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Background: Opioid use disorder and its consequences are a persistent public health concern for Australians. Web activity has been used to understand the perception of drug safety and diversion of drugs in contexts outside of Australia. The anonymity of the internet offers several advantages for surveilling and inquiring about specific covert behaviors, such as diversion or discussion of sensitive subjects where traditional surveillance approaches might be limited., Objective: This study aims to characterize the content of web posts and compare reports of illicit sales of tapentadol and oxycodone from sources originating in Australia. First, post content is evaluated to determine whether internet discussion encourages or discourages proper therapeutic use of the drugs. Second, we hypothesize that tapentadol would have lower street price and fewer illicit sales than oxycodone., Methods: Web posts originating in Australia between 2017 and 2019 were collected using the Researched Abuse, Diversion, and Addiction-Related Surveillance System Web Monitoring Program. Using a manual coding process, unstructured post content from social media, blogs, and forums was categorized into topics of discussion related to the harms and behaviors that could lead to harm. Illicit sales data in a structured format were collected through a crowdsourcing website between 2016 and 2019 using the Researched Abuse, Diversion, and Addiction-Related Surveillance System StreetRx Program. In total, 2 multivariable regression models assessed the differences in illicit price and number of sales., Results: A total of 4.7% (28/600) of tapentadol posts discussed an adverse event, whereas 10.27% (95% CI 9.32-11.21) of oxycodone posts discussed this topic. A total of 10% (60/600) of tapentadol posts discussed unsafe use or side effects, whereas 20.17% (95% CI 18.92-21.41) of oxycodone posts discussed unsafe use or side effects. There were 31 illicit sales reports for tapentadol (geometric mean price per milligram: Aus $0.12 [US $0.09]) and 756 illicit sales reports for oxycodone (Aus $1.28 [US $0.91]). Models detected no differences in the street price or number of sales between the drugs when covariates were included, although the potency of the pill significantly predicted the street price (P<.001) and availability predicted the number of sales (P=.03)., Conclusions: Australians searching the web for opinions could judge tapentadol as safer than oxycodone because of the web post content. The illicit sales market for tapentadol was smaller than that of oxycodone, and drug potency and licit availability are likely important factors influencing the illicit market., (©Joshua Black, Zachary R Margolin, Gabrielle Bau, Richard Olson, Janetta L Iwanicki, Richard C Dart. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 20.12.2021.)

Background: Dendritic cells (DCs) are usually immunogenic, but they are also capable of inducing tolerance under anti-inflammatory conditions. Immunotherapy based on autologous DCs loaded with an allogeneic melanoma cell lysate (TRIMEL/DCs) induces immunological responses and increases melanoma patient survival. Glucocorticoids can suppress DC maturation and function, leading to a DC-mediated inhibition of T cell responses., Methods: The effect of dexamethasone, a glucocorticoid extensively used in cancer therapies, on TRIMEL/DCs phenotype and immunogenicity was examined., Results: Dexamethasone induced a semi-mature phenotype on TRIMEL/DC with low maturation surface marker expressions, decreased pro-inflammatory cytokine induction (IL-1β and IL-12) and increased release of regulatory cytokines (IL-10 and TGF-β). Dexamethasone-treated TRIMEL/DCs inhibited allogeneic CD4 + T cell proliferation and cytokine release (IFNγ, TNF-α and IL-17). Co-culturing melanoma-specific memory tumor-infiltrating lymphocytes with dexamethasone-treated TRIMEL/DC inhibited proliferation and effector T cell activities, including cytokine secretion and anti-melanoma cytotoxicity., Conclusions: These findings suggest that dexamethasone repressed melanoma cell lysate-mediated DC maturation, generating a potent tolerogenic-like DC phenotype that inhibited melanoma-specific effector T cell activities. These results suggest that dexamethasone-induced immunosuppression may interfere with the clinical efficacy of DC-based melanoma vaccines, and must be taken into account for optimal design of cellular therapy against cancer., (Copyright © 2019. Published by Elsevier GmbH.)

Urinary tract infection (UTI) is one of the most common bacterial infections with frequent recurrence being a major medical challenge. Development of effective therapies has been impeded by the lack of knowledge of events leading to adaptive immunity. Here, we establish conclusive evidence that an adaptive immune response is generated during UTI, yet this response does not establish sterilizing immunity. To investigate the underlying deficiency, we delineated the naïve bladder immune cell compartment, identifying resident macrophages as the most populous immune cell. To evaluate their impact on the establishment of adaptive immune responses following infection, we measured bacterial clearance in mice depleted of either circulating monocytes, which give rise to macrophages, or bladder resident macrophages. Surprisingly, mice depleted of resident macrophages, prior to primary infection, exhibited a nearly 2-log reduction in bacterial burden following secondary challenge compared to untreated animals. This increased bacterial clearance, in the context of a challenge infection, was dependent on lymphocytes. Macrophages were the predominant antigen presenting cell to acquire bacteria post-infection and in their absence, bacterial uptake by dendritic cells was increased almost 2-fold. These data suggest that bacterial uptake by tissue macrophages impedes development of adaptive immune responses during UTI, revealing a novel target for enhancing host responses to bacterial infection of the bladder.

Background: The rupture of an aortic aneurysm is the most frequent and most severe complication, with an incidence of approximately 20-40/100,000 persons each year. The aim of this study was to identify the preoperative, intraoperative and postoperative factors that may influence the mortality rate., Methods: Between January 1996 and December 1999 145 patients underwent emergency abdominal aortic repair surgery. One hundred and twenty-three patients represented a ruptured AAA and 22 a fissured aneurysm. One hundred and thirty-one patients were males and 14 were females; their mean age was 75+/-5.06 years. We selected a number of parameters after a review of the international literature and these were analysed in the two classes of survivors. No statistical analyses were performed on fissured aneurysms owing to the scant number of cases examined., Results: Mortality was 41.4% (44.7% in ruptured aneurysms alone). The following were negative preoperative prognostic factors: old age, hypertension, ASA V, intraoperative anuria and platelet count <100,000. Intraoperative factors included: hypotension, cardiac arrest, onset of anuria, aortic clamping in more than one site, duration of surgery, quantity of RBC and plasma transfused. The main postoperative variables correlated to mortality were: hypotension, hypothermia, onset of anuria, need for further transfusions, high creatinine levels., Conclusions: Rapid intervention can minimise mortality in structures with expert teams of surgeons and anesthetists experienced in treating this type of pathology.

Penile metastases are extremely uncommon, with less than 300 reported cases. The primary sites of the responsible carcinoma have been bladder, rectum, prostate, kidney, testis, lung, nasopharynx and melanoma in that order. We report a case confirming the same data: no therapy has been shown to be helpful, the prognosis is very poor, with an average survival of less than one year. On the other hand we pointed out the importance of CT scan as a diagnostic tool for assessing the spread of neoplasm.