Mechanism-based therapeutic targets of pemphigus vulgaris: A scoping review of pathogenic molecular pathways.

Pemphigus vulgaris (PV) is a potentially fatal autoimmune blistering disease characterised by cell-cell detachment or acantholysis. The mechanisms which follow antibody (Ab) binding and culminate in acantholytic changes and skin/mucosal blistering have not been fully clarified. Current treatment strategies are not specific to PV pathophysiology and although life-saving, harbour considerable side effects. We aimed to systematically assess the molecules amenable to targeted treatments that follow Ab binding and are associated with PV acantholysis. The resulting scoping review was conducted under PRISMA-ScR guidelines with clear inclusion and exclusion criteria and focused specifically on kinases, caspases, proteases, hydrolytic enzymes and other molecules of interest postulated to take part in the pathophysiology of PV. The review process resulted in the identification of 882 articles, of which 56 were eligible for qualitative synthesis. From the included articles, the majority (n = 42) used PV-IgG as the pathogenic agent, mainly via in vitro (n = 16) and in vivo (n = 10) models. Twenty-five molecules were found to play a pathogenic role in PV, including uPA, ADAM10, EGFR, Src, PKC, cdk2, ERK, PLC, calmodulin, NOS, p38MAPK and caspase-3. Selective inhibition of these molecules resulted in varying degrees of reduction in acantholysis and blistering. The pathogenic molecules identified in this review represent potential candidates for clinical translation.

Neutrophil to lymphocyte ratio is an independent predictor of outcome for patients undergoing definitive resection for stage IV melanoma.

BACKGROUND AND OBJECTIVES: The aim of this study was to perform a retrospective analysis of survival rates and determine prognostic indicators for patients who underwent definitive surgical resection of stage IV melanoma. METHODS: Patients included were those who underwent complete resection of metastatic melanoma. Data was analyzed using IBM SPSS 2.0. Survival estimates were derived from Kaplan-Meier, log-rank, and Breslow tests. RESULTS: The study population (n = 95) consisted of 60 males and 35 females. Median overall survival (OS) from the first metastasectomy was 49 months (95% confidence interval, 31-67 months). OS at 1, 2, and 5 years was 92%, 87%, and 50% respectively. Predictors of survival included clear surgical margins compared to patients with positive margins (median OS 53 vs 20 months, P = .026). A preoperative neutrophil to lymphocyte ratio less than 5 experienced a median OS of 65 months compared to 15 months ( P = .006; multivariable analysis for OS: hazard ratio 3.590, P = .009). CONCLUSION: This study's results are consistent with previous findings demonstrating favourable long-term outcomes following selective resection of metastatic melanoma. In addition to achieving clear surgical margins, a low preoperative neutrophil to lymphocyte ratio was associated with improved outcomes. These factors may help identify surgical candidates.

Comparative clinical outcomes between stock vs custom temporomandibular total joint replacement systems.

With the evolution of temporomandibular (TMJ) prosthetic total joint replacement, there has been much debate around the advantages of custom over stock prostheses. The aim of this study is to compare the clinical outcomes of a TMJ stock prosthesis (Zimmer-Biomet) to a custom prosthesis (OMX). Clinical data from 139 prosthetic joints placed in 117 patients was retrospectively collected and analysed. All patients were diagnosed with end-stage joint osteoarthritis and were treated by a single surgeon. Minimum follow up was 2 years post-surgery. The cohort was divided into 2 groups, 60 stock prosthetic joints in 54 patients and 79 custom prosthetic joints in 63 patients. This comprised of 110 males and 7 females. The average age at the time of surgery was 53.4yr ± 12.7yr. There was no statistical difference in pre-operative MIO and pain scores between the two groups. Post-operatively, patients fitted with a custom prosthesis showed statistically significant (P = 0.013) improvement in Maximum Interincisal Opening (MIO) (+6.33 mm vs +2.53 mm) and fewer complications. Following surgery, no difference noted in pain scores and patient satisfaction between the two groups. In experienced hands, both stock and custom TMJ implants work well. However, the added advantages of custom prostheses together with growing access to digital technology is likely to result in custom devices dominating the market in TMJ total joint replacement systems.

Biomet stock temporomandibular joint prosthesis: Long-term outcomes of the use of titanium condyles secured with four or five condylar fixation screws.

PURPOSE: The aim of this study was to determine the long-term outcomes following TMJ replacement using the stock Zimmer-Biomet TMJ device. In particular, investigated whether the titanium condylar implant and number of screws used to fixate it to the mandibular ramus had any impact on outcomes. METHODS: Subjects who underwent surgical implantation of a stock Zimmer-Biomet TMJ prosthesis were identified for this retrospective study. All patients received a titanium condylar component secured with four or five screws and ultra-high molecular weight polyethylene (UHMWPE) fossa with no metal reinforcement. Pre- and postoperative pain scores (VAS) and maximum interincisal opening (MIO) data were collected. Additional data included patient demographics, as well as operative, postoperative and follow-up details. Data were analysed with IBM SPSS 2.0 through the use of paired t-tests, and ANOVA and ANCOVA analysis. RESULTS: 190 subjects were identified. Following exclusions, the remaining study population (n = 60) consisted of 58 females and two males with a mean age of 53.5 years at time of surgery. Preoperative VAS and MIO values were 6.08 (SD = 2.24) and 31.88 mm (SD = 7.38 mm), respectively. 90% of the cohort required four screws to fix the prosthetic condylar component in place. After a median follow up of 5.2 years (95% CI: 4.73-5.62 years), with a range of 2-9 years, the VAS was 0.91 (SD = 1.89; p < 0.001) and the MIO was 34.8 mm (SD = X; p = 0.015). Only one device failed over the 9-year study period. CONCLUSION: The results of this study demonstrate good VAS and MIO outcomes following the implantation of a stock Zimmer-Biomet TMJ device. Additionally, good long-term outcomes were obtained with a titanium condylar component, fixed to the mandibular ramus with only four or five screws, and a UHMWPE fossa with no metal reinforcement.