Percutaneous Dilatational Tracheostomy in a Cardiac Surgical Intensive Care Unit: A Single-Center Experience

BACKGROUND: A significant proportion of cardiac surgery intensive care unit (CSICU) patients require long-term ventilation, necessitating tracheostomy placement. The goal of this study was to evaluate the long-term postoperative outcomes and complications associated with percutaneous dilatational tracheostomy (PDT) in CSICU patients. METHODS: All patients undergoing PDT after cardiac, thoracic, or vascular operations in the CSICU between January 1, 2013 and January 1, 2021 were identified. They were evaluated for mortality, decannulation time, and complications including bleeding, infection, and need for surgical intervention. Multivariable regression models were used to identify predictors of early decannulation and the complication rate. RESULTS: Ninety-three patients were identified for this study (70 [75.3%] male and 23 [24.7%] female). Furthermore, 18.3% of patients had chronic obstructive pulmonary disease (COPD), 21.5% had history of stroke, 7.5% had end-stage renal disease, 33.3% had diabetes, and 59.1% were current smokers. The mean time from PDT to decannulation was 39 days. Roughly one-fifth (20.4%) of patients were on dual antiplatelet therapy and 81.7% had anticoagulation restarted 8 hours post-tracheostomy. Eight complications were noted, including 5 instances of bleeding requiring packing and 1 case of mediastinitis. There were no significant predictors of decannulation prior to discharge. Only COPD was identified as a negative predictor of decannulation at any point in time (hazard ratio, 0.28; 95% confidence interval, 0.08-0.95; p=0.04). CONCLUSION: Percutaneous tracheostomy is a safe and viable alternative to surgical tracheostomy in cardiac surgery ICU patients. Patients who undergo PDT have a relatively short duration of tracheostomy and do not have major post-procedural complications

Expression levels of MHC class I molecules are inversely correlated with promiscuity of peptide binding.

Highly polymorphic major histocompatibility complex (MHC) molecules are at the heart of adaptive immune responses, playing crucial roles in many kinds of disease and in vaccination. We report that breadth of peptide presentation and level of cell surface expression of class I molecules are inversely correlated in both chickens and humans. This relationship correlates with protective responses against infectious pathogens including Marek's disease virus leading to lethal tumours in chickens and human immunodeficiency virus infection progressing to AIDS in humans. We propose that differences in peptide binding repertoire define two groups of MHC class I molecules strategically evolved as generalists and specialists for different modes of pathogen resistance. We suggest that differences in cell surface expression level ensure the development of optimal peripheral T cell responses. The inverse relationship of peptide repertoire and expression is evidently a fundamental property of MHC molecules, with ramifications extending beyond immunology and medicine to evolutionary biology and conservation.Wellcome Trust Programme grant 089305; Biotechnology and Biological Sciences Research Council (BBSRC) Core Funding to the Pirbright Institute; Biotechnology and Biological Sciences Research Council (BBSRC); Wellcome Trust.This is the final published version. It first appeared at http://elifesciences.org/content/4/e05345

Toward a loss of functional diversity in stream fish assemblages under climate change

The assessment of climate change impacts on biodiversity has so far been biased toward the taxonomic identification of the species likely either to benefit from climate modifications or to experience overall declines. There have still been few studies intended to correlate the characteristics of species to their sensitivity to climate change, even though it is now recognized that functional trait-based approaches are promising tools for addressing challenges related to global changes. In this study, two functional indices (originality and uniqueness) were first measured for 35 fish species occurring in French streams. They were then combined to projections of range shifts in response to climate change derived from species distribution models. We set out to investigate: (1) the relationship between the degrees of originality and uniqueness of fish species, and their projected response to future climate change; and (2) the consequences of individual responses of species for the functional diversity of fish assemblages. After accounting for phylogenetic relatedness among species, we have demonstrated that the two indices used measure two complementary facets of the position of fish species in a functional space. We have also rejected the hypothesis that the most original and/or less redundant species would necessarily experience the greatest declines in habitat suitability as a result of climate change. However, individual species range shifts could lead simultaneously both to a severe decline in the functional diversity of fish assemblages, and to an increase in the functional similarity among assemblages, supporting the hypothesis that disturbance favors communities with combination of common traits and biotic homogenization as well. Our findings therefore emphasize the importance of going beyond the simple taxonomic description of diversity to provide a better assessment of the likely future effects of environmental changes on biodiversity, thus helping to design more effective conservation and management measures

Are specialists at risk under environmental change? Neoecological, paleoecological and phylogenetic approaches

The question ‘what renders a species extinction prone’ is crucial to biologists. Ecological specialization has been suggested as a major constraint impeding the response of species to environmental changes. Most neoecological studies indicate that specialists suffer declines under recent environmental changes. This was confirmed by many paleoecological studies investigating longer-term survival. However, phylogeneticists, studying the entire histories of lineages, showed that specialists are not trapped in evolutionary dead ends and could even give rise to generalists. Conclusions from these approaches diverge possibly because (i) of approach-specific biases, such as lack of standardization for sampling efforts (neoecology), lack of direct observations of specialization (paleoecology), or binary coding and prevalence of specialists (phylogenetics); (ii) neoecologists focus on habitat specialization; (iii) neoecologists focus on extinction of populations, phylogeneticists on persistence of entire clades through periods of varying extinction and speciation rates; (iv) many phylogeneticists study species in which specialization may result from a lack of constraints. We recommend integrating the three approaches by studying common datasets, and accounting for range-size variation among species, and we suggest novel hypotheses on why certain specialists may not be particularly at risk and consequently why certain generalists deserve no less attention from conservationists than specialists

Percutaneous Dilatational Tracheostomy in a Cardiac Surgical Intensive Care Unit: A Single-Center Experience

Background: A significant proportion of cardiac surgery intensive care unit (CSICU) patients require long-term ventilation, necessitating tracheostomy placement. The goal of this study was to evaluate the long-term postoperative outcomes and complications associated with percutaneous dilatational tracheostomy (PDT) in CSICU patients. Methods: All patients undergoing PDT after cardiac, thoracic, or vascular operations in the CSICU between January 1, 2013 and January 1, 2021 were identified. They were evaluated for mortality, decannulation time, and complications including bleeding, infection, and need for surgical intervention. Multivariable regression models were used to identify predictors of early decannulation and the complication rate. Results: Ninety-three patients were identified for this study (70 [75.3%] male and 23 [24.7%] female). Furthermore, 18.3% of patients had chronic obstructive pulmonary disease (COPD), 21.5% had history of stroke, 7.5% had end-stage renal disease, 33.3% had diabetes, and 59.1% were current smokers. The mean time from PDT to decannulation was 39 days. Roughly one-fifth (20.4%) of patients were on dual antiplatelet therapy and 81.7% had anticoagulation restarted 8 hours post-tracheostomy. Eight complications were noted, including 5 instances of bleeding requiring packing and 1 case of mediastinitis. There were no significant predictors of decannulation prior to discharge. Only COPD was identified as a negative predictor of decannulation at any point in time (hazard ratio, 0.28; 95% confidence interval, 0.08–0.95; p=0.04). Conclusion: Percutaneous tracheostomy is a safe and viable alternative to surgical tracheostomy in cardiac surgery ICU patients. Patients who undergo PDT have a relatively short duration of tracheostomy and do not have major post-procedural complications

Emergent Esophagectomy in Patients with Esophageal Malignancy Is Associated with Higher Rates of Perioperative Complications but No Independent Impact on Short-Term Mortality

Background: Data on perioperative outcomes of emergent versus elective resection in esophageal cancer patients requiring esophagectomy are lacking. We investigated whether emergent resection was associated with increased risks of morbidity and mortality. Methods: Data on patients with esophageal malignancy who underwent esophagectomy from 2005 to 2020 were retrospectively analyzed from the American College of Surgeons National Surgical Quality Improvement Program database. Thirty-day complication and mortality rates were compared between emergent esophagectomy (EE) and non-emergent esophagectomy. Logistic regression assessed factors associated with complications and mortality. Results: Of 10,067 patients with malignancy who underwent esophagectomy, 181 (1.8%) had EE, 64% had preoperative systemic inflammatory response syndrome, sepsis, or septic shock, and 44% had bleeding requiring transfusion. The EE group had higher American Society of Anesthesiologists (ASA) class and functional dependency. More transhiatal esophagectomies and diversions were performed in the EE group. After EE, the rates of 30-day mortality (6.1% vs. 2.8%), overall complications (65.2% vs. 44.2%), bleeding, pneumonia, prolonged intubation, and positive margin (17.7% vs. 7.4%) were higher, while that of anastomotic leak was similar. On adjusted logistic regression, older age, lower albumin, higher ASA class, and fragility were associated with increased complications and mortality. McKeown esophagectomy and esophageal diversion were associated with a higher risk of postoperative complications. EE was associated with 30-day postoperative complications (odds ratio, 2.39; 95% confidence interval, 1.66–3.43; p<0.0001). Conclusion: EE was associated with a more than 2-fold increase in complications compared to elective procedures, but no independent increase in short-term mortality. These findings may help guide data-driven critical decision-making for surgery in select cases of complicated esophageal malignancy

Exposure to Atmospheric Particulate Matter Enhances Th17 Polarization through the Aryl Hydrocarbon Receptor

<div><p>Lung diseases, including asthma, COPD, and other autoimmune lung pathologies are aggravated by exposure to particulate matter (PM) found in air pollution. IL-17 has been shown to exacerbate airway disease in animal models. As PM is known to contain aryl hydrocarbon receptor (AHR) ligands and the AHR has recently been shown to play a role in differentiation of Th17 T cells, the aim of this study was to determine whether exposure to PM could impact Th17 polarization in an AHR-dependent manner. This study used both cell culture techniques and <i>in vivo</i> exposure in mice to examine the response of T cells to PM. Initially experiments were conducted with urban dust particles from a standard reference material, and ultimately repeated with freshly collected samples of diesel exhaust and cigarette smoke. The readout for the assays was increased T cell differentiation as indicated by increased generation of IL-17A in culture, and increased populations of IL-17 producing cells by intracellular flow cytometry. The data illustrate that Th17 polarization was significantly enhanced by addition of urban dust in a dose dependent fashion in cultures of wild-type but not AHR^-/- mice. The data further suggest that polycyclic aromatic hydrocarbons played a primary role in this enhancement. There was both an increase of Th17 cell differentiation, and also an increase in the amount of IL-17 secreted by the cells. In summary, this paper identifies a novel mechanism whereby PM can directly act on the AHR in T cells, leading to enhanced Th17 differentiation. Further understanding of the molecular mechanisms responsible for pathologic Th17 differentiation and autoimmunity seen after exposure to pollution will allow direct targeting of proteins involved in AHR activation and function for treatment of PM exposures.</p> </div

Th17 differentiation <i>in</i><i>vitro</i> is enhanced with addition of SRM1649b to culture conditions.

<p>A-B: Naïve CD4⁺ T cells were isolated from the spleens of male C57BL/6 mice (B6) and cultured in Th17 conditions (anti-CD3/CD28 antibody + mIL-6 (20 ng/ml) + huTGF-β (5 ng/ml)) for 4 days in the absence or presence of SRM1649b (10, 20 or 40 μg/ml) or FICZ (200 nM). Triplicate culture supernatant was harvested and ELISA measured the concentration of IL-17A and IL-22 (A). Data presented is representative of 3 experiments. In separate experiments, total RNA was harvested from cells and the relative levels of IL-17A, IL-22 and IL-23R mRNA were determined by qRT-PCR (B). Data is relative to cells treated with anti-CD3/CD28 antibody stimulation but without mIL-6 and huTGF-β. Fold increase results from cultures with (w/) SRM1649b were compared for significance with cultures without (w/o) SRM1649b using the paired student’s t-test. The number in parenthesis indicates the number of individual assays used for that target gene. C-D: Naïve B6 CD4⁺ T cells were cultured in Th17 conditions (anti-CD3/CD28 antibody + mIL-6 (20 ng/ml) and varying concentrations of huTGF-β (0 - 5 ng/ml)) for 4 days in the absence or presence of SRM1649b (40 μg/ml). Cells were harvested from and subjected to intracellular cytokine analysis to determine the percent of IL-17A and IFN-γ expressing CD4⁺ T cells present after culture. Data from 3 separate experiments were pooled and statistical comparison was made between the cultures with versus cultures without SRM1649b at each concentration of huTGF-β. *, p < 0.05; **, p < 0.01; ***, p < 0.001.</p

Investigation of the specific components of SRM1649b that contain Th17 enhancing activity.

<p>A: Mouse Hepa1 cells that were transfected with luciferase reporter gene fused to the dioxin-responsive elements (DRE) were seeded at 0.6x10⁶ cells per well. Cells were then exposed to media (Control), media + SRM1649b suspended in PBS (SRM/PBS), media + DMSO (DMSO), media + SRM1649b suspended in DMSO (SRM/DMSO) or the organic fraction of SRM1649b suspended in DMSO (fSRM/DMSO) for 4 hours. Luciferase activity was measured on a luminometer. B: Naïve B6 CD4⁺ T cells in Th17 conditions in the presence of fractioned SRM1649b and controls. After 4 days, total RNA was harvested. Using qRT-PCR, the relative levels of IL-17A and Cyp1a1 mRNA were determined. Data presented are the mean and standard deviation of 2 separate experiments and is relative to cells treated with anti-CD3/CD28 antibody stimulation but without mIL-6 and huTGF-β. C: Naïve B6 CD4⁺ T cells in Th17 conditions in the presence varying concentrations of the PAHs benzo[a]pyrene (BaP), benzo[e]pyrene (BeP) and benzo[k]fluoranthene (BkF). Culture supernatant was harvested and ELISA measured the concentration of IL-17A. The line indicates the level of IL-17A expression in cultures exposed to DMSO vehicle only. D: Naïve B6 or AHR^-/- CD4⁺ T cells in Th17 conditions in the presence of BkF. Cells were harvested and subjected to intracellular cytokine analysis to determine the percent of IL-17A-expressing CD4⁺ T cells present after culture. Data from 3 separate experiments was pooled and statistical comparison was made between the cultures with versus cultures without BkF.</p

AHR is required for upregulation of Th17 cells in response to SRM1649b.

<p>A-B: Naïve B6 CD4⁺ T cells were cultured in Th17 conditions (anti-CD3/CD28 antibody + mIL-6 (20 ng/ml) and varying concentrations of huTGF-β (5 ng/ml) for 4 days in the absence or presence of SRM1649b (40 μg/ml) after which total RNA was harvested. Relative levels of AHR and cyp 1a1 mRNA were determined by qRT-PCR. Data are relative to cells treated with anti-CD3/CD28 antibody stimulation but without mIL-6 and huTGF-β. Fold increase results from cultures with (w/) SRM1649b were compared for significance with cultures without (w/o) SRM1649b using the paired student’s t-test. B: Cells were harvested after 4 days and stained with anti-AHR antibody during intracellular cytokine analysis to determine the percent of AHR-expressing CD4⁺ T cells cultured with (solid line) or without (shaded) huTGF-β. C: Naïve CD4⁺ T cells were isolated from the spleens of male B6 or AHR^-/- mice and cultured in Th17 conditions (anti-CD3/CD28 antibody + mIL-6 (20 ng/ml) +/- huTGF-β (5 ng/ml) for 4 days in the varying concentrations SRM1649b. Supernatants were analyzed by ELISA. D - E: Naïve CD4⁺ T cells were isolated from the spleens of AHR^-/- (D) or DREC^-/- (E) mice and cultured in Th17 conditions (anti-CD3/CD28 antibody + mIL-6 (20 ng/ml) +/- huTGF-β (5 ng/ml) for 4 days +/- SRM1649b. Total RNA was harvested and, the relative levels of IL-17A, and IL-22 mRNA were determined by qRT-PCR. Data is relative to cell treated with anti-CD3/CD28 antibody stimulation but without added mIL-6 and huTGF-β. Fold increase results from cultures with (w/) SRM1649b were compared for significance with cultures without (w/o) SRM1649b using the paired student’s t-test. The number in parenthesis indicates the number of individual assays used for that target gene. *, p < 0.05; **, p < 0.01; ***, p < 0.001.</p