency in bottomed plugs as compared to unbottomed reconstructions (P = 0.04). However, no differences in histological subsidence scoring between bottomed and unbottomed plugs were found. The transplanted articular cartilage of both bottomed and unbottomed plugs was vital. Only at the edges some matrix destaining, chondrocyte death and cluster formation was observed. At the subchondral bone level, active remodeling occurred, whereas integration at the cartilaginous surface of the osteochondral plugs failed to occur. Subchondral cysts were found in both groups. CONCLUSIONS: In this animal model, subsidence tendency was significantly lower after 'bottomed' versus 'unbottomed' osteochondral transplants on gross appearance, whereas for histological scoring no significant differences were encountered. Since the clinical outcome may be negatively influenced by subsidence, the use of 'bottomed' grafts is recommended for osteochondral transplantation in patients