The photophysical and electrochemical properties of the diiron hydrogenase mimic complex, [Fe2(dpet)(CO)6] (dpet = 1,2-diphenylethene-1,2-dithiol) have been studied using a combination of spectroscopic and electrochemical techniques including cyclic voltammetry, infrared spectroelectrochemistry (IR-SEC), ultrafast transient absorption (TA) spectroscopy and time-resolved infrared spectroscopy (TRIR), with the data interpretation aided by density functional theory (DFT). The complex is a viable catalyst for electrochemical hydrogen evolution, as shown by its electrochemical reversibility and significant increase in the catalytic current upon addition of trifluoroacetic acid (TFA). IR-SEC was used to identify the first and second reduction products, where formation of a bridging mu-CO species was observed. The ultrafast spectroscopy data show that CO loss is only a minor excited state relaxation pathway, unlike other previously reported [FeFe] catalysts, in agreement with steady-state photolysis. The excited state lifetime obtained for this complex (135 ps in DCM and 237 ps in MeCN) is insufficient for [Fe2(dpet)(CO)6] to function as a photocatalyst on its own. However, the photostability of the complex opens up an opportunity for its future use in conjunction with a photosensitiser in photochemical hydrogen evolution.
BACKGROUND:Casualties of military conflicts suffer a multitude of injuries, and recent research has documented a significant number develop acute respiratory distress syndrome (ARDS). The present study undertakes a scoping review of research on the treatment of ARDS in combat casualties near the battlefield. METHODS:We review the extent of the current ARDS care, from intubation and mechanical ventilation (MV) to the use of extracorporeal membrane oxygenation (ECMO), and how the respective echelons of care across the Military Health System (MHS) are involved in the care of these patients. Online databases were used to identify article published 1988-2022, from which we selected 112 publications from various countries including the USA, UK, Germany, Italy, and India that used military relevant keywords (i.e., battlefield, combat, deployed, military trauma), in the titles or abstract in conjunction with the MeSH descriptors for battlefield respiratory failure, and MV or ECMO. RESULTS:Mechanical ventilation and ECMO have clearly moved forward with progressions in technologies and now are routinely used and are well documented in the prehospital setting and during aeromedical transport. Overview of the MHS and descriptive analysis of battlefield casualties are well represented in the literature. There are multiple publications on airway management on the battlefield and innumerable regarding the somewhat comparable civilian prehospital trauma airway management. CONCLUSION:While there is an abundance of publications on MV in the prehospital and combat environments, there are few case examples of the use of ECMO on the battlefield. Although MV may be required for many combat casualties, airway management failure remains the second leading cause of preventable death on the battlefield.
INTRODUCTION:Deployed military personnel may be at risk for developing acute and chronic lung disease. Prior studies of this patient population have revealed that unexplained exertional dyspnea is the most common diagnosis despite an extensive evaluation. There is a concern that an occult disorder may be affecting this population. This study evaluated the role for bronchoalveolar lavage (BAL) fluid analysis in the evaluation of chronic deployment-associated dyspnea. MATERIALS AND METHODS:Military personnel who reported chronic respiratory symptoms were evaluated as part of the Study of Active Duty Military for Pulmonary Disease Related to Environmental Deployment Exposures III study. Participants underwent bronchoscopy with BAL as part of a standardized evaluation. RESULTS:A total of 308 patients with a mean age of 38 ± 8.6 years underwent bronchoscopy with BAL. BAL cell-count percentages of macrophages, lymphocytes, neutrophils, and eosinophils were: 76.2 ± 17.0%, 16.3 ± 13.4%, 6.6 ± 8.9%, and 0.9 ± 3.2%, respectively. There was no clear differentiation between groups based on increases in lymphocyte counts (P = .640), although lymphocyte values were more elevated (21.4 ± 12.1%) in the interstitial lung disease category. Neutrophil counts (6.6 ± 8.9%) were elevated compared to the reported normal reference values and were increased in the isolated pulmonary function test abnormality (9.4 ± 11.6%), large airway disorder (10.0 ± 7.5%), miscellaneous (10.9 ± 20.2%), and obstructive lung disease (11.0 ± 15.6%) groups. Eosinophil counts were within normal limits (0.9 ± 3.2%) and showed no differences between groups (P = .545); asthma patients trended higher (1.6 ± 5.7%). BAL counts for the exertional dyspnea group were within normal reference values and showed no differences from the entire cohort. CONCLUSIONS:The addition of BAL cytology did not help differentiate those patients with unexplained dyspnea from other etiologies.
Introduction: The ability of military clinicians to conduct military medical research is often limited because of competing priorities and a lack of research mentorship. The Clinician-Scientist Investigator Opportunity Network (CSION) was developed with the intent of training clinicians how to engage in requirements-driven research within the DoD. Materials and Methods: Three to five academic medical faculties were selected from a pool of applicants each year to participate in a 2-year research fellowship. To be eligible for the CSION program, applicants had to meet the following criteria: (1) Completed residency graduate medical education training, (2) not be currently enrolled as a graduate medical education trainee, and (3) obtained permission from their department leadership to focus 25% of their duty hours on CSION participation to include didactic and research efforts. The remaining 75% of fellows' time was dedicated to clinical duties. Monthly didactics, intensive mentorship, and consistent support were offered to each fellow by the CSION leadership team. Metrics were recorded to include both research and clinical productivity. Results: Between January 2019 and December 2022, 12 CSION fellows graduated from the program (four in the class of 2020, three in 2021, and five in 2022). From 2019 to 2021, the 12 CSION fellows initiated 204 research protocols, generated 489 publications/presentations, and secured 33 research grants. All graduates of the program remain active in clinical research with multiple graduates currently assigned to research positions. Conclusions: The CSION research education program is a 2-year additional duty research fellowship producing clinician-scientists conducting military-relevant medical research and publications and may be considered a low-cost/highly efficient alternative to achieve the reported benefits of the MD-PhD tract. The expansion of the CSION program may improve the quality of military medical research and health care.
PURPOSE: COVID-19 has had a severe impact on force readiness across all branches of the United States military.Personnel that were symptomatic and tested positive for COVID-19 were significantly more likely to report persistent dyspnea and exercise limitation that impacted PFT scores for longer than 12 months.Symptoms in prior studies did not always correlate with imaging findings, which prompted expansion of testing to better qualify the cause of persistent cardiopulmonary symptoms. METHODS:A prospective analysis of active duty service members with persistent symptoms for 3 months after contracting COVID-19 were evaluated.Testing included full pulmonary function testing with bronchodilator (PFTs with BD), impulse oscillometry (IOS), methacholine challenge testing (MCT), high resolution computed tomography (HRCT), echocardiogram and electrocardiogram (EKG), laboratory testing, and cardiopulmonary exercise testing (CPET).RESULTS: A total of 105 AD service members with a median age of 35.9 AE 8.0 and median BMI of 28.8 AE 4.6 with persistent symptoms after COVID-19 were enrolled to further evaluate the cause of their persistent dyspnea.Ten of these participants had been hospitalized between 1-12 days.Significant pulmonary function test findings included MCT positivity in 12 patients (11.4%),FEV 1 below the lower limit of normal in 12 patients (11.4%),TLC below the lower limit of normal in 9 patients (8.6%), residual volume above the upper limit of normal in 4 patients (3.8%) and low diffusion capacity in 15 patients (14%).Significant imaging findings included air trapping in 24 of patients (22.3%), ground glass opacities in 10 patients (9.5%), and reticulation in 4 patients (3.8%).IOS data was significant for R5 below predicted in 53 patients (50.5%) and R20 below predicted in 70 patients (66.7%).No significant reduction in VO 2 max was noted on CPET and there were no significant echocardiographic findings.CONCLUSIONS: This prospective study of non-hospitalized active duty service members with persistent symptoms after contracting COVID-19 found a predominant pattern of obstructive airway disease and isolated reduction in DLCO.No respiratory abnormalities in exercise capacity were noted and echocardiographic findings were unremarkable.Additional enrollment may allow for more subset analysis based on time since diagnosis and improvements in exercise capacity.CLINICAL IMPLICATIONS: Persistent symptoms associated with COVID 19 infection continue to be investigated extensively and have evolved as the severity of infection has changed.In this study, the predominant etiolgoy of ongoing dyspnea on exertion is obstruction with reduced DLCO as a close second.This understanding may help target therapies that may offer more symptom relief.
PURPOSE: Interstitial lung diseases (ILD) are a unique group of lung disease that carries significant morbidity and mortality with increased incidence and prevalence with age.The heterogeneity and evolution of diagnosis has made defining true incidence and characteristics of disease difficult.This study aims to describe the etiology and characteristic in a young healthy military population with various deployment exposures. METHODS:A retrospective chart review was conducted using the electronic medical record for active duty service members with a diagnosis of ILD.Basic demographic data, diagnosis, pulmonary function testing, chest imaging, and pathologic results were reviewed.The groups were then subdivided for further analysis based on exposure and deployment history.Further subgroup analysis was performed on the major idiopathic interstitial pneumonias (IIP) and connective tissue disease related ILD (CTD-ILD) within this cohort.RESULTS: Initial review of medical records identified 323 individuals with a diagnosis of ILD of which only 158 were analyzed.The cohort was 70.9% male with a mean age of 38.9 years.Chest imaging was performed in 158 (100%) patients while PFTs were done in 147 (93%) patients.Average FVC 3.52 L (77% predicted), FEV1 2.75 L (75% predicted), FEV1/FVC 79%, TLC 6.32 L (78% predicted), and DLCO 18.8 mL/Hg/min (63% predicted).Tissue diagnosis was made in 39.2 % of patients.BAL was performed in 20.9% of patients.Notably, 82 (51.9%) individuals were under the age of 40 while the remaining 76 (48.1%) over 40 years old.32.3% had a diagnosis characterized as a major IIP, 29.7% with CTD-ILD, and 38% alternative diagnosis.There was a notable higher proportion of females in CTD-ILD subgroup when compared to Major IIPs (44.7% vs 21.6%). CONCLUSIONS:In this study we describe the etiology and characteristics of active duty military members diagnosed with ILD during military service.Despite a young population a variety of causes were found for underlying ILD.A higher proportion of females were noted to have CTD-ILD when compared to other subgroups.PFT data reviewed showed more subtle changes suggestive of early ILD.Further characterization based on military occupation and deployment is ongoing.CLINICAL IMPLICATIONS: This study aims to help further describe the incidence and distribution of ILD in an otherwise healthy population.ILD is typically diagnosed later in life and early detection may help decrease long term morbidity and mortality.Further investigation should be performed to evaluate any relationship of ILD to deployment or other exposures during military service.
INTRODUCTION:Coccidioidomycosis disease is caused by the endemic, invasive dimorphic fungi Coccidioides immitis/ posadasii.Treatment recommendations are dependent on clinical, radiographic, and serologic testing by immunodiffusion (ID) and complement fixation (CF), which are typically positive on initial presentation and recurrent disease [1, 2, 3].We present a rare case of recurrent pulmonary coccidiomycosis in the setting of negative ID and CF diagnostic testing. CASE PRESENTATION:A 58-year-old Caucasian female living in Arizona with no past medical history was diagnosed with pulmonary coccidioidomycosis in November 2020 and treated with voriconazole for approximately 8 months.CF titers at the start and end of treatment were 1:8 and <1:2, respectively.She continued to experience fatigue and shortness of breath after cessation of therapy and eventually moved to San Antonio, Texas.Computed tomography (CT) of the chest in December 2021 showed right upper and lower lobe consolidations that were also fluorodeoxyglucose (FDG)-avid on FDG-positron emission tomography (PET) in February 2022.Endobronchial ultrasound bronchoscopy (EBUS) performed in March 2022 was unremarkable and repeated in September 2022.The patient was admitted 1 week after her last EBUS with new fever, headache, hemoptysis, and bone and joint pain of her left ankle and worsening fatigue and shortness of breath.Lumbar puncture and magnetic resonance imaging (MRI) of the brain and spine were negative for coccidioidal meningitis and MRI of the left ankle showed no findings to suggest coccidioidal osteomyelitis.Coccidioides serology for both ID and CF were repeated and negative.The patient had no history of immunocompromising conditions with negative human immunodeficiency virus testing.Due to negative Coccidioides serology, immunoglobulins (IgA, IgE, IgG, and IgM) were checked and all within the normal range.Prior to discharge, her fungal culture from bronchoscopy isolated Coccidioides species and the patient was diagnosed with recurrence of pulmonary coccidioidomycosis.The patient was started on oral fluconazole, but due to adverse side effects, she was discharged on oral posaconazole with plans to repeat CT chest imaging following 3 months on therapy.DISCUSSION: Coccidioidomycosis disease can present with both pulmonary and extrapulmonary clinical manifestations.Patients with concern for Coccidioidomycosis disease should undergo Coccidioides serology testing and be evaluated for extrapulmonary manifestations.Both serologic and disease recurrence is common in patients with or without treatment and occurs more frequently in those with chronic coccidioidomycosis with pulmonary, meningeal, or disseminated disease [1, 3].CF serologies can be used quantitatively and a titer >1:16 is associated with disease severity and disseminated disease [3].Negative ID and CF serologies in our patient with extensive pulmonary disease that was PET-avid and with isolation of Coccidioides from bronchoscopy fungal cultures is exceedingly rare in the absence of immunocompromising conditions and hypogammaglobulinemia.CONCLUSIONS: This case highlights that coccidioidomycosis can reoccur after treatment and providers should maintain a high index of suspicion for disease when clinical symptoms are present even in the absence of negative serologic testing.
PURPOSE:Asthma is among the most common diagnoses in military personnel who endorse chronic dyspnea.There is concern that airborne exposures in the deployed environment may contribute to or exacerbate asthma symptoms.Current fitness standards allow for active-duty service members with well-controlled asthma to be retained for duty, but those with severe symptoms are recommended for separation.This study sought to characterize the phenotype of medically separated military personnel with career limiting asthma in order to help identify and risk stratify those more likely to have severe symptoms requiring separation from active-duty service. METHODS:A retrospective chart review of military personnel who underwent fitness for duty evaluation (Medical Evaluation Board) for asthma between 2010-2020 and were separated with a minimum 30% conditional disability rating was performed.Only patients who were diagnosed with asthma by a pulmonologist and had spirometry data were evaluated.Demographics, spirometry, and laboratory data to include immunoglobulin E (IgE) levels, allergen panels, and eosinophil counts were collected.RESULTS: A total of 141 patients were evaluated with a mean age of 42, mean eosinophil (EOS) count of 390 cells/mL and mean serum IgE level of 305 IU/ml.Serum allergen panels were positive in 74.4% (n¼104) patients.The patients were further categorized into four subgroups.Group A: IgE 0-100 IU/mL and EOS 0-300 cells/mL(n¼45; 32%), Group B: IgE>100 IU/mL and EOS 0-300 cells/mL (n¼44; 31%), Group C: IgE 0-100 IU/mL and EOS >300 cells/mL(n¼6; 1%), and Group D: IgE>100 IU/mL, EOS >300 cells/mL (n¼46; 33%).Mean spirometry data for forced vital capacity (FVC), forced expiratory volume (FEV1), FEV1/ FVC ratio pre-bronchodilator was 89%, 75%, 70% predicted respectively.Post-bronchodilator spirometry revealed a mean improvement in FVC and FEV1 of 8% and 17% respectively.CONCLUSIONS: Despite a significant correlation between the severity of asthma and IgE/EOS levels in the general population being reported in prior studies, the majority of active-duty service members (ADSM) with career-limiting asthma do not have concordant elevations in IgE/EOS levels and a significant proportion are within the normal range.This suggests that the majority of ADSM with career limiting asthma may have a non-T2, non-atopic, and/or smoking associated asthma phenotype. CLINICAL IMPLICATIONS:The majority of ADSM with career limiting asthma may have a non-T2, non-atopic, and/or smoking associated asthma phenotype.
INTRODUCTION:Evaluation of chronic respiratory symptoms in deployed military personnel has been conducted at Brooke Army Medical Center as part of the Study of Active Duty Military for Pulmonary Disease Related to Environmental Deployment Exposures III study. Although asthma and airway hyperreactivity have been the most common diagnoses, the clinical findings in these patients may be multifactorial. This study aims to evaluate the utility of impulse oscillometry (IOS) in diagnosing airway obstruction in patients undergoing multiple pulmonary function testing (PFT) studies. METHODS:Military personnel referred for deployed-related pulmonary symptoms underwent a standardized evaluation at Brooke Army Medical Center and Walter Reed National Military Medical Center over a 5-year span. Initial studies included laboratory tests, high-resolution computed tomography imaging, cardiac evaluation with electrocardiogram, and echocardiography. PFT consisted of full PFTs, forced inspiratory/expiratory pressures, post-spirometry bronchodilator testing, IOS, exhaled nitric oxide, and methacholine challenge testing. RESULTS:A total of 360 patients have completed an evaluation to date. In this cohort, 108 patients (30.0%) have evidence of obstruction by spirometry, whereas 74 (20.6%) had IOS values of both an R5 > 150% and X5 < -1.5. Only 32 (8.9%) had evidence of obstruction by both spirometry and IOS, whereas 210 (57.3%) had neither. A comparison among R5 (resistance at 5 Hz), R20 (resistance at 20 Hz), and X5 (reactance at 5 Hz) was performed in those individuals with and without spirometric obstruction. R5 (% predicted) was 156.2 ± 57.4% (obstruction) vs. 129.1 ± 39.6% (no obstruction) (P < .001); R20 (% predicted) was 138.1 ± 37.7% (obstruction) vs. 125.3 ± 31.2% (no obstruction) (P = .007); and X5 (cmH2O/L/s) was -1.62 ± 1.28 (obstruction) vs. -1.25 ± 0.55 (no obstruction) (P < .001). DISCUSSION:Impulse oscillometry has been advocated as a supplemental pulmonary function test to aid in the diagnosis of airway obstruction. The use of IOS has been primarily used in pediatrics and elderly populations as a validated tool to establish a diagnosis of airway obstruction but is limited in the adult population because of a well-validated set of reference values. Prior studies in adults have most often demonstrated a correlation with an elevated R5 > 150%, elevated resonant frequency, and a negative X5 < -1.5 or a decrease of 30 to 35% in R5 post-bronchodilator. CONCLUSION:Impulse oscillometry may serve as an adjunct to diagnosis but likely cannot replace a standard spirometric evaluation. Our study highlights the future utility for diagnosing early obstructive disease in the symptomatic individual.
INTRODUCTION:Granulomatosis with polyangiitis (GPA) is an antineutrophil cytoplasmic antibodies (ANCA) associated vasculitis that affects small and medium sized blood vessels with primarily lung and kidney involvement.We present a case of diffuse alveolar hemorrhage (DAH) in GPA, a rare aggressive manifestation, that was ANCA negative. CASE PRESENTATION:A 65-year-old man with past medical history of CAD s/p CABG, GPA with pulmonary involvement on rituximab, recent admission for bilateral pulmonary embolism (PE) presents with worsening fever, non-productive cough, and dyspnea on exertion of 1 month in duration.On presentation, the patient required BiPAP, and broad-spectrum antibiotics including Bactrim were initiated.Labs were positive for rhinovirus on the respiratory panel, elevated CRP, ESR.Otherwise, he had a negative extensive infectious workup.ANCA profile (MPO, PR3) and anti-GBM were negative.Imaging showed stable bilateral pulmonary embolism and generalized worsening diffuse ground glass opacities.Bronchoscopy was performed and was consistent with DAH, and the patient was diagnosed with DAH secondary to a GPA flare and rhinovirus.He underwent a 3-day course of pulse dose steroids, cyclophosphamide infusion and 3 sessions of plasmapheresis with improvement in respiratory status down to 5L nasal cannula.He was ultimately discharged with prolonged steroid taper and a close follow up.DISCUSSION: DAH is a respiratory emergency which requires prompt diagnosis and treatment.Most are associated with autoimmune diseases and can be a result of coagulation disorders, drugs, inhaled toxins, or transplantation.Pathophysiology involves presence of cellular inflammation, vessel destruction and tissue necrosis.Degree of hypoxemia upon presentation remains the most important predictor of respiratory failure.Bronchoscopy with increasing RBCs in serial aliquot dilutional bronchoalveolar samples from one location is diagnostic.While laboratory analysis of anti-neutrophil antibodies has become a mainstay in the initial diagnosis of small vessel vasculitides, their utility in monitoring disease activity remains controversial.Persistently high ANCA titers have been shown to place patients at increased risk for relapse after induced remission and provide a significant positive predictive value in clinical context of relapse in DAH or glomerulonephritis.However, ANCA titers in the setting of acute vasculitic relapse has been shown to be of little diagnostic value given a low sensitivity with rates of ANCA negative relapse anywhere from 13-54%.It is essential that immune vasculitis remains high on the differential diagnosis in a patient who presents with diffuse alveolar hemorrhage and a history of necrotizing small vessel vasculitis regardless of ANCA positivity.CONCLUSIONS: This case highlights the limited clinical utility of negative ANCA titers in the setting of relapsing necrotizing small vessel vasculitis.
PURPOSE Although BRCA1/ 2 testing in ovarian cancer improves outcomes, it is vastly underutilized. Scalable approaches are urgently needed to improve genomically guided care. METHODS We developed a Natural Language Processing (NLP) pipeline to extract electronic medical record information to identify recipients of BRCA testing. We applied the NLP pipeline to assess testing status in 308 patients with ovarian cancer receiving care at a National Cancer Institute Comprehensive Cancer Center (main campus [MC] and five affiliated clinical network sites [CNS]) from 2017 to 2019. We compared characteristics between (1) patients who had/had not received testing and (2) testing utilization by site. RESULTS We found high uptake of BRCA testing (approximately 78%) from 2017 to 2019 with no significant differences between the MC and CNS. We observed an increase in testing over time (67%-85%), higher uptake of testing among younger patients (mean age tested = 61 years v untested = 65 years, P = .01), and higher testing among Hispanic (84%) compared with White, Non-Hispanic (78%), and Asian (75%) patients ( P = .006). Documentation of referral for an internal genetics consultation for BRCA pathogenic variant carriers was higher at the MC compared with the CNS (94% v 31%). CONCLUSION We were able to successfully use a novel NLP pipeline to assess use of BRCA testing among patients with ovarian cancer. Despite relatively high levels of BRCA testing at our institution, 22% of patients had no documentation of genetic testing and documentation of referral to genetics among BRCA carriers in the CNS was low. Given success of the NLP pipeline, such an informatics-based approach holds promise as a scalable solution to identify gaps in genetic testing to ensure optimal treatment interventions in a timely manner.
SESSION TITLE: Pulmonary Manifestations of Systemic Disease Case PostersSESSION TYPE: Case Report PostersPRESENTED ON: 10/19/2022 12:45 pm - 01:45 pmINTRODUCTION: Anti-neutrophil cytoplasmic antibodies are antibodies directed towards neutrophil and lysosomal granules. Their presence is linked to the necrotizing small-vessel vasculitis syndromes of granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA) and microscopic polyangiitis (MPA). Lung involvement is a common feature across all subtypes but is most seen in GPA and is present at some point during the clinical course in 85-90% of all of those diagnosed. While less common, pulmonary involvement accounts for half of those diagnosed with MPA [1]. This case represents a unique presentation of isolated pulmonary MPA with diffuse alveolar hemorrhage.CASE PRESENTATION: A 49-year-old female presented with one month of daily hemoptysis along with new-onset dyspnea and was found to have acute hypoxemic respiratory failure. She denied myalgias, arthralgias, fevers, neuropathy, ulcers, and hematuria. Family history was significant for the patient's mother and brother with biopsy-proven sarcoidosis. On examination, lung auscultation was normal and no skin lesions or rashes were present. CBC, urinalysis, and renal and liver function tests were normal. Infectious workup was negative. Complement components C3 and C4 were normal. Serology revealed positive ANA with titer 1:640 in a homogeneous pattern and positive P-ANCA-MPO. CT Chest revealed multifocal nodular airspace opacities with upper lobe and peripheral predominance. BAL performed consistent with diffuse alveolar hemorrhage in the right upper lobe. Tissue biopsy revealed nongranulomatous capillaritis consistent with MPA. She was treated with a 6-week course of prednisone and started on weekly rituximab infusions with resolution of her symptoms.DISCUSSION: Classically, ANCA-associated vasculitis presents with multi-organ involvement including neuropathy, skin lesions, and renal involvement. However, this is not always the case. In MPO-ANCA associated vasculitis, lung involvement often precedes systemic symptoms in up to 85% of cases. Achieving a diagnosis and treatment to induce remission is paramount in these patients as their pulmonary manifestations can often progress into diffuse alveolar hemorrhage which carries a mortality of up to 80%. Additionally, these patients require further renal monitoring. Despite their initially limited disease, the majority of patients with pulmonary-limited MPA eventually exhibit renal involvement with crescentic glomerulonephritis.CONCLUSIONS: Classic presentations with hematuria, skin lesions and neuropathy can be diagnosed confidently with immunofluorescence assays and enzyme immunoassay testing for ANCA and ANCA specific antibodies. However, MPA often presents with isolated pulmonary symptoms prior to additional organ involvement. This case demonstrates the importance of tissue biopsy for diagnosis of isolated pulmonary involvement of MPA without constitutional symptoms.Reference #1: Alba MA, Flores-Suárez LF, Henderson AG, et al. Interstitial lung disease in ANCA vasculitis. Autoimmun Rev. 2017;16(7):722-729. doi:10.1016/j.autrev.2017.05.008Reference #2: Kadura, Suha, and Ganesh Raghu. "Antineutrophil Cytoplasmic Antibody-Associated Interstitial Lung Disease: A Review.” European Respiratory Review, vol. 30, no. 162, 2021, p. 210123., https://doi.org/10.1183/16000617.0123-2021.DISCLOSURES: No relevant relationships by JING DINo relevant relationships by Madison HardestyNo relevant relationships by Michael Morris SESSION TITLE: Pulmonary Manifestations of Systemic Disease Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Anti-neutrophil cytoplasmic antibodies are antibodies directed towards neutrophil and lysosomal granules. Their presence is linked to the necrotizing small-vessel vasculitis syndromes of granulomatosis with polyangiitis (GPA), eosinophilic granulomatosis with polyangiitis (EGPA) and microscopic polyangiitis (MPA). Lung involvement is a common feature across all subtypes but is most seen in GPA and is present at some point during the clinical course in 85-90% of all of those diagnosed. While less common, pulmonary involvement accounts for half of those diagnosed with MPA [1]. This case represents a unique presentation of isolated pulmonary MPA with diffuse alveolar hemorrhage. CASE PRESENTATION: A 49-year-old female presented with one month of daily hemoptysis along with new-onset dyspnea and was found to have acute hypoxemic respiratory failure. She denied myalgias, arthralgias, fevers, neuropathy, ulcers, and hematuria. Family history was significant for the patient's mother and brother with biopsy-proven sarcoidosis. On examination, lung auscultation was normal and no skin lesions or rashes were present. CBC, urinalysis, and renal and liver function tests were normal. Infectious workup was negative. Complement components C3 and C4 were normal. Serology revealed positive ANA with titer 1:640 in a homogeneous pattern and positive P-ANCA-MPO. CT Chest revealed multifocal nodular airspace opacities with upper lobe and peripheral predominance. BAL performed consistent with diffuse alveolar hemorrhage in the right upper lobe. Tissue biopsy revealed nongranulomatous capillaritis consistent with MPA. She was treated with a 6-week course of prednisone and started on weekly rituximab infusions with resolution of her symptoms. DISCUSSION: Classically, ANCA-associated vasculitis presents with multi-organ involvement including neuropathy, skin lesions, and renal involvement. However, this is not always the case. In MPO-ANCA associated vasculitis, lung involvement often precedes systemic symptoms in up to 85% of cases. Achieving a diagnosis and treatment to induce remission is paramount in these patients as their pulmonary manifestations can often progress into diffuse alveolar hemorrhage which carries a mortality of up to 80%. Additionally, these patients require further renal monitoring. Despite their initially limited disease, the majority of patients with pulmonary-limited MPA eventually exhibit renal involvement with crescentic glomerulonephritis. CONCLUSIONS: Classic presentations with hematuria, skin lesions and neuropathy can be diagnosed confidently with immunofluorescence assays and enzyme immunoassay testing for ANCA and ANCA specific antibodies. However, MPA often presents with isolated pulmonary symptoms prior to additional organ involvement. This case demonstrates the importance of tissue biopsy for diagnosis of isolated pulmonary involvement of MPA without constitutional symptoms. Reference #1: Alba MA, Flores-Suárez LF, Henderson AG, et al. Interstitial lung disease in ANCA vasculitis. Autoimmun Rev. 2017;16(7):722-729. doi:10.1016/j.autrev.2017.05.008 Reference #2: Kadura, Suha, and Ganesh Raghu. "Antineutrophil Cytoplasmic Antibody-Associated Interstitial Lung Disease: A Review.” European Respiratory Review, vol. 30, no. 162, 2021, p. 210123., https://doi.org/10.1183/16000617.0123-2021. DISCLOSURES: No relevant relationships by JING DI No relevant relationships by Madison Hardesty No relevant relationships by Michael Morris
SESSION TITLE: Imaging Across the Care Spectrum SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm PURPOSE: Inhalation exposure during deployment to Southwest Asia has been postulated as a cause of respiratory symptoms in military service members, raising concern about the long-term effects of environmental and occupational exposures to include burn pits, geologic dust, and exhaust. Despite surgical lung biopsy evidence of constricting bronchiolitis in this population, extensive studies of symptomatic service members returning from Southwest Asia has not demonstrated systemic lung disease. Radiographic evidence of pulmonary changes in theater could elucidate an etiology for chronic respiratory symptoms. This pilot study is the first to compare baseline to post-deployment chest imaging. METHODS: 30 service members were enrolled in a randomized prospective study with two CT scans (non-contrast 64-slice with 3 high resolution cuts): baseline within 72 hours of landing at Task Force Med, Baghdad Diplomatic Support Center, Iraq, and post-deployment 7-9 months later. Pre- and post-deployment questionnaires collected prior exposure, demographic, and symptom data. Radiographic abnormalities indicative of pulmonary disease was the primary endpoint. RESULTS: 28 of 30 service members (ages 20 to 49, 19 male and 9 female, 12 with previous international deployments) completed the protocol excluding 2 enrollees who were re-deployed early. 9 of 14 service members with baseline CT abnormalities had previously deployed. Post-deployment versus pre-deployment CT abnormalities were present in 16 versus 14 of 28 service members (57% vs. 50%) notable for air trapping (10, 36% vs. 9, 32%), opacities (4, 14% vs. 2, 7%), airway thickening (2, 7% vs. 0), and airway secretions or debris (4, 14% vs. 0). CONCLUSIONS: Human immune and respiratory systems are uniquely developed to prevent long-term sequelae of inhaled particulate matter. Although non-specific changes were observed, post-deployment compared to pre-deployment CT images do not suggest systemic lung disease in service members returning from Southwest Asia. Alternative etiologies for chronic respiratory symptoms such as asthma should be further investigated. CLINICAL IMPLICATIONS: Strong importance to further understand if inhalation exposure during deployment cause respiratory symptoms in military service members, raising concern about the long-term effects of environmental and occupational exposures to include burn pits, geologic dust, and exhaust. DISCLOSURES: no disclosure on file for Sally Delvecchio; No relevant relationships by Benjamin Iliff No relevant relationships by Giovanni Lorenz Speaker/Speaker's Bureau relationship with Janssen Please note: $1001 - $5000 by Michael Morris, value=Honoraria Speaker/Speaker's Bureau relationship with GSK Please note: $1001 - $5000 by Michael Morris, value=Honoraria Removed 03/29/2022 by Michael Morris No relevant relationships by Tyson Sjulin
Point-of-Care Ultrasound (POCUS) refers to clinician-performed and interpreted ultrasonography at the patient's bedside. Interpreting these images requires a high level of expertise, which may not be available during emergencies. In this paper, we support POCUS by developing classifiers that can aid medical professionals by diagnosing whether or not a patient has pneumothorax. We decomposed the task into multiple steps, using YOLOv4 to extract relevant regions of the video and a 3D sparse coding model to represent video features. Given the difficulty in acquiring positive training videos, we trained a small-data classifier with a maximum of 15 positive and 32 negative examples. To counteract this limitation, we leveraged subject matter expert (SME) knowledge to limit the hypothesis space, thus reducing the cost of data collection. We present results using two lung ultrasound datasets and demonstrate that our model is capable of achieving performance on par with SMEs in pneumothorax identification. We then developed an iOS application that runs our full system in less than 4 seconds on an iPad Pro, and less than 8 seconds on an iPhone 13 Pro, labeling key regions in the lung sonogram to provide interpretable diagnoses.
Obesity is a complex disease that is the result of a number of different factors including genetic, environmental, and endocrine abnormalities. Given that monogenic forms of obesity are rare, it is important to identify other mechanisms that contribute to its etiology. Methyl-Cp-G binding protein 2 (MeCP2) is a neuroepigenetic factor that binds to methylated regions of DNA to influence transcription. Past studies demonstrate that disruption in MeCP2 function produces obesity in mice. Using a diet-induced obesity mouse model, we show that perinatal exposure to high fat diet significantly decreases MeCP2 protein expression in the hypothalamus of female mice, effects not seen when high fat diet is given to mice during adulthood. Moreover, these effects are seen specifically in a subregion of the hypothalamus known as the arcuate nucleus with females having decreased MeCP2 expression in rostral areas and males having decreased MeCP2 expression in intermediate regions of the arcuate nucleus. Interestingly, mice gain more weight when exposed to high fat diet during adulthood relative to mice exposed to high fat diet perinatally, suggesting that perhaps high fat diet exposure during adulthood may be affecting mechanisms independent of MeCP2 function. Collectively, our data demonstrate that there are developmentally sensitive periods in which MeCP2 expression is influenced by high fat diet exposure and this occurs in a sexually dimorphic manner.
TOPIC: Diffuse Lung Disease TYPE: Original Investigations PURPOSE: Eosinophilic pneumonias, both acute and chronic, form a rare subset of interstitial lung disease. Glucocorticoids are the cornerstone for the treatment of eosinophilic pneumonia given their well-documented anti-eosinophil properties. There are many cases where patients require prolonged courses of glucocorticoids to achieve remission, and then require repeat courses for relapse. Given the numerous side effects of steroids, there is interest in the use of steroid-sparing agents, such as anti-eosinophil biologic agents, in treating steroid-refractory or relapsed eosinophilic pneumonia in those patients requiring prolonged treatment. The purpose of this study was to review cases of chronic eosinophilic pneumonia and identify cases where biologic therapies were used. METHODS: Using the electronic medical record that services the entire DOD, a retrospective chart review of individuals carrying a diagnosis of eosinophilic pneumonia was performed. We searched for cases between 2014 and 2020 and identified 295 patients for whom these diagnoses were listed. We then excluded patients with hypereosinophilic syndromes, those without bronchoalveolar lavage (BAL) results or BAL eosinophilia < 20%. RESULTS: A total of 53 cases were identified that were defined as eosinophilic pneumonia based on BAL findings; 12 patients were currently receiving treatment with either mepolizumab or benralizumab. These cases had either relapsing disease or were refractory to attempts at weaning glucocorticoid therapy. The patient population was 40% male with a mean age of 57 ± 6 years. Of the 12 patients identified, all patients, once placed on biologic therapy, had sustained radiographic and/or clinical and/or physiologic (i.e. PFT) improvement and did not require additional steroid therapy. CONCLUSIONS: We identified a dozen patients with eosinophilic pneumonia who were placed on biologic therapy and had a marked response with disease stability. These patients had favorable responses, specifically symptomatic improvement without significant side effects. Currently, there are no controlled trials comparing efficacy of these agents to steroid therapy. Our retrospective review suggests that there is a use for anti-eosinophilic agents in steroid-refractory eosinophilic lung disease with favorable results. Further research should be done to rigorously compare these therapeutic modalities. CLINICAL IMPLICATIONS: To the best of our knowledge, we present the first systematic chart review of this size, looking at the use of biologic therapies in eosinophilic pneumonia. Our results support the conclusion of several case reports and case series suggesting the efficacy of these drugs in refractory disease. Given the known complications of long-term steroid use, our study provides ample evidence to support using such agents in recalcitrant eosinophilic pneumonia to achieve excellent clinical, radiographic and physiologic results with a favorable side-effect profile. DISCLOSURES: No relevant relationships by Cyrus Askin, source=Web Response Speaker/Speaker's Bureau relationship with Janssen Please note: $1001 - $5000 Added 12/02/2020 by Michael Morris, source=Web Response, value=Honoraria Speaker/Speaker's Bureau relationship with GSK Please note: $1001 - $5000 Added 12/02/2020 by Michael Morris, source=Web Response, value=Honoraria
PURPOSE:The long-term implications of COVID-19 pneumonia remain under investigation.Many of those that suffered from the illness continue to experience symptoms weeks to months following their initial recovery.We assessed patients with COVID-19 pneumonia who were discharged from the hospital to an outpatient-based continuous remote patient monitoring (CRPM) program. METHODS:Forty hospitalized patients diagnosed with COVID-19 pneumonia between the ages of 28 and 78 were referred to a designated CRPM team for evaluation and enrollment in a remote monitoring pilot program prior to discharge between the dates of December 2020 and April 2021.Enrolled patients were issued an FDA-approved biophysiologic monitoring device, digital tablet for video teleconferencing, and an in-home Wi-Fi/Mobile Data hub following nursing-led training prior to departing the medical facility.The provided equipment was capable of continuous, near-real time monitoring of SpO2, heart rate, respiration rate, surface/axillary temperature, and mobility data; intermittent data was also collected via a linked automatic blood pressure cuff and portable spirometer.Patients were monitored 24 hours, 7 days per week during their enrollment by dedicated tele-health nursing staff and received serial automated prompts to perform blood pressure assessments and spirometry using the included equipment.Initial and final pulse oximetry and spirometric data was reviewed, consisting of forced vital capacity (FVC), forced expiratory volume at one second (FEV 1 ), FEV 1 /FVC ratio.Patients were disenrolled from the program in the following circumstances: the patient was readmitted to the hospital, the patient chose to disenroll themselves, or the supervising physician determined the patient to be stable for $ 72 hours.RESULTS: Forty patients enrolled in the pilot program.Twenty-seven of these patients completed initial and final spirometry and pulse oximetry prior to program discharge.Total days of enrollment were on average 31 AE 25 days.Initial pulse oximetric data returned with a mean of 95 AE 1.6%.Of note, 13 of the 27 patients required supplemental oxygen following hospital discharge.Initial spirometric data for these individuals returned with mean values for FVC (L) of 1.77 AE 0.82, FEV 1 (L) of 1.22 AE 0.47, and FEV 1 /FVC of 75 AE 20%.Prior to program disenrollment, mean pulse oximetry was measured at 97 AE 1.9% with only 2 of the 27 patients continuing to require oxygen.Final spirometric data returned with mean values for FVC (L) of 2.61 AE 1.16, FEV 1 (L) of 1.89 AE 0.72, and FEV 1 /FVC of 78 AE 19%.CONCLUSIONS: This study evaluated early and late home-tested spirometry and pulse oximetry in patients with COVID-19 pneumonia discharged from the hospital to a CRPM pilot program.Nearly half of the patients (48%) required supplemental oxygen at the time of discharge with only 7.4% requiring oxygen once discharged from the pilot program.Spirometric data indicated an increase of 47.5% in FVC, an increase of 55% for FEV 1 , an increase of 4.1% in FEV 1 /FVC between initial and final testing.Correlation with in-lab spirometry testing and percent predicted values will aid in determining the accuracy of the deficits identified on home testing. CLINICAL IMPLICATIONS:This study provides insight into the rate of lung function recovery in hospitalized COVID-19 pneumonia patients, and introduces a novel method to closely monitor recovering patients on an outpatient-basis.