Good Quality Care for Cancer Patients Dying in Hospitals, but Information Needs Unmet: Bereaved Relatives' Survey within Seven Countries.

BACKGROUND: Recognized disparities in quality of end-of-life care exist. Our aim was to assess the quality of care for patients dying from cancer, as perceived by bereaved relatives, within hospitals in seven European and South American countries. MATERIALS AND METHODS: A postbereavement survey was conducted by post, interview, or via tablet in Argentina, Brazil, Uruguay, U.K., Germany, Norway, and Poland. Next of kin to cancer patients were asked to complete the international version of the Care Of the Dying Evaluation (i-CODE) questionnaire 6-8 weeks postbereavement. Primary outcomes were (a) how frequently the deceased patient was treated with dignity and respect, and (b) how well the family member was supported in the patient's last days of life. RESULTS: Of 1,683 potential participants, 914 i-CODE questionnaires were completed (response rate, 54%). Approximately 94% reported the doctors treated their family member with dignity and respect "always" or "most of the time"; similar responses were given about nursing staff (94%). Additionally, 89% of participants reported they were adequately supported; this was more likely if the patient died on a specialist palliative care unit (odds ratio, 6.3; 95% confidence interval, 2.3-17.8). Although 87% of participants were told their relative was likely to die, only 63% were informed about what to expect during the dying phase. CONCLUSION: This is the first study assessing quality of care for dying cancer patients from the bereaved relatives' perspective across several countries on two continents. Our findings suggest many elements of good care were practiced but improvement in communication with relatives of imminently dying patients is needed. (ClinicalTrials.gov Identifier: NCT03566732). IMPLICATIONS FOR PRACTICE: Previous studies have shown that bereaved relatives' views represent a valid way to assess care for dying patients in the last days of their life. The Care Of the Dying Evaluation questionnaire is a suitable tool for quality improvement work to help determine areas where care is perceived well and areas where care is perceived as lacking. Health care professionals need to sustain high quality communication into the last phase of the cancer trajectory. In particular, discussions about what to expect when someone is dying and the provision of hydration in the last days of life represent key areas for improvement.

hsa­miR­455­3P as a predictive biomarker of anemia in patients with non­small cell lung cancer treated with carboplatin plus paclitaxel.

Lung cancer is the leading cause of cancer-related morbidity and mortality worldwide. The initial treatment of lung cancer depends on the definition of the tumor type and its staging. The most common treatment is chemotherapy, and the first-line treatment is a combination of carboplatin and paclitaxel. Although this treatment has good efficacy, there is a high prevalence of adverse events, particularly hematological reactions. Studies on new biomarkers related to these adverse events, such as circulating microRNAs (miRNAs/miRs), are important for optimizing the quality of life of patients. miRNAs have high stability in several biological fluids and they have specific expressions in different tissues or pathologies. Thus, the present study aimed to assess the relationship between circulating miRNAs and adverse hematologic reactions caused by treatment with carboplatin + paclitaxel in patients with lung cancer. Blood was collected from patients before and 15 days after chemotherapy for hematological adverse reaction analysis, microarray and quantitative (q)PCR validation. Adverse reactions were classified according to the Common Terminology Criteria for Adverse Events v4.0. Microarray analysis was performed using plasma from six patients without anemia and six patients with anemia, and nine miRNAs were differentially expressed. miR-1273g-3p, miR-3613-5p and miR-455-3p, identified using microarray, were assessed using qPCR in 20 patients without anemia and 26 patients with anemia. Bioinformatic analyses of miR-455-3p were performed using miRWalk, the Database for Annotation, Visualization and Integrated Discovery and GeneMania software. Microarray analysis of patients with and without anemia revealed nine significant differentially-expressed plasma miRNAs among these patients. Of these, miR-1273g-3p, miR-3613-5p and miR-455-3p were chosen for further assessment. Only miR-455-3p demonstrated a significant reduction in expression (P=0.04) between the groups before chemotherapy with carboplatin + paclitaxel. Bioinformatics analysis of miR-455-3p revealed a relationship between this miRNA and the hematopoietic pathway, particularly with respect to the RUNX family transcription factor 1 (RUNX1) and TAL bHLH transcription factor 1, erythroid differentiation factor (TAL1) genes. The most prevalent adverse reactions in patients with lung cancer treated with carboplatin + paclitaxel were hematological, particularly anemia. This adverse reaction, caused by dysfunction of the hematopoietic system, may be explained by a possible association between the important genes in this system, RUNX1 and TAL1, and hsa-miR-455-3p.

Association of Fibrinolytic Potential and Risk of Mortality in Cancer Patients.

Cancer is a leading cause of death, and the fibrinolytic system shows cooperative effects that facilitate the growth of tumors and the appearance of metastases. This prospective study aimed to evaluate the fibrinolytic potential in cancer patients and its association with mortality outcomes using the fluorometric method of simultaneous thrombin and plasmin generation. The study included 323 cancer patients and 148 healthy individuals. During the 12-month follow-up, 68 patients died. Compared to the control group, cancer patients showed alterations in thrombin production consistent with a hypercoagulability profile, and an increase in plasmin generation. Mortality risk was associated with two parameters of thrombin in both univariate and multivariable analysis: maximum amplitude (Wald 11.78, p < 0.001) and area under the curve (Wald 8.0, p < 0.005), while such associations were not observed for plasmin. In conclusion, this was the first study able to demonstrate the simultaneous evaluation of thrombin and plasmin generation in newly diagnosed untreated cancer patients. Patients with cancer have been observed to exhibit a hypercoagulable profile. During the study, two parameters linked to thrombin generation, MA and AUC, were identified and found to have a potential association with mortality risk. However, no associations were found with parameters related to plasmin generation.

Clusters of SARS-CoV-2 Lineage B.1.1.7 Infection after Vaccination with Adenovirus-Vectored and Inactivated Vaccines.

A SARS-CoV-2 B.1.1.7 variant of concern (VOC) has been associated with increased transmissibility, hospitalization, and mortality. This study aimed to explore the factors associated with B.1.1.7 VOC infection in the context of vaccination. On March 2021, we detected SARS-CoV-2 RNA in nasopharyngeal samples from 14 of 22 individuals vaccinated with a single-dose of ChAdOx1 (outbreak A, n = 26), and 22 of 42 of individuals with two doses of the CoronaVac vaccine (outbreak B, n = 52) for breakthrough infection rates for ChAdOx1 of 63.6% and 52.4% for CoronaVac. The outbreaks were caused by two independent clusters of the B.1.1.7 VOC. The serum of PCR-positive symptomatic SARS-CoV-2-infected individuals had ~1.8-3.4-fold more neutralizing capacity against B.1.1.7 compared to the serum of asymptomatic individuals. These data based on exploratory analysis suggest that the B.1.1.7 variant can infect individuals partially immunized with a single dose of an adenovirus-vectored vaccine or fully immunized with two doses of an inactivated vaccine, although the vaccines were able to reduce the risk of severe disease and death caused by this VOC, even in the elderly.

Influence of p53 codon 72 exon 4, GSTM1, GSTT1 and GSTP1*B polymorphisms in lung cancer risk in a Brazilian population.

PURPOSE: Glutathione S-transferases (GST) modulates the effects of various cytotoxic and genotoxic agents, particularly those derived from benzo[a]pyrene, which is one of the main tobacco carcinogens. Both the mu 1 (GSTM1) and theta 1 (GSTT1) genes have a null variant allele in which the entire gene is absent. The GSTP1*B allele has an A to G transition at nucleotide 313 (codon 105) in exon 5, causing a change of isoleucine (Ile) to valine (Val), which affects the electrophile binding site of GSTP1 and results in an enzyme with reduced activity. Polymorphisms in these metabolizing enzymes may alter the response to benzo[a]pirene-induced DNA damage. Polymorphisms in p53 may also modulate the risk of lung cancer (LC) carcinogenesis. The aim of our study was to measure the frequency of GSTM1, GSTT1, GSTP1*B and p53 gene polymorphisms in a Brazilian population and determine the possible contribution of these genetic variations to LC risk. PATIENTS AND METHODS: Genomic DNA was obtained from 200 Brazilian patients with LC and 264 blood donors (control group). All samples were analyzed by PCR and PCR-RFLP to determine GSTM1, GSTT1, GSTP1*B and p53 codon 72 genotypes. Multiple logistic regressions were used to adjust for confounding factors in this case-control study. RESULTS: No statistical significance was observed between GSTM1, GSTT1 and GSTP1*B genetic polymorphisms, either isolated or combined, with LC incidence in the studied population. However, our data showed a higher frequency of p53 codon 72 A/P plus P/P genotype in African-Brazilian than Caucasian-Brazilian patients with LC, and we also found a higher frequency of the P/P genotype of the p53 gene in non-smokers compared to smokers with LC. CONCLUSIONS: Genetic polymorphisms of GST and p53 codon 72 did not increase the risk of LC in Brazilian patients. The A/P plus P/P genotype of p53 codon 72 is more common in LC patients with African ethnical background and the P/P genotype more prevalent in non-smoking related LC.

Pulmonary silicosis and systemic lupus erythematosus in men: a report of two cases.

We reporttwo cases of coexistence of pulmonary silicosis and systemic lupus erythematosus (SLE). The patients are two men with SLE exposed to silica for 20 years. The hypothesis that silica exposure is linked to a wide variety of known or suspected autoimmune diseases, including SLE, has been discussed in the last decade but few cases of pulmonary silicosis and SLE were reported. Our purpose was to bring attention to the increasing evidence that silica may also cause or stimulate SLE, and to suggest that the researchers look for occupational exposure, mainly in male SLE patients.

Clinical variables of preoperative risk in thoracic surgery.

CONTEXT: Pulmonary complications are the most common forms of postoperative morbidity in thoracic surgery, especially atelectasis and pneumonia. The first step in avoiding these complications during the postoperative period is to detect the patients that may develop them. OBJECTIVE: To identify risk variables leading to early postoperative pulmonary complications in thoracic surgery. DESIGN: Prospective study. SETTING: Hospital das Clínicas, Faculdade de Ciências Médicas, Universidade Estadual de Campinas. PATIENTS: 145 patients submitted to elective surgery were classified as low, moderate and high risk for postoperative pulmonary complications using a risk assessment scale. PROCEDURES: The patients were followed up for 72 hours after the operation. Postoperative pulmonary complications were defined as atelectasis, pneumonia, tracheobronchitis, wheezing, prolonged intubation and/or prolonged mechanical ventilation. MAIN MEASUREMENTS: Univariate analysis was applied in order to study these independent variables: age, nutritional status, body mass index, respiratory disease, smoking habit, spirometry and surgery duration. Multivariate logistic regression analysis was performed in order to evaluate the relationship between independent and dependent variables. RESULTS: The incidence of postoperative complications was 18.6%. Multivariate logistic regression analysis showed that the variables increasing the chances of postoperative pulmonary complications were wheezing (odds ratio, OR = 6.2), body mass index (OR = 1.15), smoking (OR = 1.04) and surgery duration (OR = 1.007). CONCLUSION: Wheezing, body mass index, smoking and surgery duration increase the chances of postoperative pulmonary complications in thoracic surgery

EGFR activating mutations and their association with response to platinum-doublet chemotherapy in Brazilian non-small cell lung cancer patients.

The aim of the study was to analyze the frequency of epidermal growth factor receptor (EGFR) mutations in Brazilian non-small cell lung cancer patients and to correlate these mutations with response to benefit of platinum-based chemotherapy in non-small cell lung cancer (NSCLC). Our cohort consisted of prospective patients with NSCLCs who received chemotherapy (platinum derivates plus paclitaxel) at the [UNICAMP], Brazil. EGFR exons 18-21 were analyzed in tumor-derived DNA. Fifty patients were included in the study (25 with adenocarcinoma). EGFR mutations were identified in 6/50 (12 %) NSCLCs and in 6/25 (24 %) adenocarcinomas; representing the frequency of EGFR mutations in a mostly self-reported White (82.0 %) southeastern Brazilian population of NSCLCs. Patients with NSCLCs harboring EGFR exon 19 deletions or the exon 21 L858R mutation were found to have a higher chance of response to platinum-paclitaxel (OR 9.67 [95 % CI 1.03-90.41], p = 0.047). We report the frequency of EGFR activating mutations in a typical southeastern Brazilian population with NSCLC, which are similar to that of other countries with Western European ethnicity. EGFR mutations seem to be predictive of a response to platinum-paclitaxel, and additional studies are needed to confirm or refute this relationship.

Use of non-invasive ventilation in acute pulmonary edema and chronic obstructive pulmonary disease exacerbation in emergency medicine: predictors of failure. / Utilização da ventilação não invasiva em edema agudo de pulmão e exacerbação da doença pulmonar obstrutiva crônica na emergência: preditores de insucesso.

OBJECTIVE: This study analyzed acute respiratory failure caused by acute pulmonary edema, as well as chronic obstructive pulmonary disease exacerbation, that was treated with non-invasive mechanical ventilation to identify the factors that are associated with the success or failure non-invasive mechanical ventilation in urgent and emergency service. METHODS: This study was a prospective, descriptive and analytical study. We included patients of both genders aged >18 years who used non-invasive mechanical ventilation due to acute respiratory failure that was secondary to acute pulmonary edema or chronic obstructive pulmonary disease exacerbation. Patients with acute respiratory failure that was secondary to pathologies other than acute pulmonary edema and chronic obstructive pulmonary disease or who presented with contraindications for the technique were excluded. Expiratory pressures between 5 and 8 cmH2O and inspiratory pressures between 10 and 12 cmH2O were used. Supplemental oxygen maintained peripheral oxygen saturation at >90%. The primary outcome was endotracheal intubation. RESULTS: A total of 152 patients were included. The median non-invasive mechanical ventilation time was 6 hours (range 1 - 32 hours) for chronic obstructive pulmonary disease patients (n=60) and 5 hours (range 2 - 32 hours) for acute pulmonary edema patients (n=92). Most (75.7%) patients progressed successfully. However, reduced APACHE II scores and lower peripheral oxygen saturation were observed. These results were statistically significant in patients who progressed to intubation (p<0.001). BiPAP (Bi-level Positive Airway Pressure portable ventilator), as continuous positive airway pressure use increased the probability of endotracheal intubation 2.3 times (p=0.032). Patients with acute pulmonary edema and elevated GCS scores also increased the probability of success. CONCLUSION: Respiratory frequency >25 rpm, higher APACHE II scores, BiPAP use and chronic obstructive pulmonary disease diagnosis were associated with endotracheal intubation. Higher GCS and SpO2 values were associated with NIV success. Non-invasive mechanical ventilation can be used in emergency services in acute respiratory failure cases caused by acute pulmonary edema and chronic obstructive pulmonary disease exacerbation, but patients with variables related to a higher percentage of endotracheal intubation should be specially monitored.

Mature autologous dendritic cell vaccines in advanced non-small cell lung cancer: a phase I pilot study.

BACKGROUND: Overall therapeutic outcomes of advanced non-small-cell lung cancer (NSCLC) are poor. The dendritic cell (DC) immunotherapy has been developed as a new strategy for the treatment of lung cancer. The purpose of this study was to evaluate the feasibility, safety and immunologic responses in use in mature, antigen-pulsed autologous DC vaccine in NSCLC patients. METHODS: Five HLA-A2 patients with inoperable stage III or IV NSCLC were selected to receive two doses of 5 × 107 DC cells administered subcutaneous and intravenously two times at two week intervals. The immunologic response, safety and tolerability to the vaccine were evaluated by the lymphoproliferation assay and clinical and laboratorial evolution, respectively. RESULTS: The dose of the vaccine has shown to be safe and well tolerated. The lymphoproliferation assay showed an improvement in the specific immune response after the immunization, with a significant response after the second dose (p = 0.005). This response was not long lasting and a tendency to reduction two weeks after the second dose of the vaccine was observed. Two patients had a survival almost twice greater than the expected average and were the only ones that expressed HER-2 and CEA together. CONCLUSION: Despite the small sample size, the results on the immune response, safety and tolerability, combined with the results of other studies, are encouraging to the conduction of a large clinical trial with multiples doses in patients with early lung cancer who underwent surgical treatment. TRIAL REGISTRATION: Current Controlled Trials: ISRCTN45563569.

Evolution of performance status, body mass index, and six-minute walk distance in advanced lung cancer patients undergoing chemotherapy.

OBJECTIVE: To evaluate the effect of chemotherapy on the physical condition of patients with advanced lung cancer. METHODS: We evaluated 50 patients with non-small cell lung cancer (in stages IIIB and IV) and Eastern Cooperative Oncology Group (ECOG) performance status scale scores between zero and two. All patients underwent chemotherapy using paclitaxel and platinum derivatives and were evaluated at three time points (prechemotherapy, postchemotherapy and six months after starting the treatment), at which the ECOG scale, the body mass index (BMI) and the six-minute walk distance (6MWD) were assessed. RESULTS: Of the 50 patients included in the study, 14 died, 5 were excluded due to the worsening of their performance status, and 31 completed the six-month follow-up. There was no statistically significant difference between the time points of assessment for BMI (prechemotherapy vs. postchemotherapy, p = 1.00; and prechemotherapy vs. six months later, p = 0.218) or for 6MWD. Performance status improved, and this was especially due to the increase in the number of asymptomatic patients after the six-month follow-up (p = 0.031). CONCLUSIONS: Chemotherapy had a beneficial effect on the performance status of the patients. No significant changes in BMI or 6MWD were found during the study period, which might suggest the maintenance of the physical condition of the patients.

Há Concordância Entre as Medidas das Pressões Respiratórias Máximas Realizadas com Manovacuômetro Digital e Analógico em Pneumopatas? / Is There Consensus among the Measures of Maximal Respiratory Pressures in Analog and Digital Manometer in Patients with Lung Disease?

A avaliação da pressão gerada pelos músculos respiratórios é útil para avaliação, diagnóstico e prognóstico em pacientes com disfunçõesrespiratórias. O objetivo deste estudo foi avaliar possíveis diferenças entre os manovacuômetros analógico e digital, comparando-se aos valorespreditos para a população brasileira. Foi realizado um estudo prospectivo e transversal, utilizando-se aparelho digital (GlobalMed MVD 300®) e analógico (Comercial Médica®), em 120 pacientes, pneumopatas. Foram analisadas as medidas em cada um dos testes e os resultados foramcomparados com os valores preditos. Ambos os aparelhos concordam entre si para PImax e para PEmax, de acordo com o coeficiente de correlação intraclasses (CCI), com melhor valor para PImax (CCI= 0,876) que para PEmax (CCI= 0,781). As pressões médias obtidas nos equipamentos analógico e digital foram respectivamente: PImax -71 ± 25,2 e -72,6 ± 26,5 (p= 0,2974) e a PEmax 87,4 ± 26,6 e 93,6 ± 34,5 (p= 0,0008), sendo a PEmax no aparelho analógico menor que no aparelho digital em 72 sujeitos. O valor de referência de PImax foi de -96,8 ± 17,1, e quando comparado aos valores de ambos equipamentos, apresentou p <0,0001 e CCI -0,005. Para PEmax, o valor de referência foi 100,2 ± 22,1, quando comparado aos valores do aparelho digital (p=0,0294) e analógico (p<0,0001), com CCI 0,298 e 0,256, respectivamente. Houve concordância entre os equipamentos e entre as medidas quando classificadas pelos valores preditos, porém estão superestimados na literatura para os pacientes pneumopatas brasileiros em ambos os gêneros.

The evaluation of the pressure generated by the respiratory muscles is useful for assessment, diagnosis, and prognosis in patients with respiratorydisease. This study aimed to evaluate possible differences between the analog and digital manometer by comparing their predicted values forhealthy Brazilian population. A prospective study, cross-sectional, using a digital device (MVD GlobalMed 300 ®) and analog (Commercial Medical ®) was performed with 120 patients with lung disease. The results were compared with the predicted values. Both devices have similar responses for MIP and MEP, according to the intraclass correlation coefficient (ICC), with best value for MIP (ICC=0.876) than MEP (ICC = 0.781). The mean pressures obtained from analog and digital equipment were MIP 71±25.2 and -72.6 ± 26.5 (p=0.2974) and 87.4 ± 26.6 MEP and 93.6 ± 34 5 (p=0.0008), the MEP was smaller in the analog apparatus when compared to the the digital apparatus for 72 subjects. The MIP reference value was -96.8 ± 17.1 when compared to the values of both devices, with p < 0.0001 and CCI -0.005. The MEP reference value was 100.2 ± 22.1, when compared to the values of the digital device with p= 0.0294 and analog p < 0.0001, with CCI of 0.298 and 0.256 respectively. Although an agreement between equipment and measures with respect to the predicted value was observed, these measures are overestimated in literature for lung disease Brazilian patients in both gender.

Polymorphism of the CYP1A1*2A gene and susceptibility to lung cancer in a Brazilian population.

OBJECTIVE: To estimate and compare the frequency of CYP1A1*2A gene polymorphisms in a Brazilian population and determine the possible contribution of these genetic variations to lung cancer risk. METHODS: The study population included 200 patients with lung cancer, and the control group consisted of 264 blood donors. Genomic DNA was obtained from peripheral blood samples. The PCR-RFLP method was used for analysis of the CYP1A1*2A gene. RESULTS: There was no statistically significant difference between the lung cancer patients and the controls in terms of the distribution of CYP1A1*2A polymorphisms (p = 0.49). A multivariate logistic regression model analysis by ethnic group revealed that, within the lung cancer group, the CYP1A1*2A genotype CC plus TC was more common among the African-Brazilian patients than among the White patients (adjusted OR = 3.19; 95% CI: 1.53-6.65). CONCLUSIONS: The CYP1A1*2A gene cannot be linked with lung cancer risk in Brazilian patients at this time. Larger epidemiologic studies are needed in order to establish whether the CC plus TC polymorphism increases the risk of lung cancer in African-Brazilians.

[Acute respiratory failure as a manifestation of eosinophilia-myalgia syndrome associated with L-tryptophan intake]. / Insuficiência respiratória aguda como manifestação da síndrome de eosinofilia-mialgia associada à ingestão de L-triptofano.

Eosinophilia-myalgia syndrome was described in 1989 in patients who presented progressive and incapacitating myalgia and eosinophilia in blood, fluids and secretions. Most patients report previous L-tryptophan intake. Respiratory manifestations are found in up to 80% of the cases, occasionally as the only manifestation. Treatment includes drug discontinuation and administration of corticosteroids. Here, we describe the case of a 61-year-old female admitted with acute respiratory failure after using L-tryptophan, hydroxytryptophan and other drugs. The patient presented eosinophilia, together with elevated eosinophil counts in the bronchoalveolar lavage and pleural effusion. After discontinuation of the drugs previously used, corticosteroids were administered, resulting in clinical and radiological improvement within just a few days.