Auranofin Induces Lethality Driven by Reactive Oxygen Species in High-Grade Serous Ovarian Cancer Cells.

High-grade serous ovarian cancer (HGSOC) accounts for 70% of ovarian cancer cases, and the survival rate remains remarkably low due to the lack of effective long-term consolidation therapies. Clinical remission can be temporarily induced by platinum-based chemotherapy, but death subsequently results from the extensive growth of a platinum-resistant component of the tumor. This work explores a novel treatment against HGSOC using the gold complex auranofin (AF). AF primarily functions as a pro-oxidant by inhibiting thioredoxin reductase (TrxR), an antioxidant enzyme overexpressed in ovarian cancer. We investigated the effect of AF on TrxR activity and the various mechanisms of cytotoxicity using HGSOC cells that are clinically sensitive or resistant to platinum. In addition, we studied the interaction between AF and another pro-oxidant, L-buthionine sulfoximine (L-BSO), an anti-glutathione (GSH) compound. We demonstrated that AF potently inhibited TrxR activity and reduced the vitality and viability of HGSOC cells regardless of their sensitivities to platinum. We showed that AF induces the accumulation of reactive oxygen species (ROS), triggers the depolarization of the mitochondrial membrane, and kills HGSOC cells by inducing apoptosis. Notably, AF-induced cell death was abrogated by the ROS-scavenger N-acetyl cysteine (NAC). In addition, the lethality of AF was associated with the activation of caspases-3/7 and the generation of DNA damage, effects that were also prevented by the presence of NAC. Finally, when AF and L-BSO were combined, we observed synergistic lethality against HGSOC cells, which was mediated by a further increase in ROS and a decrease in the levels of the antioxidant GSH. In summary, our results support the concept that AF can be used alone or in combination with L-BSO to kill HGSOC cells regardless of their sensitivity to platinum, suggesting that the depletion of antioxidants is an efficient strategy to mitigate the course of this disease.

Home hemodialysis technique survival: insights and challenges.

Home hemodialysis (HHD) offers several clinical, quality of life and cost-saving benefits for patients with end-stage kidney disease. While uptake of this modality has increased in recent years, its prevalence remains low and high rates of discontinuation remain a challenge. This comprehensive narrative review aims to better understand what is currently known about technique survival in HHD patients, elucidate the clinical factors that contribute to attrition and expand on possible strategies to prevent discontinuation. With increasing efforts to encourage home modalities, it is imperative to better understand technique survival and find strategies to help maintain patients on the home therapy of their choosing. It is crucial to better target high-risk patients, examine ideal training practices and identify practices that are potentially modifiable to improve technique survival.

Impact of the abandonment of assistive technologies for mobility on the incidence of serious falls in older adults living at home: Results of the ECOCAT study.

Purpose: To examine the impact of discontinuing the use of assistive technology for mobility (ATM) devices on the 6-months incidence of falls in older adults (OA) living at home. Materials and methods: A medico-socioeconomic survey was performed to collect information on the quality of life and well-being of older adults, before and 6 months after being loaned an ATM device. Personal data (medical, social, and economic) were collected via a geriatric survey. Results: In all, 102 OA participated in the study. Over the 6-months observation period, 17 (n = 81) serious falls were recorded among participants who were using their ATM device optimally; in those who discontinued device use, 12 falls (n = 21) were recorded (57.1%; p = 0.001). Factors significantly associated with falls at home were living in an urban area (odds ratio [OR]: 11.46; 95% confidence interval [CI]: 1.48; 88.98; p = 0.020), an Instrumental Activities of Daily Living Scale score > 4 (OR: 34.04; 95% CI: 1.59; 727.86; p = 0.024), and discontinuation of ATM device use (OR: 17.41; 95% CI: 2.59; 117.02; p = 0.003). Conclusion: Discontinuation of ATM device use was associated with an increased risk for serious falls.

The Spectrum of Clinical Characteristics and Complications of Tetanus: A Retrospective Cross-Sectional Study From a Developing Nation.

Introduction While tetanus has largely been eradicated with the advent of the tetanus vaccine, its prevalence in Pakistan remains alarmingly high due to insufficient uptake of the vaccination program. The clinical presentations that the disease elicits range from mere opisthotonos to more sinister complications, including respiratory failure and death, often posing an insurmountable challenge for hospitals. Methods A retrospective cross-sectional study was conducted and analyzed the medical charts of 43 patients with a confirmed diagnosis of tetanus infection. The charts were perused for the patients' demographics, clinical characteristics, and disease outcomes. The prevalence of various clinical symptoms and complications were reported in terms of frequencies and percentages. Results The mean age of the patients hovered at 29.53 ± 16.53 years, with a range of 12 to 65 years. Of those affected, 83.7% were males while 16.3% were females. Notably, none of the infected patients had a prior history of vaccination against tetanus. Trismus was noted to be the most prevalent clinical manifestation and was found in 90.70% of the patients while paraesthesia at the site of infection, found in 6.98%, was the least prevalent. The overall mortality was noted to hover at 46.5%. Conclusion While tetanus has largely been eradicated, its prevalence in Pakistan remains alarmingly high. The complications noted in the study have implications for the country's public health system and aims to better inform the current state of the national vaccination program.

Evaluation of a home-based 7-day infection control strategy for healthcare workers following high-risk exposure to severe acute respiratory coronavirus virus 2 (SARS-CoV-2): A cohort study.

OBJECTIVE: Evidence-based infection control strategies are needed for healthcare workers (HCWs) following high-risk exposure to severe acute respiratory coronavirus virus 2 (SARS-CoV-2). In this study, we evaluated the negative predictive value (NPV) of a home-based 7-day infection control strategy. METHODS: HCWs advised by their infection control or occupational health officer to self-isolate due to a high-risk SARS-CoV-2 exposure were enrolled between May and October 2020. The strategy consisted of symptom-triggered nasopharyngeal SARS-CoV-2 RNA testing from day 0 to day 7 after exposure and standardized home-based nasopharyngeal swab and saliva testing on day 7. The NPV of this strategy was calculated for (1) clinical coronavirus disease 2019 (COVID-19) diagnosis from day 8-14 after exposure, and for (2) asymptomatic SARS-CoV-2 detected by standardized nasopharyngeal swab and saliva specimens collected at days 9, 10, and 14 after exposure. Interim results are reported in the context of a second wave threatening this essential workforce. RESULTS: Among 30 HCWs enrolled, the mean age was 31 years (SD, ±9), and 24 (80%) were female. Moreover, 3 were diagnosed with COVID-19 by day 14 after exposure (secondary attack rate, 10.0%), and all cases were detected using the 7-day infection control strategy: the NPV for subsequent clinical COVID-19 or asymptomatic SARS-CoV-2 detection by day 14 was 100.0% (95% CI, 93.1%-100.0%). CONCLUSIONS: Among HCWs with high-risk exposure to SARS-CoV-2, a home-based 7-day infection control strategy may have a high NPV for subsequent COVID-19 and asymptomatic SARS-CoV-2 detection. Ongoing data collection and data sharing are needed to improve the precision of the estimated NPV, and here we report interim results to inform infection control strategies in light of a second wave threatening this essential workforce.

Coronavirus Disease 2019 Presenting as Abdominal Distension in a Mesothelioma Patient: Do We Need to Think Outside the Box?

The coronavirus disease 2019 (COVID-19) remains a major source of mortality globally. Although it usually presents with flu-like symptoms such as fever and sore throat, the intensity of the symptoms varies, constituting a spectrum ranging from asymptomatic to severe cases of acute respiratory failure. The highest proportion of severe cases occurs in older individuals and in those who have underlying health conditions and chronic comorbidities. We chronicle an atypical case of a 46-year-old male with stage IV mesothelioma who presented exclusively with complaints of acute abdominal pain and distension. Despite his cancer status, the patient's respiratory functions remained unremarkable, accentuating the peculiarity of the case.