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Background In the UK it is estimated that 10-15% of lung cancer cases occur in never-smokers. This study demonstrates the changes of the demographic characteristics, including the smoking status, of all the patients referred to the thoracic malignancy unit at Guy's Cancer Centre, South East London, between 2010 and 2021. Methods We included patients with a documented ICD10 diagnosis of bronchus and lung malignancy who were referred to Guy's thoracic malignancy unit from 2010 until 2021. A total of 6861 patients with a diagnosis of lung cancer were identified. We collected baseline demographic and clinical characteristics, including smoking status and socio-economic status for all the patients. Descriptive statistics were utilised to highlight the dynamic changes over the years of the referred patients. Results The number of referrals per year remained overall stable from 2010 until 2019, with a decrease in the number of referrals in 2020 and 2021, most likely due to the COVID-19 pandemic. We observed a gradual increase in the percentage of never smokers among the lung cancer patients: 5%, 8%, 10% and 13% of the referred patients were never smokers in the years 2010, 2015, 2018 and 2021 respectively. Median age remained stable across the years (range 68-71 years). Male percentage was 56%, 55%, 53% and 53% in 2010, 2015, 2018 and 2021 respectively. From the patients that we had a documented ethnic background the proportion of White/Black/Asian/Other or Mixed ethnicity remained stable across the years with a median 87%, 7%, 3%, and 3% respectively. The most common histological diagnosis was adenocarcinoma, followed by squamous cell carcinoma and small cell lung carcinoma. Conclusions The proportion of never-smoking to smoking related lung cancer has gradually increased between 2010 and 2021. There was little variability in age, sex and ethnic background. Never-smoking lung cancer is a distinct biological entity, therefore, further research should focus on the understanding of the aetiology and the risk factors leading to the development of lung cancer, in the absence of a history of tobacco exposure. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc.
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Background: Patients recovered from COVID-19 often present with reduced exercise capacity and persistent exertional breathlessness, yet the mechanisms are still poorly understood. Method(s): We aimed to test patients formerly hospitalized for COVID-19 pneumonia with normal chest computed tomography (CT) at 6-month follow up but with persistent exertional breathlessness. Spirometry, chest CT, incremental cycle exercise test with arterial line, resting echocardiography and ventilation/perfusion (V/Q) scan were performed. Result(s): Data represents one patient and 4 healthy controls (CTRL) used for comparison. Patient (age: 41 vs. average 41.5 years in CTRL) was never smoker with FEV1 of 86 %predicted, normal chest CT and normal resting echocardiogram. Patient reported significant activity-related dyspnea (baseline dyspnea index score: 7). During exercise, peak work rate, ventilation, and oxygen update were within normal. Yet, patient had greater dyspnea intensity, ventilatory requirements and ventilatory equivalent for CO during exercise, with 4% drop in O2 saturation, 2 figure. Patient and CTRL had similar tidal volume (VT), rest-to-peak change in dead space/VT, and O2 pulse. V/Q scan showed multiple perfusion defects. Conclusion(s): Preliminary data shows that reduced ventilatory efficiency during exercise, suggesting pulmonary vascular abnormalities, could possibly explain persistent breathlessness in patients recovered from COVID pneumonia.
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Introduction: We have previously described pneumothorax (PTX) and pneumomediastinum (PM) in COVID-19. Incidence is approx. 1%, and usually associated with a poor prognosis. Method(s): With Caldicott approval, all patients with Covid-19 with PTX and PM are flagged to the pleural service for ongoing analysis. Demographics and outcomes are collected. Result(s): 46 were identified (Total: 4506, 01/03/20-02/01/22): mean age 57.5 years (range 19-91). 37 (82%) male, 45 white Caucasian, 1 South East Asian, 20 ex-smokers, 8 never smokers, 1 current smoker & the rest unknown. Respiratory comorbidity was most commonly COPD (12), asthma (4), combined pulmonary fibrosis and emphysema (1), previous TB (1), & active lung cancer (1). Average estimated frailty score was 2 (range 1-6). Mean BMI was 28 (range 18.5-46.7), mean height 1.72m (range 1.55-1.84). Average number of days to air leaks is 13.29 patients had PTX [16 isolated PTX (including 6 bilateral)] & 22 had PM (4 isolated PNM). 18 patients had concurrent surgical emphysema. 10 patients were intubated at the time of air leak, 16 on CPAP or HFNC, 13 on oxygen, the rest on air. 32 were managed conservatively. Others had a variety of small, large bore and subcutaneous drains and 1 was transferred for ECMO. There were 10 deaths with 1 directly due to PTX in a 91 yr old, CFS of 6 and intercurrent stroke. 1 was associated with PM, CFS 2 & lung cancer, 1 85 yr old with CFS 4 & COPD, 1 82 yr old with CFS 3 on CPAP & the rest were on mechanical ventilation). Conclusion(s): Inpatient incidence of PTX and PM is still approximately 1%. Survival is better as overall Covid19 survival improves(direct mortality from air leak approx. 21 %) with mortality due to other factors rather than the air leak.
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Objectives: There has been a significant increase in pulmonary embolism (PE) cases during the coronavirus disease of 2019 (COVID-19) pandemic. In this study, we aimed to compare the effects of COVID-19 positivity on morbidity and mortality in patients treated with a diagnosis of high-risk PE. Method(s): In this single-center and observational study, patients who were referred to our center with the diagnosis of PE between January 1, 2019 and 2021 were retrospectively evaluated. Patients with moderate- and low-risk PE according to the European Society of Cardiology PE guidelines, those who did not undergo computed tomography pulmonary angiography (CTPA) or the ones who did not accept treatment were excluded from the study. The patients included in the study were divided into two groups, as those with and without COVID-19, and compared in terms of demographic data, comorbidities, symptoms, thromboembolism in vessels other than the pulmonary artery, laboratory parameters, treatments, and prognosis. Result(s): A total of 384 PE cases were identified during the study period. Among them, 322 cases that were in the intermediate or low-risk category, 21 cases who did not undergo CTPA, and one case who did not accept thrombolytic therapy were excluded from the study. A total of 40 cases were included in the study. The groups with and without COVID-19 consisted of 23 and 17 patients, respectively. In the group of patients with COVID-19, inflammatory markers were higher, Wells score was lower, and thromboembolism was seen in vessels other than the pulmonary artery. The two groups were similar in terms of other laboratory parameters, demographic data, comorbidities, symptoms, treatment, and prognosis. Conclusion(s): While the involvement of COVID-19 in PE etiology does not change mortality, it may cause more thrombosis development in both venous and arterial systems outside the pulmonary area by significantly increasing inflammation. However, the lower Wells scores in COVID-19 PE cases in our study indicate that new clinical assessment tools are needed to detect PE risk in COVID-19 patients.©Copyright 2022 by The Cardiovascular Thoracic Anaesthesia and Intensive Care.
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SESSION TITLE: COPD Medications and Treatment Outcomes SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm PURPOSE: Conclusive data on whether inhaled corticosteroids (ICS) have a protective effect on COVID-19 hospitalization rates or outcomes are lacking. The main objective of our study was to assess the impact of pre-hospitalization ICS use on the clinical course of hospitalized COVID-19 patients with underlying obstructive lung diseases - asthma and chronic obstructive pulmonary disease (COPD). METHODS: We conducted a retrospective chart review study of all COVID-19 patients hospitalized at our institution between March 1st - June 3th, 2020. Diagnosis of asthma and COPD was determined using ICD-10 codes. Demographics, information about pre-hospitalization ICS use and clinical data were recorded through chart review. Outcomes of interest were all-cause 28-day mortality and need for intubation. Chi-square or Fischer’s exact test was used to assess univariate associations. Linear and logistic regression models were constructed to adjust for potential confounders. RESULTS: Data was analyzed from 356 hospitalized COVID-19 patients with prior diagnosis of obstructive lung disease;219/356 (62%) had asthma, 137/356 (38%) had COPD. Hospitalized COVID-19 patients with asthma were younger (mean age 61 [range: 51-71] vs 74 [range:67-81] years, p<0.01), more likely to be female (69% vs 48%, p<0.01), Hispanic (43% vs 25%, p<0.01) and never smokers (52% vs 20%, p<0.01) compared to those with COPD. There was no difference in the use of pre-hospitalization ICS between the two groups (35.2% in Asthma vs 38% in COPD, p=0.59). Overall, COVID-19 patients with COPD were more likely to die compared to those with asthma (47% vs 25%, p<0.01). Pre-hospitalization ICS use was not significantly associated with all-cause 28-day mortality (asthma: OR 0.9 [95%CI 0.4-2.0], p=0.85;COPD: OR 0.7 [95%CI 0.3-1.5], p=0.3) or need for intubation (asthma: OR 1.0 [95%CI 0.5-2.0], p=0.94;COPD: OR 0.7 [95%CI 0.3-1.7],p=041) after adjusting for potential confounders. CONCLUSIONS: Mortality among hospitalized COVID-19 patients with COPD was higher compared to those with asthma. While the pre-hospitalization use of ICS was similar between the two groups, it did not protect hospitalized COVID-19 patients in either group from intubation or mortality. High mortality rates among COVID-19 patients with COPD is likely due to concomitant risk factors such as older age, and comorbidities such as diabetes and chronic kidney disease. Being a retrospective study, the quality of our data was limited and dependent on documentation accuracy. CLINICAL IMPLICATIONS: Pre-hospitalization ICS use did not improve outcomes in hospitalized COVID-19 patients with asthma or COPD. Further studies are required to investigate the role of ICS in preventing COVID-19 related hospitalizations, morbidity and mortality in randomized control settings. DISCLOSURES: No relevant relationships by Hammad Aleem No relevant relationships by Denisa Ferastraoaru No relevant relationships by Manuel Hache Marliere No relevant relationships by Gabriel Hernández Romero No relevant relationships by Christa McPhee No relevant relationships by Francine Palmares No relevant relationships by Divya Reddy No relevant relationships by Felix Reyes No relevant relationships by Deborah Schwartz
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SESSION TITLE: Lung Cancer Imaging Case Report Posters 2 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: SARS-CoV-2 pneumonia typically presents with ground-glass and consolidative pulmonary opacities, atypically small cavities may be seen in severe cases. In patients with cavities persisting beyond 12 weeks, an underlying malignancy is a worrisome concern. We present a case of a 39-year old female without significant risk factors for pulmonary malignancy who was found, surprisingly, to have a cavitating adenocarcinoma in the setting of COVID-19 Pneumonia. CASE PRESENTATION: A 39 year old obese African American female, never smoker, with co-existing metabolic syndrome presented to our institution with a four day history of productive cough (without hemoptysis), body aches, fever and fatigue. She denied weight loss or loss of appetite. No known family history of malignancy. She tested positive for SARS-CoV-2. She was clinically stable, hence discharged home with recommendations for quarantine and supportive care. She returned the following day with worsening dyspnea. Her chest radiograph noted a supra-hilar opacity with central lucency, Chest CT revealed wedge-shaped ground-glass and consolidative density in the right lower lobe and a 3.8 x 4.1 cm cavitary right upper lobe mass with mediastinal lymphadenopathy. She received parenteral antibiotic therapy and underwent infectious and autoimmune workup, which was negative. Repeat CT imaging, approximately three months post discharge, revealed persisting cavitary lesion and enlarging mediastinal lymphadenopathy. She underwent Electromagnetic Navigational Bronchoscopy with biopsy and fine needle aspiration of mediastinal lymph nodes (stations 7 and 4R) via endobronchial ultrasound. Biopsy results and fine needle aspiration of lymph nodes revealed adenocarcinoma with tumor cells being positive for TTF-1 and negative for CK20, CDX2, GATA3, PAX8 and Synaptophysin. Next generation sequencing reported several variants including EGFR and Tp53, there was also noted amplification of CDK4 and MDM2. PDL-1 was negative. DISCUSSION: A cavity is a gas-filled space, seen as a lucency or low-attenuation area, within a nodule, mass, or area of parenchymal consolidation. Underlying etiologies are typically classified as infectious, autoimmune and malignant. Cavities are atypical findings on CT imaging in patients with viral pneumonias, including SARS-CoV-2. Those cavities persisting beyond 12 weeks are typically classified as being chronic, with malignancy a key concern in these patients. The most common type of primary cavitary lung cancer is squamous cell carcinoma, in fact Primary Pulmonary Adenocarcinomas are unlikely to cavitate. Treatment options, depending on the presence of targetable mutations, include concurrent chemoradiation, chemoimmunotherapy or oral targeted agent. CONCLUSIONS: Though an atypical presentation, Pulmonary Adenocarcinoma may present as a cavitary lesion, particularly in the presence of persisting or enlarging lymphadenopathy. Reference #1: Gafoor K, Patel S, Girvin F, Gupta N, Naidich D, Machnicki S, Brown KK, Mehta A, Husta B, Ryu JH, Sarosi GA, Franquet T, Verschakelen J, Johkoh T, Travis W, Raoof S. Cavitary Lung Diseases: A Clinical-Radiologic Algorithmic Approach. Chest. 2018 Jun;153(6):1443-1465. doi: 10.1016/j.chest.2018.02.026. Epub 2018 Mar 6. PMID: 29518379. Reference #2: Radiological Society of North America Expert Consensus Document on Reporting Chest CT Findings Related to COVID-19: Endorsed by the Society of Thoracic Radiology, the American College of Radiology, and RSNA Scott Simpson, Fernando U. Kay, Suhny Abbara, Sanjeev Bhalla, Jonathan H. Chung, Michael Chung, Travis S. Henry, Jeffrey P. Kanne, Seth Kligerman, Jane P. Ko, and Harold Litt Radiology: Cardiothoracic Imaging 2020 2:2 DISCLOSURES: No relevant relationships by Mark Bowling, value=Consulting fee Removed 04/02/2022 by Mark Bowling No relevant relationships by Mark Bowling, value=Consulting fee Removed 04/02/2022 by Mark Bowling No releva t relationships by Mark Bowling, value=Consulting fee Removed 04/02/2022 by Mark Bowling No relevant relationships by Sulaiman Tijani
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SESSION TITLE: COVID-19 Case Report Posters 2 SESSION TYPE: Case Report Posters PRESENTED ON: 10/19/2022 12:45 pm - 01:45 pm INTRODUCTION: Much has been learned about the immune dysregulation and release of pro-inflammatory cytokines since the emergence of the COVID-19 pandemic.1 Patients with interstitial lung disease are often on immunosuppressive agents, such as rituximab, which is a B-cell depleting agent. There has been a large retrospective cohort study showing that rituximab therapy was the only immunosuppressive medication with a trend towards in-hospital death.2 We present a case of COVID-19 in a patient on rituximab with ANCA vasculitis. CASE PRESENTATION: A 51-year-old male, never smoker, with ANCA positive vasculitis (positive MPO and PR3) and interstitial lung disease (on 4-5L of oxygen) presented to the hospital with nausea and fever for 2 days and was found to have a positive SARS-CoV-2 PCR. At the time of presentation, he was on rituximab 1000 mg x 2 doses every 6 months with last infusion one month prior to presentation, azathioprine 150 mg daily, prednisone 15 mg daily, nintedanib 100 mg BID, and IVIG monthly. Spirometry showed FVC of 1.60L/37% predicted and an FEV1 1.28L/39% predicted. Patient had 2 COVID vaccinations and one booster (all Pfizer mRNA), the latter 3 months prior to presentation. On admission, he was saturating at 55% on 4L and placed on 15L non-rebreather;he was afebrile, normotensive, and with a pulse of 110 BPM. Exam was notable for a cough, wheezing, and tachypnea. Lab work was notable for positive SARS-COV-2 PCR, a total white blood cell count of 5.3x103 uL, and a normal hemoglobin and platelet count. He had a CO2 of 34, normal creatinine, and no transaminitis. Lactate dehydrogenase (LDH) was elevated at 318 U/L, and lactate was elevated at 3.5 mmol/L. His chest x-ray on admission demonstrated patchy filling opacities and low lung volumes. He received dexamethasone, remdesivir, and the monoclonal antibodies casirivimab and imdevimab (REGEN-COV) on the first day of admission. Patient also received his monthly IVIG dose inpatient. After a week, he was weaned back to his home oxygen and symptomatically back to baseline. Most recent PFTs on the same outpatient immunosuppressive regimen as prior to admission are unchanged. Patient received two doses of preventative monoclonal antibodies (EVUSHELD) 3 months after admission. DISCUSSION: Here we discuss a case of a patient with severe COVID-19 pneumonia requiring inpatient hospitalization despite three COVID mRNA vaccinations, likely secondary to difficulty in mounting an immune response to the vaccinations given his use of immunosuppressive medications. This is also an example of the early use of monoclonal antibodies in an inpatient with long term preservation of his underlying lung function.3 CONCLUSIONS: We recommend counseling and close observation of patients on rituximab due to risk of severe COVID-19 infection as well the use of preventative monoclonal antibodies (EVUSHELD). Reference #1: Jamal M, Bangash HI, Habiba M, Lei Y, Xie T, Sun J, Wei Z, Hong Z, Shao L, Zhang Q. Immune dysregulation and system pathology in COVID-19. Virulence. 2021 Dec;12(1):918-936. doi: 10.1080/21505594.2021.1898790. PMID: 33757410;PMCID: PMC7993139. Reference #2: Andersen, K. M., Bates, B. A., Rashidi, E. S., Olex, A. L., Mannon, R. B., Patel, R. C., Singh, J., Sun, J., Auwaerter, P. G., Ng, D. K., Segal, J. B., Garibaldi, B. T., Mehta, H. B., Alexander, G. C., Haendel, M. A., & Chute, C. G. (2022). Long-term use of immunosuppressive medicines and in-hospital COVID-19 outcomes: A retrospective cohort study using data from the National COVID Cohort Collaborative. The Lancet Rheumatology, 4(1), e33–e41. https://doi.org/10.1016/S2665-9913(21)00325-8 Reference #3: Weinreich, D. M., Sivapalasingam, S., Norton, T., Ali, S., Gao, H., Bhore, R., Xiao, J., Hooper, A. T., Hamilton, J. D., Musser, B. J., Rofail, D., Hussein, M., Im, J., Atmodjo, D. Y., Perry, C., Pan, C., Mahmood, A., Hosain, R., Davis, J. D., Yancopoulos, G. D. (2021). Regen-cov antibody combination and outcomes in outpatients with covid-19. New England Journal of Medicine, 385(23), e81. https://doi.org/10.1056/NEJMoa2108163 DISCLOSURES: Advisory Committee Member relationship with Genentech Please note: 2019-2022 Added 06/06/2022 by Ayodeji Adegunsoye, value=Consulting fee Advisory Committee Member relationship with Boehringer Ingelheim Please note: 2018-2022 Added 06/06/2022 by Ayodeji Adegunsoye, value=Consulting fee Speaker/Speaker's Bureau relationship with Boehringer Ingelheim Please note: 2018-2022 Added 06/06/2022 by Ayodeji Adegunsoye, value=Honoraria Consultant relationship with Genentech Please note: 2018-2020 by Ayodeji Adegunsoye, value=Consulting fee Removed 06/06/2022 by Ayodeji Adegunsoye No relevant relationships by Cathryn Lee No relevant relationships by Kavitha Selvan PI relationship with Boehringer-Ingelheim Please note: >$100000 by Mary Strek, value=Grant/Research Support PI relationship with Galapagos Please note: $70,000-100,00 by Mary Strek, value=Grant/Research Support Endpoint Adjudication Committee Member relationship with Fibrogen Please note: $1-$1000 by Mary Strek, value=Honoraria No relevant relationships by Rachel Strykowski
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SESSION TITLE: TB and TB-Involved Case Posters SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: Pulmonary Aspergillus infection has a wide array of manifestations. Chronic Pulmonary Aspergillosis is an uncommon progressive respiratory disease, with the Subacute Invasive Pulmonary Aspergillosis form, one of the most challenging to manage. Typically it presents with rapidly progressive infection (of less than 3 months) in mild to moderately immunocompromised patients with underlying structural lung disease. We herein report the case of a 69-year old female with post-tuberculous cavity with disease progression, in approximately 6 weeks, associated with Aspergillus infection. CASE PRESENTATION: Patient is a 69-year old African American female, never smoker, with known history of Type 2 Diabetes Mellitus and previously treated mycobacterium tuberculosis with residual small right upper lobe cavity (measuring approximately 35 x 40 mm). She was being followed in our outpatient thoracic oncology clinic with serial imaging for surveillance, CT Chest initially every 3 - 6 months then annually thereafter with PET scan as clinically indicated. The cavity remained relatively unchanged for approximately 5 years. In October 2021, her CT Chest had revealed a stable cavity, even despite SARS-CoV-2 Pneumonia infection the previous year. The following month she was admitted to an outside hospital for hyperglycemia with notable significant increase in size of the right upper lobe cavity to 69 x 72 mm with surrounding nodularity. She completed a course of antibiotics and was seen in our clinic 3 months post discharge with a repeat CT Chest which now revealed a mass like area of consolidation with large area of lucency and superimposed fungus ball (now measuring 80 mm x 70mm). She underwent Electromagnetic Navigational Bronchoscopy with transbronchial biopsy and right upper lobe bronchoalveolar lavage. BAL culture identified Aspergillus niger, with no other pathogens (including acid fast bacilli isolated) or malignant cells observed. Biopsy revealed marked mixed inflammation and fungal hyphae. Patient is currently undergoing long-term oral antifungal therapy with plan for close surgical follow-up. DISCUSSION: The diagnosis of Chronic Pulmonary Aspergillosis requires a combination of clinical, radiological and histopathological characteristics present for atleast 3 months for diagnosis. This includes the presence of one or more cavities on thoracic imaging, evidence of aspergillus infection or an immunological response to aspergillus as well as excluding alternative diagnoses. Advances in diagnostic tools have improved early diagnosis and subsequent management as noted in our case. Surgical resection is recommended for simple aspergilloma, however rapidly progressive disease processes are recommended to be managed as invasive aspergillosis. CONCLUSIONS: Post-tuberculosis chronic pulmonary aspergillosis is an emerging disease with significant associated morbidity and likely health burden. Reference #1: Chronic pulmonary aspergillosis: rationale and clinical guidelines for diagnosis and management David W. Denning, Jacques Cadranel, Catherine Beigelman-Aubry, Florence Ader, Arunaloke Chakrabarti, Stijn Blot, Andrew J. Ullmann, George Dimopoulos, Christoph Lange European Respiratory Journal Jan 2016, 47 (1) 45-68;DOI: 10.1183/13993003.00583-2015 Reference #2: Bongomin F. Post-tuberculosis chronic pulmonary aspergillosis: An emerging public health concern. PLoS Pathog. 2020;16(8):e1008742. Published 2020 Aug 20. doi:10.1371/journal.ppat.1008742 DISCLOSURES: No relevant relationships by Omotooke Babalola No relevant relationships by Mark Bowling, value=Consulting fee Removed 04/02/2022 by Mark Bowling No relevant relationships by Mark Bowling, value=Consulting fee Removed 04/02/2022 by Mark Bowling No relevant relationships by Mark Bowling, value=Consulting fee Removed 04/02/2022 by Mark Bowling No relevant relationships by Sulaiman Tijani
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SESSION TITLE: Uncommon Presentations and Complications of Chest Infections SESSION TYPE: Rapid Fire Case Reports PRESENTED ON: 10/18/2022 10:15 am - 11:10 am INTRODUCTION: Cryptococcus is a ubiquitous fungus in the environment. Infections can occur in humans when Cryptococcus is aerosolized and inhaled. Severity of clinical presentation varies from asymptomatic pulmonary colonization to disseminated life-threatening infection such as meningitis. These infections usually occur with deficiencies in T-cell-mediated immunity, including those with HIV/AIDS and immunosuppression due to transplantation. Herein we present a case of isolated pulmonary cryptococcosis in an immunocompetent host. CASE PRESENTATION: The patient is a 36-year-old never-smoker male with history of recurrent left spontaneous pneumothorax status post VATS blebectomy, negative for alpha-1 antitrypsin deficiency and cystic fibrosis. A year later, he presented with fatigue, shortness of breath, and dry cough after a recent trip to Ohio. Viral panel including COVID-19 was negative. A chest x-ray showed a new 4 cm rounded opacity in the right middle lobe (RML). A CT scan of the chest showed 2 mass-like and nodular areas of consolidation with surrounding GGOs within the RML (Figure 1). He underwent navigational bronchoscopy with transbronchial biopsy (TBBx) of RML, BAL, and EBUS with transbronchial needle aspiration (TBNA). Cytology was negative for malignant cells. BAL showed rare yeast. Pathology of the TBBx showed the airway wall with chronic inflammation including granulomatous inflammation, positive for yeast, most consistent with Cryptococcus with positive Grocott methenamine silver (GMS) stain (Figure 2). Culture of the TBNA grew C. neoformans var. grubii. Other cultures were negative. Serum Cryptococcal antigen was positive. HIV test was negative. He started treatment with oral fluconazole with improvement of symptoms. DISCUSSION: Clinical presentation of pulmonary cryptococcosis can include a variety of symptoms in which immune status is critical for determining the course of infection. Infection can vary from asymptomatic infection to severe pneumonia and respiratory failure, and meningitis. Similarly, imaging findings can also vary and be characterized as pulmonary nodules, consolidations, cavitary lesions, and/or a diffuse interstitial pattern. The diagnosis of Cryptococcus is made using histology, fungal cultures, serum cryptococcal antigen, and radiography in the appropriate clinical and radiological context. Treatment recommendations are determinant on immune status of the patient as well as symptoms. Asymptomatic and localized disease in immunocompetent patients can be monitored and mild/moderate disease can be treated with fluconazole. Those with severe or disseminated infection warrant induction therapy with an amphotericin B and flucytosine CONCLUSIONS: Clinical and radiological presentation of cyptococcosis varies depending on immune status. Disease can occur in both immunocompromised and competent hosts. Immune status determines disease course and treatment. Reference #1: Huffnagle GB, Traynor TR, McDonald RA, Olszewski MA, Lindell DM, Herring AC, et al. Leukocyte recruitment during pulmonary Cryptococcus neoformans infection. Immunopharmacology. 2000 Jul 25;48(3):231–6. Reference #2: Kd B, Jw B, Pg P. Pulmonary cryptococcosis. Semin Respir Crit Care Med [Internet]. 2011 Dec [cited 2022 Apr 2];32(6). Available from: https://pubmed.ncbi.nlm.nih.gov/22167400/ Reference #3: Ms S, Rj G, Ra L, Pg P, Jr P, Wg P, et al. Practice guidelines for the management of cryptococcal disease. Infectious Diseases Society of America. Clin Infect Dis Off Publ Infect Dis Soc Am [Internet]. 2000 Apr [cited 2022 Apr 1];30(4). Available from: https://pubmed.ncbi.nlm.nih.gov/10770733/ DISCLOSURES: No relevant relationships by Mina Elmiry No relevant relationships by Brenda Garcia No relevant relationships by Zein Kattih no disclosure on file for Priyanka Makkar;No relevant relationships by Jonathan Moore
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SESSION TITLE: Post-COVID-19 Infection Complications SESSION TYPE: Case Report Posters PRESENTED ON: 10/17/2022 12:15 pm - 01:15 pm INTRODUCTION: The COVID-19 pandemic has been full of obstacles for the medical field. Considerable advancements have been made, yet we continue to discover new associations with this novel virus. In this case, we discuss a patient who was hospitalized for COVID-19 on 7/18/2020 in the intensive care unit. He developed a persistent cough with hemoptysis several months after discharge and was found to have active tuberculosis. The COVID-19 pandemic has continued to raise concerns regarding the repercussions of this infection, and as this case shows, includes reactivation of latent tuberculosis infections (LTBI) in affected patients. CASE PRESENTATION: A 59-year-old Latino male never-smoker with a history of diabetes (A1c 8.4%) presented 07/18/2020 for complaints of shortness of breath and cough. At that time, he tested positive for COVID-19. He was escalated to the ICU and required intubation. During his hospitalization, he received remdesivir for 5 days and dexamethasone 6 mg daily for 10 days with taper prior to his discharge. He was able to be extubated and oxygen requirement decreased to 2 liters nasal cannula. Patient was subsequently discharged on 09/14/2020. He began developing a persistent cough with noted hemoptysis in 02/2021 and was referred to pulmonology at that time. High resolution CT scan of the chest was ordered and revealed thick-walled cavitary lesions of various sizes throughout both lungs although with an upper lobe predominance and tree-in-bud nodularity as well as tracheomegaly. AFB and QuantiFERON Gold assay were positive. Patient reported he had done multiple mission trips to endemic areas before COVID pandemic but had not been during the pandemic. Patient underwent quarantine and treatment for active tuberculosis. DISCUSSION: Tuberculosis reactivation results from previous latent bacteria that becomes active either from inducible factors or spontaneously. Risk factors for reactivation include HIV/AIDS, steroid use, diabetes, kidney disease, and smoking. [1] The primary basis of these risk factors is the immunosuppression conferred to the patient. COVID-19 has the potential to cause a disruption of the immune system which could predispose a patient to reactivation of LTBI. Studies have shown that defects or interference of the IFN-γ pathway can cause susceptibility to intracellular infections, including tuberculosis.[2] There may be an acquired disruption in this pathway caused by COVID-19, although more research is required. CONCLUSIONS: The COVID-19 pandemic has raised concerns for increased risk of reactivation of latent infection as well. In this case, the patient had multiple risk factors, but certainly a diagnosis of COVID-19 could weaken the immune system allowing for the reactivation of LTBI. This association will require more research to solidify. It is important, as seen in the case discussed above, to continue to be vigilant in diagnosis and treatment of our patients. Reference #1: Riley L. UpToDate. UpToDate – Evidence-based Clinical Decision Support ;Wolters Kluwer. Published September 15, 2021. Accessed February 2, 2022. https://www.uptodate.com/contents/tuberculosis-natural-history-microbiology-and-pathogenesis?search=tuberculosis&source=search_result&selectedTitle=4~150&usage_type=default&display_rank=4 Reference #2: Kampmann B, Hemingway C, Stephens A, et al. Acquired predisposition to mycobacterial disease due to autoantibodies to IFN-gamma. J Clin Invest 115: 2480-2488, 2005. DISCLOSURES: No relevant relationships by Steven Colby No relevant relationships by Radhika Shah
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Background: In first line (L1) for EGFR-mutated (mEGFR) advanced NSCLC (aNSCLC), osimertinib (osi) has been the preferred option since 2018. First generation anti-EGFR TKI (1G) alone followed by osi, or 1G + anti-angiogenic or 1G + chemotherapy are other options. We aimed to assess the subgroups of patients (pts) that do not benefit from 1G alone compared with osimertinib L1 in mEGFR aNSCLC. Methods: Retrospective international study including pts with mEGFR aNSCLC treated with either osi or the sequence of 1G followed by osi (seq group). Primary endpoint was the PFS of the global strategy (PFSglob) defined as the time between L1 start and progression after L2 treatment or death. Subgroups analyses included pts with high tumour burden (high-TM;> 3 metastatic sites and/or central nervous system (CNS) involvement), poor performance status (PS), and T790M negative (seq subgroup only). Results: A total of 235 pts were included: 104 in the seq group, 118 in the osi L1 group. 15 had T790M negative at PD after 1G, they received osi as a therapeutic test. From these pts, 222 had an exon19 or 21 EGFR mut, 13 had uncommon mEGFR. Mean age was 65 years, 64% were female, and 60% never smokers. Pts from the osi L1 group had poorer PS (23% vs 10%), higher rate of co-mutations (23% vs 19%) and more CNS involvement (47% vs 19%). After a median (m) follow up of 30.6 months in the exon 19 and 21 population, mPFSglob was 27.4 mo (23.0-31.0) and mPFS L1 was 15.5mo (13.7-18.4) Table. The sequence was associated with shorter PFS L1 compared with osi L1 particularly in high-TM (10.5 mo vs 17.1 mo, p<0.0001);PFS was numerically shorter in poor PS (≥2) population (11.0 mo vs 15.6 mo, p=0.1). [Formula presented] Conclusions: 1G TKI followed by osi seemed to be detrimental compared with os L1 for pts with high-TM or poor PS mEGFR aNSCLC. In this population, the intensification of L1 treatment with osimertinib or a combination of 1G with anti-angiogenic or chemotherapy could be the better option in the first-line setting. Updated results will be presented at the congress. Legal entity responsible for the study: Institut Gustave Roussy. Funding: Has not received any funding Disclosure: E. Auclin: Financial Interests, Personal, Advisory Board: Sanofi, Amgen. N. Girard: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, MSD, Roche, Pfizer, Mirati, Amgen, Novartis, Sanofi;Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Pfizer, Janssen, Boehringer, Novartis, Sanofi, AbbVie, Amgen, Lilly, Grunenthal, Takeda, Owkin;Financial Interests, Institutional, Research Grant, Local: Roche, Sivan, Janssen;Financial Interests, Institutional, Funding: BMS;Non-Financial Interests, Officer, International Thymic malignancy interest group, president: ITMIG;Other, Other, Family member is an employee: AstraZeneca. M.T. Moran Bueno: Financial Interests, Personal, Advisory Board, Advisory Role: AstraZeneca, Boehringer Ingelheim, BMS;Financial Interests, Personal, Advisory Board, Advisory role: Roche. B. Besse: Financial Interests, Institutional, Funding: 4D Pharma, AbbVie, Amgen, Aptitude Health, AstraZeneca, BeiGene, Blueprint Medicines, Boehringer Ingelheim, Celgene, Cergentis, Cristal Therapeutics, Daiichi Sankyo, Eli Lilly, GSK, Janssen, Onxeo, Ose Immunotherapeutics, Pfizer, Roche-Genentech, Sanofi, Takeda, Tolero Pharmaceuticals;Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical, EISAI, Genzyme Corporation, Inivata, Ipsen, Turning Point Therapeutics. L. Mezquita: Financial Interests, Personal, Advisory Board: Takeda, AstraZeneca, Roche;Financial Interests, Personal, Invited Speaker: Roche, BMS, AstraZeneca, Takeda;Financial Interests, Personal, Research Grant, SEOM Beca Retorno 2019: BI;Financial Interests, Personal, Research Grant, ESMO TR Research Fellowship 2019: BMS;Financial Interests, Institutional, Research Grant, COVID research Grant: Amgen;Financial Interests, Institutional, Invited Speaker: Inivata, Stilla. All other authors have declared no conflicts of interest.
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Background: RET fusions are found in 1-2% of patients (pts) with advanced non-small cell lung cancer (aNSCLC). Targeted therapy with RET inhibitors (RETi) significantly improved prognosis. Molecular mechanisms of resistance are still incompletely characterized. Methods: This multicentric retrospective study included 24 centres. Eligible pts had a RET+ aNSCLC, were treated with a RETi and had at least one molecular profile by next-generation sequencing (NGS), performed before and/or after RETi, on tissue and/or plasma samples. Primary resistance under RETi was defined as disease progression (PD) within 6 months of therapy. Results: 95 patients were included with 112 biopsies: 93 at baseline, 19 at PD. 17 patients had paired NGS (baseline and PD). Median age was 65 years (range 56-72);62% were female, 54% were never smokers, 17% had brain metastasis (BM) at diagnosis. 55 patients received pralsetinib, 36 selpercatinib, 4 other RETi. Overall, median PFS under RETi was 17.1 months (95%CI 12.6-28). Primary resistance to RETi occurred in 22 (23%) patients. Primary resistant versus durable responders to RETi had non-adenocarcinoma histology in 9% vs 46% (p=0.61), smoking history in 57% vs 40% (p=0.21), BM in 5% vs 21% (p=0.1), TP53 mutations in 37% vs 22% (p=0.23). KRAS G12V mutation and SMARCA4 alterations were found only in poor responders (4.5% vs 0%, p=0.2;and 25% vs 0%, p=0.04, respectively). Among biopsies at PD (N=19, 13 liquid and 6 tissue biopsies), 7/13 (54%) liquid biopsies failed due to insufficient ctDNA. In 12 evaluable pts, 3 (25%) acquired secondary RET mutations (2 G810S and 1 S904F), 3 (25%) had novel RET rearrangements (2 in intron 11, 1 RET-DOCK1, 1 RET-CSGALNACT2) and 3 (25%) pts had off-target alterations (2 MET and 1 MYC amplification). Three pts (25%) developed novel TP53 mutations, while 3 (25%) had no novel identifiable alterations at PD. Conclusions: SMARCA4 and KRAS co-mutations may have a role in primary resistance to RETi. Secondary RET mutations, novel RET rearrangements and MET/MYC amplifications were identified after treatment with RETi. More than half of pts had insufficient ctDNA at PD, making tissue biopsy essential to identify resistance mechanisms. Legal entity responsible for the study: Institut Gustave Roussy. Funding: Has not received any funding. Disclosure: V. Fallet: Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, Takeda, Roche, Pfizer, Sanofi, Sandoz, Jansen;Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, Takeda, Pfizer, MSD;Financial Interests, Personal, Expert Testimony: GSK, Boehringer. C. Audigier-Valette: Financial Interests, Personal, Advisory Role: AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Ipsen, Eli Lilly, Novartis, Pfizer, and Roche. A. Russo: Financial Interests, Personal, Advisory Board: Pfizer, AstraZeneca, MSD, Novartis;Financial Interests, Personal, Writing Engagements: AstraZeneca, Novartis. A. Calles Blanco: Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Pfizer, Roche, Lilly, Merck Sharp & Dohme, Novartis, Bristol-Myers Squibb, Takeda, Sanofi;Financial Interests, Personal, Other, Speaker honoraria: Bayer;Financial Interests, Institutional, Research Grant, Drug-only for Investigator-initiated trial: Merck Sharp & Dohme. P. Iranzo Gomez: Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb Recipient, F. Hoffmann, La Roche AG, Merck Sharp & Dohme, Boehringer Ingelheim, MSD Oncology, Rovi, Yowa Kirin, Grunenthal Pharma S.A., Pfizer. M. Tagliamento: Financial Interests, Personal, Other, medical writer: Novartis, Amgen;Financial Interests, Personal, Invited Speaker, travel/accommodation: Roche, Bristol-Myers Squibb, AstraZeneca, Takeda. L. Mezquita: Financial Interests, Personal, Advisory Board: Takeda, AstraZeneca, Roche;Financial Interests, Personal, Invited Speaker: Roche, BMS, AstraZeneca, Takeda;Financial Interests, Personal, Research Grant, SEOM Beca Retorno 2019: BI;Financial Interests, Personal, Research Grant, ESMO TR Research Fellowship 2019: BMS;Financial Interests, Institutional, Research Grant, COVID research Grant: Amgen;Financial Interests, Institutional, Invited Speaker: Inivata, Stilla. C. Lindsay: Financial Interests, Institutional, Principal Investigator: Roche, Amgen, BI;Financial Interests, Personal, Advisory Role: CBPartners, Amgen. S. Ponce: Financial Interests, Institutional, Principal Investigator: Merck Sharp and Dohme, F. Hoffmann-La Roche, Foundation Medicine, PharmaMar. Personal fees: Merck Sharp and Dohme, Bristol-Myers Squibb, F. Hoffmann-La Roche, Foundation Medicine, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Pfizer, Amgen, Celgene.;Financial Interests, Personal, Advisory Board: Merck Sharp and Dohme, Bristol-Myers Squibb, F. Hoffmann-La Roche, Foundation Medicine, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Pfizer, Amgen, Celgene.;Non-Financial Interests, Personal, Other: Merck Sharp and Dohme, Bristol-Myers Squibb, F. Hoffmann-La Roche. M. Aldea: Financial Interests, Personal, Invited Speaker, travel/accommodation: Sandoz. All other authors have declared no conflicts of interest.
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Background: Patients with SARS-CoV-2 with a diagnosis of cancer have increased risk of severe COVID-19 outcomes compared to patients without cancer. However, little is known regarding outcomes of patients with COVID-19 and cancer in the setting of human immunodeficiency virus (HIV). Given the unique risks of this population, we sought to understand COVID-19 outcomes using registry data. Methods: This is a descriptive research study utilizing the CCC19 registry, an international multi-institutional registry with healthcare provider-reported cases of patients with cancer and COVID-19. Between March 2020-December 2021, 116 persons with HIV (PWH) and 10,642 persons without HIV (PWOH) with laboratory-confirmed SARS-CoV-2 infection were identified as eligible for the analysis. Results: Median follow-up time for both groups was 90 days, with interquartile range (IQR) 30-180 days. Most PWH were actively receiving antiretroviral therapy (ART) at the time of COVID-19 diagnosis, with 71% (n = 82) having named drug information available;bictegravir/emtricitabine/tenofovir was the most common ART (n = 25). PWH were of younger age (median 57.5 yrs [IQR 46.5-63.25] vs 65 yrs [IQR 55-74]), male (81% vs 47%), and either non-Hispanic Black or Hispanic (71% vs 34%) compared to PWOH. 12% of PWH (n = 14) were current smokers compared to 6% of PWOH (n = 638), and more than half in each group were never smokers (51% of PWH and 53% of PWOH). The following comorbidities were identified in PWH vs PWOH: cardiovascular (16% vs 20%), pulmonary (16% vs 20%), renal (15% vs 14%), and diabetes mellitus (18% vs 27%). A higher proportion of PWH had hematologic malignancy compared to PWOH (33% vs 19%). More PWH had active cancer which was progressing at the time of SARS-CoV-2 infection compared to PWOH (24% vs 14%). 44% of PWH (n = 51) had received active systemic anticancer therapy within the 3 months preceding SARS-CoV-2 infection (including cytotoxic, targeted, endocrine therapies, and immunotherapy) compared to 51% of PWOH (n = 5,420). PWH had an increased rate of hospitalization (58% vs 55%) compared to PWOH. Although a lower proportion of PWH required supplemental oxygen during hospitalization compared to PWOH (34% vs 38%) and ICU admission rates were identical between the two groups (16% vs 16%), PWH had an increased rate of mechanical ventilation (14% vs 10%) and death (24% vs 18%) compared to PWOH. Conclusions: This is the first known study describing outcomes of patients with cancer and COVID-19 in the PWH population from a large multinational dataset. PWH have characteristics associated with adverse outcomes in prior analyses (male sex, non-Hispanic Black or Hispanic, hematologic malignancy, progressing cancer) but are notably younger and have fewer comorbidities. HIV infection may portend increased risk of severe COVID-19 and death;however, additional analyses, including multivariable regression, are warranted.
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Background: Patients (pts) with thoracic cancers have a high rate of hospitalization and death from COVID-19. Smoking has been associated with increased risk for severe COVID-19. However, there is limited data evaluating the impact of smoking recency on COVID-19 severity in pts with cancer. We aimed to characterize the clinical outcomes of COVID-19 based on the recency of smoking in pts with thoracic cancers (TC) and all other cancers (OC). Methods: Adult pts with cancer and lab-confirmed SARS-CoV-2 and smoking history recorded in the CCC19 registry (NCT0435470) were included. Pts were stratified by cancer type (TC or OC) and further stratified into subgroups based on the recency of smoking cessation: current smoker;former smokers who quit < 1 yr. ago;1-5 yr. ago;6-10 yr. ago;quit > 10 yr. ago;and never smoker. 30-day all-cause mortality was the primary endpoint. Secondary endpoints were any hospitalization;hospitalization with supplemental O2;ICU admission;and mechanical ventilation. Results: From January 2020 to December 2021, 752 pts from TC group and 8,291 pts from OC group met the inclusion criteria. 78% of patients in TC group ever smoked compared to 36% patients in the OC group. In both groups, the majority of never-smokers were females (70% and 60% in TC and OC respectively). The burden of smoking and the rate of pulmonary comorbidities (PC) was higher in the TC group (PC 22-69%) compared to OC group (PC 12-26%) across all smoking strata. Overall, 30-day all-cause mortality was 21% and 11% in pts with TC and OC respectively. Former smokers who quit < 1 year ago in TC group had the highest rate of mortality and severe COVID-19 outcomes. However, in the OC group, there was no consistent trend of higher mortality or severe COVID-19 outcomes in specific subgroups based on smoking recency. Conclusions: To our knowledge this is the largest study evaluating the effect of granular phenotypes of smoking recency on COVID-19 outcomes in pts with cancer. Recent smokers who quit < 1 year ago in TC group had the highest rate of mortality and severe COVID-19. Further analysis exploring the factors (e.g., smoking pack years) associated with severe outcomes in this subgroup is planned.
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Background: Cancer is known to increase the risk of VTE when compared to the non-cancer population. Additionally, SARS-CoV-2 infection has been associated with hypercoagulability and VTE. A study by Patell et al noted similar cumulative incidence of thrombotic events (arterial and venous) in patients hospitalized with COVID-19 with active cancer than those without cancer (14.2% vs 18.2%). Data from the COVID-19 and Cancer Consortium (CCC19) Registry reported incidence of VTE of 7.6% in cancer patients within 90 days of hospitalization for COVID-19. However, it is unknown whether patients with cancer are at significantly higher risk for VTE in the setting of COVID-19 compared to cancer patients without COVID-19. Our study objectives were to: 1) determine the overall incidence of VTE in patients with cancer with and without COVID-19, regardless of hospitalization status;2) assess the relative risk of VTE due to COVID-19 in cancer patients;3) examine risk for VTE in cancer patients with COVID-19 based on certain demographic characteristics and comorbidities. Methods: An institutional retrospective cohort analysis was performed from March 1, 2020 through July 31, 2021. 228 patients with COVID-19 and cancer were identified and compared to matched controls without COVID-19 (n = 448) during the same study period based on age, gender, and BMI. Results: Incidence of VTE in cancer patients with COVID-19 was significantly higher than in cancer patients without COVID-19 (11% vs 3.1%) [RR 3.45, 95% CI 1.85-6.67]. There was no significantly increased risk of VTE in cancer patients with COVID-19 based on the following characteristics: non-White race, male gender, diabetes mellitus, hypertension, coronary artery disease, congestive heart failure, chronic obstructive pulmonary disease, chronic kidney disease, and end-stage renal disease receiving dialysis. However, patients with any history of smoking (including current smokers) had increased risk of VTE compared to never-smokers (RR 2.2756, 95% CI 1.0498-4.9326). Conclusions: COVID-19 further increases the risk of VTE in cancer patients, a population with an independent risk factor for VTE at baseline. Whether the increased risk is additive or synergistic is currently unknown. Demographic factors and comorbidities that have been associated with increased severity of COVID-19 in other studies do not appear to significantly increase risk of VTE in cancer patients with COVID-19, with the exception of smoking status (either current or past). Given the impact on morbidity and mortality, further analyses, including with larger datasets, are warranted.
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Background: Molecular profiling of tumor tissue is the gold standard for treatment decision making in advanced non-small cell lung cancer. Results may be delayed or unavailable due to insufficient tissue samples or prolonged wait times for biopsy, pathology assessment and testing. We piloted the use of plasma molecular testing as part of the initial diagnostic work-up for patients with suspected advanced lung cancer (NCT04863924). Methods: Patients with radiologic evidence of advanced lung cancer referred to the lung rapid diagnostic program underwent plasma circulating tumor DNA (ctDNA) testing using InVisionFirst-Lung, a next-generation sequencing (NGS) assay targeting 37 genes. Standard tissue testing was performed with comprehensive NGS (Oncomine). The primary endpoint was time to treatment in stage IV NSCLC patients compared to an historical pre-COVID-19 cohort (2018-9). Secondary endpoints included actionable targets identified in plasma, % of patients starting targeted therapy based on liquid biopsy and result turnaround time (TAT). Results: Between July 1 to December 31, 2021, 60 patients were enrolled. Median age was 70 years (range 33-91), 52% were female, 57% Caucasian, 48% never smokers. Of these, 73% had NSCLC, 12% small cell, 10% non-lung pathology and 5% declined tissue biopsy. Of 44 NSCLC patients, 5 (11%) had early-stage disease and underwent curative therapy. Most stage IV patients (79%) had systemic treatment. Median time to treatment initiation in the study cohort was 34 days (n = 31, range 10-90) versus 62 days (n = 101, range 13- 159) in the historical cohort (p<0.0001). Two thirds (N = 23) of stage IV NSCLC patients had actionable alterations identified, (30% in current/ex-smokers);18 started targeted therapy including 10 based on plasma results before tissue results were available. Median TAT was 7 days for plasma from blood draw to reporting (range 4-14) and 26 days for tissue molecular testing (range 11-42), p<0.0001. Concordance was high between plasma and tissue testing (70%). Liquid biopsy identified actionable alterations for 3 patients not identified by tissue NGS. In 4 cases, plasma testing failed to identify actionable alterations detected in tissue, due to undetectable plasma ctDNA. Conclusions: Liquid biopsy in the initial diagnostic workup of patients with suspected advanced NSCLC leads to faster molecular results and shortens time to treatment compared to tissue testing alone. Supplementing the current standard of tissue molecular testing with a plasma-first approach during the diagnostic work up of patients with suspected advanced lung cancer may increase access to precision medicine and improve patient outcomes. (Table Presented).
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Background: SARS-Cov-2 infection had a major impact on patients with infam-matory rheumatic diseases. Spondyloarthritis (SpA) patients were one of the most affected groups of these patients. Objectives: To assess the impact of Covid19 in spondyloarthritis patients under biological disease modifying anti-rheumatic drugs (bDMARDs). Methods: A retrospective observational study was conducted using registry data of patients with SpA under bDMARD therapy, followed at a tertiary level hospital, that have been diagnosed with COVID19 from March 2019 to December 2021. At least one evaluation previous (t0) and two evaluations after SARS-CoV-2 infection (t1, t2) were included in our analysis. Sociodemographic, clinical, disease activity, therapeutic response, function and general health status data were collected. Statistical analysis (signifcance at p < 0.05) was performed using paired T-test, Wilcoxon test and McNemar tests for paired samples. Linear and logistic regression models were performed to assess direction and strength of association Results: Thirty-two patients with SpA under bDMARD had COVID19, mostly women (20, 62.5%), with a disease course time averaged 18.65 (± 9.69) years, mainly with axial involvement (19, 59.4%) and positive for HLA-B27 antigen (11, 64.7%). The majority were under TNF inhibitors (30, 93.75%), with golimumab being the most common (9, 28.1%), and with a median bDMARD persistence of 2.63 (5.09) years. Seven (21.9%) were under a cDMARD, 3 (9.4%) under NSAID and 18 (56.3%) under corticosteroids. Three (9.4%) were already vaccinated against SARS-CoV-2, 2 (66.6%) with the mRNA-1273 vaccine, presenting a medium time since inoculation of 240 (± 234.01) days. Arterial hypertension was the most common comorbidity (5, 15.6%) and one patient (3.1%) had a previous diagnosis of type 2 diabetes. Most were never-smokers (17, 53.1%) and never-drinkers (29, 90.6%). The average age at infection was 40.97 (± 6.15) years and the most common symptom was cough (22, 68.8%), followed by headache (20, 62.5%) and myalgia (19, 59.4%). Event tree analysis didn't show association with SpA subtype, education level, work status, tobacco or alcohol consumption. Only one patient needed hospital admission but without needing of oxygen, therapy, ventilator or ECMO. Only one patient had an overlaid bacterial infection and no thromboembolic complications were observed. Two patients needed specific SARS CoV-2 infection treatment, one with hydroxychloroquine and another with azithromycin. Twelve (37.5%) patients suspended bDMARD at the time of infection, with only 2 (6.3%) maintaining suspension at the time of the first post-infection visit. When comparing clinical variables, higher disease activity was seen at t1 only for BASDAI mean values, without statistical signifcance. Higher all domains VAS scores were also observed at t1, but not at t2, also without statistical signifcance;moreover, physical function didn't change signifcantly. No differences were observed according to gender or SpA subtype, nor with the use of cDMARDs, NSAIDs or corticosteroids. The only statistically signifcant difference concerned MASES score between t0 and t1 (1 ± 4 vs. 2 ± 6, p=0.04), but not between t0 and t2. Higher baseline tender joint score (p < 0.01) and higher baseline LEI (p=0.03) negatively correlated with MASES score variation. Several baseline variables correlated positively with MASES at t1, including female gender (p < 0.01), corticosteroid use (p = 0.04), BASDAI (p < 0.01), ASDAS-ESR (p < 0.01), ASDAS-CRP (p < 0.01), DAS28 (p < 0.01), SPARCC (p = 0.04), physician VAS (p = 0.03) and total spine VAS (p = 0.01). Working status varied signifcantly after SARS-Cov-2 infection (at least part-time-29, 90.6% vs. 22, 68.8%, p= 0.016). Conclusion: SpA patients on bDMARD had a mild course of SARS-CoV-2 infection, with slight changes in enthesitis score in the short term, the latter particularly in those with higher disease activity in the pre-infection period. Long-term effects on work status could represent confounding factors related to the e onomic constraints of the pandemic.
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Introduction: With the strain placed on the medical system by the ongoing surges of the Covid-19 pandemic, inpatient surgery is often suspended, and same day discharge rates are increasing. Sacrospinous ligament fixation (SSLF) is an apical suspension procedure performed retroperitoneally;retroperitoneal hemorrhage and nerve injury are potential severe complications. Given these risks, providers vary in their preference for same day discharge vs. routine overnight admission after this procedure. Objective: To establish the safety of outpatient SSLF and evaluate the frequency of complications identified during the hospital stay. Methods: This is a retrospective cohort study of women who underwent SSLF by Urogynecologists at our large, academic institution between March 2018 and October 2021. Patients were identified from the Gynecologic Enhanced Recovery Surgical database, which includes all surgical patients in the department of OBGYN. The data was collected from the electronic medical record (EMR) to track compliance and outcomes in real time for quality improvement purposes during implementation of our enhanced recovery protocol. Institutional IRB approval was obtained. Descriptive statistics were performed. Student's t-test and two-sample tests-of-proportions were used, with a p-value <0.05 denoting statistical significance. Results: A total of 165 patients underwent SSLF;23 were outpatient, and 142 were admitted for at least one night. Over 90% of patients in both groups identified as white, non-Hispanic, and English-speaking. The mean BMI for both groups was 28.8 kg/m2. The outpatient group was younger (57.9 years compared to 64.7 years;P = 0.0051);outpatients were more likely to have commercial insurance (P = 0.0143) and inpatients to have Medicare (P = 0.0282). Almost double the proportion of those in the inpatient group had anxiety and depression, but this did not achieve statistical significance. Outpatients were more likely to be never smokers (P = 0.0175) and use narcotics preoperatively (P = 0.0385). They had a lower mean ASA score (P = 0.0067), Charleston Comorbidity Index score (P = 0.0452), total length of surgery (P < 0.001), total length of anesthesia (P < 0.001), and estimated blood loss (P = 0.0142). Those who went home the same day were more likely to have been the first case (P = 0.0123), and same-day discharge rates increased significantly after the onset of the Covid-19 pandemic (P = 0.0039). Both complications that required operative intervention were identified in the post-anesthesia care unit on the day of surgery. Notably, 30-day post-operative complications were proportionally lower in the outpatient group, but this did not achieve significance. Most of the complications were urinary tract infections, including the sole complication identified in the outpatient group. Conclusions: With the ongoing Covid-19 pandemic and rapidly evolving practice patterns, it is important to establish the safety of outpatient surgery. Our study demonstrates that outpatient SSLF is safe for appropriately selected patients after routine post-operative monitoring including serial vital signs and assessment of neuropathic pain. Severe complications requiring reoperation can often be identified immediately after surgery. Thirty-day post-operative complication rates did not significantly differ between patients undergoing outpatient versus inpatient SSLF.
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RATIONALE The COVID-19 pandemic has disrupted national spirometric surveillance of active and former U.S. coal miners since March 2020. Consequently data collected by the Health Resources and Services Administration (HRSA)-funded Black Lung Clinics Program (BLCP) represents the only major source of recent health data on U.S. former coal miners. Using the first available year of national BLCP data we examined associations between mining region and radiographic disease and lung function impairment. METHODS We analyzed pre-bronchodilator spirometry and International Labour Office chest radiograph classifications from miners seen across 15 BLCP grantees from July 1 2020 to June 30 2021. We calculated percent predicted (PP) and lower limits of normal (LLN) for forced expiratory volume in one second (FEV1) forced vital capacity (FVC) and FEV1/FVC ratio. We determined prevalence of patterns of spirometric abnormality (restrictive obstructive/mixed) and moderate to severe impairment (FEV1<70PP). We classified miners who worked the majority of their coal mining career in Kentucky Virginia or West Virginia as Central Appalachian miners. We examined associations between region worked and lung function impairment using logistic regression. RESULTS The 2,891 miners were predominantly non- Hispanic white (98.1%) and male (99.4%) with mean age 66 years (SD9.3). Mean coal mining tenure was 26 years (SD10.7) and 66% (n=1,900) were Central Appalachian miners. Thirty-seven percent had never smoked. Among those with chest radiographs (n=2,464 85%) Central Appalachian miners had a significant three-fold increase in progressive massive fibrosis (PMF) prevalence compared to miners who worked elsewhere in the U.S. (9% vs 3% p<.0001). Smoking history and spirometry were available in 66% (n=1,918). Of these 40% of never-smokers had abnormal spirometry (obstruction/mixed 10%;restriction 30%);among ever-smokers, 54% had abnormal spirometry (obstruction/mixed 27%;restriction 27%). Abnormal FEV1 was present in 30% of never smokers and 42% of ever-smokers. Mean FEV1PP was significantly lower among Central Appalachian miners compared to miners from other regions. Controlling for age, tenure, and pack-years, Central Appalachian miners had significantly elevated odds of having FEV1 impairment compared to non-Central Appalachian miners (OR 1.31, 95%CI 1.06,1.62). A subanalysis controlling for category of radiographic disease showed that odds of impairment remained elevated among Central Appalachian miners (OR 1.24, 95%CI 0.97,1.60). CONCLUSIONS Controlling for smoking, age, and tenure, former miners who worked most of their career in Central Appalachia have significantly increased odds of disabling impairment. These findings highlight the important role of HRSA-funded black lung clinics in understanding work-related lung disease among U.S. coal miners.
ABSTRACT
Introduction: Antisynthetase syndrome(ASS) is a rare autoimmune disease characterized by myositis, arthritis, cutaneous findings and interstitial lung disease (ILD). In 15-30% cases of ASS, ILD can be the presenting feature making this a very challenging diagnosis to make, especially during the COVID 19 pandemic. We present a unique case of ILD as presenting feature of ASS. Case: A 31 yr old female, never smoker, with asthma and obesity was referred to the pulmonary clinic for dyspnea of 2 months. Dyspnea was on exertion, associated with cough and pleuritic chest pain. Oxygen saturation on exam was 91% at rest and 86% on exertion. PCR and antibodies for COVID was negative. CXR showed bilateral infiltrates. She was treated with several courses of antibiotics and steroids. Her symptoms improved with steroids yet returned when course completed. Chest CT revealed bilateral parenchyma opacities with sparing of the lung apices. This was repeated 3 months after her course of antibiotics and steroids which revealed worsening of ground glass opacities, now diffuse with areas of organizing pneumonia. Bronchoalveolar lavage showed alveolar macrophages with a mixture of acute and chronic inflammatory cells. PFTs revealed severe restrictive lung disease. Infectious work up including bacterial, viral and fungal causes was negative. Complete blood count with differential was normal. B-type natriuretic peptide, creatine kinase, liver function test, basic metabolic panel, HIV and fungal serologies were unrevealing. A rheumatologic work up revealed elevated ESR (48), CRP (6.9), aldolase (48) with positive anti OJ antibodies. She underwent VATs with wedge lung biopsy which revealed cellular non specific interstitial pneumonia (NSIP). She was diagnosed with ASS and started on a gradual taper of high dose steroids and steroid sparing agent Mycophenolate Mofetil. With time her respiratory symptoms improved and she no longer required supplemental oxygen. She was enrolled in pulmonary rehabilitation and encouraged to loose weight as her BMI of 55 could preclude lung transplantation if needed. Discussion: ASS is a rare autoimmune connective tissue disorder characterized by myositis, polyarthritis, cutaneous findings and ILD. It occurs more commonly in women with average age of onset in 50s. ILD has been reported in 69-100% with NSIP being most common followed by cryptogenic organizing pneumonia and UIP. Treatment consists of steroids, with or without a steroid-sparing agent. Timely diagnosis of ASS is imperative for patients presenting with ILD as delay can lead to progression of ILD which serves as a predictor for morbidity and mortality. (Figure Presented).