Reliability of portal control procedure in irradiation of breast cancer: a Bayesian analysis.

BACKGROUND AND PURPOSE: To determine whether the information gathered from a fixed number of periodic verification films accurately reflects the true imprecision in patient positioning during the whole radiation therapy of early breast cancer. PATIENTS AND METHODS: A total of 204 medial and lateral treatment fields were evaluated in 102 breast cancer patients treated with conservative surgery and radiation therapy. For each treatment field, the central lung distance was measured on portal films obtained from one simulation and four treatment controls at weekly intervals during breast irradiation. Systematic and random errors in patient positioning throughout all treatment fractions were estimated from the available controls using Bayesian methods. RESULTS: The average systematic and random errors during treatment controls were 2.7 and 1.9 mm, respectively. For these mean control values, the probabilities that the true systematic and random errors remain below 5mm during all treatment fractions were 99 and 100%, respectively. CONCLUSIONS: Reproducibility of patient positioning was supported by a virtually null probability for systematic or random errors greater than 5 mm during the whole radiation therapy. Weekly verification films seem to be sufficient to estimate patient positioning errors with high accuracy in radiotherapy of early breast cancer.     

Aumento de Óbitos Domiciliares devido a Parada Cardiorrespiratória em Tempos de Pandemia de COVID-19

BackgroundCardiovascular diseases constitute an important group of causes of death in the country. Ischemic heart diseases that are the main causes of cardiopulmonary arrest, leading to an impact on the mortality of the cardiovascular diseases in the health system.ObjectiveAssess the number of home deaths by cardiopulmonary arrest notified by the Mobile Emergency Medical Service (SAMU) in March 2018, 2019 and 2020.MethodsObservational study carried out from the analysis of cardiopulmonary arrest mortality data of citizens assisted by SAMU in Belo Horizonte, Minas Gerais, Brazil. Social and clinical characteristics and occurrence information of the patients were analyzed. The mortality rate due to cardiopulmonary arrest in relation to the total number of attendances was assessed. A significance level of 95% was considered.ResultsThere was increase of home deaths due to cardiopulmonary arrest in March 2020 compared to March 2018 (p<0.001) and March 2019 (p=0.050). Of the deaths reported in 2020, 63.8% of the patients were aged 60 years or older, 63.7% of the occurrences were performed in the afternoon and approximately 87% of the cardiopulmonary arrest notified had associated clinical comorbidities, with systemic arterial hypertension and heart failure represented by 22.87% and 13.03% of the reported cases, respectively. The majority of the evaluated sample of this study did not have any medical care follow-up (88.7%).ConclusionConsidering the increase in the number of the deaths, we suggest reflections and readjustments regarding the monitoring of chronic non-transmissible diseases during a pandemic, as well as improvements in death surveillance. (Arq Bras Cardiol. 2021; 116(2):266-271)     

Urinary bladder inflammation induces changes in urothelial nerve growth factor and TRPV1 channels

Background and Purpose

The urinary bladder urothelium expresses various receptors and in response to chemical and mechanical stimuli releases mediators, thereby modulating bladder sensory pathways. Transient receptor potential vanilloid 1 (TRPV1) ion channels and nerve growth factor (NGF) in those cells are implicated in this modulatory effect and play a role in sensitizing pain-related afferent pathways during inflammation. In this study, we investigated the interaction between NGF and TRPV1 channels in urothelial cells.

Experimental Approach

Urothelial cells from female Sprague-Dawley rat bladders were cultured to quantify membrane expression of TRPV1 channels and capsaicin-induced ATP release in the presence of NGF alone or with TrKA or PI3K inhibitors. Pain scores from rats with cyclophosphamide (CYP)-induced bladder inflammation were assessed after treatment with a TrkA antagonist. Bladders (from control and CYP rats) were collected and analysed for NGF content and TRPV1 channel expression.

Key Results

Cultured cells responded to NGF with increased TRPV1 channel expression in the cell membrane and increased release of ATP. Both responses were blocked by either a TrkA antagonist or a PI3K inhibitor. Treatment in vivo with the TrkA antagonist alleviated pain symptoms and reduced CYP-induced NGF overexpression in the mucosa. Furthermore, in urothelial cells from animals with bladder inflammation, expression of TRPV1 channels in the membrane was significantly increased.

Conclusions and Implications

During bladder inflammation, increased production of NGF in urothelial cells induced increased expression and activity of TRPV1 channels in the cell membrane. This effect was primarily mediated by the PI3K pathway.     

Association between the HLA-G molecule and lymph node metastasis in papillary thyroid cancer

Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer and can present as lymph node metastasis in 30 to 65% of cases when initially diagnosed. High frequency recurrence, distant metastasis and treatment resistance can be found in cases of PTC so early diagnosis and treatment are critical for improved prognosis and better survival rates. The characterization of new biomarkers has proved useful for the diagnosis and follow-up of these patients. HLA-G is a non-classical HLA class I molecule whose expression in cancer cells has been associated with tumor evasion of immune response. Therefore, the aim of this study was to investigate the HLA-G expression and its clinical significance in PTC. Paraffin-embedded thyroid biopsies of 70 PTC patients (40 of whom had presented with metastasis) were evaluated. HLA-G-staining was observed in tumor cells in PTC, and the HLA-G expression was significantly associated with an increased occurrence of lymph node metastasis (p = 0.0006) and capsular invasion (p = 0.02). This preliminary data shows the HLA-G expression in thyroid carcinoma specimens for the first time and suggests that this expression could impair efficient anti-tumor immunity in PTC. This would indicate that HLA-G could have an independent prognostic value in PTC, principally for tumor recurrence.     

Characterisation of cannabinoid 1 receptor expression in the perikarya, and peripheral and spinal processes of primary sensory neurons

The cannabinoid 1 (CB1) receptor is expressed by a sub-population of primary sensory neurons. However, data on the neurochemical identity of the CB1 receptor-expressing cells, and CB1 receptor expression by the peripheral and central terminals of these neurons are inconsistent and limited. We characterised CB1 receptor expression in dorsal root ganglia (DRG) and spinal cord at the lumbar 4–5 level, as well as in the urinary bladder and glabrous skin of the hindpaw. About 1/3 of DRG neurons exhibited immunopositivity for the CB1 receptor, the majority of which showed positivity for the nociceptive markers calcitonin gene-related peptide (CGRP) or/and Griffonia (bandeiraea) simplicifolia IB4 isolectin-binding. Virtually all CB1 receptor-immunostained fibres showed immunopositivity for CGRP in the skin, while very few did in the urinary bladder. No CB1 receptor-immunopositive nerve fibres were IB4 positive in either peripheral tissue. Spinal laminae I and II-outer showed the highest density of CB1 receptor-immunopositive punctae, the majority of which showed positivity for CGRP or/and IB4 binding. These data indicate that a major sub-population of nociceptive primary sensory neurons expresses CB1 receptors that are transported to both peripheral and central terminals of these cells. Therefore, the present data suggest that manipulation of endogenous CB1 receptor agonist levels in these areas may significantly reduce nociceptive input into the spinal cord.     

Analysis of HLA-G gene polymorphism and protein expression in invasive breast ductal carcinoma

The human leukocyte antigen G (HLA-G) is a non-classical HLA class I molecule predominantly expressed in trophoblastic placental cells to protect the fetus during pregnancy. However, evidence has shown that this molecule may be implicated in the immune escape mechanism of tumor cells. Thus, the aim of this study was to evaluate the frequency of 14-bp insertion/deletion HLA-G polymorphism, as well as the expression of this molecule in patients with invasive breast ductal carcinoma (IDC). A significant association between the expression of HLA-G and the presence of metastasis in lymph nodes (p = 0.01) was observed and the expression of HLA-G was significantly higher in patients with shorter survival time (p = 0.03). The analysis suggests that the polymorphism observed in patients with IDC may be inducing a higher expression of the HLA-G molecule, which may possibly contribute to shorter survival time and a worse clinical prognosis for such patients.     

Vitamin D Deficiency and Gestational Diabetes Mellitus in Relation to Body Mass Index

A relationship between vitamin D deficiency (VDD) and gestational diabetes mellitus (GDM) has been described. Considering that GDM prevalence depends on body mass index (BMI), our main objective was to determine if VDD is associated with GDM, independent of BMI. A cross-sectional study with 886 pregnant women was conducted in Elda (Spain) from September 2019 to June 2020. To assess the association, Poisson regression models with robust variance were used to estimate the prevalence ratio (PR). The observed GDM prevalence was 10.5%, while the VDD prevalence was 55.5%. In the crude model, both VDD and obesity were associated with GDM, but in the adjusted model, only VDD was statistically significant (PR = 1.635, p = 0.038). A secondary event analysis did not detect differences in VDD, but BMI yielded a higher frequency of births by cesarean section and newborns with a >90 percentile weight in the obesity group. In conclusion, VDD is associated with GDM, independent of BMI. Future longitudinal studies could provide information on causality.