RationaleRobust COVID-19 outcomes classification is important for ongoing epidemiology research on acute and post-acute COVID-19 conditions. Protocolized medical record review is an established method to validate endpoints for clinical trials and cardiovascular epidemiology cohorts; however, a protocol to adjudicate hospitalizations for COVID-19 among epidemiology cohorts was lacking.ObjectivesWe developed a protocol to ascertain and adjudicate hospitalized COVID-19 across a meta-cohort of 14 US prospective cohort studies. This report describes the first three years of protocol implementation (October 1, 2020-October 1, 2023) and evaluates its repeatability and performance compared to classification by administrative codes.MethodsThe protocol was adapted from cohort approaches to clinical cardiovascular events ascertainment and adjudication. Potential COVID-19 hospitalizations and deaths were identified by self-/proxy-report and, in some cases, active surveillance. Medical records were requested from hospitals and adjudicated for COVID-19 outcomes by clinically trained personnel according to a standardized rubric. Inter-rater agreement was assessed. The sensitivity and specificity of discharge diagnosis codes was compared to adjudicated diagnoses.Measurements and main resultsThe study obtained medical records for 1,167 potential COVID-19 hospitalizations, which underwent protocolized adjudication. Adjudication confirmed COVID-19 infection was present for 1,030 (88%) events, of which COVID-19 was not the cause of hospitalization for 78 (8%). Of 952 hospitalizations determined by adjudicators to be caused by COVID-19, 319 (34%) participants were critically ill and 210 (22%) died. Pneumonia was confirmed in 822 (86%) and acute kidney injury in 350 (37%); other cardiovascular and thrombotic complications were rare (2-5%). Interrater reliability among adjudicators was high (kappa = 0.85-1.00) except for myocardial infarction (kappa = 0.60). Compared to adjudication, sensitivity of discharge diagnosis codes was higher for pneumonia (84%) and pulmonary embolism (81%) than for other complications (48-70%).ConclusionsProtocolized adjudication confirmed four out of five COVID-19 hospitalizations in a US meta-cohort and confirmed cases of pneumonia, pulmonary embolism, and other conditions that were not indicated by discharge diagnosis codes. These results highlight the importance of validating health outcomes for use in research on COVID-19 and post-COVID-19 conditions, and some limitations of claims-based data.

Background Endocarditis is a life-threatening condition with protean manifestations. The clinical syndrome continues to evolve with an aging population, the opioid epidemic, and changing microbiological profiles. Much of the clinical data for endocarditis comes from tertiary care centers with on-site cardiac surgery. Previous community cohorts do not reflect the current patient populations or current microbiology and predate the current opioid epidemic. We retrospectively reviewed the baseline clinical characteristics, microbiologic spectrum, surgical indication, tertiary referral, and outcomes for patients presenting to a community hospital with infective endocarditis (IE). Methods We retrospectively reviewed all adult medical patient admitted over a 5-year period with a clinical diagnosis of IE, from February 2016 to September 2021, to a single suburban safety net community hospital without on-site cardiac surgery. Results We identified 99 patients with a clinical diagnosis of IE. We observed a bimodal age distribution, with more comorbidities and predisposing cardiac conditions in the older patients and more intravenous drug use in the younger patients. Surgical indications were present in 44% of patients. Staphylococcus aureus was the most common pathogen. Overall survival was associated with fewer comorbidities and the absence of methicillin-resistant S. aureus infection. There was no difference in survival between patients with and without surgical indications. Conclusions IE continues to primarily affect older patients with comorbidities and results in a high 1-year mortality of 33%. A simple score including age, Charlson comorbidity index of 6.5, and methicillin-resistant S. aureus infection was predictive for in-patient, 30-day, and 1-year mortality.

Introduction Endotracheal tubes (ETT) are used in patients who require ventilatory support.Colonization of ETTs by microorganisms is associated with developing ventilator- associated pneumonia (VAP). Thus, this meta-analysis aims to compare conventional endotracheal tubes with those made using materials designed to prevent colonization. Methods This analysis was conducted according to the PRISMA guidelines. During May, 2024, we searched multiple databases (PubMed,Cochrane and Embase) for randomized controlled trials (RCT) comparing the incidence of ventilator-associated pneumonia between conventional and coated tubes. Studies with patients with less than 48 hours of intubation were excluded. Our primary endpoint was the incidence of VAP in patients intubated with either conventional or coated endotracheal tubes. Statistical analysis was performed using Review Manager Software, and a The Mantel-Haenszel test was performed using a random effects model, and risk ratios (RR) were calculated for binary outcomes. Subgroup analyses were conducted using a fixed effects model when heterogeneity was low. Risk assessment was carried out using the Risk of Bias 2 tool. Results Our search identified 6 RCTs eligible in our inclusion criteria, enrolling 2680 patients, with 1361 (50,78%) undergoing intubation using a polymer-coated tube. The statistical data indicated that coated endotracheal tubes perform better in preventing pneumonia than conventional tubes (RR 0.57 Cl 95% 0.45- 0.90; p<0.001; I2 0%). Additionally, conventional tubes were also associated with higher bacterial colonization (47.02 CI 95% 26.88-68.18; p<0.01; I2 81%) compared to coated tubes. Conclusions These findings indicate that utilizing a silver-coated endotracheal tube for intubation is more efficacious than conventional tubes, presenting it as a strategy to combat ventilator-associated pneumonia.

Objectives: Administrative criteria are often used to define COVID-19 outcomes despite challenges in differentiating hospitalization “for” vs “with” COVID-19 and unknown reliability for identifying COVID-related cardiopulmonary complications. We implemented a protocol to adjudicate COVID-related events across 14 studies participating in C4R. Methods: C4R cohorts ascertained COVID-related hospitalizations and deaths via questionnaires or ongoing surveillance. Medical records were reviewed by C4R physicians using a standardized protocol to assign COVID-related diagnoses as definite or probable. C4R diagnoses were compared against ICD codes assigned to the events. This report includes data from events centrally adjudicated by C4R as of September 2022. Results: Among 144 events ascertained across 7 cohorts as potentially COVID-related, SARS-CoV-2 infection was confirmed in 107/117 (91%) non-fatal hospitalizations and 26/27 (96%) deaths. Of confirmed infections, COVID-19 illness was diagnosed as the cause of 101/107 (94%) hospitalizations and 24/26 (92%) deaths ( Table ). Of non-fatal hospitalizations with infection, 72% were diagnosed with severe or critical COVID-19, 78% with COVID-associated pneumonia, and 29% with renal failure; other complications were less common. C4R review did not validate diagnoses indicated by ICD codes for 1 COVID-19 infection, 5 pneumonias, 1 stroke, and 7 renal failure cases. C4R review did identify diagnoses that were not ICD-coded for 13 infections, 31 pneumonias, 6 myocardial infarctions, 5 venous thromboses, and 21 renal failure cases. Conclusions: Protocolized medical records review by C4R confirmed COVID-19 as the cause of hospitalization or death in 87% of events ascertained as potentially COVID-related and 94% of those in which SARS-CoV-2 infection was confirmed. Both false-positive and false-negative misclassification by ICD criteria was observed. Protocolized review may be useful to identify and validate COVID-related events for epidemiologic research.

Background: Cardiac stress biomarkers (growth differentiation factor 15 [GDF-15], soluble ST-2 [ST2], high-sensitivity troponin I [hsTnI]) and B-type natriuretic peptide [BNP]) are associated with incident heart failure (HF) and left ventricular mass (LVM). It is unclear if biomarker levels and their prognostic significance vary according to LV hypertrophy (LVH) pattern and extent. We hypothesized that concentric & eccentric LVH would be associated with highest biomarker levels; presence of both LVH and higher biomarker levels would indicate high HF risk. Methods and Results: We evaluated 2,425 Framingham Study participants free of HF (57% women, mean age 58 years) attending a routine examination, with available biomarker and echocardiographic measurements. We defined 4 LVH patterns: a. normal (normal LVM and Relative Wall Thickness [RWT]); b. concentric remodeling (normal LVM, elevated RWT); c. eccentric hypertrophy (elevated LVM, normal RWT); and d. concentric hypertrophy (elevated LVM and RWT). Adjusting for age & sex, biomarker levels (except BNP) increased sequentially across LVH patterns a-d ( Figure ). BNP levels were lowest in concentric remodeling and highest in eccentric LVH. In multivariable models, all biomarkers were associated with incident HF (106 cases, 12 yrs follow-up). We observed a significant interaction only between BNP and LVM (p=0.02). In stratified analyses, higher LVM was associated with incident HF in both BNP strata (Hazard Ratios [HR] per SD increase in LVM = 2.24 [ Conclusions: In our large community-based sample, cardiac stress biomarker levels varied by LVH pattern. Contrary to our hypothesis, BNP levels were more strongly associated with HF in individuals with lesser degree of LVH.

Tumor necrosis factor-alpha (TNF-α) inhibitors are associated with lupus-like disease, known as anti-TNF-α-induced lupus (ATIL). Cytomegalovirus (CMV) was reported to exacerbate lupus in the literature. To date, systemic lupus erythematosus (SLE) triggered by adalimumab in the setting of CMV infection has never been described. We present an unusual case of a 38-year-old female with a past medical history of seronegative rheumatoid arthritis (SnRA) who developed SLE associated with the use of adalimumab and CMV infection. She had severe SLE features including lupus nephritis and cardiomyopathy. The medication was discontinued. She was initiated on pulse steroid therapy and discharged with an aggressive regimen for SLE, including prednisone, mycophenolate mofetil, and hydroxychloroquine. She remained on the medications until a year later upon follow-up. ATIL from adalimumab usually manifests only mild symptoms of SLE such as arthralgia, myalgia, and pleurisy. Nephritis is very rare, and cardiomyopathy is unprecedented. Concomitant CMV infection might contribute to disease severity. Patients with SnRA may have an increased risk of developing SLE later when exposed to such medications and infection.

SESSION TITLE: Medical Student/Resident Pulmonary Manifestations of Systemic Disease Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Anti-synthetase syndrome, considered a subset of dermatomyositis and polymyositis, is a chronic idiopathic inflammatory disorder involving skin and muscles, notable for progressive muscle weakness and or cutaneous eruption. In addition to skin, muscle, and joint involvement, it can have pulmonary manifestations, mainly interstitial lung disease. Its’ prevalence ranges from 20 to 80% and is a major cause of morbidity and mortality in patients with PM and DM. The most common radiological findings are diffuse reticular and nodular opacities, but pleural effusions are rarely seen. In review of the literature, only 10 cases have been reported of dermatomyositis or polymyositis associated with pleural effusions. CASE PRESENTATION: We report a case of a 48 year old male with no past medical history who presented with persistent cough, fatigue, bilateral shoulder weakness and stiffness in his knuckles, knees, and fingers for several months; the physical exam was notable for fissures and roughness and scaling on the pulp of the fingers, typical of “mechanic’s hands” and tenderness to palpation on 3rd and 4th proximal interphalangeal (PIP) joint of left and right hand. Chest radiography and tomography revealed reticular patchy airspace disease in the lower lobes, scarring in the right lung and moderate right sided effusion, no symptoms or features of infection were present. Thoracentesis showed exudative lymphocytic predominant fluid, no bacterial, and negative cytology. Serum serology revealed high ANA speckled titers (1:2560), highly positive anti-Jo 1 antibody, and high CPK; other anti-synthetase antibodies such as anti-EJ, SRP, Mi-2, anti-PM-Scl, and Anti-Ku were not available in our institution. He was then referred to a rheumatologist and diagnosed with anti-synthetase syndrome. Treatment was established with corticosteroids and mycophenolate mofetil with symptom improvement and complete resolution of the pleural effusion. DISCUSSION: In a series of dermatomyositis- or polymyositis-related ILD the prevalence of pleural effusion was estimated as 5%. In review of the literature, we find that only 10 cases of clinically important pleural effusion with PM-DM have been reported. Glucocorticoids are the first line of treatment. Prednisone is initially given at high doses (1 mg/kg per day) for 4–6 weeks to achieve disease control; then tapered slowly over 9–12 months to the lowest effective dose to maintain remission and to avoid the undesired effects of steroids. CONCLUSIONS: In conclusion, pleural effusion in ASS is a rare clinical manifestation. We need to be aware that lymphocytic pleural effusion may be the first presenting features of ASS. Fortunately, there was a significant response to steroid and immunosuppressive treatments in our case, but further information is needed to clarify the optimal treatment of these cases and elucidate the underlying pathogenesis of these conditions. Reference #1: 1. Saketkoo LA, Ascherman DP, Cottin V, Christopher-Stine L, Danoff SK, Oddis CV. Interstitial Lung Disease in Idiopathic Inflammatory Myopathy. Curr Rheumatol Rev. 2010;6(2):108-119. 2. Witt LJ, Curran JJ, Strek ME. The Diagnosis and Treatment of Antisynthetase Syndrome. Clin Pulm Med. 2016;23(5):218-226. 3. Badshah A, Haider I, Pervez S, Humayun M. Antisynthetase syndrome presenting as interstitial lung disease: a case report. J Med Case Rep. 2019;13(1):241. 4. Lega JC, Reynaud Q, Belot A, Fabien N, Durieu I, Cottin V. Idiopathic inflammatory myopathies and the lung. Eur Respir Rev. 2015;24(136):216-238. 5. Saito G, Kono M, Tsutsumi A, et al. Anti-PL-7 Antisynthetase Syndrome with Eosinophilic Pleural Effusion. Intern Med. 2018;57(15):2227-2232. 6. Friedman AW, Targoff IN, Arnett FC. Interstitial lung disease with autoantibodies against aminoacyl-tRNA synthetases in the absence of clinically apparent myositis. Semin Arthritis Rheum. 1996;26(1):459-467. 7. Nishikai M, Reichlin M. Heterogeneity of precipitating antibodies in polymyositis and dermatomyositis. Characterization of the Jo-1 antibody system. Arthritis Rheum. 1980;23(8):881-888. 8. Connors GR, Christopher-Stine L, Oddis CV, Danoff SK. Interstitial lung disease associated with the idiopathic inflammatory myopathies: what progress has been made in the past 35 years? Chest. 2010;138(6):1464-1474. 9. Solomon J, Swigris JJ, Brown KK. Myositis-related interstitial lung disease and antisynthetase syndrome. J Bras Pneumol. 2011;37(1):100-109. 10. Dugar M, Cox S, Limaye V, Blumbergs P, Roberts-Thomson PJ. Clinical heterogeneity and prognostic features of South Australian patients with anti-synthetase autoantibodies. Intern Med J. 2011;41(9):674-679. 11. Hamaguchi Y, Fujimoto M, Matsushita T, et al. Common and distinct clinical features in adult patients with anti-aminoacyl-tRNA synthetase antibodies: heterogeneity within the syndrome. PLoS One. 2013;8(4):e60442. 12. Marie I, Josse S, Decaux O, et al. Comparison of long-term outcome between anti-Jo1- and anti-PL7/PL12 positive patients with antisynthetase syndrome. Autoimmun Rev. 2012;11(10):739-745. 13. Hervier B, Meyer A, Dieval C, et al. Pulmonary hypertension in antisynthetase syndrome: prevalence, aetiology and survival. Eur Respir J. 2013;42(5):1271-1282. 14. Fathi M, Lundberg IE, Tornling G. Pulmonary complications of polymyositis and dermatomyositis. Semin Respir Crit Care Med. 2007;28(4):451-458. 15. Karkhanis VS, Joshi JM. Pleural effusion: diagnosis, treatment, and management. Open Access Emerg Med. 2012; 4:31-52. 16. Matsuoka N, Asano T, Sato S, et al. A case of dermatomyositis complicated with pleural effusion and massive ascites. Fukushima J Med Sci. 2020;65(3):140-145. 17. González-Gay MA, Montecucco C, Selva-O'Callaghan A, et al. Timing of onset affects arthritis presentation pattern in antisyntethase syndrome. Clin Exp Rheumatol. 2018;36(1):44-49. 18. Bartoloni E, Gonzalez-Gay MA, Scirè C, et al. Clinical follow-up predictors of disease pattern change in anti-Jo1 positive anti-synthetase syndrome: Results from a multicenter, international and retrospective study. Autoimmun Rev. 2017;16(3):253-257. 19. Roach DG, Salter WM. Polymyositis with pulmonary infiltrate and pleural effusion. Minn Med. 1980;63(4):277-279, 281. 20. Miyata M, Fukaya E, Takagi T, et al. Two patients with polymyositis or dermatomyositis complicated with massive pleural effusion. Intern Med. 1998;37(12):1058-1063. 21. Araya J, Nagai T, Oda H, et al. [Polymyositis-induced respiratory failure in the presence of antecedent pleural effusion]. Nihon Kokyuki Gakkai Zasshi. 1998;36(8):713-716. 22. Maeshima E, Nishimoto T, Yamashita M, Mune M, Yukawa S. Progressive systemic sclerosis-polymyositis overlap syndrome with eosinophilic pleural effusion. Rheumatol Int. 2003;23(5):252-254. 23. Iwai H, Koike R, Ogawa J, et al. [Case of dermatomyositis complicated with massive pleural effusion that preceded the myopathy]. Nihon Rinsho Meneki Gakkai Kaishi. 2002;25(3):270-276. 24. Mogulkoc N, Kabasakal Y, Ekren PK, Bishop PW. An unusual presentation of anti-Jo-1 syndrome, mimicking lung metastases, with massive pleural and pericardial effusions. J Clin Rheumatol. 2006;12(2):90-92. 25. Sugie K, Tonomura Y, Ueno S. Characterization of dermatomyositis with coexistence of anti-Jo-1 and anti-SRP antibodies. Intern Med. 2012;51(7):799-802. 26. Wu Y, Chhaya S, Hurowitz B, Ardiles T, Carlson R. Clinically Amyopathic Dermatomyositis Complicated by Pleural Effusion Case Report, Literature Review, and Proposed Mechanism. Bull Hosp Jt Dis (2013). 2015;73(3):217-220. DISCLOSURES: No relevant relationships by lucas chen, source=Web Response No relevant relationships by Jessica Liu, source=Web Response No relevant relationships by Aba Somers, source=Web Response

Innate airway hyperresponsiveness (AHR) and augmented responses to ozone, an asthma trigger, are characteristics of obese mice. Systemic inflammation, a condition of increased circulating concentrations of inflammatory moieties, occurs in obesity. We hypothesized that TNF-α, via its effects as a master effector of this systemic inflammation, regulates innate AHR and augmented responses to ozone in obese mice. Therefore, we examined pulmonary inflammation and airway responsiveness in unexposed or ozone-exposed (2 ppm for 3 h) lean wild-type and obese Cpe fat mice that were TNF-α sufficient or deficient. Cpe fat mice lack carboxypeptidase E, which regulates satiety. Compared with wild type, Cpe fat mice had elevated serum IL-17A, G-CSF, KC, MCP-1, IL-9, MIG, and leptin, indicating systemic inflammation. Despite reductions in most of these moieties in TNF-α-deficient vs. -sufficient Cpe fat mice, we observed no substantial difference in airway responsiveness in these two groups of mice. Ozone-induced increases in bronchoalveolar lavage (BAL) neutrophils and macrophages were lower, but ozone-induced AHR and increases in BAL hyaluronan, osteopontin, IL-13, and protein carbonyls, a marker of oxidative stress, were augmented in TNF-α-deficient vs. -sufficient Cpe fat mice. Our data indicate that TNF-α has an important role in promoting the systemic inflammation but not the innate AHR of obesity, suggesting that the systemic inflammation of obesity is not the major driver of this AHR. TNF-α is required for the augmented effects of acute ozone exposure on pulmonary inflammatory cell recruitment in obese mice, whereas TNF-α protects against ozone-induced AHR in obese mice, possibly by suppressing ozone-induced oxidative stress.

Ozone is an air pollutant that causes pulmonary symptoms. In mice, ozone exposure causes pulmonary injury and increases bronchoalveolar lavage macrophages and neutrophils. We have shown that IL-17A is important in the recruitment of neutrophils after subacute ozone exposure (0.3 ppm for 24-72 h). We hypothesized that γδ T cells are the main producers of IL-17A after subacute ozone. To explore this hypothesis we exposed wildtype mice and mice deficient in γδ T cells (TCRδ-/-) to ozone or room air. Ozone-induced increases in BAL macrophages and neutrophils were attenuated in TCRδ-/- mice. Ozone increased the number of γδ T cells in the lungs and increased pulmonary Il17a mRNA expression and the number of IL-17A+ CD45+ cells in the lungs and these effects were abolished in TCRδ-/- mice. Ozone-induced increases in factors downstream of IL-17A signaling, including G-CSF, IL-6, IP-10 and KC were also decreased in TCRδ-/- versus wildtype mice. Neutralization of IL-17A during ozone exposure in wildtype mice mimicked the effects of γδ T cell deficiency. TNFR2 deficiency and etanercept, a TNFα antagonist, also reduced ozone-induced increases in Il17a mRNA, IL-17A+ CD45+ cells and BAL G-CSF as well as BAL neutrophils. TNFR2 deficient mice also had decreased ozone-induced increases in Ccl20, a chemoattractant for IL-17A+ γδ T cells. Il17a mRNA and IL-17A+ γδ T cells were also lower in obese Cpefat versus lean WT mice exposed to subacute ozone, consistent with the reduced neutrophil recruitment observed in the obese mice. Taken together, our data indicate that pulmonary inflammation induced by subacute ozone requires γδ T cells and TNFα-dependent recruitment of IL-17A+ γδ T cells to the lung.

Obese mice exhibit innate airway hyperresponsiveness (AHR), a feature of asthma. Tumor necrosis factor alpha (TNFα) is implicated in the disease progression and chronic inflammatory status of both obesity and asthma. TNF acts via two TNF receptors, TNFR1 and TNFR2. To examine the role of TNFR2 in the AHR observed in obese mice, we generated obese Cpe(fat) mice that were either sufficient or deficient in TNFR2 (Cpe(fat) and Cpe(fat)/TNFR2(-/-) mice, respectively) and compared them with their lean controls (WT and TNFR2(-/-) mice). Compared to WT mice, Cpe(fat) mice exhibited AHR to aerosolized methacholine (measured using the forced oscillation technique) which was ablated in Cpe(fat)/TNFR2(-/-) mice. Bioplex or ELISA assay indicated significant increases in serum leptin, G-CSF, IL-7, IL-17A, TNFα, and KC in obese versus lean mice, as well as significant obesity-related increases in bronchoalveolar lavage fluid (BALF) G-CSF and IP-10, regardless of TNFR2 status. Importantly, BALF IL-17A was significantly increased over lean controls in Cpe(fat) but not Cpe(fat)/TNFR2(-/-) mice. Functional annotation clustering of significantly affected genes identified from microarray analysis comparing gene expression in lungs of Cpe(fat) and WT mice, identified blood vessel morphogenesis as the gene ontology category most affected by obesity. This category included several genes associated with AHR, including endothelin and trkB. Obesity increased pulmonary mRNA expression of endothelin and trkB in TNFR2 sufficient but not deficient mice. Our results indicate that TNFR2 signaling is required for the innate AHR that develops in obese mice, and suggest that TNFR2 may act by promoting IL-17A, endothelin, and/or trkB expression.

BACKGROUND:Acute ozone (O(3)) exposure results in greater inflammation and airway hyperresponsiveness (AHR) in obese versus lean mice. OBJECTIVES:We examined the hypothesis that these augmented responses to O(3) are the result of greater signaling through tumor necrosis factor receptor 2 (TNFR2) and/or interleukin (IL)-13. METHODS:We exposed lean wild-type (WT) and TNFR2-deficient (TNFR2(-/-)) mice, and obese Cpe(fat) and TNFR2-deficient Cpe(fat) mice (Cpe(fat)/TNFR2(-/-)), to O(3) (2 ppm for 3 hr) either with or without treatment with anti-IL-13 or left them unexposed. RESULTS:O(3)-induced increases in baseline pulmonary mechanics, airway responsiveness, and cellular inflammation were greater in Cpe(fat) than in WT mice. In lean mice, TNFR2 deficiency ablated O(3)-induced AHR without affecting pulmonary inflammation; whereas in obese mice, TNFR2 deficiency augmented O(3)-induced AHR but reduced inflammatory cell recruitment. O(3) increased pulmonary expression of IL-13 in Cpe(fat) but not WT mice. Flow cytometry analysis of lung cells indicated greater IL-13-expressing CD(4+) cells in Cpe(fat) versus WT mice after O(3) exposure. In Cpe(fat) mice, anti-IL-13 treatment attenuated O(3)-induced increases in pulmonary mechanics and inflammatory cell recruitment, but did not affect AHR. These effects of anti-IL-13 treatment were not observed in Cpe(fat)/TNFR2(-/-) mice. There was no effect of anti-IL-13 treatment in WT mice. CONCLUSIONS:Pulmonary responses to O(3) are not just greater, but qualitatively different, in obese versus lean mice. In particular, in obese mice, O(3) induces IL-13 and IL-13 synergizes with TNF via TNFR2 to exacerbate O(3)-induced changes in pulmonary mechanics and inflammatory cell recruitment but not AHR.

The purpose of this study was to examine the role of tumor necrosis factor receptor 1 (TNFR1) in the airway hyperresponsiveness characteristic of obese mice. Airway responsiveness to intravenous methacholine was measured using the forced oscillation technique in obese Cpe(fat) mice that were either sufficient or genetically deficient in TNFR1 (Cpe(fat) and Cpe(fat)/TNFR1(-/-) mice) and in lean mice that were either sufficient or genetically deficient in TNFR1 [wild-type (WT) and TNFR1(-/-) mice]. Compared with lean WT mice, Cpe(fat) mice exhibited airway hyperresponsiveness. Airway hyperresponsives was also greater in Cpe(fat)/TNFR1(-/-) than in Cpe(fat) mice. Compared with WT mice, Cpe(fat) mice had increases in bronchoalveolar lavage fluid concentrations of several inflammatory moieties including eotaxin, IL-9, IP-10, KC, MIG, and VEGF. These factors were also significantly elevated in Cpe(fat)/TNFR1(-/-) vs. TNFR1(-/-) mice. Additional moieties including IL-13 were also elevated in Cpe(fat)/TNFR1(-/-) vs. TNFR1(-/-) mice but not in Cpe(fat) vs. WT mice. IL-17A mRNA expression was greater in Cpe(fat)/TNFR1(-/-) vs. Cpe(fat) mice and in TNFR1(-/-) vs. WT mice. Analysis of serum indicated that obesity resulted in systemic as well as pulmonary inflammation, but TNFR1 deficiency had little effect on this systemic inflammation. Our results indicate that TNFR1 is protective against the airway hyperresponsiveness associated with obesity and suggest that effects on pulmonary inflammation may be contributing to this protection.

Context: Chamber studies in adult humans indicate reduced responses to acute ozone with increasing age. Age-related changes in TNF alpha have been observed. TNF alpha induced inflammation is predominantly mediated through TNFR1.Objective: To examine the impact of aging on inflammatory responses to acute ozone exposure in mice and determine the role of TNFR1 in age-related differences.Materials and methods: Wildtype and TNFR1 deficient (TNFR1(-/-)) mice aged 7 or 39 weeks were exposed to ozone (2 ppm for 3 h). Four hours after exposure, bronchoalveolar lavage (BAL) was performed and BAL cells, cytokines, chemokines, and protein were examined.Results: Ozone-induced increases in BAL neutrophils and in neutrophil chemotactic factors were lower in 39- versus 7-week-old wildtype, but not (TNFR1(-/-)) mice. There was no effect of TNFR1 genotype in 7-week-old mice, but in 39-week-old mice, BAL neutrophils and BAL concentrations of MCP-1, KC, MIP-2, IL-6 and IP-10 were significantly greater following ozone exposure in TNFR1(-/-) versus wildtype mice. BAL concentrations of the soluble form of the TNFR1 receptor (sTNFR1) were substantially increased in 39-week-old versus 7-week-old mice, regardless of exposure.Discussion and conclusion: The data suggest that increased levels of sTNFR1 in the lungs of the 39-week-old mice may neutralize TNF alpha and protect these older mice against ozone-induced inflammation.

Knowledge of hepatic arterial vascularization and its variations have a significant relevance for the daily practice of hepato-biliary surgeon as well as radiologists. Human cadaver livers (n=60) were obtained from routine autopsies. Resections were carried out en bloc with liver, celiac trunk (CT), left gastric artery (LGA), lesser omentum, superior mesenteric artery (SMA) and head of the pancreas. We have found one case with an exceptional anatomic variation, replaced left hepatic artery (LHA) coming off the SMA directly to the hepatic left lobe. We would like to draw attention for this particularly anatomic variation of the origin of the LHA ensuring that no damage will be made during gastrointestinal surgery.

Background: The swine is an essential model for carrying out preclinical research and for teaching complex surgical procedures. There is a lack of experimental models describing anatomical and surgical aspects of total pancreatectomy in the pig. Materials and Methods: The experiments were performed on 10 white male swine weighing 27–33 kg. The animals were premedicated with midazolam (0.4 mg/kg, i.m.) and ketamine (4 mg/kg, i.m.). Anesthesia was induced with propofol (1–2 mg/kg, i.v.) and was maintained with propofol and fentanyl (0.3 mg and 0.1 µg/kg/min, respectively, i.v.). The surgical period ranged from 44 to 77 min. The pancreas anatomy, and the main arterial, venous and pancreatic duct anatomy were assessed. Results: The pancreas anatomy was composed of 3 lobes, the ‘splenic’, ‘duodenal’ and ‘connecting’ lobe which is attached to the anterior portion of the portal vein. The splenic artery and the junction of the splenic vein and portal vein were divided. The left gastric artery was dissected and separated from its origin at the splenic artery. The head of the pancreas is disposed in a C shape. The pancreas was dissected and liberated from the right portion of the portal vein and the infrahepatic vena cava. The pancreas was separated from the duodenum preserving the pancreaticoduodenal artery, then we performed the total pancreatectomy preserving the duodenum, common bile duct and spleen. Conclusion: Total pancreatectomy with duodenum, bile duct and spleen preservation in the pig is feasible and an important instrument for research purposes and teaching surgical technique.