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

Management of Coronavirus Disease 2019 Patients With Lung Cancer: Experience From a Thoracic Oncology Center

Background: Cancer patients appear to be at a higher risk of complications from coronavirus disease 2019 (COVID-19). Specific data related to lung cancer (LC) patient management, active treatment, and/or recent diagnosis are still very limited. Here, we aimed to investigate the clinical presentation, baseline features, and clinical outcomes of LC patients with COVID-19. Methods: A retrospective case study was performed at Centro Hospitalar Universitário de São Joao, a tertiary hospital in the North of Portugal. Data from LC patients diagnosed with COVID-19 were collected during the first 10 months of the COVID-19 pandemic (March 2020–January 2021). Results: Twenty-eight patients with active LC were diagnosed with COVID-19, being adenocarcinoma the most common histological type present (n = 13, 46.4%). Sixteen patients had metastatic stage IV LC (61.5%). Twenty-five patients (89.3%) had relevant comorbidities including hypertension (39.3%) and chronic obstructive pulmonary disease (32.1%). For patients undergoing antineoplastic treatment, the median time from the last chemotherapy administration to COVID-19 diagnosis was of 16 days (interquartile range = 13–41 days). Half of patients were previously on corticosteroid therapy. Twenty patients (71.4%) needed hospitalization, 18 received oxygen therapy (64.3%), 3 (10.7%) of them received high-flow nasal cannula with good tolerability, and 1 (3.6%) needed non-invasive ventilation. Hydroxychloroquine and antibiotics were given to 4 (14.3%) and 12 (42.9%) patients, respectively. Seven patients (25%) died at a median time of 5 days following COVID-19 diagnosis. Conclusion: This is one of the first studies reporting the adverse outcomes associated with COVID-19 in LC patients at same time that adds evidence regarding the need to create protocols and guidelines to reduce the infection risk in such patients.NC-M acknowledges the Portuguese Foundation for Science and Technology under the Horizon 2020 Program (PTDC/PSI-GER/28076/2017)

Chest associated to motor physiotherapy improves cardiovascular variables in newborns with respiratory distress syndrome

<p>Abstract</p> <p>Background</p> <p>We aimed to evaluate the effects of chest and motor physiotherapy treatment on hemodynamic variables in preterm newborns with respiratory distress syndrome.</p> <p>Methods</p> <p>We evaluated heart rate (HR), respiratory rate (RR), systolic (SAP), mean (MAP) and diastolic arterial pressure (DAP), temperature and oxygen saturation (SO₂%) in 44 newborns with respiratory distress syndrome. We compared all variables between before physiotherapy treatment vs. after the last physiotherapy treatment. Newborns were treated during 11 days. Variables were measured 2 minutes before and 5 minutes after each physiotherapy treatment. We applied paired Student t test to compare variables between the two periods.</p> <p>Results</p> <p>HR (148.5 ± 8.5 bpm vs. 137.1 ± 6.8 bpm - p < 0.001), SAP (72.3 ± 11.3 mmHg vs. 63.6 ± 6.7 mmHg - p = 0.001) and MAP (57.5 ± 12 mmHg vs. 47.7 ± 5.8 mmHg - p = 0.001) were significantly reduced after 11 days of physiotherapy treatment compared to before the first session. There were no significant changes regarding RR, temperature, DAP and SO₂%.</p> <p>Conclusions</p> <p>Chest and motor physiotherapy improved cardiovascular parameters in respiratory distress syndrome newborns.</p

Adolescent Binge Drinking Leads to Changes in Alcohol Drinking, Anxiety, and Amygdalar Corticotropin Releasing Factor Cells in Adulthood in Male Rats

Heavy episodic drinking early in adolescence is associated with increased risk of addiction and other stress-related disorders later in life. This suggests that adolescent alcohol abuse is an early marker of innate vulnerability and/or binge exposure impacts the developing brain to increase vulnerability to these disorders in adulthood. Animal models are ideal for clarifying the relationship between adolescent and adult alcohol abuse, but we show that methods of involuntary alcohol exposure are not effective. We describe an operant model that uses multiple bouts of intermittent access to sweetened alcohol to elicit voluntary binge alcohol drinking early in adolescence (∼postnatal days 28–42) in genetically heterogeneous male Wistar rats. We next examined the effects of adolescent binge drinking on alcohol drinking and anxiety-like behavior in dependent and non-dependent adult rats, and counted corticotropin-releasing factor (CRF) cell in the lateral portion of the central amygdala (CeA), a region that contributes to regulation of anxiety- and alcohol-related behaviors. Adolescent binge drinking did not alter alcohol drinking under baseline drinking conditions in adulthood. However, alcohol-dependent and non-dependent adult rats with a history of adolescent alcohol binge drinking did exhibit increased alcohol drinking when access to alcohol was intermittent. Adult rats that binged alcohol during adolescence exhibited increased exploration on the open arms of the elevated plus maze (possibly indicating either decreased anxiety or increased impulsivity), an effect that was reversed by a history of alcohol dependence during adulthood. Finally, CRF cell counts were reduced in the lateral CeA of rats with adolescent alcohol binge history, suggesting semi-permanent changes in the limbic stress peptide system with this treatment. These data suggest that voluntary binge drinking during early adolescence produces long-lasting neural and behavioral effects with implications for anxiety and alcohol use disorders

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

A separated vortex ring underlies the flight of the dandelion

Wind-dispersed plants have evolved ingenious ways to lift their seeds1,2. The common dandelion uses a bundle of drag-enhancing bristles (the pappus) that helps to keep their seeds aloft. This passive flight mechanism is highly effective, enabling seed dispersal over formidable distances3,4; however, the physics underpinning pappus-mediated flight remains unresolved. Here we visualized the flow around dandelion seeds, uncovering an extraordinary type of vortex. This vortex is a ring of recirculating fluid, which is detached owing to the flow passing through the pappus. We hypothesized that the circular disk-like geometry and the porosity of the pappus are the key design features that enable the formation of the separated vortex ring. The porosity gradient was surveyed using microfabricated disks, and a disk with a similar porosity was found to be able to recapitulate the flow behaviour of the pappus. The porosity of the dandelion pappus appears to be tuned precisely to stabilize the vortex, while maximizing aerodynamic loading and minimizing material requirements. The discovery of the separated vortex ring provides evidence of the existence of a new class of fluid behaviour around fluid-immersed bodies that may underlie locomotion, weight reduction and particle retention in biological and manmade structures

Sustained Action of Developmental Ethanol Exposure on the Cortisol Response to Stress in Zebrafish Larvae and Adults

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are creditedThis study was supported by the National Centre for the replacement, refinement and reduction of animals in research

Miiuy Croaker Hepcidin Gene and Comparative Analyses Reveal Evidence for Positive Selection

Hepcidin antimicrobial peptide (HAMP) is a small cysteine-rich peptide and a key molecule of the innate immune system against bacterial infections. Molecular cloning and genomic characterization of HAMP gene in the miiuy croaker (Miichthys miiuy) were reported in this study. The miiuy croaker HAMP was predicted to encode a prepropeptide of 99 amino acids, a tentative RX(K/R)R cleavage motif and eight characteristic cysteine residues were also identified. The gene organization is also similar to corresponding genes in mammals and fish consisting of three exons and two introns. Sequence polymorphism analysis showed that only two different sequences were identified and encoded two proteins in six individuals. As reported for most other species, the expression level was highest in liver and an up-regulation of transcription was seen in spleen, intestine and kidney examined at 24 h after injection of pathogenic bacteria, Vibrio anguillarum, the expression pattern implied that miiuy croaker HAMP is an important component of the first line defense against invading pathogens. In addition, we report on the underlying mechanism that maintains sequences diversity among fish and mammalian species, respectively. A series of site-model tests implemented in the CODEML program revealed that moderate positive Darwinian selection is likely to cause the molecular evolution in the fish HAMP2 genes and it also showed that the fish HAMP1 genes and HAMP2 genes under different selection pressures