Abstract Purpose T1 bladder cancer is known for its high progression and recurrence rates. Identifying aggressive tumours at the non-muscle-invasive stage is crucial to allow early interventions and subsequently increase patient survival. This study aimed to investigate the potential of the cubilin/myeloperoxidase (CUBN/MPO) ratio as a high-grade T1 bladder cancer biomarker. Methods Urine samples were collected from 30 patients who underwent transurethral resection of the tumour with high-grade T1 bladder cancer (June 2015 to December 2019) before surgery. The urinary proteome was analysed using high-resolution mass spectrometry and the CUBN/MPO ratio was calculated. The primary outcome was the recurrence during the follow-up (around 31.5 months after resection). Univariate Cox regression and Kaplan–Meier curves were used for data analysis. Results Patients with a low CUBN/MPO ratio exhibited upregulated MPO and/or downregulated CUBN. This group of patients had a higher incidence of disease recurrence and progression. Low CUBN/MPO ratio was significantly associated with a higher likelihood of recurrence, progression, and death. It is worth noting that this study was exploratory and conducted on a small sample size, so further research is needed to validate these findings in larger cohorts. Conclusion This study highlights the potential of the CUBN/MPO ratio as a prognostic biomarker for high-grade T1 bladder cancer.
Abstract Background Up to 70% of pregnant women in Africa have an intestinal parasitic infection (IPI), but the associated adverse birth outcomes (ABOs) remain unclear, with gaps to be addressed. IPI prevalence among pregnant women in Sao Tome & Principe (STP) was found to be up to 60%, mainly due to Ascaris lumbricoides . Schistosoma intercalatum and Entamoeba histolytica IPIs were also identified. Despite this high-IPI prevalence, the impact of IPIs on maternal and neonatal health is unknown and has never been studied in STP. Therefore, this study sought to identify whether there were ABOs, including maternal anaemia (haemoglobin <11 g/dL), preterm birth (PTB) for gestational age <37 weeks, low birth weight (LBW) <2500 g and stillbirths associated with pregnant women with an IPI compared to their noninfected counterpart. Methods A hospital-based cross-sectional study was conducted among pregnant women admitted for delivery at the only maternity hospital in STP. Only women with an antenatal care (ANC) copro-parasitological screening were included. Pregnant women with HIV, sickle cell, malaria and STHs who were adequately treated were excluded. Data were abstracted from ANC pregnancy cards, newborns’ medical records, and a structured face-to-face interviewer-administered questionnaire. Pregnant women with an IPI (n=210) were compared to noninfected women (n=151). Subgroup analyses were conducted comparing ABOs in noninfected (no-IPI group) with ABOs in i ) monoparasitic-IPI (n=145), ii ) polyparastic-IPI (n=25), iii ) STHs (n=162), iv ) S intercalatum (n=11), and v ) E histolytica (n=7). Data analysis was performed using SPSS version 25.0. Chi-square and Fisher´s exact tests were used to identify associations between ABOs and IPI in pregnant women at p value <0.05. Results A total of 361 women with a mean age of 26.96 (SD: 7.00) were included, 43.6% (156) practiced open defecation, 15.8% (57) had no access to improved water, and 53.6% (192) lived in a rural area. The ABOs identified were 127 (39.6%) maternal anaemia, 26 (8.1%) PTB, 48 (14.9%) LBW and 8 (2.5%) stillbirths. ABOs in the monoparasitic-IPI and no-IPI groups were 46.7% vs 38.7% maternal anaemia, 6.2% vs 10.6% PTB, 11% vs 19.2% LBW and 3.4% vs 1.3% stillbirth, respectively. No statistically significant difference ( p 0.182, p 0.175, p 0.07, p 0.275) was found between the two groups. ABOs for S. intercalatum were anaemia 4 (36.4%) and LBW 1 (9.1%). A statistically significant difference was not found between ABOs in the no-IPI group compared to S. intercalatum or to other IPI-subgroups (polyparasitic-IPI, STHs, and E. histolytica ). Conclusion Maternal anaemia was found in almost half of pregnant women, but an association with IPI was not established. ABOs-related to IPIs are linked to the type of parasite, pathogenesis, intensity, and timing of the infection. Thus, the predominant parasite type – Ascaris lumbricoides – a low pathogenicity parasite, can support this study´s lack of association between IPIs and ABOs. Therefore, it is very important to know the country specific-setting of IPI epidemiology. To achieve a schistosomiasis elimination status, women-of-reproductive age and pregnant women should be included in the country preventive chemotherapy programmes.
Abstract Background Scarce information is available about the relationships between indoor air quality ( IAQ ) at day care centers ( DCC ), the estimated predisposition for asthma, and the actual wheezing susceptibility. Methods In the Phase II of ENVIRH study, 19 DCC were recruited after cluster analysis. Children were evaluated firstly using the ISAAC questionnaire and later by a follow‐up questionnaire about recent wheezing. A positive asthma predictive index ( API ) was considered as predisposition for asthma. Every DCC was audited for IAQ and monitored for chemical and biologic contaminants. Results We included 1191 children, with a median age of 43 (P 25 –P 75 : 25–58) months. Considering the overall sample, in the first questionnaire, associations were found between CO 2 concentration (increments of 200 ppm) and diagnosis of asthma ( OR : 1.10; 95% CI : 1.00–1.20). Each increment of 100 μg/m 3 of total volatile organic compounds ( TVOC ) and 1 μg of Der p1/g of dust were associated with wheezing in the previous 12 months ( OR : 1.06; 95% CI : 1.01–1.11 and OR : 1.06; 95% CI : 0.99–1.12, respectively). In the follow‐up questionnaire, TVOC were again associated with wheezing ( OR : 1.05; 95% CI : 1.00–1.11). Children exposed to fungal concentration above the 75th percentile had also higher odds of wheezing at follow‐up. TVOC were associated with wheezing in children with either negative or positive API . Conclusions IAQ in DCC seems to be associated with wheezing, in children with and without predisposition for asthma.
Increased left atrial (LA) size is a prognostic marker of mortality in the general population. LA size varies considerably in patients with dilated cardiomyopathy (DCM), but its clinical significance has not been widely studied. To evaluate the long-term prognostic value of LA volume (LAV) in patients with DCM. We prospectively studied patients admitted between January and December 2004 with a diagnosis of DCM, in sinus rhythm. Complete echocardiographic study at rest and after pharmacological stress was performed in all patients. The composite endpoint of mechanical ventricular assistance (MVA), heart transplantation or death during follow-up was assessed by univariate and multivariate analysis using a Cox regression model. The study population consisted of 35 patients (68.6% male, mean age 52.0) with DCM, 82.9% of non-ischemic etiology. Ejection fraction (EF) at rest was 31.1±9.4%. During follow-up, eight patients died, one was placed on MVA and one underwent transplantation. Univariate Cox analysis showed various potential echocardiographic markers of prognosis in our population, including LA size in M-mode (HR 1.12, CI: 0.99–1.26, p=0.067), LAV (HR 1.03, CI: 1.00–1.07, p=0.046), LAV adjusted for body surface area (HR 1.03, CI: 0.99–1.26, p=0.049), E/A ratio (HR 0.99; CI: 0.99–1.81; p=0.060); E/A >2 (HR 7.00, CI: 1.48–32.43, p=0.014) and mitral E/E’ ratio (HR 1.04, CI: 1.00–1.09, p=0.074). The only variable that remained in the multivariate model was LAV, with a cut-off value of 63 ml (HR 7.7, CI: 0.97–60.61, p=0.05). LAV was the only echocardiographic determinant of MVA, heart transplantation or death in our population with DCM. The echocardiographic parameters commonly used for risk stratification such as EF, left ventricular end-diastolic diameter and contractile reserve did not show prognostic significance in our study. O aumento da aurícula esquerda (AE) é um marcador de mortalidade na população geral. Os doentes com miocardiopatia dilatada (MCD) têm um amplo espetro de tamanhos de AE, mas a importância clínica desta observação tem sido pouco estudada. Avaliar a importância prognóstica a longo prazo do volume da AE (VAE) em doentes com MCD. Estudo prospetivo de doentes admitidos durante o ano de 2004 com o diagnóstico de MCD, em ritmo sinusal. Foi realizado estudo ecocardiográfico completo em repouso e após stress farmacológico. O endpoint composto considerou a assistência ventricular mecânica (AVM), a transplantação cardíaca ou a morte. Foram incluídos 35 doentes (68,6% sexo masculino, idade média 52,0), 82,9% etiologia não isquémica. Fração ejeção em repouso 31,1 ± 9,4%. Durante o seguimento, oito doentes morreram, um foi colocado em AVM e um foi transplantado. A análise de Cox univariável revelou potenciais marcadores ecocardiográficos de prognóstico na amostra tais como a dimensão da AE em modo M (HR-1,12; IC: 0,99-1,26; p = 0,067); VAE (HR-1,02; IC: 1,00-1,04; p = 0,046); VAE ajustado à superfície corporal (HR-1,03; IC: 1,00-1,07; p = 0,049); E/A (HR-0,99; IC: 0,99-1,81; p = 0,060); E/A > 2 (HR-7,00; IC:1,48-32,43; p = 0,014) e E/E’ mitral (HR-1,04; IC: 1,00-1,09; p = 0,074). Na análise multivariável a única variável que permaneceu no modelo foi o VAE com o ponto de corte de 63 ml (HR-7,7, IC: 0,97-60,61, p = 0,05). Nesta amostra, o VAE foi o único parâmetro ecocardiográfico determinante de AVM, transplantação cardíaca ou morte. Os parâmetros ecocardiográficos habitualmente utilizados para estratificação de risco, tais como a fração ejeção do ventrículo esquerdo, a dimensão do ventrículo esquerdo e a reserva contrátil não tiveram valor prognóstico na nossa amostra.
Background Inflammation is a crucial component in carcinogenesis. The neutrophil-to-eosinophil ratio (NER) has been studied as a biomarker of prognosis and predictive of response in metastatic renal cell carcinoma (mRCC). In the present study, we evaluated the relevance of baseline NER on the progression-free survival (PFS) and overall survival (OS) outcomes in real-world patients with mRCC treated with nivolumab in second or subsequent lines. We also assessed the association of baseline NER with objective response, as well as with toxicity and histology. Methods In this multicenter retrospective analysis of patients with mRCC treated with nivolumab, the last systemic absolute neutrophil and eosinophil count before treatment with nivolumab was used to calculate the NER. An additive Cox proportional hazards model was used to identify the cut-off point for NER considering PFS and the patients were allocated into low and high NER groups. Median OS and median PFS were estimated using the Kaplan-Meier estimator, and survival curves of groups were compared using the log-rank test. Univariable and multivariable Cox regression models were used to study OS and PFS and Fisher's exact test was performed to evaluate the association of NER with the response, toxicity, and histology. Results The 49 analyzed patients had a median follow-up of nine months. The NER cut-off was established at 48, locating 29 patients in the low NER group (NER < 48) and 20 in the high NER group (NER ≥ 48). Median PFS and median OS were significantly shorter in patients with high NER versus low NER (3 vs. 30 months (p < 0.001) and 6 vs. 24 months (p = 0.002), respectively). Multivariable analyses showed that NER (HR 3.92 (95% CI: 1.66-9.23), p = 0.002) was an independent factor for PFS and that NER (HR 3.85 (95% CI: 1.33-11.17), p = 0.013) and progressive disease (HR 5.62 (95% CI: 1.88-16.83), p = 0.002) were independent factors for OS. NER was significantly associated with objective response rate (ORR) (NER ≥ 48-12.5% vs. NER < 48-87.5%, p = 0.003), immune-related adverse events (irAEs) (NER ≥ 48-10.0% vs. NER < 48-42.9%, p = 0.014), and tumor's histology as patients of high NER group had more non-clear cell carcinoma than low NER group (35.0% vs. 7.4%, p = 0.017). Conclusion Our real-world data analysis of NER in patients with mRCC confirmed the prognostic value of this biomarker, supporting clinical utility in predicting survival. Results also suggested an association between lower NER and better ORR, and that irAEs occur more frequently in patients with a lower NER. However, further large-scale prospective studies are needed to confirm these findings and to validate this biomarker.
Introduction. The Test for Respiratory and Asthma Control in Kids (TRACK) is a tool to assess asthma control in preschool children. This study aims to validate the Portuguese from Portugal version of the TRACK questionnaire. Methods. A prospective cohort study was carried out to assess their psychometric characteristics. Caregivers of 141 children under age 5 with asthma symptoms were enrolled. Results. Internal reliability was close to 0.70 (Cronbach's α). The test-retest reliability was 0.87. TRACK scores were different between well, partially, and non-controlled asthma groups (p less than 0.001). Patients rated as having better control showed an increase in TRACK scores. Conclusions. The Portuguese version of the TRACK questionnaire is accurate and reliable for monitoring asthma control. Its use may help to overcome challenges with the management of this age group.
Systemic inflammation has been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD) systemic effects. However, most COPD patients do not suffer from persistent systemic inflammation even after exacerbations and exercise and scientific evidence has provided conflicting results. Our aim is to evaluate inflammatory gene expression at rest and at 1 and 24h after strenuous exercise in COPD patients and study the patient variables associated with inflammatory expression. A cross-sectional study was conducted in COPD patients who were recruited on entry to a pulmonary rehabilitation (PR) program. Demographic, clinical and functional data were collected. Blood samples were collected and gene expression was analyzed by reverse transcriptase polymerase chain reaction for IFNg, IL1b, IL6, IL8, TNFa, TGFb1 and iNOS. The study included 21 patients (15 men, 71.4%), mean age 66.1 years old (SD=8.27), mean FEV1 46.76% (SD 20.90%), 67% belonging to GOLD grade D, mean BODE index of 3.9, 90.5% with smoking history, mean BMI 25.81 (SD=4.87), median of 1.29 exacerbations in the previous year. There was no statistical significant difference between inflammatory expression at rest and at 1h and 24h after the maximal exercise test for all tested genes. We found an association between BMI and inflammatory expression at all the points of time checked, a slight inverse association occurs with low BMI for mRNA IL1b, IL6, TNFa, TGFb1 and iNOS, and there was a more pronounced positive association for obese patients for all tested genes. This preliminary study did not show an enhanced inflammatory gene expression from rest to 1h and 24h after short-term exercise, but did show an increased inflammatory gene expression in both BMI extremes, both at rest and after exercise, suggesting not only malnourishment, but also obesity as potential links between COPD and systemic inflammation. Studies with larger samples and designed to definitely exclude OSA or OHS as confounding factors in obese patients are required.
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