Phase II study of sodium valproate in combination with oral etoposide in platinum-resistant ovarian cancer.

Patients with platinum-resistant ovarian cancer (PROC) have limited therapeutic options and poor survival. There is a need for the development of newer therapies. Sodium valproic acid (VPA) is a short-chain fatty acid histone deacetylase (HDAC) inhibitor with antitumor activity in preclinical models of PROC. Synergism with conventional cytotoxic agents like etoposide has been demonstrated. In this prospective, single-arm, open-label, phase 2 study, we included patients ≥ 18 years with histologically or cytologically confirmed PROC and Eastern Cooperative Oncology Group performance status (ECOG-PS) 0-3. Patients received oral VPA 60 mg/kg/day in three divided doses for 3 days (D1-D3), followed by oral etoposide 50 mg once daily for two consecutive weeks (D4-D17). Serum samples were collected to assess peak VPA drug levels. The primary endpoint was the overall response rate (ORR). The secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicity. We sought to show an improvement in response rate from 25% (historically with oral etoposide) to 40% with the addition of VPA. 27 patients were enrolled in the study, and 18 [median age: 52 (45-59) years; serous histology:17 (94%); ECOG-PS 2 or 3: 14 (78%)] were evaluable for the response after 4 months. Nine patients were lost from follow-up before achieving the primary endpoint (mainly due to Covid-related lockdown issues). The median number of prior lines of treatment was 2 (1-3). ORR was 0% according to GCIG criteria. The disease was stable in two patients [clinical benefit rate (CBR) of 11%]. The median OS and PFS were 7 months and 2 months, respectively. Grade ≥ 3 adverse events were reported in 6 (33%) patients. The addition of valproic acid to oral etoposide in patients with PROC and poor general condition was not helpful and failed to improve responses compared to those historically achieved with single-agent etoposide. However, further phase 2 randomized controlled trials with larger sample size can be done to confirm the findings.

Economical gold recovery cycle from bio-sensing AuNPs: an application for nanowaste and COVID-19 testing kits.

We report the controlled growth of biologically active compounds: gold nanoparticles (AuNPs) in various shapes, including their green synthesis, characterization, and studies of their applications towards biological, degradation and recycling. Using spectroscopic methods, studies on responsive binding mechanisms of AuNPs with biopolymers herring sperm deoxyribonucleic acid (hsDNA), bovine serum albumin (BSA), dyes degradation study, and exquisitely gold separation studies/recovery from nanowaste, COVID-19 testing kits, and pregnancy testing kits are discussed. The sensing ability of the AuNPs with biopolymers was investigated via various analytical techniques. The rate of degradation of various dyes in the presence and absence of AuNPs was studied by deploying stirring, IR, solar, and UV-Vis methods. AuNPs were found to be the most active cytotoxic agent against human breast cancer cell lines such as MCF-7 and MDAMB-468. Furthermore, an economical process for the recovery of gold traces from nanowaste, COVID-19 detection kits, and pregnancy testing kits was developed using inexpensive and eco-friendly α-cyclodextrin sugar. This method was found to be easy and safest in comparison with the universally accepted cyanidation process. In the future, small gold jewelry makers and related industries would benefit from the proposed gold-recycling process and it might contribute to their socio-economic growth. The methodologies proposed are also beneficial for trace-level forensic investigation.

Could combustion-generated nanoparticles induce cytotoxicity also at the extremely low doses typical of indoor environments?

SUMMARY: The presence of nanoparticles in the environment is mainly attributed to outdoor sources but sub-10 nm particles may also form indoor as effect of domestic activities such as cooking, heating, air freshening. Today, due to the COVID-19 pandemic, people are staying home for longer periods of times, thus being exposed to a poor indoor air quality. Due to elevated numerical concentration and large surface area, the health effect of sub-10 nm particles can go beyond what expected from their low mass concentration in the atmosphere. The objective of this study is to find, based on analysis of recent in vitro studies, a dose-effect correlation based on particle size/surface more than on particle mass. Such a correlation cold be useful to assess the health effects of people exposed to very low mass doses of nanoparticles either indoor or outdoor.

Impaired Cytotoxic CD8+ T Cell Response in Elderly COVID-19 Patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection induces a T cell response that most likely contributes to virus control in COVID-19 patients but may also induce immunopathology. Until now, the cytotoxic T cell response has not been very well characterized in COVID-19 patients. Here, we analyzed the differentiation and cytotoxic profile of T cells in 30 cases of mild COVID-19 during acute infection. SARS-CoV-2 infection induced a cytotoxic response of CD8+ T cells, but not CD4+ T cells, characterized by the simultaneous production of granzyme A and B as well as perforin within different effector CD8+ T cell subsets. PD-1-expressing CD8+ T cells also produced cytotoxic molecules during acute infection, indicating that they were not functionally exhausted. However, in COVID-19 patients over the age of 80 years, the cytotoxic T cell potential was diminished, especially in effector memory and terminally differentiated effector CD8+ cells, showing that elderly patients have impaired cellular immunity against SARS-CoV-2. Our data provide valuable information about T cell responses in COVID-19 patients that may also have important implications for vaccine development.IMPORTANCE Cytotoxic T cells are responsible for the elimination of infected cells and are key players in the control of viruses. CD8+ T cells with an effector phenotype express cytotoxic molecules and are able to perform target cell killing. COVID-19 patients with a mild disease course were analyzed for the differentiation status and cytotoxic profile of CD8+ T cells. SARS-CoV-2 infection induced a vigorous cytotoxic CD8+ T cell response. However, this cytotoxic profile of T cells was not detected in COVID-19 patients over the age of 80 years. Thus, the absence of a cytotoxic response in elderly patients might be a possible reason for the more frequent severity of COVID-19 in this age group than in younger patients.

Regional outcomes of severe acute respiratory syndrome coronavirus 2 infection in hospitalised patients with haematological malignancy.

OBJECTIVES: We sought to characterise the outcomes of patients with haematological malignancy and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in hospital in our regional network of 7 hospitals. METHODS: Consecutive hospitalised patients with haematological malignancy and SARS-CoV-2 infection were identified from 01/03/2020 to 06/05/2020. Outcomes were categorised as death, resolved or ongoing. The primary outcome was preliminary case fatality rate (pCFR), defined as the number of cases resulting in death as a proportion of all diagnosed cases. Analysis was primarily descriptive. RESULTS: 66 Patients were included, overall pCFR was 51.5%. Patients ≥ 70 years accounted for the majority of hospitalised cases (42, 63%) and fatalities (25, 74%). Mortality was similar between females (52%) and males (51%). Immunosuppressive or cytotoxic treatment within 3 months of the diagnosis of SARS-CoV-2 infection was associated with a significantly higher pCFR of 70%, compared with 28% in those not on active treatment (P = .0013, 2 proportions z test). CONCLUSIONS: Mortality rates in patients with haematological malignancy and SARS-CoV-2 infection in hospital are high supporting measures to minimise the risk of infection in this population.