Ibuprofen, other NSAIDs and COVID-19: a narrative review.

At the start of the coronavirus disease 2019 (COVID-19) pandemic (March 2020), there was speculation that non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, used to manage some of the symptoms of COVID-19, could increase the susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and negatively impact clinical outcomes. In the absence of any robust mechanistic and clinical evidence, this speculation led to confusion about the safety of ibuprofen, contributing to the so-called 'infodemic' surrounding COVID-19. A wealth of evidence has been generated in subsequent years, and this narrative review aims to consider the body of in vitro and in vivo research, observational studies, systematic reviews and meta-analyses on the use of NSAIDs, including ibuprofen, in COVID-19. Overall, the direction of evidence supports that NSAIDs do not increase susceptibility to infection, nor worsen disease outcomes in patients with COVID-19. Neither do they impact the immune response to COVID-19 vaccines. There is no basis to limit the use of NSAIDs, and doing so may deprive patients of effective self-care measures to control symptoms.

Dual inhibition of MEK1/2 and AKT by binimetinib and MK2206 induces apoptosis of chronic lymphocytic leukemia cells under conditions that mimic the tumor microenvironment.

Several key pathways mediate signaling via the B-cell receptor, including the mitogen-activated protein kinase-ERK1/2 pathway. However, inhibition of MEK1/2, a key component of the MAPK-ERK1/2 signaling cascade, results in paradoxical activation of AKT in chronic lymphocytic leukemia (CLL) cells. In the current study we demonstrate synergy between the MEK1/2 inhibitor binimetinib and the AKT inhibitor MK2206, which combined induce apoptosis of primary CLL cells and restrict the cell cycle progression and proliferation of the OSU-CLL cell line. The mechanisms of action of the drug combination involve dual inhibition of MAPK-ERK1/2 and AKT signaling and down-regulation of Mcl-1 expression. Collectively, these data suggest that dual inhibition of MEK1/2 and AKT may represent a therapeutic option for CLL, capable of overcoming the pro-survival effects of the lymph node and bone marrow microenvironments.

Successful use of Bruton's kinase inhibitor, ibrutinib, to control paraneoplastic pemphigus in a patient with paraneoplastic autoimmune multiorgan syndrome and chronic lymphocytic leukaemia.

We present the case of a 51-year-old man who developed paraneoplastic pemphigus (PNP) in the context of chronic lymphocytic leukemia (CLL). His CLL was successfully controlled with ibrutinib. Concurrently, there was significant improvement of his PNP, suggesting that ibrutinib may be a very useful addition to the treatment options in this potentially life-threatening autoimmune disorder.

Sociodemographic factors and utilization of eye care services: is there an association with patients presenting to a tertiary referral hospital in acute angle-closure?

BACKGROUND: The aim of this study is to examine the relationship between sociodemographic factors and utilization of eye care services in patients presenting in acute angle-closure (AAC). DESIGN: A hospital-based retrospective, case-control study. PARTICIPANTS: Fifty-five patients consecutively presenting to the emergency department of the Royal Victorian Eye and Ear Hospital with AAC (cases), and 43 patients consecutively referred to the outpatient department for prophylactic laser peripheral iridotomy (controls) over a 3-year period. METHODS: Standardized telephone questionnaires. MAIN OUTCOME MEASURES: Comparisons were made for sociodemographic factors, utilization of eye care services and provision of information on glaucoma and premonitory symptoms of AAC. RESULTS: No significant differences across a range of socioeconomic and demographic factors were found. Fewer cases reported having attended an eye care professional ever (P = 0.02), or in the 12 months preceding their acute hospital attendance (P = 0.002), and had less awareness of angle closure glaucoma (P = 0.001). Logistic regression modelling demonstrated premonitory symptoms of AAC (odds ratio 3.96, [95% confidence interval 1.52-10.32], P < 0.001) and a period of greater than 12 months since the last eye examination (odds ratio 3.89, [95% confidence interval 1.64-9.21]) were significantly associated with the risk of AAC. CONCLUSIONS: No significant differences in socioeconomic or demographic parameters between cases and controls were identified. Control subjects had a history of more frequent and recent access to eye care services than cases. The finding that more than one-third of patients presenting with AAC had consulted an eye care provider in the preceding year suggests that a significant proportion of individuals at risk of AAC remain undetected.