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Lower Airway Dysbiosis Augments Lung Inflammatory Injury in Mild-to-Moderate Chronic Obstructive Pulmonary Disease

Sulaiman, Imran; Wu, Benjamin G; Chung, Matthew; Isaacs, Bradley; Tsay, Jun-Chieh J; Holub, Meredith; Barnett, Clea R; Kwok, Benjamin; Kugler, Matthias C; Natalini, Jake G; Singh, Shivani; Li, Yonghua; Schluger, Rosemary; Carpenito, Joseph; Collazo, Destiny; Perez, Luisanny; Kyeremateng, Yaa; Chang, Miao; Campbell, Christina D; Hansbro, Philip M; Oppenheimer, Beno W; Berger, Kenneth I; Goldring, Roberta M; Koralov, Sergei B; Weiden, Michael D; Xiao, Rui; D'Armiento, Jeanine; Clemente, Jose C; Ghedin, Elodie; Segal, Leopoldo N
PMID: 37677136
ISSN: 1535-4970
CID: 5606572

Pleural fluid microbiota as a biomarker for malignancy and prognosis

Kwok, Benjamin; Wu, Benjamin G; Kocak, Ibrahim F; Sulaiman, Imran; Schluger, Rosemary; Li, Yonghua; Anwer, Raheel; Goparaju, Chandra; Ryan, Daniel J; Sagatelian, Marla; Dreier, Matthew S; Murthy, Vivek; Rafeq, Samaan; Michaud, Gaetane C; Sterman, Daniel H; Bessich, Jamie L; Pass, Harvey I; Segal, Leopoldo N; Tsay, Jun-Chieh J
Malignant pleural effusions (MPE) complicate malignancies and portend worse outcomes. MPE is comprised of various components, including immune cells, cancer cells, and cell-free DNA/RNA. There have been investigations into using these components to diagnose and prognosticate MPE. We hypothesize that the microbiome of MPE is unique and may be associated with diagnosis and prognosis. We compared the microbiota of MPE against microbiota of pleural effusions from non-malignant and paramalignant states. We collected a total of 165 pleural fluid samples from 165 subjects; Benign (n = 16), Paramalignant (n = 21), MPE-Lung (n = 57), MPE-Other (n = 22), and Mesothelioma (n = 49). We performed high throughput 16S rRNA gene sequencing on pleural fluid samples and controls. We showed that there are compositional differences among pleural effusions related to non-malignant, paramalignant, and malignant disease. Furthermore, we showed differential enrichment of bacterial taxa within MPE depending on the site of primary malignancy. Pleural fluid of MPE-Lung and Mesothelioma were associated with enrichment with oral and gut bacteria that are commonly thought to be commensals, including Rickettsiella, Ruminococcus, Enterococcus, and Lactobacillales. Mortality in MPE-Lung is associated with enrichment in Methylobacterium, Blattabacterium, and Deinococcus. These observations lay the groundwork for future studies that explore host-microbiome interactions and their influence on carcinogenesis.
PMID: 36755121
ISSN: 2045-2322
CID: 5426932

Contemporary practice patterns and outcomes of systemic thrombolysis in acute pulmonary embolism

Gayen, Shameek; Katz, Alyson; Dikengil, Fusun; Kwok, Benjamin; Zheng, Matthew; Goldenberg, Ronald; Jamin, Catherine; Yuriditsky, Eugene; Bashir, Riyaz; Lakhter, Vladimir; Panaro, Joseph; Cohen, Gary; Mohrien, Kerry; Rali, Parth; Brosnahan, Shari B
OBJECTIVE:Although systemic thrombolysis (ST) is the standard of care in the treatment of high-risk pulmonary embolism (PE), large variations in real-world usage exist, including its use to treat intermediate-risk PE. A paucity of data is available to define the outcomes and practice patterns of the ST dose, duration, and treatment of presumed and imaging-confirmed PE. METHODS:We performed a multicenter retrospective study to evaluate the real-world practice patterns of ST use in the setting of acute PE (presumed vs imaging-confirmed intermediate- and high-risk PE). Patients who had received tissue plasminogen activator for PE between 2017 and 2019 were included. We compared the baseline clinical characteristics, tissue plasminogen activator practice patterns, and outcomes for patients with confirmed vs presumed PE. RESULTS:A total of 104 patients had received ST for PE: 52 with confirmed PE and 52 with presumed PE. Significantly more patients who had been treated for presumed PE had experienced cardiac arrest (n = 47; 90%) compared with those with confirmed PE (n = 23; 44%; P < .01). Survival to hospital discharge was 65% for the patients with confirmed PE vs 6% for those with presumed PE (P < .01). The use of ST was contraindicated for 56% of the patients with confirmed PE, with major bleeding in 26% but no intracranial hemorrhage. CONCLUSIONS:The in-hospital mortality of patients with confirmed acute PE has remained high (35%) in contemporary practice for those treated with ST. A large proportion of these patients had had contraindications to ST, and the rates of major bleeding were significant. Those with confirmed PE had had a higher survival rate compared with those with presumed PE, including those with cardiac arrest. This observation suggests a limited role for empiric thrombolysis in cardiac arrest situations.
PMID: 35714905
ISSN: 2213-3348
CID: 5282852

Pulmonary Pathology of End-Stage COVID-19 Disease in Explanted Lungs and Outcomes After Lung Transplantation

Flaifel, Abdallah; Kwok, Benjamin; Ko, Jane; Chang, Stephanie; Smith, Deane; Zhou, Fang; Chiriboga, Luis A; Zeck, Briana; Theise, Neil; Rudym, Darya; Lesko, Melissa; Angel, Luis; Moreira, Andre; Narula, Navneet
OBJECTIVES/OBJECTIVE:Patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may develop end-stage lung disease requiring lung transplantation. We report the clinical course, pulmonary pathology with radiographic correlation, and outcomes after lung transplantation in three patients who developed chronic respiratory failure due to postacute sequelae of SARS-CoV-2 infection. METHODS:A retrospective histologic evaluation of explanted lungs due to coronavirus disease 2019 was performed. RESULTS:None of the patients had known prior pulmonary disease. The major pathologic findings in the lung explants were proliferative and fibrotic phases of diffuse alveolar damage, interstitial capillary neoangiogenesis, and mononuclear inflammation, specifically macrophages, with varying numbers of T and B lymphocytes. The fibrosis varied from early collagen deposition to more pronounced interstitial collagen deposition; however, pulmonary remodeling with honeycomb change was not present. Other findings included peribronchiolar metaplasia, microvascular thrombosis, recanalized thrombi in muscular arteries, and pleural adhesions. No patients had either recurrence of SARS-CoV-2 infection or allograft rejection following transplant at this time. CONCLUSIONS:The major pathologic findings in the lung explants of patients with SARS-CoV-2 infection suggest ongoing fibrosis, prominent macrophage infiltration, neoangiogenesis, and microvascular thrombosis. Characterization of pathologic findings could help develop novel management strategies.
PMID: 34999755
ISSN: 1943-7722
CID: 5118212

Microbial Signatures in Malignant Pleural Effusions [Meeting Abstract]

Kwok, B.; Wu, B. G.; Kocak, I. F.; Anwer, R.; Li, Y.; Goparaju, C.; Schluger, R.; Murthy, V.; Rafeq, S.; Bessich, J. L.; Tsay, J. J.; Pass, H. I.; Segal, L. N.
ISSN: 1073-449x
CID: 5266102

Pulmonary Embolism Response Team activation during the COVID-19 pandemic in a New York City Academic Hospital: a retrospective cohort analysis

Kwok, Benjamin; Brosnahan, Shari B; Amoroso, Nancy E; Goldenberg, Ronald M; Heyman, Brooke; Horowitz, James M; Jamin, Catherine; Sista, Akhilesh K; Smith, Deane E; Yuriditsky, Eugene; Maldonado, Thomas S
Coronavirus disease 2019 (COVID-19) is associated with increased rates of deep vein thrombosis (DVT) and pulmonary embolism (PE). Pulmonary Embolism Response Teams (PERT) have previously been associated with improved outcomes. We aimed to investigate whether PERT utilization, recommendations, and outcomes for patients diagnosed with acute PE changed during the COVID-19 pandemic. This is a retrospective cohort study of all adult patients with acute PE who received care at an academic hospital system in New York City between March 1st and April 30th, 2020. These patients were compared against historic controls between March 1st and April 30th, 2019. PE severity, PERT utilization, initial management, PERT recommendations, and outcomes were compared. There were more cases of PE during the pandemic (82 vs. 59), but less PERT activations (26.8% vs. 64.4%, p < 0.001) despite similar markers of PE severity. PERT recommendations were similar before and during the pandemic; anticoagulation was most recommended (89.5% vs. 86.4%, p = 0.70). During the pandemic, those with PERT activations were more likely to be female (63.6% vs. 31.7%, p = 0.01), have a history of DVT/PE (22.7% vs. 1.7%, p = 0.01), and to be SARS-CoV-2 PCR negative (68.2% vs. 38.3% p = 0.02). PERT activation during the pandemic is associated with decreased length of stay (7.7 ± 7.7 vs. 13.2 ± 12.7 days, p = 0.02). PERT utilization decreased during the COVID-19 pandemic and its activation was associated with different biases. PERT recommendations and outcomes were similar before and during the pandemic, and led to decreased length of stay during the pandemic.
PMID: 32910409
ISSN: 1573-742x
CID: 4589422

Lower Airway Microbiota Predicts Malignancy Recurrence of Surgically Resected Early-Stage Lung Cancer [Meeting Abstract]

Kwok, B.; Tsay, J. J.; Sulaiman, I; Wu, B. G.; Li, Y.; Pass, H., I; Segal, L. N.
ISSN: 1073-449x
CID: 5266092

Exercise-Induced Small Airway Dysfunction Detected by Oscillometry Uncovers Mechanisms for Unexplained Dyspnea [Meeting Abstract]

Sharpe, A. L.; Oppenheimer, B. W.; Goldring, R. M.; Sterman, D. H.; Addrizzo-Harris, D. J.; Weinstein, T.; Kwok, B.; Bohart, I.; Berger, K. I.
ISSN: 1073-449x
CID: 5266052

Thrombolytics in Cardiac Arrest: Is It Beneficial in Confirmed or Suspected PE? [Meeting Abstract]

Gayen, S.; Dikengil, F.; Zheng, M.; Katz, A.; Kwok, B.; Brosnahan, S.; Rali, P.
ISSN: 1073-449x
CID: 5266062

Time to Systemic Thrombolysis in Confirmed Massive Pulmonary Embolism in a Single Center [Meeting Abstract]

Kwok, B.; Katz, A.; Dikengil, F.; Gayen, S.; Zheng, M.; Rali, P.; Brosnahan, S. B.
ISSN: 1073-449x
CID: 5266072