Deregulated immune cell recruitment orchestrated by c-MET impairs pulmonary inflammation and fibrosis.

BACKGROUND: Pulmonary fibrosis (PF) represents the pathologic end stage of several interstitial lung diseases (ILDs) associated with high morbidity and mortality rates. However, current treatments can only delay disease progression rather than provide a cure. The role of inflammation in PF progression is well-established, but new insights into immune regulation are fundamental for developing more efficient therapies. c-MET signaling has been implicated in the migratory capacity and effector functions of immune cells. Nevertheless, the role of this signaling pathway in the context of PF-associated lung diseases remains unexplored. METHODS: To determine the influence of c-MET in immune cells in the progression of pulmonary fibrosis, we used a conditional deletion of c-Met in immune cells. To induce pulmonary fibrosis mice were administered with bleomycin (BLM) intratracheally. Over the course of 21 days, mice were assessed for weight change, and after euthanasia at different timepoints, bronchoalveolar lavage fluid cells and lung tissue were assessed for inflammation and fibrosis. Furthermore, c-MET expression was assessed in cryobiopsy sections, bronchoalveolar lavage fluid cells samples and single cell RNA-sequencing dataset from human patients with distinct interstitial lung diseases. RESULTS: c-MET expression was induced in lung immune cells, specifically in T cells, interstitial macrophages, and neutrophils, during the inflammatory phase of BLM-induced PF mouse model. Deletion of c-Met in immune cells correlated with earlier weight recovery and improved survival of BLM-treated mice. Moreover, the deletion of c-Met in immune cells was associated with early recruitment of the immune cell populations, normally found to express c-MET, leading to a subsequent attenuation of the cytotoxic and proinflammatory environment. Consequently, the less extensive inflammatory response, possibly coupled with tissue repair, culminated in less exacerbated fibrotic lesions. Furthermore, c-MET expression was up-regulated in lung T cells from patients with fibrosing ILD, suggesting a potential involvement of c-MET in the development of fibrosing disease. CONCLUSIONS: These results highlight the critical contribution of c-MET signaling in immune cells to their enhanced uncontrolled recruitment and activation toward a proinflammatory and profibrotic phenotype, leading to the exacerbation of lung injury and consequent development of fibrosis.

The impact of nintedanib and pirfenidone on lung function and survival in patients with idiopathic pulmonary fibrosis in real-life setting.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a chronic, fibrosing interstitial pneumonia of unknown cause that is associated with radiological and/or histological features of usual interstitial pneumonia (UIP). A mean survival of 2-5 years was reported previously to the advent of antifibrotics. According to clinical trials, nintedanib and pirfenidone induce a significant delay in functional decline, with a favorable impact on survival. METHODS: A real-life retrospective and longitudinal study was conducted to assess the efficacy and tolerability of antifibrotics in IPF patients, between January 2014 and December 2020. Two groups (under nintedanib or pirfenidone) were analyzed at diagnosis through their clinical features and radiological patterns. Lung function was assessed at diagnosis (time 0) and after 6, 12 and 24 months of treatment. We also compared this antifibrotic cohort with an older naïve antifibrotic cohort, mainly treated with immunosuppressive drugs and/or N- acetylcysteine. Survival was analyzed and prognostic features were also studied. Statistical analysis was performed with IBM® SPSS®. RESULTS: A cohort of 108 patients under antifibrotics (nintedanib n = 54; pirfenidone n = 54) was assessed. Lung function analysis showed an overall stabilization in FVC and DLCO mean predicted percentages at 6, 12 and 24 months of treatment. The mean decline in FVC and DLCO, at 12 months, was -40.95 ± 438.26 mL and -0.626 ± 1.31 mL/min/mmHg, respectively. However, during this period, 34.2% of the patients died mostly due to acute exacerbation associated with a poorer lung function at diagnosis. Mean survival in the naïve antifibrotic cohort was significantly lower than in the antifibrotic cohort (39.9 months versus 58.2 months; p < 0.005). Regarding lung function evolution and survival, we found no differences between definitive or probable UIP radiological patterns, both on patients under nintedanib and pirfenidone (p = 0.656). CONCLUSIONS: In this real-life observational study, the positive impact of antifibrotic therapy on the IPF clinical course and on survival was corroborated. Regarding efficacy, there was no difference between patients taking nintedanib or pirfenidone. The need for an early treatment was also demonstrated, since a worse outcome is clearly associated with lower lung volumes and lower diffusing capacity at diagnosis.

Osteoporosis screening using machine learning and electromagnetic waves.

Osteoporosis is a disease characterized by impairment of bone microarchitecture that causes high socioeconomic impacts in the world because of fractures and hospitalizations. Although dual-energy X-ray absorptiometry (DXA) is the gold standard for diagnosing the disease, access to DXA in developing countries is still limited due to its high cost, being present only in specialized hospitals. In this paper, we analyze the performance of Osseus, a low-cost portable device based on electromagnetic waves that measures the attenuation of the signal that crosses the medial phalanx of a patient's middle finger and was developed for osteoporosis screening. The analysis is carried out by predicting changes in bone mineral density using Osseus measurements and additional common risk factors used as input features to a set of supervised classification models, while the results from DXA are taken as target (real) values during the training of the machine learning algorithms. The dataset consisted of 505 patients who underwent osteoporosis screening with both devices (DXA and Osseus), of whom 21.8% were healthy and 78.2% had low bone mineral density or osteoporosis. A cross-validation with k-fold = 5 was considered in model training, while 20% of the whole dataset was used for testing. The obtained performance of the best model (Random Forest) presented a sensitivity of 0.853, a specificity of 0.879, and an F1 of 0.859. Since the Random Forest (RF) algorithm allows some interpretability of its results (through the impurity check), we were able to identify the most important variables in the classification of osteoporosis. The results showed that the most important variables were age, body mass index, and the signal attenuation provided by Osseus. The RF model, when used together with Osseus measurements, is effective in screening patients and facilitates the early diagnosis of osteoporosis. The main advantages of such early screening are the reduction of costs associated with exams, surgeries, treatments, and hospitalizations, as well as improved quality of life for patients.

Does the placement of a collagen-fibrin sealant reduce complications of radical inguinal lymph node dissection? - Comparative study in patients with penile cancer.

OBJECTIVE: Management of patients with penile cancer (PeC) with palpable inguinal lymph nodes (ILNs) relies on radical ILN dissection (RILND). Low burden of nodal metastatic disease may lead to long-lasting survival with surgical management. Nevertheless, RILND involves significant postoperative morbidity. We compared the complications of patients undergoing RILND with (RILND-T) and without (RILND-0T) placement of a collagen-fibrin sealant patch on the resection bed. MATERIALS AND METHODS: We conducted an observational retrospective study. Data from men submitted to RILND-T and RILND-0T from Jan/2001 to Feb/2022, in a tertiary care centre were compared. The primary endpoint was the overall incidence of complications until 1 month after the procedure and their respective severity in both cohorts (Clavien-Dindo classification system). Secondarily, length of hospital stay (LOHS) was analysed. The placement of a collagen-fibrin sealant patch was left at the surgeon's discretion. RESULTS: Seven patients underwent RILND-T and 20 underwent RILND-0T, respectively. There were no differences in pathologic TNM stage nor in the total number of ILNs removed (17 ± 4 vs. 20 ± 8, p = 0.37). Overall, 23 (85.2%) patients had complications. The complication rate was similar in both cohorts (85.7% vs 85%, p = 0.73). Surgical wound infection (3/7 vs. 11/20) and lymphocele (4/7 vs. 11/20) were the most reported complications. Patients undergoing RILND-T were discharged faster (mean length of hospital stay 9 ± 3 vs 19 ± 20 days, p = 0.22). CONCLUSIONS: The application of a collagen-fibrin sealant patch on the resection bed does not seem to reduce the postoperative complication rate in patients undergoing RILND. Nevertheless, a trend towards a shorter LOHS in patients with RILND-T cannot be excluded and should be validated by further studies with a higher number of patients.

Diagnostic yield and safety of transbronchial lung cryobiopsy and surgical lung biopsy in interstitial lung diseases: a systematic review and meta-analysis.

INTRODUCTION: Transbronchial lung cryobiopsy (TBLC) is increasingly being used as an alternative to video-assisted thoracoscopic surgery (VATS) biopsy to establish the histopathologic pattern in interstitial lung disease (ILD). METHODS: A systematic literature search of the PubMed and Embase databases, from October 2010 to October 2020, was conducted to identify studies that reported on diagnostic yield or safety of VATS or TBLC in the diagnosis of ILD. RESULTS: 43 studies were included. 23 evaluated the diagnostic yield of TBLC after multidisciplinary discussion, with a pooled diagnostic yield of 76.8% (95% confidence interval (CI) 70.6-82.1), rising to 80.7% in centres that performed ≥70 TBLC. 10 studies assessed the use of VATS and the pooled diagnostic yield was 93.5% (95% CI 88.3-96.5). In TBLC, pooled incidences of complications were 9.9% (95% CI 6.8-14.3) for significant bleeding (6.9% for centres with ≥70 TBLC), 5.6% (95% CI 3.8-8.2) for pneumothorax treated with a chest tube and 1.4% (95% CI 0.9-2.2) for acute exacerbation of ILD after TBLC. The mortality rates were 0.6% and 1.7% for TBLC and VATS, respectively. CONCLUSIONS: TBLC has a fairly good diagnostic yield, an acceptable safety profile and a lower mortality rate than VATS. The best results are obtained from more experienced centres.

Neoadjuvant chemotherapy for muscle-invasive bladder cancer: does variant histology matter?

PURPOSE: The most frequent histology of bladder tumors is urothelial carcinoma. Most are pure urothelial carcinomas (PUC) but up to one-third of the cases present variant histological (VH) features. The aim of this study was to evaluate the role of variant histology in neoadjuvant chemotherapy (NAC) response in patients with urothelial muscle-invasive bladder cancer. METHODS: We retrospectively analyzed data from 77 patients with bladder cancer who performed neoadjuvant chemotherapy at two institutions. RESULTS: Complete pathological response (ypT0) was higher in patients with PUC (38.5%), comparing with VH (12%). Logistic regression analysis demonstrated that variant histology is associated with an 89% lesser likelihood of tumor downstaging, with advanced clinical T stages and positive smoking history as independent predictors. The estimated mean cancer-specific survival was 68.91 months for PUC patients and 50.23 months for VH patients (log rank test, P = 0.024). Multivariate Cox regression analysis demonstrated that VH and clinical T stage were independent predictors of cancer-specific survival, indicating a worse outcome for patients with VH and advanced clinical T stages. CONCLUSIONS: There are only a few retrospective studies evaluating the clinical impact of variant histology tumors, which are mainly managed as PUC. Our results demonstrate that VH is associated with a worse likelihood of tumor downstaging after NAC and a worse cancer-specific survival in bladder cancer patients. There is a need for further studies and genetic analysis to identify the patients most likely to achieve ypT0 status and downstaging after NAC.

Predictive value of common genetic variants in idiopathic pulmonary fibrosis survival.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, fibrosing interstitial pneumonia of unknown etiology. The role of genetic risk factors has been the focus of numerous studies probing for associations of genetic variants with IPF. We aimed to determine whether single-nucleotide polymorphisms (SNPs) of four candidate genes are associated with IPF susceptibility and survival in a Portuguese population. A retrospective case-control study was performed with 64 IPF patients and 74 healthy controls. Ten single-nucleotide variants residing in the MUC5B, TOLLIP, SERPINB1, and PLAU genes were analyzed. Single- and multi-locus analyses were performed to investigate the predictive potential of specific variants in IPF susceptibility and survival. Multifactor dimensionality reduction (MDR) was employed to uncover predictive multi-locus interactions underlying IPF susceptibility. The MUC5B rs35705950 SNP was significantly associated with IPF: T allele carriers were significantly more frequent among IPF patients (75.0% vs 20.3%, P < 1.0 × 10-6). Genotypic and allelic distributions of TOLLIP, PLAU, and SERPINB1 SNPs did not differ significantly between groups. However, the MUC5B-TOLLIP T-C-T-C haplotype, defined by the rs35705950-rs111521887-rs5743894-rs5743854 block, emerged as an independent protective factor in IPF survival (HR = 0.37, 95% CI 0.17-0.78, P = 0.009, after adjustment for FVC). No significant multi-locus interactions correlating with disease susceptibility were detected. MUC5B rs35705950 was linked to an increased risk for IPF, as reported for other populations, but not to disease survival. A haplotype incorporating SNPs of the MUC5B-TOLLIP locus at 11p15.5 seems to predict better survival and could prove useful for prognostic purposes and IPF patient stratification. KEY MESSAGES : The MUC5B rs35705950 minor allele is associated with IPF risk in the Portuguese. No predictive multi-locus interactions of IPF susceptibility were identified by MDR. A haplotype defined by MUC5B and TOLLIP SNPs is a protective factor in IPF survival. The haplotype may be used as a prognostic tool for IPF patient stratification.

Variant histologies of urothelial carcinoma: Does it change the survival outcomes in patients managed with radical cystectomy?

OBJECTIVE: To investigate the impact of variant histologies (VH) of urothelial carcinoma (UC) on survival outcomes after radical cystectomy (RC). MATERIALS AND METHODS: Data from 181 patients with UC treated with RC between January 2013 and December 2019 at a single tertiary care referral center were retrospectively accessed. All RC specimens were assigned by genitourinary dedicated pathologists. Overall survival (OS), disease-specific survival (DSS) and recurrence-free survival (RFS) were evaluated using the Kaplan-Meier methodology and the Cox proportional hazards regression. RESULTS: Of 181 patients, 43.1% (n = 78) had VH, with the most common being squamous differentiation (n = 29), followed by mixed variants (n = 18), micropapillary variant (n = 10) and other subtypes (n = 21). The median (range) follow-up was 35 (18-59) months. Kaplan-Meier survival analysis shows that median OS and DS were significantly worse for VH patients (78 vs 31 months, p = 0.038; not reached vs 42 months; p = 0.016). At 5 years, VH was associated with a 12% and 14% decrease in OS and DSS, respectively. No significant statistical difference between the two groups was reached regarding RFS. However, after adjusting for confounders, such as, demographics characteristics, comorbidities and pathological features, VH were not associated with any survival outcomes. CONCLUSIONS: Our study evidenced the high incidence of bladder cancers with VH. Although clearly associated with features of more aggressive behavior, VH had not any significant impact in survival expectancies when all confounders are adjusted in multivariate analyses.

Epigenetically-regulated miR-30a/c-5p directly target TWF1 and hamper ccRCC cell aggressiveness.

Clear cell renal cell carcinoma (ccRCC) is highly prone to metastasize and displays an extremely low 5-year survival rate. Not only miRNAs (miRs) are key gene expression regulators but can also be epigenetically modified. Abnormal miR expression has been linked with epithelial-mesenchymal transition (EMT)-driven ccRCC progression. MiR-30a/c-5p were found downregulated in ccRCC and associated with aggressiveness. Herein, we sought to unravel miR-30a/c-5p mechanistic role in ccRCC. RNA sequencing and genome-wide methylome data of ccRCC and normal tissue samples from The Cancer Genome Atlas database were integrated to identify candidate miRs cytosine-phosphate-guanine (CpG) loci deregulated in ccRCC. TargetScan was searched to identify miR putative targets. MiR-30a/c-5p expression and promoter methylation was evaluated in vitro, by PCR. Western blot, functional and luciferase assays were performed after cell transfection with either pre-miR, antimiR, or siRNA against twinfilin-1 (TWF1). Immunohistochemistry (IHC) was performed in ccRCC tissues. We found miR-30c-5p downregulation and aberrant promoter methylation in ccRCC tissues. In vitro studies revealed concomitant miR-30a/c-5p downregulation and increased promoter methylation, as well as a significant re-expression following decitabine treatment. Functional assays demonstrated that both miRs significantly decreased cell aggressiveness and the protein levels of EMT-promoting players, while upregulating epithelial markers, namely Claudin-1 and ZO-1. Importantly, we confirmed TWF1 as a direct target of both miRs, and its potential involvement in epithelial-mesenchymal transition/mesenchymal-epithelial transition regulation. IHC analysis revealed higher TWF1 expression in primary tissues from patients that developed metastases, after surgical treatment. Our results implicate miR-30a/c-5p in ccRCC cells' aggressiveness attenuation by directly targeting TWF1 and hampering EMT.

European Respiratory Society guidelines on transbronchial lung cryobiopsy in the diagnosis of interstitial lung diseases.

BACKGROUND: In patients with interstitial lung diseases (ILD), histopathological input is often required to obtain a diagnosis. Surgical lung biopsy (SLB) is considered the reference standard, but many patients are clinically unfit to undergo this invasive procedure, and adverse events, length of hospitalisation and costs are considerable. This European Respiratory Society (ERS) guideline provides evidence-based clinical practice recommendations for the role of transbronchial lung cryobiopsy (TBLC) in obtaining tissue-based diagnosis in patients with undiagnosed ILD. METHODS: The ERS Task Force consisted of clinical experts in the field of ILD and/or TBLC and methodological experts. Four PICO (Patient, Intervention, Comparator, Outcomes) questions and two narrative questions were formulated. Systematic literature searches were performed in MEDLINE and Embase (up to June 2021). GRADE (Grading, Recommendation, Assessment, Development and Evaluation) methodology was applied. RESULTS: In patients with undiagnosed ILD and an indication to obtain histopathological data: 1) TBLC is suggested as a replacement test in patients considered eligible to undergo SLB, 2) TBLC is suggested in patients not considered eligible to undergo SLB, 3) SLB is suggested as an add-on test in patients with a non-informative TBLC, 4) no recommendation is made for or against a second TBLC in patients with a non-informative TBLC and 5) TBLC operators should undergo training, but no recommendation is made for the type of training required. CONCLUSIONS: TBLC provides important diagnostic information in patients with undiagnosed ILD. Diagnostic yield is lower compared to SLB, at reduced serious adverse events and length of hospitalisation. Certainty of the evidence is mostly "very low".

Pentraxin 3 Inhibits Complement-driven Macrophage Activation to Restrain Granuloma Formation in Sarcoidosis.

Rationale: Sarcoidosis is a multisystemic inflammatory disease characterized by the formation of granulomas in response to persistent stimuli. The long pentraxin PTX3 (pentraxin 3) has emerged as a component of humoral innate immunity with essential functions in the resolution of inflammation, but its role during granuloma formation is unknown. Objectives: To evaluate PTX3 as a modulator of pathogenic signals involved in granuloma formation and inflammation in sarcoidosis. Methods: Peripheral blood mononuclear cells obtained from patients with sarcoidosis harboring loss-of-function genetic variants and gene-deleted mice were used to assess the role of PTX3 in experimental models of granuloma formation in vitro and in vivo. The identified mechanisms of granulomatous inflammation were further evaluated in tissue and BAL samples and correlated with the disease course. Measurements and Main Results: We have identified a molecular link between PTX3 deficiency and the pathogenic amplification of complement activation to promote granuloma formation. Mechanistically, PTX3 deficiency licensed the complement component C5a-mediated activation of the metabolic checkpoint kinase mTORC1 (mammalian target of rapamycin complex 1) and the reprogramming of macrophages toward increased glycolysis to foster their proliferation and aggregation. This process sustained the further recruitment of granuloma-promoting immune cells and the associated proinflammatory microenvironment and influenced the clinical course of the disease. Conclusions: Our results identify PTX3 as a pivotal molecule that regulates complement-mediated signaling cues in macrophages to restrain granulomatous inflammation and highlight the therapeutic potential of this signaling axis in targeting granuloma formation in sarcoidosis.

Pleuroparenchymal fibroelastosis as a complication of chemotherapy: A case report.

Pleuroparenchymal fibroelastosis (PPFE) is a rare and recently described distinct pattern of lung apical fibrosis involving the upper lobe parenchyma and pleural dome. PPFE has definable and reproducible clinical, radiological and histopathological criteria, which allowed its classification as an independent interstitial lung disease. Several factors have been associated with PPFE, such as chemotherapy, especially with alkylating agents. The authors present a case of a 34-year-old female with previous history of Hodgkin lymphoma treated with first line chemotherapy (doxorubicin, bleomycin, vinblastine and dacarbazine). The patient had no other known comorbidities or relevant exposure to lung irritants. A total of 2 years after completing cancer treatment, the patient developed clinical and radiological features of PPFE. Given their previous history of malignancy, a biopsy of the lesion was obtained, which confirmed the diagnosis of PPFE. The authors present this case to raise awareness of this disease and to demonstrate that PPFE can develop months to years following chemotherapy treatment. Moreover, to date, none of these chemotherapy agents have been associated with the development of PPFE.

The Role of Ultrasonography in the Diagnosis and Decision Algorithm for the Management of Pneumothorax after Transbronchial Lung Cryobiopsy.

BACKGROUND: Pneumothorax is one of the main complications of transbronchial lung cryobiopsy (TBLC). Chest ultrasound (CUS) is a radiation-free alternative method for pneumothorax detection. OBJECTIVE: We tested CUS diagnostic accuracy for pneumothorax and assessed its role in the decision algorithm for pneumothorax management. Secondary objectives were to evaluate the post-procedure pneumothorax occurrence and risk factors. METHODS: Eligible patients underwent TBLC, followed by chest X-ray (CXR) evaluation 2 h after the procedure, as our standard protocol. Bedside CUS was performed within 30 min and 2 h after TBLC. Pneumothorax by CUS was defined by the absence of lung sliding and comet-tail artefacts and confirmed with the stratosphere sign on M-mode. Pneumothorax size was determined through lung point projection on CUS and interpleural distance on CXR and properly managed according to clinical status. RESULTS: Sixty-seven patients were included. Nineteen pneumothoraces were detected at 2 h after the procedure, of which 8 (42.1%) were already present at the first CUS evaluation. All CXR-detected pneumothoraces had a positive CUS detection. There were 3 discordant cases (κ = 0.88, 95% CI: 0.76-1.00, p < 0.001), which were detected by CUS but not by inspiration CXR. We calculated a specificity of 97.5% (95% CI: 86.8-99.9) and a sensitivity of 100% (95% CI: 87.2-100) for CUS. Pneumothorax rate was higher when biopsies were taken in 2 lobes and if histology had pleural representation. Final diagnosis was achieved in 79.1% of patients, with the most frequent diagnosis being hypersensitivity pneumonitis. Regarding patients with large-volume pneumothorax needing drainage, the rate of detection was similar between CUS and CRX. CONCLUSION: CUS can replace CXR in detecting the presence of pneumothorax after TBLC, and the lung point site can reliably indicate its size. This useful method optimizes time spent at the bronchology unit and allows immediate response in symptomatic patients, helping to choose optimal treatment strategies, while preventing ionizing radiation exposure.

AGO2 expression levels and related genetic polymorphisms: influence in renal cell progression and aggressive phenotypes.

Aim: Renal cell carcinoma (RCC) is the most lethal urological cancer and up to 40% of patients submitted to surgery will relapse. Thus, the study aim was to analyze the associations of AGO2 SNPs with RCC patients' prognosis, and evaluate their effect on AGO2 mRNA levels. Materials & methods: The AGO2 rs4961280, rs3928672 and rs11996715 polymorphisms and the relative quantification of AGO2 mRNA levels were analyzed by real-time PCR. Results: We observed that AGO2 rs4961280 AC + AA genotypes carriers presented a higher cancer progression risk (odds ratio= 3.13, p < 0.001), a reduced progression-free survival (log rank test, p = 0.003) and an increased risk of an early relapse (hazard ratio= 2.26, p = 0.008). In fact, these patients also presented higher circulating levels of AGO2 mRNA (p = 0.043), with the high levels being associated with more aggressive tumors. Conclusion: The AGO2 rs4961280 AA/AC genotypes are unfavorable RCC prognostic biomarkers, with the AGO2 levels being a useful RCC aggressive phenotype biomarker.

Demographic, clinical and pathological characterisation of patients with colorectal and anal cancer followed between 2013 and 2016 at Maputo Central Hospital, Mozambique.

PURPOSE: The aim of this study was to investigate colorectal cancer (CRC) data and anal cancer data from Maputo Central Hospital (MCH), the largest hospital and a reference for oncological diseases in Mozambique, with the aim of characterising the disease profile in view to define an appropriate control programme. METHODS: MCH records from the Pathology and Surgery Services and MCH Cancer Registry database were assessed to obtain retrospective clinical and pathologic data of patients with CRC or anal cancer admitted to and treated between 13 December 2013 and 23 March 2016. RESULTS: The female gender was more prevalent (54.8%), even when anal cancers were excluded. Median age was 54 years (20-99). Most patients (51.6%) lived in the city of Maputo. The most common presenting symptom was found to be rectal bleeding. Adenocarcinoma was the most frequent histological type, and the most prevalent anatomical site was the rectum. Most of the cases were diagnosed at MCH in advanced stages. Colostomy was the most frequent surgical procedure and performed in 38.7% of the patients. Most cases of anal cancer occurred in human immunodeficiency virus-infected patients. Most patients had a poor prognosis due to advanced stage at first diagnosis. CONCLUSION: We observed an increase in cases of CRC and anal cancer in Mozambique and mostly diagnosed at advanced stages, which anticipates a dismal prognosis. Our data supports the urgent need of a comprehensive public health programme dedicated to solving this growing concern.

miRNAs as biomarkers for early cancer detection and their application in the development of new diagnostic tools.

Over the last decades, microRNAs (miRNAs) have emerged as important molecules associated with the regulation of gene expression in humans and other organisms, expanding the strategies available to diagnose and handle several diseases. This paper presents a systematic review of literature of miRNAs related to cancer development and explores the main techniques used to quantify these molecules and their limitations as screening strategy. The bibliographic research was conducted using the online databases, PubMed, Google Scholar, Web of Science, and Science Direct searching the terms "microRNA detection", "miRNA detection", "miRNA and prostate cancer", "miRNA and cervical cancer", "miRNA and cervix cancer", "miRNA and breast cancer", and "miRNA and early cancer diagnosis". Along the systematic review over 26,000 published papers were reported, and 252 papers were returned after applying the inclusion and exclusion criteria, which were considered during this review. The aim of this study is to identify potential miRNAs related to cancer development that may be useful for early cancer diagnosis, notably in the breast, prostate, and cervical cancers. In addition, we suggest a preliminary top 20 miRNA panel according to their relevance during the respective cancer development. Considering the progressive number of new cancer cases every year worldwide, the development of new diagnostic tools is critical to refine the accuracy of screening tests, improving the life expectancy and allowing a better prognosis for the affected patients.

Predictors of survival and technical success of bronchoscopic interventions in malignant airway obstruction.

BACKGROUND: Malignant airway obstruction (MAO) leads to quality of life impairment and increased mortality. Interventional bronchoscopy allows airway patency restoring, leading to a better survival. We investigated predictors of survival and successful bronchoscopic intervention among MAO patients. METHODS: This observational prospective study enrolled 100 patients who were newly diagnosed with MAO. Survival was estimated with Kaplan-Meier method and curves compared by log-rank test. Multivariate analyses were performed using Cox proportional hazard models. Univariate and multivariate logistic regression were used for odds ratio calculation. RESULTS: A proportion of 73% of the patients were male with a median age was 62.5 years (range, 21-88 years). Lung cancer was the most common primary malignancy (74%). The majority had single (61%), endoluminal (62%) lesions and were classified as grade III in Myer Cotton scale (57%). The most used techniques comprised mechanical debulking (n=81) and laser therapy (n=68). Twenty-two airway stents were placed. While eleven patients were considered untreatable, technical success was achieved in 78%. Haemorrhage was the most common acute complication (16%). No deaths occurred as a result of the procedure. Median global survival was 8 months. Adjusting for age and Eastern Cooperative Oncology Group Performance Status (ECOG), extrinsic compression or mixed airway obstructions [hazard ratio (HR) =2.075; P=0.012], successful bronchoscopic intervention (HR =0.468; P=0.025) and initiation of cancer treatment (HR =0.373; P=0.006) were independent predictors of survival. The absence of distal airway patency on thoracic CT was independently associated with failure of the intervention [odds ratio (OR) =0.013; P<0.001]. CONCLUSIONS: Interventional bronchoscopy has proven to be an efficient and safe strategy to manage MAO patients. The patients who benefit the most in terms of survival are those with purely endoluminal lesions, in whom technical success was achieved and those whose cancer-specific treatment was initiated. Distal airway patency on thoracic CT predicts the technical success of bronchoscopic intervention.

Uma análise das teleconsultorias assíncronas em saúde auditiva do Núcleo de Telessaúde do Rio Grande do Norte / An analysis of asynchronous hearing health teleconsulting at the Rio Grande do Norte Telehealth Center

RESUMO Objetivo identificar o perfil das teleconsultorias assíncronas na área da saúde auditiva do Núcleo Técnico Científico de Telessaúde do Rio Grande do Norte (RN). Métodos este estudo é retrospectivo e descritivo. Foram analisados os registros das teleconsultorias de janeiro de 2015 a dezembro de 2019 na plataforma de teleconsultoria do Núcleo de Telessaúde do RN. As teleconsultorias foram filtradas e categorizadas por dois fonoaudiólogos quanto a estado de origem, gênero e profissão do solicitante, tema e objetivo da questão. Resultados entre as teleconsultorias realizadas no período, foram incluídas, neste estudo, as teleconsultorias na área da saúde auditiva. Em ordem decrescente de frequência, os profissionais solicitantes foram: agentes comunitários de saúde, fonoaudiólogos, agentes de combate a endemias, médicos, enfermeiros, agentes de saúde pública, técnicos e auxiliares de enfermagem e outros. Quanto aos objetivos das teleconsultorias, de maior a menor frequência, foram constatadas perguntas sobre condutas, avaliação, tratamento, relações entre fatores, etiologias, prevenção, sintomas, implantação, acesso ao sistema de saúde e outras. Em relação às temáticas, em ordem descendente, foram observadas perguntas sobre hipoacusia, dispositivos auxiliares de audição, zumbido, otite, programa saúde na escola, emissões otoacústicas, otalgia, labirintite e perfuração timpânica. Conclusão as teleconsultorias assíncronas sobre saúde auditiva tiveram maior frequência por solicitantes do gênero feminino, agentes comunitários de saúde e fonoaudiólogos, sobre a temática da hipoacusia e de dispositivos auxiliares de audição, com objetivo de tomada de decisões para condutas e avaliação na área da saúde auditiva.

ABSTRACT Objective To identify the profile of asynchronous hearing health teleconsulting ​​ at the Scientific-Technical Center for Telehealth in Rio Grande do Norte (RN). Methods This study is retrospective and descriptive. Teleconsulting records from January 2015 to December 2019 on the telehealth platform of the Telehealth Center of RN were analyzed. The teleconsultations were filtered and categorized by two speech-language therapists regarding the applicant's state of origin, gender and profession, theme and objective of the question. Results Among the teleconsultations carried out in the period, the ones regarding the hearing health area were included in this study. In decreasing order of frequency, the requesting professionals were: community health agents, speech-language therapists, endemic disease control agents, doctors, nurses, public health agents, nursing technicians and assistants and others. As for the objectives of teleconsulting, from higher to lower frequency, were identified questions about: conduct, evaluation, treatment, relations among factors, etiologies, prevention, symptoms, implementation, access to the health system and others. Concerning the themes, in descending order, were observed questions about hearing loss, hearing aid devices, tinnitus, otitis, school health program, otoacoustic emissions, otalgia, labyrinthitis and tympanic perforation. Conclusion Asynchronous teleconsulting on hearing health was more frequent on female applicants, community health agents and speech-language therapists, concerning the theme of hearing loss and hearing aid devices, to make decisions for conducts and evaluation in the health area hearing.

Cytokine gene polymorphisms in Pigeon Breeder's Disease expression.

BACKGROUND: Exaggerated immunological response to repeated inhalation of organic or chemical dusts may lead to Hypersensitivity Pneumonitis among sensitized individuals. Only a few exposed individuals became ill and disease expression pattern is highly variable which suggest that genetic factors may play a role. AIM: To investigate interferon (IFN)-γ, tumour necrosis factor (TNF)-α, interleukin (IL)-6, transforming growth factor (TGF)-ß, and IL-10 gene polymorphisms in a cohort of pigeon breeder's disease (PBD) patients in comparison with exposed but healthy controls and the association with different patterns of disease. METHODS: We evaluated 40 PBD patients and 70 exposed controls. IFN-γ, TNF-α, IL-6, TGF-ß, and IL-10 polymorphisms were determined by polymerase chain reaction-sequence specific primer amplification. RESULTS: Polymorphism analysis of IFN-γ, TNF-α, IL-6, TGF-ß, and IL-10 genotypes and allele frequencies showed no differences between patients and controls. IFN-γ T/T genotype frequency was increased among patients with chronic presentation (RR=2.33, p=0.047) compared with those with acute/subacute presentation. Also, chronic presenting patients had an increased frequency of IFN-γ T allele (50% vs 22.5%, RR=1.76, p=0.011). No differences were found in TNF-α, IL-6, TGF-ß, and IL-10 genotypes neither allelic frequencies between both groups of patients. IL-6 C/C genotype was more frequent in patients who showed chronic evolution (RR=2.54, p=0.017), when comparing with patients with disease resolution. CONCLUSION: IFN-γ T/T and the IL-6 C/C genotypes seem to play a role in HP expression due to avian exposure, as their frequencies are increased in chronic presentations or in those with chronic evolution one year after the initial diagnosis, respectively. (Sarcoidosis Vasc Diffuse Lung Dis 2020; 37 (3): e2020004).