Ability of single anesthesia for combined robotic-assisted bronchoscopy and surgical lobectomy to reduce time between detection and treatment in stage I non-small cell lung cancer.

Background: Background: Early identification, diagnosis, and treatment of lung cancer is associated with improved clinical outcomes. Robotic-assisted bronchoscopy improves the ability to diagnose early stage lung malignancies and, when combined with robotic-assisted lobectomy under single anesthesia, could reduce time from identification to intervention in early stage lung cancer in a select patient population. Methods: Methods: A retrospective case-control single-center study compared patients with radiographic stage I non-small cell carcinoma (NSCCA) undergoing robotic navigational bronchoscopy and surgical resection (N = 22) with historical controls (N = 63). The primary outcome was time from initial radiographic identification of a pulmonary nodule to therapeutic intervention. Secondary outcomes included times between identification to biopsy, biopsy to surgery, and procedural complications. Results: Results: Patients with suspected stage I NSCCA who received single anesthesia for diagnosis and intervention with robotic-assisted bronchoscopy and robotic-assisted lobectomy had shorter times between identification of a pulmonary nodule and intervention compared to controls (65 vs 116 days, P = 0.005). Cases had lower rates of complications (0% vs 5%) and shorter hospitalizations after surgery (3.6 vs 6.2 days, P = 0.017). Conclusion: Conclusion: Our findings support that implementing a multidisciplinary thoracic oncology team and single-anesthesia biopsy-to-surgery approach in management of stage I NSCCA significantly reduced times from identification to intervention, biopsy to intervention, and length of hospital stays in management of lung cancer.

Relation of masking policy to COVID-19 positivity rate in Texas school districts.

Understanding of the impact of masking in schools to prevent COVID transmission is limited since much of the data considers factors in addition to masking. We collected data from 30 school districts in Texas, contrasting districts where masks were mandated with those where masks were optional. Results showed that mandatory masking was associated with a reduction in COVID-19 positivity among student populations, but not in staff populations.

Association of Healthcare Access With Intensive Care Unit Utilization and Mortality in Patients of Hispanic Ethnicity Hospitalized With COVID-19.

BACKGROUND: Racial and ethnic minority groups in the United States experience a disproportionate burden of COVID-19 deaths. OBJECTIVE: To evaluate whether outcome differences between Hispanic and non-Hispanic COVID-19 hospitalized patients exist and, if so, to identify the main malleable contributing factors. DESIGN, SETTING, PARTICIPANTS: Retrospective, cross-sectional, observational study of 6097 adult COVID-19 patients hospitalized within a single large healthcare system from March to November 2020. EXPOSURES: Self-reported ethnicity and primary language. MAIN OUTCOMES AND MEASURES: Clinical outcomes included intensive care unit (ICU) utilization and in-hospital death. We used age-adjusted odds ratios (OR) and multivariable analysis to evaluate the associations between ethnicity/language groups and outcomes. RESULTS: 32.1% of patients were Hispanic, 38.6% of whom reported a non-English primary language. Hispanic patients were less likely to be insured, have a primary care provider, and have accessed the healthcare system prior to the COVID-19 admission. After adjusting for age, Hispanic inpatients experienced higher ICU utilization (non-English-speaking: OR, 1.75; 95% CI, 1.47-2.08; English-speaking: OR, 1.13; 95% CI, 0.95-1.33) and higher mortality (non-English-speaking: OR, 1.43; 95% CI, 1.10-1.86; English-speaking: OR, 1.53; 95% CI, 1.19-1.98) compared to non-Hispanic inpatients. There were no observed treatment disparities among ethnic groups. After adjusting for age, Hispanic inpatients had elevated disease severity at admission (non-English-speaking: OR, 2.27; 95% CI, 1.89-2.72; English-speaking: OR, 1.33; 95% CI, 1.10- 1.61). In multivariable analysis, the associations between ethnicity/language and clinical outcomes decreased after considering baseline disease severity (P < .001). CONCLUSION: The associations between ethnicity and clinical outcomes can be explained by elevated disease severity at admission and limited access to healthcare for Hispanic patients, especially non-English-speaking Hispanics.

Wood smoke particle exposure in mice reduces the severity of influenza infection.

Elevated ambient temperatures and extreme weather events have increased the incidence of wildfires world-wide resulting in increased wood smoke particle (WSP). Epidemiologic data suggests that WSP exposure associates with exacerbations of respiratory diseases, and with increased respiratory viral infections. To assess the impact of WSP exposure on host response to viral pneumonia, we performed WSP exposures in rodents followed by infection with mouse adapted influenza (HINI-PR8). C57BL/6 male mice aged 6-8 weeks were challenged with WSP or PBS by oropharyngeal aspiration in acute (single dose) or sub-acute exposures (day 1, 3, 5, 7 and 10). Additional groups underwent sub-acute exposure followed by infection by influenza or heat-inactivated (HI) virus. Following exposures/infection, bronchoalveolar lavage (BAL) was performed to assess for total cell counts/differentials, total protein, protein carbonyls and hyaluronan. Lung tissue was assessed for viral counts by real time PCR. When compared to PBS, acute WSP exposure associated with an increase in airspace macrophages. Alternatively, sub-acute exposure resulted in a dose dependent increase in airspace neutrophils. Sub-acute WSP exposure followed by influenza infection was associated with improved respiratory viral outcomes including reduced weight loss and increased blood oxygen saturation, and decreased protein carbonyls and viral titers. Flow cytometry demonstrated dynamic changes in pulmonary macrophage and T cell subsets based on challenge with WSP and influenza. This data suggests that sub-acute WSP exposure can improve host response to acute influenza infection.

Case series of acute appendicitis association with SARS-CoV-2 infection.

BACKGROUND: Describe the indications for surgical interventions in asymptomatic patients with SARS-CoV-2. We are unaware of previous reports of an association between SARS-CoV-2 and acute appendicitis. METHODS: We performed a single institution retrospective review of SARS-CoV-2 pre-procedure testing and indications for surgical intervention. Statistical comparisons were performed using Chi Square analysis or two-tailed Student T test. RESULTS: We report a high prevalence of SARS-CoV-2 in both all testing and pre-procedure testing during the enrollment period. We observe a high prevalence of acute appendicitis among patients identified to be SARS-CoV-2 positive during pre-procedure testing and without recognized symptoms of COVID19. CONCLUSION: We report a previously unrecognized association between SARS-CoV-2 and acute appendicitis.

TLR5 participates in the TLR4 receptor complex and promotes MyD88-dependent signaling in environmental lung injury.

Lung disease causes significant morbidity and mortality, and is exacerbated by environmental injury, for example through lipopolysaccharide (LPS) or ozone (O3). Toll-like receptors (TLRs) orchestrate immune responses to injury by recognizing pathogen- or danger-associated molecular patterns. TLR4, the prototypic receptor for LPS, also mediates inflammation after O3, triggered by endogenous hyaluronan. Regulation of TLR4 signaling is incompletely understood. TLR5, the flagellin receptor, is expressed in alveolar macrophages, and regulates immune responses to environmental injury. Using in vivo animal models of TLR4-mediated inflammations (LPS, O3, hyaluronan), we show that TLR5 impacts the in vivo response to LPS, hyaluronan and O3. We demonstrate that immune cells of human carriers of a dominant negative TLR5 allele have decreased inflammatory response to O3 exposure ex vivo and LPS exposure in vitro. Using primary murine macrophages, we find that TLR5 physically associates with TLR4 and biases TLR4 signaling towards the MyD88 pathway. Our results suggest an updated paradigm for TLR4/TLR5 signaling.

Immune cells in the lung help guard against infections. On the surface of these cells are proteins called TLR receptors that recognize dangerous molecules or DNA from disease-causing microbes such as bacteria. When the immune cells detect these invaders, the TLR receptors spring into action and trigger an inflammatory response to destroy the microbes. This inflammation usually helps the lung clear infections. But it can also be harmful and damage the lung, for example when inflammation is caused by non-infectious substances such as pollutants in the atmosphere. There are several TLR receptors that each recognize a specific molecule. In 2010, researchers showed that the receptor TLR4 is responsible for causing inflammation in the lung after exposure to pollution. Another receptor called TLR5 also helps activate the immune response in the lung. But it was unclear whether this receptor also plays a role in pollution-linked lung damage. Now, Hussain, Johnson, Sciurba et al. ­ including one of the researchers involved in the 2010 study ­ have investigated the role of TLR5 in immune cells from the lungs of humans and mice. The experiments showed that TLR5 works together with TLR4 and helps trigger an inflammatory response to both pollutants and bacteria. Hussain et al. found that people lacking a working TLR5 receptor (which make up 3­10% of the population) are less likely to experience lung inflammation when exposed to pollution or bacterial proteins that activate TLR4. These findings suggest that people without TLR5 may be protected from pollution-induced lung injury. Further research into the role of TLR5 could help develop genetic tests for identifying people who are more sensitive to damage from pollution. This information could then be used to determine the likelihood of a patient experiencing certain lung diseases.

Making 'Chemical Cocktails' - Evolution of Urban Geochemical Processes across the Periodic Table of Elements.

Urbanization contributes to the formation of novel elemental combinations and signatures in terrestrial and aquatic watersheds, also known as 'chemical cocktails.' The composition of chemical cocktails evolves across space and time due to: (1) elevated concentrations from anthropogenic sources, (2) accelerated weathering and corrosion of the built environment, (3) increased drainage density and intensification of urban water conveyance systems, and (4) enhanced rates of geochemical transformations due to changes in temperature, ionic strength, pH, and redox potentials. Characterizing chemical cocktails and underlying geochemical processes is necessary for: (1) tracking pollution sources using complex chemical mixtures instead of individual elements or compounds; (2) developing new strategies for co-managing groups of contaminants; (3) identifying proxies for predicting transport of chemical mixtures using continuous sensor data; and (4) determining whether interactive effects of chemical cocktails produce ecosystem-scale impacts greater than the sum of individual chemical stressors. First, we discuss some unique urban geochemical processes which form chemical cocktails, such as urban soil formation, human-accelerated weathering, urban acidification-alkalinization, and freshwater salinization syndrome. Second, we review and synthesize global patterns in concentrations of major ions, carbon and nutrients, and trace elements in urban streams across different world regions and make comparisons with reference conditions. In addition to our global analysis, we highlight examples from some watersheds in the Baltimore-Washington DC region, which show increased transport of major ions, trace metals, and nutrients across streams draining a well-defined land-use gradient. Urbanization increased the concentrations of multiple major and trace elements in streams draining human-dominated watersheds compared to reference conditions. Chemical cocktails of major and trace elements were formed over diurnal cycles coinciding with changes in streamflow, dissolved oxygen, pH, and other variables measured by high-frequency sensors. Some chemical cocktails of major and trace elements were also significantly related to specific conductance (p<0.05), which can be measured by sensors. Concentrations of major and trace elements increased, peaked, or decreased longitudinally along streams as watershed urbanization increased, which is consistent with distinct shifts in chemical mixtures upstream and downstream of other major cities in the world. Our global analysis of urban streams shows that concentrations of multiple elements along the Periodic Table significantly increase when compared with reference conditions. Furthermore, similar biogeochemical patterns and processes can be grouped among distinct mixtures of elements of major ions, dissolved organic matter, nutrients, and trace elements as chemical cocktails. Chemical cocktails form in urban waters over diurnal cycles, decades, and throughout drainage basins. We conclude our global review and synthesis by proposing strategies for monitoring and managing chemical cocktails using source control, ecosystem restoration, and green infrastructure. We discuss future research directions applying the watershed chemical cocktail approach to diagnose and manage environmental problems. Ultimately, a chemical cocktail approach targeting sources, transport, and transformations of different and distinct elemental combinations is necessary to more holistically monitor and manage the emerging impacts of chemical mixtures in the world's fresh waters.

Biogas Stoves Reduce Firewood Use, Household Air Pollution, and Hospital Visits in Odisha, India.

Traditional cooking using biomass is associated with ill health, local environmental degradation, and regional climate change. Clean stoves (liquefied petroleum gas (LPG), biogas, and electric) are heralded as a solution, but few studies have demonstrated their environmental health benefits in field settings. We analyzed the impact of mainly biogas (as well as electric and LPG) stove use on social, environmental, and health outcomes in two districts in Odisha, India, where the Indian government has promoted household biogas. We established a cross-sectional observational cohort of 105 households that use either traditional mud stoves or improved cookstoves (ICS). Our multidisciplinary team conducted surveys, environmental air sampling, fuel weighing, and health measurements. We examined associations between traditional or improved stove use and primary outcomes, stratifying households by proximity to major industrial plants. ICS use was associated with 91% reduced use of firewood (p < 0.01), substantial time savings for primary cooks, a 72% reduction in PM2.5, a 78% reduction in PAH levels, and significant reductions in water-soluble organic carbon and nitrogen (p < 0.01) in household air samples. ICS use was associated with reduced time in the hospital with acute respiratory infection and reduced diastolic blood pressure but not with other health measurements. We find many significant gains from promoting rural biogas stoves in a context in which traditional stove use persists, although pollution levels in ICS households still remained above WHO guidelines.

Flow Cytometric Analysis of Myeloid Cells in Human Blood, Bronchoalveolar Lavage, and Lung Tissues.

Clear identification of specific cell populations by flow cytometry is important to understand functional roles. A well-defined flow cytometry panel for myeloid cells in human bronchoalveolar lavage (BAL) and lung tissue is currently lacking. The objective of this study was to develop a flow cytometry-based panel for human BAL and lung tissue. We obtained and performed flow cytometry/sorting on human BAL cells and lung tissue. Confocal images were obtained from lung tissue using antibodies for cluster of differentiation (CD)206, CD169, and E cadherin. We defined a multicolor flow panel for human BAL and lung tissue that identifies major leukocyte populations. These include macrophage (CD206(+)) subsets and other CD206(-) leukocytes. The CD206(-) cells include: (1) three monocyte (CD14(+)) subsets, (2) CD11c(+) dendritic cells (CD14(-), CD11c(+), HLA-DR(+)), (3) plasmacytoid dendritic cells (CD14(-), CD11c(-), HLA-DR(+), CD123(+)), and (4) other granulocytes (neutrophils, mast cells, eosinophils, and basophils). Using this panel on human lung tissue, we defined two populations of pulmonary macrophages: CD169(+) and CD169(-) macrophages. In lung tissue, CD169(-) macrophages were a prominent cell type. Using confocal microscopy, CD169(+) macrophages were located in the alveolar space/airway, defining them as alveolar macrophages. In contrast, CD169(-) macrophages were associated with airway/alveolar epithelium, consistent with interstitial-associated macrophages. We defined a flow cytometry panel in human BAL and lung tissue that allows identification of multiple immune cell types and delineates alveolar from interstitial-associated macrophages. This study has important implications for defining myeloid cells in human lung samples.

Genetic variation in SP-A2 leads to differential binding to Mycoplasma pneumoniae membranes and regulation of host responses.

Mycoplasma pneumoniae is an extracellular pathogen that colonizes mucosal surfaces of the respiratory tract and is associated with asthma exacerbations. Previous reports demonstrate that surfactant protein-A (SP-A) binds live M. pneumoniae and mycoplasma membrane fractions (MMF) with high affinity. Humans express a repertoire of single-amino acid genetic variants of SP-A that may be associated with lung disease, and our findings demonstrate that allelic differences in SP-A2 (Gln223Lys) affect the binding to MMF. We show that SP-A(-/-) mice are more susceptible to MMF exposure and have significant increases in mucin production and neutrophil recruitment. Novel humanized SP-A2-transgenic mice harboring the hSP-A2 223K allele exhibit reduced neutrophil influx and mucin production in the lungs when challenged with MMF compared with SP-A(-/-) mice. Conversely, mice expressing hSP-A2 223Q have increased neutrophil influx and mucin production that are similar to SP-A(-/-) mice. Using tracheal epithelial cell cultures, we show that enhanced mucin production to MMF occurs in the absence of SP-A and is not dependent upon neutrophil recruitment. Increased phosphorylation of the epidermal growth factor receptor (EGFR) was evident in the lungs of MMF-challenged mice when SP-A was absent. Pharmacologic inhibition of EGFR prior to MMF challenge dramatically reduced mucin production in SP-A(-/-) mice. These findings suggest a protective role for SP-A in limiting MMF-stimulated mucin production that occurs through interference with EGFR-mediated signaling. SP-A interaction with the EGFR signaling pathway appears to occur in an allele-specific manner that may have important implications for SP-A polymorphisms in human diseases.