Effect of Low-Dose Radiotherapy on the Circulating Levels of Paraoxonase-1-Related Variables and Markers of Inflammation in Patients with COVID-19 Pneumonia.

The aim of our study was to investigate the changes produced by low-dose radiotherapy (LDRT) in the circulating levels of the antioxidant enzyme paraoxonase-1 (PON1) and inflammatory markers in patients with COVID-19 pneumonia treated with LDRT and their interactions with clinical and radiological changes. Data were collected from the IPACOVID prospective clinical trial (NCT04380818). The study included 30 patients treated with a whole-lung dose of 0.5 Gy. Clinical follow-up, as well as PON1-related variables, cytokines, and radiological parameters were analyzed before LDRT, at 24 h, and 1 week after treatment. Twenty-five patients (83.3%) survived 1 week after LDRT. Respiratory function and radiological images improved in survivors. Twenty-four hours after LDRT, PON1 concentration significantly decreased, while transforming growth factor beta 1 (TGF-ß1) increased with respect to baseline. One week after LDRT, patients had increased PON1 activities and lower PON1 and TGF-ß1 concentrations compared with 24 h after LDRT, PON1 specific activity increased, lactate dehydrogenase (LDH), and C-reactive protein (CRP) decreased, and CD4+ and CD8+ cells increased after one week. Our results highlight the benefit of LDRT in patients with COVID-19 pneumonia and it might be mediated, at least in part, by an increase in serum PON1 activity at one week and an increase in TGF-ß1 concentrations at 24 h.

CD68 and CD83 immune populations in non-metastatic axillary lymph nodes are of prognostic value for the survival and relapse of breast cancer patients.

BACKGROUND: The foremost cause of death of breast cancer (BC) patients is metastasis, and the first site to which BC predominantly metastasizes is the axillary lymph node (ALN). Thus, ALN status is a key prognostic indicator at diagnosis. The immune system has an essential role in cancer progression and dissemination, so its evaluation in ALNs could have significant applications. In the present study we aimed to investigate the association of clinical-pathological and immune variables in the primary tumour and non-metastatic ALNs (ALNs-) of a cohort of luminal A and triple-negative BC (TNBC) patients with cancer-specific survival (CSS) and time to progression (TTP). METHODS: We analysed the differences in the variables between patients with different outcomes, created univariate and multivariate Cox regression models, validated them by bootstrapping and multiple imputation of missing data techniques, and used Kaplan-Meier survival curves for a 10-years follow-up. RESULTS: We found some clinical-pathological variables at diagnosis (tumour diameter, TNBC molecular profile and presence of ALN metastasis), and the levels of several immune markers in the two studied sites, to be associated with worse CSS and TTP. Nevertheless, only CD68 and CD83 in ALNs- were confirmed as independent prognostic factors for TTP. CONCLUSIONS: The study identified the importance of macrophage and dendritic cell markers as prognostic factors of relapse for BC. We highlight the importance of studying the immune response in ALNs-, which could be relevant to the prediction of BC patients' outcome.

Current and Emerging Therapies for Metastatic Castration-Resistant Prostate Cancer (mCRPC).

Metastatic castration-resistant prostate cancer (mCRPC) encompasses a heterogeneous wide range of molecular tumor behavior and a high risk of progression. Early detection and treatment are therefore crucial in these patients. Treatment has improved drastically in recent years and many novel therapeutic agents are currently under investigation. However, due to the rapidly changing therapeutic landscape in mCRPC, it is difficult for clinicians to keep up to date with the latest innovations in this area. In the present narrative review, we discuss the current and emerging therapies for mCRPC as well as the clinical and molecular factors that can help predict which patients are most likely to benefit from these novel agents.

Brief Report: Young Age and Sex Work Are Associated With HIV Seroconversion Among Transgender Women in São Paulo, Brazil.

BACKGROUND: Transgender women worldwide have the highest prevalence of HIV and the lowest access to prevention among groups at risk of HIV. However, few longitudinal studies have directly measured HIV incidence and identified predictors of HIV acquisition among transgender women. SETTING: São Paulo, Latin America's largest city. METHODS: We conducted a longitudinal study among transgender women in São Paulo. Participants were recruited by a long-chain peer referral process from May 2017 to July 2019. Those aged 18 years and older and who were HIV-negative at baseline were retested every 6 months up to 18 months. HIV incidence was calculated by dividing the number of seroconversions by the person-years (PYs) of follow-up; 95% confidence intervals (CIs) were constructed assuming a Poisson distribution. Conditional maximum likelihood ratios assessed differences in HIV incidence by risk factors. RESULTS: A racially/ethnically diverse sample of 545 HIV-negative transgender women was enrolled. In 485.5 PYs of follow-up, 13 seroconversions were observed, yielding an incidence of 2.68 per 100 PYs (95% CI: 1.43 to 4.58). HIV incidence was significantly higher among transgender women aged 18-24 years (rate ratio 3.85, 95% CI: 1.24 to 12.93) and among those who engaged in sex work in the preceding month (rate ratio 5.90, 95% CI: 1.71 to 26.62). CONCLUSIONS: HIV transmission continues at a high rate among transgender women in Brazil. Factors such as young age, lower level of education, and limited employment opportunities may lead to dependence on sex work that in turn increases HIV risk. Transgender-friendly prevention services, particularly programs delivering pre-exposure prophylaxis, are urgently needed.

Identification of potential metabolic biomarkers of rectal cancer and of the effect of neoadjuvant radiochemotherapy.

We report a pilot study on the feasibility of determinations of circulating levels of paraoxonase-1 (PON1) and compounds related to energy metabolism as biomarkers for the evaluation of patients with rectal cancer (RC), and the effects produced by neoadjuvant radiochemotherapy (NRCT). We studied 32 patients treated with radiotherapy plus capecitabine concomitant chemotherapy and 48 control subjects. We identified pre-NRCT PON1 and α-ketoglutarate as the parameters that best discriminated between RC patients and the control group. Receiver operating characteristics analysis of the combination of the two parameters showed an area under the curve (AUC) of 0.918. Moreover, patients who presented a pathological complete response (pCR) to treatment had lower plasma pre-NRCT valine concentrations (AUC of 0.826). Patients who had a relapse had lower concentrations of succinate (AUC of 0.833). The results of the present study illustrate the usefulness of investigating alterations in oxidative stress and metabolism in RC. Due to the small number of patients studied, our results must be considered preliminary, but they suggest that the determination of circulating levels of PON1 and α-ketoglutarate might be a valuable tool for the early diagnosis of RC, while the determination of valine and succinate might effectively predict pCR and the appearance of relapse.