Radiotherapy during the COVID-19: a review about management and treatment strategies

BackgroundThe administration of radiotherapy should be encouraged despite the emergency of COVID-19; therefore, our aim is to analyze management and therapeutic interventions to be implemented in a Radiotherapy department to allow patients to continue their treatment and health professionals to continue their work safely.Materials and methodsA Pubmed search was performed, in which all articles specific to Radiotherapy and COVID-19 were included. Those articles that were too specific about the COVID-19, surgery and chemiotherapy, were excluded.Results315 articles were selected, of which 35 were about therapeutic strategies and 25 about management strategies. In the first category, 5 articles were about how radiotherapy could be a weapon to be used for COVID-19 positive patients with important lung problems. While 30 articles described priorities and new treatment plans for oncology patients who have to undergo radiotherapy during the pandemic. In the second category, almost all the articles explained how triage can be a preventive and monitoring way against COVID-19 in an operating unit with many patients and professionals, and other articles developed a telemedicine system, too, which allows patients to make scheduled visits without coming to the hospital and also for the staff, who can work remotely. In addition, 5 articles concerning psychological aspects of both patients and health care providers were included.ConclusionThis document can be used as a summary in the coming months/years, during the recovery phase from COVID-19 pandemic outbreak and as a starting point to be used in case of further pandemic break-out.     

A Comparative Oncology Study of Iniparib Defines Its Pharmacokinetic Profile and Biological Activity in a Naturally-Occurring Canine Cancer Model

Development of iniparib as an anti-cancer agent was hindered in part by lingering questions regarding its mechanism of action, the activity of its metabolites, and their potential accumulation in tumors. Due to strong similarities in metabolism of iniparib between humans and dogs, a veterinary clinical trial in pet dogs with spontaneous cancers was designed to answer specific questions pertaining to pharmacokinetic exposures and tolerability of iniparib. Dogs were treated with iniparib alone and in combination with carboplatin chemotherapy. Iniparib doses ranged between 10–70 mg/kg intravenously (IV). Plasma, tumor and normal tissue samples were collected before and at various time points scheduled after exposure for pharmacokinetic and biologic analysis. The primary endpoints included characterization of dose-limiting toxicities (DLT) and determination of the drug exposures that could be achieved in both normal and tumor tissues. Nineteen dogs were treated. DLT included fever, anorexia, diarrhea, neutropenia, and thrombocytopenia; most effects were attributable to carboplatin based on the timing of adverse event onset. The maximum tolerated dose (MTD) of iniparib was not identified. Moderate to high variability in plasma exposure was noted for iniparib and all metabolites between animals. When quantifiable, iniparib and metabolite plasma:tumor ratios were < 0.088 and <1.7, respectively. In this study, iniparib was well tolerated as a single agent and in combination with carboplatin over a range of doses. However, clinically relevant concentrations of the parent drug and selected metabolites were not detectable in canine tumor tissues at any studied dose, thus eliminating expectations for clinical responses in dogs or humans. Negative clinical trials in humans, and the uncertainties of its mechanism of action, ultimately led to the decision to stop clinical development of the drug. Nevertheless, the questions that can be asked and answered within the comparative oncology approach are evident from this successfully executed comparative clinical trial and exemplify the value of such studies in drug development.     

Life Satisfaction and Morbidity among Postmenopausal Women

Objective

To investigate associations between morbidity and global life satisfaction in postmenopausal women taking into account type and number of diseases.

Materials and Methods

A total of 11,084 women (age range 57–66 years) from a population-based cohort of Finnish women (OSTPRE Study) responded to a postal enquiry in 1999. Life satisfaction was measured with a 4-item scale. Self-reported diseases diagnosed by a physician and categorized according to ICD-10 main classes were used as a measure of morbidity. Enquiry data on health and lifestyle were used as covariates in the multivariate logistic models.

Results

Morbidity was strongly associated with life dissatisfaction. Every additional disease increased the risk of life dissatisfaction by 21.1% (p < .001). The risk of dissatisfaction was strongest among women with mental disorders (OR = 5.26; 95%CI 3.84–7.20) and neurological disorders (OR = 3.62; 95%CI 2.60–5.02) compared to the healthy (each p < .001). Smoking, physical inactivity and marital status were also associated with life dissatisfaction (each p < .001) but their introduction to the multivariate model did not attenuate the pattern of associations.

Conclusions

Morbidity and life dissatisfaction have a disease-specific and dose-dependent relationship. Even if women with mental and neurological disorders have the highest risk for life dissatisfaction, monitoring life satisfaction among aging women regardless of disorders should be undertaken in order to intervene the joint adverse effects of poor health and poor well-being.     

Genome-Wide Association Study of Serum Creatinine Levels during Vancomycin Therapy

Vancomycin, a commonly used antibiotic, can be nephrotoxic. Known risk factors such as age, creatinine clearance, vancomycin dose / dosing interval, and concurrent nephrotoxic medications fail to accurately predict nephrotoxicity. To identify potential genomic risk factors, we performed a genome-wide association study (GWAS) of serum creatinine levels while on vancomycin in 489 European American individuals and validated findings in three independent cohorts totaling 439 European American individuals. In primary analyses, the chromosome 6q22.31 locus was associated with increased serum creatinine levels while on vancomycin therapy (most significant variant rs2789047, risk allele A, β = -0.06, p = 1.1 x 10^-7). SNPs in this region had consistent directions of effect in the validation cohorts, with a meta-p of 1.1 x 10^-7. Variation in this region on chromosome 6, which includes the genes TBC1D32/C6orf170 and GJA1 (encoding connexin43), may modulate risk of vancomycin-induced kidney injury.     

Trypanosoma cruzi: acute and long-term infection in the vertebrate host can modify the response to benznidazole

We analyzed the influence of Trypanosoma cruzi maintenance in different hosts (dog and mouse) on its susceptibility to benznidazole treatment. Five T. cruzi stocks were isolated from dogs inoculated with Be-62 or Be-78 strain (both sensitive to benznidazole) 2-10 years ago, and the benznidazole sensitivity was then determined using the mouse as experimental model. The different T. cruzi stocks obtained from long-term infected dogs showed 50-90% drug resistance right after isolation. However, maintenance of these T. cruzi stocks in mice, by successive blood passages (2.5 years), led to either a decrease or stability of the drug resistance pattern and an increase in parasite virulence. We also demonstrated the effectiveness of the induction of parasitemia reactivation by cyclophosphamide immunosuppression in the evaluation of the response to the specific drug treatment.     

Linking oxidative and salinity stress tolerance in barley: can root antioxidant enzyme activity be used as a measure of stress tolerance?

Aims

A causal relationship between salinity and oxidative stress tolerance and a suitability of using root antioxidant activity as a biochemical marker for salinity tolerance in barley was investigated.

Methods

Net ion fluxes were measured from the mature zone of excised roots of two barley varieties contrasting in their salinity tolerance using non-invasive MIFE technique in response to acute and prolonged salinity treatment. These changes were correlated with activity of major antioxidant enzymes; ascorbate peroxidase, catalase, and superoxide dismutase.

Results

It was found that genotypic difference in salinity tolerance was largely independent of root integrity, and observed not only for short-term but also long-term NaCl exposures. Higher K⁺ retention ability (and, hence, salinity tolerance) positively correlated with oxidative stress tolerance. At the same time, antioxidant activities were constitutively higher in a sensitive but not tolerant variety, and no correlation was found between SOD activity and salinity tolerance index during large-scale screening.

Conclusion

Although salinity tolerance in barley correlates with its oxidative stress tolerance, higher antioxidant activity at one particular time does not correlate with salinity tolerance and, as such, cannot be used as a biochemical marker in barley screening programs.     

Repeat HIV Testing at Voluntary Testing and Counseling Centers in Croatia: Successful HIV Prevention or Failure to Modify Risk Behaviors?

HIV testing plays a critical role in preventing the spread of the virus and identifying infected individuals in need of care. Voluntary counseling and testing centers (VCTs) not only conduct testing but they also provide counseling. Since a proportion of people who test negative for HIV on their previous visit will return for retesting, the frequency of retesting and the characteristics of those who retest may provide insights into the efficacy of testing and counseling strategies. In this cross-sectional, retrospective study of 1,482 VCT clients in Croatia in 2010, 44.3% had been tested for HIV before. The rate of repeat HIV testing is lower in Croatia than in other countries. Men who have sex with men (MSM) clients, those with three or more sexual partners in the last 12 months, consistent condom users with steady partners, and intravenous drug users were more likely to be repeat testers. This finding suggests that clients presenting for repeat HIV testing are those who self-identify as being at a higher risk of infection. Our data showed that testing positive for HIV was not associated with repeat testing. However, the effects of repeat testing on HIV epidemiology needs to be explored.     

The polymorphism − 1131T > C in apolipoprotein A5 gene is associated with dyslipidemia in Brazilian subjects

Background

Polymorphisms in apolipoprotein A5 gene (APOA5) have been associated with higher triglyceride levels in many populations. The aim of the study was to determine the allelic and genotypic distribution of the APOA5 − 1131T > C polymorphism and to identify the association of the genetic variant and the risk for dyslipidemia.

Methods

We genotyped 109 dyslipidemic subjects and 107 controls. The total cholesterol, triglycerides and HDL-c were determined enzymatically. Comparison of means among groups was calculated by ANOVA. Significant differences among groups were evaluated by Student–Newman–Keuls test.

Results

The minor allele C was more frequent in dyslipidemic subjects than controls (p = 0.019) and confers an increased individual risk for dyslipidemia (OR = 1.726, CI 95% = 1.095–2.721). The genotype analysis by gender showed that this allele was more frequent in dyslipidemic males (p = 0.037; OR = 2.050, CI 95% = 1.042–4.023). When participants were analyzed according to genotypes TT and TC/CC, C-carriers presented higher cholesterol and triglycerides levels than TT homozygous (p = 0.046 and 0.049, respectively).

Conclusions

The allele C confers higher total cholesterol and triglycerides levels in dyslipidemic adults. The APOA5 − 1131T > C polymorphism is associated with dyslipidemia in male subjects.     

Temporal dissociation of taste mixture components

Reaction times to salty and bitter tastes as single stimuliand in mixture were measured using response time deadlines rangingfrom 300 to 2500 ms. Salty reaction times were the same whethersalty was in mixture with bitter or a single stimulus, and theywere always shorter than bitter reaction times. Reaction timeto bitter was slower in mixture with salty than as a singletaste. Salty, alone and in mixture, was correctly identifiedon {small tilde}80% of the trials within 500 ms while correctbitter identifications did not reach similar levels until 1000ms. Bitter in mixture with salty never reached that level ofcorrect responding and correct responses actually decreasedslightly at response time deadlines of 2500 ms. The resultsshow that differences in taste onset latency are great enoughto allow identification of single tastes in mixtures.