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Administration of Human MSC-Derived Extracellular Vesicles for the Treatment of Primary Sclerosing Cholangitis: Preclinical Data in MDR2 Knockout Mice.
No full textPrimary Sclerosing Cholangitis (PSC) is a progressive liver disease for which there is no effective medical therapy. PSC belongs to the family of immune-mediated biliary disorders and it is characterized by persistent biliary inflammation and fibrosis. Here, we explored the possibility of using extracellular vesicles (EVs) derived from human, bone marrow mesenchymal stromal cells (MSCs) to target liver inflammation and reduce fibrosis in a mouse model of PSC. Five-week-old male FVB.129P2-Abcb mice were intraperitoneally injected with either 100 µL of EVs (± 9.1 × 10 particles/mL) or PBS, once a week, for three consecutive weeks. One week after the last injection, mice were sacrificed and liver and blood collected for flow cytometry analysis and transaminase quantification. In FVB.129P2-Abcb4 mice, EV administration resulted in reduced serum levels of alkaline phosphatase (ALP), bile acid (BA), and alanine aminotransferase (ALT), as well as in decreased liver fibrosis. Mechanistically, we observed that EVs reduce liver accumulation of both granulocytes and T cells and dampen VCAM-1 expression. Further analysis revealed that the therapeutic effect of EVs is accompanied by the inhibition of NFkB activation in proximity of the portal triad. Our pre-clinical experiments suggest that EVs isolated from MSCs may represent an effective therapeutic strategy to treat patients suffering from PSC
Wide-awake local anaesthesia no tourniquet (WALANT) vs regional or general anaesthesia for flexor tendon repair in adults: protocol for a systematic review and meta-analysis.
No full textBACKGROUND
Flexor tendon injuries most commonly occur following a penetrating injury to the hand or wrist. These are challenging injuries and the standard treatment is surgical repair under general or regional anaesthesia. 'Wide-awake' surgery is an emerging technique in hand surgery where a conscious patient is operated on under local anaesthetic. The vasoconstrictive effect of adrenaline (epinephrine) creates a 'bloodless' operating field and a tourniquet is not required. The potential advantages include intra-operative testing of the repair; removal of the risks of general anaesthesia; reduced costs; no aerosol generation from intubation therefore reduced risk of COVID-19 spread to healthcare professionals. The aim of this study will be to systematically evaluate the evidence to determine if wide-awake surgery is superior to general/regional anaesthetic in adults who undergo flexor tendon repair.
METHODS
We designed and registered a study protocol for a systematic review and meta-analysis of comparative and non-comparative studies. The primary outcome will be functional active range of motion. Secondary outcomes will be complications, resource use (operative time) and patient-reported outcome measures. A comprehensive literature search will be conducted (from 1946 to present) in MEDLINE, EMBASE, CINAHL, and Cochrane Library. Grey literature will be identified through Open Grey, dissertation databases and clinical trials registers. All studies on wide-awake surgery for flexor tendon repair will be included. The comparator will be general or regional anaesthesia. No limitations will be imposed on peer review status or language of publication. Two investigators will independently screen all citations, full-text articles and abstract data. Potential conflicts will be resolved through discussion or referral to a third author when necessary. The study methodological quality (or bias) will be appraised using an appropriate tool. If feasible, we will conduct a random effects meta-analysis.
DISCUSSION
This systematic review will summarise the best available evidence and definitively establish if function, complications, cost, or patient-reported outcomes are improved when flexor tendons are repaired using wide-awake technique. It will determine if this novel approach is superior to general or regional anaesthesia. This knowledge will help guide hand surgeons by continuing to improve outcomes from flexor tendon injuries.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42020182196
Identification of Common Themes from Never Events Data Published by NHS England.
No full textBACKGROUND
Never events (NEs) are serious clinical incidents that cause potentially avoidable harm and impose a significant financial burden on healthcare systems. The purpose of this study was to identify common never events.
METHODS
We analysed the NHS England NE data from 2012 to 2020 to identify common never events category and themes.
RESULTS
We identified 51 common NE themes in 4 main categories out of a total of 3247 NE reported during this period. Wrong-site surgery was the most common category (n = 1307;40.25%) followed by retained foreign objects (n = 901;27.75%); wrong implant or prosthesis (n = 425;13.09%); and non-surgical/infrequent ones (n = 614; 18.9%). Wrong-side (laterality) and wrong tooth removal were the most common wrong-site NE accounting for 300 (22.95%) and 263 (20.12%) incidents, respectively. There were 197 (15%) wrong-site blocks, 125 (9.56%) wrong procedures, and 96 (7.3%) wrong skin lesions excised. Vaginal swabs were the most commonly retained items (276;30.63%) followed by surgical swabs (164;18.20%) and guidewires (152;16.87%). There were 67 (7.44%) incidents of retained parts of instruments and 48 (5.33%) retained instruments. Wrong intraocular lenses (165; 38.82%) were the most common wrong implants followed by wrong hip prostheses (n = 94; 22.11%) and wrong knees (n = 91; 21.41%). Non-surgical events accounted for 18.9% (n = 614) of the total incidents. Misplaced naso-or oro-gastric tubes (n = 178;29%) and wrong-route administration of medications were the most common events in this category (n = 111;18%), followed by unintentional connection of a patient requiring oxygen to an air flow-meter (n = 93; 15%).
CONCLUSION
This paper identifies common NE categories and themes. Awareness of these might help reduce their incidence
Achieving 62-day targets in the management of skin cancer: Lessons learned and future directions for the post-COVID era.
No full text
Fenestrated or Branched Endovascular versus Open Repair for Complex Aortic Aneurysms: Meta-Analysis of Time to Event Propensity Score Matched Data.
No full textOBJECTIVE
The aim of this review was to investigate comparative outcomes of fenestrated or branched endovascular aneurysm repair (F/BEVAR) with open repair for juxta/para/suprarenal or thoraco-abdominal aortic aneurysms.
METHODS
Electronic bibliographic sources (MEDLINE and Embase) were interrogated using the Healthcare Databases Advanced Search interface. Eligible studies compared F/BEVAR with open repair for complex aortic aneurysms using propensity score or Cox regression modelling/multivariable logistic regression analysis. Pooled estimates of peri-operative outcomes were calculated using the odds ratio (OR) and 95% confidence interval (CI). The result of time to event analysis was reported as summary hazard ratio (HR) and 95% CI. Random effects models and the inverse variance method were applied. The quality of evidence was graded using the system developed by the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) working group.
RESULTS
Eleven studies published between 2014 and 2019 were selected for inclusion in qualitative and quantitative synthesis reporting a total of at least 7 061 patients. The odds of peri-operative mortality after F/BEVAR were lower, although not significantly, than after open repair (OR 0.56, 95% CI 0.28-1.12), whereas the hazard of overall mortality during follow up was higher following F/BEVAR, but, again, without reaching statistical significance (HR 1.25, 95% CI 0.93-1.67). The hazard of re-intervention was significantly higher after endovascular therapy (HR 2.11, 95% CI 1.39-3.18). The certainty for the body of evidence for peri-operative and overall mortality during follow up was judged to be very low and moderate, respectively, and for re-intervention it was judged to be high.
CONCLUSION
The evidence is uncertain about the effect of F/BEVAR on peri-operative mortality when compared with open repair. There is probably no difference in overall survival, but F/BEVAR results in an increased re-intervention hazard. There is a need for high level evidence to inform decision making and vascular/aortic service provision
Efficacy of Gemcitabine-based Chemotherapy in Clear Cell Sarcoma of Soft Tissue.
No full textBACKGROUND/AIM
Clear cell sarcoma (CCS) is an aggressive sarcoma subtype, resistant to conventional anthracycline-based chemotherapy and radiation. The diagnosis is often challenging due to similarities with malignant melanoma.
PATIENTS AND METHODS
We aimed to analyse the activity of gemcitabine-based chemotherapy in a cohort of patients with CCS treated at the Royal Marsden Hospital.
RESULTS
Five patients with metastatic CCS received gemcitabine as first- or second-line systemic therapy. The median time-to-progression was 10 weeks. The median number of cycles of gemcitabine-based therapy was 3 (range=2-7 cycles). Median overall survival in our cohort was 66 months from the initial diagnosis but in the metastatic setting, the overall survival was reduced to 28 months.
CONCLUSION
Gemcitabine-based therapy has modest activity in CCS. There remains a significant unmet medical need for novel, effective therapies for this disease
Low Preoperative Serum Albumin Levels Are Associated With Impaired Outcome After Cytoreductive Surgery and Perioperative Intraperitoneal Chemotherapy for Peritoneal Surface Malignancies.
No full textPreoperative hypoalbuminemia is known to be associated with postoperative morbidity and mortality, as well as with poor survival after gastrointestinal cancer surgery. However, limited data exist regarding the prognostic significance of hypoalbuminemia in patients with peritoneal metastases undergoing cytoreductive surgery, combined with perioperative intraperitoneal chemotherapy. We performed a systematic literature review of the previously published studies addressing the potential association between preoperative albumin levels and overall surgical outcomes after the performance of cytoreductive surgery and perioperative intraperitoneal chemotherapy for peritoneal surface malignancies. Our research yielded a total of nine retrospective studies which met our inclusion criteria, and despite their heterogeneity; and we can conclude that preoperatively low albumin levels are associated with greater likelihood of overall and major morbidity, as well as less favorable oncological outcome after the performance of cytoreductive surgery and perioperative intraperitoneal chemotherapy