COVID-19 and cytokine storm syndrome: can what we know about interleukin-6 in ovarian cancer be applied?

Improving early diagnosis along with timely and effective treatment of COVID-19 are urgently needed. However, at present, the mechanisms underlying disease spread and development, defined prognosis, and immune status of patients with COVID-19 remain to be determined. Patients with severe disease state exhibit a hyperinflammatory response associated with cytokine storm syndrome, hypercoagulability, and depressed cell-mediated immunity. These clinical manifestations, sharing similar pathogenesis, have been well-studied in patients with advanced ovarian cancer. The present review suggests treatment approaches for COVID-19 based on strategies used against ovarian cancer, which shares similar immunopathology and associated coagulation disorders. The chronicization of the hyperinflammatory cytokine storm in patients with severe COVID-19 highlights a defective resistance phase that leads to aspecific chronic inflammation, associated with oxidative stress, which impairs specific T-cell response, induces tissue and endothelial damage, and thrombosis associated with systemic effects that lead to severe multi-organ failure and death. These events are similar to those observed in advanced ovarian cancer which share similar pathogenesis mediated primarily by Interleukin-6, which is, as well demonstrated in ovarian cancer, the key cytokine driving the immunopathology, related systemic symptoms, and patient prognosis. Consistent with findings in other disease models with similar immunopathology, such as advanced ovarian cancer, treatment of severe COVID-19 infection should target inflammation, oxidative stress, coagulation disorders, and immunodepression to improve patient outcome. Correctly identifying disease stages, based on available laboratory data, and developing a specific protocol for each phase is essential for effective treatment

Extraction of Mg(OH)2 from Mg silicate minerals with NaOH assisted with H2O: implications for CO2 capture from exhaust flue gas

The utilisation of Mg(OH)2 to capture exhaust CO2 has been hindered by the limited availability of brucite, the Mg(OH)2 mineral in natural deposits. Our previous study demonstrated that Mg(OH)2 can be obtained from dunite, an ultramafic rock composed of Mg silicate minerals, in highly concentrated NaOH aqueous systems. However, the large quantity of NaOH consumed was considered an obstacle for the implementation of the technology. In the present study, Mg(OH)2 was extracted from dunite reacted in solid systems with NaOH assisted with H2O. The consumption of NaOH was reduced by 97% with respect to the NaOH aqueous systems, maintaining a comparable yield of Mg(OH)2 extraction, i.e. 64.8–66%. The capture of CO2 from a CO2–N2 gas mixture was tested at ambient conditions using a Mg(OH)2 aqueous slurry. Mg(OH)2 almost fully dissolved and reacted with dissolved CO2 by forming Mg(HCO3)2 which remained in equilibrium storing the CO2 in the aqueous solution. The CO2 balance of the process was assessed from the emissions derived from the power consumption for NaOH production and Mg(OH)2 extraction together with the CO2 captured by Mg(OH)2 derived from dunite. The process resulted as carbon neutral when dunite is reacted at 250 °C for durations of 1 and 3 hours and CO2 is captured as Mg(HCO3)2

bird density stress markers and growth performance in the italian chicken breed milanino

Summary The Milanino is an Italian chicken breed included in a conservation project run by the University of Milan. It is characterized by good fertility, heavy body weights, high adaptation ability to adverse climate conditions, and disease resistance. Because of these characteristics, the Milanino could represent an important genetic resource for alternative production systems. This research was aimed at studying the effect of bird density on growth and slaughter performance, as well as stress response in Milanino chickens kept in outdoor pens. One hundred and sixty Milanino chickens were randomly assigned to 2 experimental groups kept at different densities (2 m2/bird and 8 m2/bird) and were slaughtered at 185 days of age. Growth and slaughter performance and stress condition were recorded. The interaction bird density * sex * age significantly affected body weight and an opposite trend was found between females and males: heavier females were found in the high-density group, while heavier males were found in the low-density group. Bird density did not affect carcass weight data. The stress marker (H/L ratio) was significantly higher in birds kept at the higher density (2 m2/bird). In conclusion, the Milanino provided satisfactory growth performance with different rearing density but the lower density, 8 m2/bird, should be preferred to minimize welfare problems for male birds

Decrease in neutrophil-to-lymphocyte ratio during neoadjuvant chemotherapy as a predictive and prognostic marker in advanced ovarian cancer

Since chronic inflammation is associated with ovarian cancer growth and progression, some clinical studies have assessed the association between the pre-treatment neutrophil-to-lymphocyte ratio (NLR) and the prognosis of ovarian cancer. The purpose of this study was to assess the dynamic behavior of the NLR during the course of neoadjuvant chemotherapy (NACT) in patients with high grade serous (HGS) advanced epithelial ovarian cancer and assess its correlation with clinical response, progression free survival (PFS) and changes in other inflammatory indexes. We performed a prospective observational study on 161 patients who underwent NACT at the Department of Gynecologic Oncology, ARNAS G. Brotzu, Cagliari, between 2009 and 2019. NLR was evaluated before starting and after three cycles of NACT. Based on response after three cycles of NACT, patients were divided into two groups: responsive and non-responsive. The primary endpoint was to assess the predictive role of NLR by comparing the responsive and non-responsive patients at baseline and after three cycles of NACT. Secondary endpoints were (a) to correlate NLR with other inflammation markers (CRP, fibrinogen, ferritin, IL-6), albumin, and modified Glasgow Prognostic Score (mGPS) with NLR at baseline and after NACT; (b) to assess the association between NLR and PFS. We found that the NLR value at baseline was not associated with response to NACT, while a decrease in NLR after three cycles was correlated with a better response to NACT. Also, values of CRP, IL-6, ferritin, and mGPS after three cycles of NACT (but not at baseline) were significantly associated with clinical response. Moreover, we found that patients with a low NLR value after 3 cycles of NACT, but not at baseline, had a significantly higher PFS than patients with high NLR after 3 cycles of NACT. In conclusion, NLR change during treatment could serve as a predictive marker of response to NACT in patients with HGS advanced ovarian cancer. This allows for the early identification of non-responsive patients who will need treatment remodeling

Antiviral activity of benzotriazole based derivatives

Background: For the last thirty years, the benzotriazole scaffold has been the object of our group interest and we have already presented some results on the antiviral activity of our compounds. Objective: In this article, we conclude the exploration of N-(4-(R-2H-benzo[d][1,2,3]triazol-2-yl)phenyl)-4-R’-benzamides and 1-(4-(R-2H-benzo[d][1,2,3]triazol-2-yl)phenyl)-3-R’-ureas by synthesizing further modified derivatives, in order to have more elements for SARs evaluation. Methods: Here, we reported the synthesis and the antiviral screening results of 38 newly synthesized benzotriazole derivatives against a panel of DNA and RNA viruses. We also analyse SARs in comparing these compounds with previously published benzotriazole analogues, taking stock of the situation. Results: Among the newly presented derivatives, compounds 17 and 18 were the most active with EC50 6.9 and 5.5 µM, respectively against Coxsackievirus B5 (CV-B5) and 20.5 and 17.5 µM against Poliovirus (Sb-1). Conclusion: we can conclude that N-(4-(2H-benzo[d] [1-3] triazol-2-yl)phenyl-R-amide is a good chemical scaffold for the development of new antiviral molecules

Cancer and systemic inflammation: treat the tumour and treat the host

Determinants of cancer progression and survival are multifactorial and host responses are increasingly appreciated to have a major role. Indeed, the development and maintenance of a systemic inflammatory response has been consistently observed to confer poorer outcome, in both early and advanced stage disease. For patients, cancer-associated symptoms are of particular importance resulting in a marked impact on day-to-day quality of life and are also associated with poorer outcome. These symptoms are now recognised to cluster with one another with anorexia, weight loss and physical function forming a recognised cluster whereas fatigue, pain and depression forming another. Importantly, it has become apparent that these symptom clusters are associated with presence of a systemic inflammatory response in the patient with cancer. Given the understanding of the above, there is now a need to intervene to moderate systemic inflammatory responses, where present. In this context the rationale for therapeutic intervention using nonselective anti-inflammatory agents is clear and compelling and likely to become a part of routine clinical practice in the near future. The published literature on therapeutic intervention using anti-inflammatory agents for cancer-associated symptoms was reviewed. There are important parallels with the development of useful treatments for the systemic inflammatory response in patients with rheumatological disease and cardiovascular disease

Long-term durability of tenofovir-based antiretroviral therapy in relation to the co-administration of other drug classes in routine clinical practice

BACKGROUND: In clinical trials, toxicity leading to tenofovir disoproxil fumarate (TDF) discontinuation is rare (3% by 2 years); however in clinical practice it seems to be higher, particularly when TDF is co-administered with ritonavir-boosted protease inhibitors (PI/r). Aims of this study were to assess the rate of TDF discontinuations in clinical practice and to identify factors associated with the risk of stopping TDF. METHODS: All antiretroviral treatment (ART)-naive patients initiating a TDF-based regimen were selected from the ICONA Foundation Study cohort. The primary outcome was TDF discontinuation regardless of the reason; secondary outcome measures were TDF discontinuation due to toxicity and selective TDF discontinuation (that is, TDF discontinuation or substitution, maintaining unchanged the remaining antiretroviral treatment). RESULTS: 3,618 ART-naïve patients were included: 54% started a PI/r-based and 46% a NNRTI-based based regimen. Two-hundred-seventy-seven patients discontinued TDF and reintroduced ART within 30 days without TDF. The probability of TDF discontinuation regardless of the reason was of 7.4% (95%CI:6.4-8.5) by 2 years and 14.1% (95%CI:12.2-16.1) by 5 years. The 5-year KM estimates in the PI/r vs. NNRTI group were 20.4% vs. 7.6%, respectively (log-rank p = 0.0001), for the outcome of stopping regardless of the reason, and 10.7% vs. 4.7% (p = 0.0001) for discontinuation due to toxicity. PI/r use and lower eGFR were associated with an increased risk of discontinuing TDF. CONCLUSION: In our cohort, the frequency of TDF discontinuations was higher than that observed in clinical trials. Co-administration of TDF with PI/r was associated with an increased rate of TDF discontinuations. Further studies are needed to clarify the mechanisms that might have led to this outcome