Proteases and their inhibitors as prognostic factors for high-grade serous ovarian cancer

Ovarian carcinoma is one of the most lethal malignancies, but only very few prognostic biomarkers are known. The degradome, comprising proteases, protease non-proteolytic homologues and inhibitors, have been involved in the prognosis of many cancer types, including ovarian carcinoma. The prognostic significance of the whole degradome family has not been specifically studied in high-grade serous ovarian cancer. A targeted DNA microarray known as the CLIP-CHIP microarray was used to identify potential prognostic factors in ten high-grade serous ovarian cancer women who had early recurrence (<1.6 years) or late/no recurrence after first line surgery and chemotherapy. In women with early recurrence, we identified seven upregulated genes (TMPRSS4, MASP1/3, SPC18, PSMB1, IGFBP2, CFI – encoding Complement Factor I – and MMP9) and one down-regulated gene (ADAM-10). Using immunohistochemistry, we evaluated the prognostic effect of these 8 candidate genes in an independent cohort of 112 high-grade serous ovarian cancer women. Outcomes were progression, defined according to CA-125 criteria, and death. Multivariate Cox proportional hazard regression models were done to estimate the associations between each protein and each outcome. High ADAM-10 expression (intensity of 2–3) was associated with a lower risk of progression (adjusted hazard ratio (HR): 0.51; 95% confidence interval (CI): 0.29-0.87). High complement factor I expression (intensity 2–3) was associated with a higher risk of progression (adjusted HR: 2.30, 95% CI: 1.17–4.53) and death (adjusted HR: 3.42; 95% CI: 1.72–6.79). Overall, we identified the prognostic value of two proteases, ADAM-10 and complement factor I, for high-grade serous ovarian cancer which could have clinical significance.     

Medical waste management and environmental assessment in the Rio University Hospital,Western Greece

At this study a multi-criteria model was developed to examine the available procedures, techniques and methods of handling infectious waste in the large healthcare unit of University Regional General Hospital of Patras, Western Greece. Particularly, this study examined the: a) current legislation and Directives issued for medical waste management at Greece and among the other EU-members, b) contribution of healthcare wastes (HCW) generation rate on social and economic parameters in selected European countries, c) available procedures, techniques, and methods upon the disposal of infectious wastes at the healthcare studied, and, d) propositions for integrated management of such hazardous wastes. Specifically, the Analytic Hierarchy Process (AHP) methodology was applied under pair wise comparison matrices in two stages: 1) the scale factors and the indicators, and 2) the criteria and their sub–criteria. The assessment of these pair wise matrices included the indicators and the sub–criteria. Subsequently, two pair wise comparison matrices, upon a) the “Fulfillment of environmental objectives” indicator and b) the “Energy consumption” sub criterion, were denoted. The AHP methodology yielded good results; however there is still space of improving the environmental performance. The normalized relative weights obtained for the criteria and sub criteria motivated specific actions that have to be handled. Particularly, the results indicated a very good value in environmental management criteria due the values obtained for the commitment towards the environmental policy standards and the waste management procedures. However, further improvements on staff awareness (such as development programs to enhance sensitivity) and more green purchasing suppliers, should be further addressed.     

Influence of luminal stenosis in aneurysmal and non-aneurysmal blunt cerebrovascular injury

Background

Current blunt cerebrovascular injury (BCVI) grading grossly differentiates injury characteristics such as luminal stenosis (LS) and aneurysmal disease. The effect of increasing degree of LS beyond the current BCVI grading scale on stroke formation is unknown.

Improvements in epidermal function prevent relapse of psoriasis: a self‐controlled study

While therapeutic approaches for psoriasis are widely available, preventive regimens are lacking. We aimed to determine whether improvements in epidermal function could prevent psoriasis relapse. Two self‐controlled cohort studies were designed, enrolling two cohorts of patients with psoriasis (n = 30 and n = 60) to be treated topically with an in‐house‐prepared emollient or ATOPALM^® cream applied twice daily to one forearm for 20 and 30 days, respectively, while the same sites on the contralateral arm served as the untreated control. Epidermal function on both arms was assessed prior to and at the end of the trials. Delayed relapse on the treated arm was seen in 54.5% and 71% of patients in the first and second cohort, respectively. The time of psoriatic relapse correlated with the extent of abnormalities in baseline epidermal function. These results suggest that improvements in epidermal function with topical emollients can prevent/attenuate the development of psoriasis.     

The efficacy and toxicity of immune checkpoint inhibitors in a real-world older patient population

ImportanceImmunotherapy has emerged as an effective treatment option for the management of advanced cancers. The effects of these immune checkpoint inhibitors in the older patient population has not been adequately assessed.ObjectiveTo understand the impact of aging on CTLA-4 and PDL-1 inhibitors efficacy and immune-related adverse events (irAE) in the context of real-world management of advanced solid cancers.Design, Setting, and ParticipantsThis retrospective study involved all non-study patients with histologically-confirmed metastatic or inoperable solid cancers receiving immunotherapy at Kingston Health Sciences Centre. We defined ‘older patient’ as age ≥ 75. All statistical analyses were conducted under SPSS IBM for Windows version 24.0.Main Outcomes and MeasuresStudy outcomes included immunotherapy treatment response, survival, as well as number, type, and severity of irAEs.ResultsOur study (N = 78) had 29 (37%) patients age <65, 26 (33%) patients age 65–74, and 23 (30%) patients age ≥75. Melanoma, non-small cell lung cancer, and renal cell carcinoma accounted for 70%, 22%, and 8% of the study population, respectively. Distributions of ipilimumab (32%), nivolumab (33%), and pembrolizumab (35%) were similar in the study. The response rates were 28%, 27%, and 39% in the age <65, age 64–74, age ≥75 groups, respectively (P = 0.585). Kaplan-Meier curve showed a median survival of 28 months (12.28–43.9, 95% CI) and 17 months (0–36.9, 95% CI) in the age <65 and age 64–74 groups, respectively; the estimated survival probability did not reach 50% in the age ≥75 group (P = 0.319). There were no statistically significant differences found in terms of irAEs, multiple irAEs, severity of grade 3 or higher, types of irAEs, and irAEs resolution status when comparing between different age groups.Conclusion and RelevanceOur results suggest that patients age ≥75 are able to gain as much benefit from immunotherapy as younger patients, without excess toxicity. Our findings suggest that single agent immunotherapy is generally well-tolerated across different age groups with no significant difference in the type, frequency or severity of irAEs. Future studies evaluating aging and combination immunotherapy are warranted.     

Generalisierter Krampfanfall während der Anlage einer axillären Plexusblockade

Die Anaesthesiologie - Eine junge Patientin erleidet während der Anlage einer axillären Plexusblockade einen generalisierten Krampfanfall. Die Mechanismen, im Wesentlichen die vermutlich...