Endotracheal aspirates, blood samples, urine samples, and nasopharyngeal swabs were obtained from the patients as soon as possible after ICU admission. Bacterial culture was performed, with the use of standard techniques, on blood samples and endotracheal aspirates. Urine antigen detection was performed for detection of L. pneumophila and S. pneumoniae. A PCR assay was performed on nasopharyngeal swabs for the detection of influenza A and B viruses and SARS-CoV-2 viruses. Fungal or mycobacterial detections, and whether to use multiplex PCR for pathogen detection, such as the FilmArray system, were determined at the discretion of the physicians.

Standard work-up for pneumonia

Subjects assigned to the mNGS group will receive etiology work-up followed the protocol used in the standard care group and additional mNGS testing for two specimen of mini-bronchoalveolar lavage and one specimen of blood samples retrieved at the same time of standard work-up.

Metagenomic NGS testing for pathogen identification will be done for airway and blood specimens using APGseq ® (Asia Pathogenomics, New Taipei City, Taiwan). The sample preparation for mNGS testing was as follows: 5-10 mL of whole blood were centrifuged at 1,600g for 10 min at 4°C to separate the plasma. Plasma samples were transferred to 2 mL sterile tubes for the following DNA or RNA extraction. In general, 300ul of plasma sample was used for DNA extraction. Total genomic DNA from samples were extracted using the column-based method (e.g. QIAamp DNA Microbiome Kit, Qiagen for DNA extraction; or QIAamp Viral RNA Mini Kit, Qiagen for RNA extraction, respectively), following the manufacturer's operational manual. The RNA was reverse transcribed and synthesized to double-stranded complementary DNA (ds cDNA) with SuperScript II Reverse Transcription Kit (Invitrogen).

Metagenomic next-generation sequencing

Patients with unresectable HCC undergo apheresis for dendric cell manufacturing and standard of care high-dose EBRT for 5 or 15 fractions over 1-3 weeks (cycle 1). Patients then receive autologous dendritic cells IT on day 1 of cycles 2-8 and pneumococcal 13-valent conjugate vaccine or other pneumococcal vaccine IM on day 1 of cycles 2-4 only. Patients also receive standard of care atezolizumab IV over 30-60 minutes and bevacizumab IV over 30-90 minutes starting on day 2 of cycles 2-8. Treatment repeats every 21 days for up to 7 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo an EGD at screening and CT, PET/CT and/or MRI, biopsy and urine and blood sample collection throughout the study.

Atezolizumab

Bevacizumab

External Beam Radiation Therapy

Pheresis

Pneumococcal 13-valent Conjugate Vaccine

Therapeutic Autologous Dendritic Cells

Esophagogastroduodenoscopy

Computed Tomography

Positron Emission Tomography

Magnetic Resonance Imaging

Biopsy Procedure

Undergo urine and blood sample collection

Biospecimen Collection

Patients with unresectable intrahepatic CCA undergo apheresis for dendric cell manufacturing and standard of care high-dose EBRT for 5 or 15 fractions over 1-3 weeks (cycle 1). Patients then receive autologous dendritic cells IT on day 1 of cycles 2-8 and pneumococcal 13-valent conjugate vaccine IM on day 1 of cycles 2-4 only. Treatment repeats every 28 days for up to 7 cycles in the absence of disease progression or unacceptable toxicity. (CLOSED WITH AMENDMENT 3)

Patients with iCCA undergo apheresis for dendric cell manufacturing and standard of care high-dose EBRT for 5 or 15 fractions over 1-3 weeks (cycle 1). Patients then receive autologous dendritic cells IT on day 1 of cycles 2-8 and pneumococcal 13-valent conjugate vaccine or other pneumococcal vaccine IM on day 1 of cycles 2-4 only. Patients also receive standard of care atezolizumab IV over 30-60 minutes and tiragolumab IV over 30-60 minutes starting on day 2 of cycles 2-8. Treatment repeats every 21 days for up to 7 cycles in the absence of disease progression or unacceptable toxicity. Additionally, patients undergo CT, PET/CT and/or MRI, biopsy and urine and blood sample collection throughout the study.

Tiragolumab

Clinical Trials Referral Office

Lewis R. Roberts, MD, PhD

All participants will receive a pneumococcal vaccine.

Conjugate Pneumococcal Vaccine 20 (PCV20)

Anne Frosch, MD

Patients receive low-dose lenalidomide PO once daily on days 1-28. Treatment repeats every 28 days for at least 24 cycles in the absence of disease progression or unacceptable toxicity. Patients also receive PCV13 IM on day 1 of courses 3 and 5.

Patients may undergo bone marrow biopsy and aspirate and CT during screening and blood sample collection throughout the study. (Blood sample collection discontinued with approval of protocol version 24 dated 3/15/2024)

Bone Marrow Aspiration

Bone Marrow Biopsy

Lenalidomide

Pneumococcal Polyvalent Vaccine

Patients receive PCV13 IM on days 1 and 78 (cycles 1 and 3). Patients also receive low-dose lenalidomide as in arm 1 beginning on day 1 of course 4. Treatment repeats every 28 days for at least 24 cycles in the absence of disease progression or unacceptable toxicity. Patients may undergo bone marrow biopsy and aspirate and CT during screening and blood sample collection throughout the study. (Blood sample collection discontinued with approval of protocol version 24 dated 3/15/2024)

특발성 폐섬유증 환자에게 흡입하는 제논 가스를 활용한 MRI로 폐 기능 변화를 관찰하는 안전한 초기 연구입니다.

Whether magnetic resonance imaging (MRI) using inhaled hyper-polarized 129 Xenon gas can help visualize impaired lung function to detect changes over time in Idiopathic Pulmonary Fibrosis (IPF) patients receiving approved IPF treatments

Hyperpolarized 129 Xenon Gas Comparing Idiopathic Pulmonary Fibrosis (IPF) Treatment

흡입 초분극 129 제논 가스를 사용하는 자기공명영상(MRI)이 승인된 IPF 치료를 받는 특발성 폐섬유증(IPF) 환자의 시간 경과에 따른 변화를 감지하기 위해 손상된 폐 기능을 시각화하는 데 도움이 될 수 있는지 여부

특발성 폐섬유증(IPF) 치료를 비교하는 과분극 129 제논 가스

제넨텍 제논 MRI 특발성 폐섬유증

Prevnar 13 (Pneumococcal 13valent Conj Vaccine Diphtheria CRM197 Protein) will be administered at the single 0.5 ml dose, by intramuscular injection with routine clinical care.

One to two years after receiving the randomly-assigned vaccination, participants may opt to receive administration of a second pneumococcal vaccine with Pneumovax 23

Pneumococcal 13valent Conj Vaccine Diphtheria CRM197 Protein

Pneumovax 23 (Pneumococcal Vaccine Polyvalent) will be administered at the single 0.5ml dose, by intramuscular injection with routine clinical care.

One to two years after receiving the randomly-assigned vaccination, participants may opt to receive administration of a second pneumococcal vaccine with Prevnar-13

Pneumococcal Vaccine Polyvalent

Pneumococcal conjugate vaccine (PCV13) .5 ml will be administered intramuscularly three times: 7 days (range 4 to 21 days) before apheresis collection and on day +30 (range +21 to +37) and day +90 (range +75 to +115) after CAR T cell infusion.

Licensed heptavalent pneumococcal conjugate vaccine (PCV13, Pneumococcal 13-valent conjugate vaccine

Pneumococcal conjugate vaccine (PCV13)

This is a personalized therapeutic approach that entails removal of T cells from patient's peripheral blood, genetic modification, activation and expansion in vitro to retarget cells against CD19 protein on the surface of B cells, and infusion of the genetically engineered cells back into the patient. CD19 is a surface protein that is expressed on B cells starting from early pre-B cells to mature fully differentiated B cells. Therefore, CD19-targeted CAR T cell therapy can effectively treat refractory B cell lymphomas.

CD19 targeted CAR T Cell Therapy

H. Lee Moffitt Cancer Center and Research Institute

Patients receive ibrutinib PO QD on days 1-28. Patients also receive pneumococcal 13-valent conjugate vaccine IM on day 1 of courses 3 and 5 and trivalent influenza vaccine IM and DTaP vaccine IM on day 1 of course 4. Treatment repeats every 28 days for up to 24 courses in the absence of disease progression or unacceptable toxicity.

Diphtheria Toxoid/Tetanus Toxoid/Acellular Pertussis Vaccine Adsorbed

Ibrutinib

Laboratory Biomarker Analysis

Pharmacological Study

Quality-of-Life Assessment

Trivalent Influenza Vaccine

Patients receive pneumococcal 13-valent conjugate vaccine IM on day 1 of courses 1 and 3 and trivalent influenza IM and DTaP vaccine IM on day 1 of course 2. Beginning in course 4, patients receive ibrutinib PO QD on days 1-28. Treatment repeats every 28 days for up to 27 courses in the absence of disease progression or unacceptable toxicity.

Patients in the FA Pneumonia Panel guided group will have a BioFire® FilmArray® Pneumonia Panel assay performed as soon as possible but within 24 hours of new antibiotic prescription for suspected respiratory infection in addition to all the investigations performed in standard care. Based on the rapid test results, antimicrobial therapy will be adjusted according to a pre-determined treatment algorithm and antimicrobial guidelines. The treatment algorithm and antimicrobial guidelines were based on the latest hospital antibiogram, procalcitonin protocol, and consensus recommendations from microbiologists, infectious disease experts and intensive care physicians at our hospital. The treating clinical team will also be given the standard microbiological culture with sensitivity results when available. The treating clinical team may override the pre-determined antimicrobial algorithm for any clinical reason at any time and the rationale will be recorded.

A single BioFire® FilmArray® Pneumonia Panel assay will be performed on a respiratory clinical specimen.

FA Pneumonia Panel

Patients in the standard care group will receive antimicrobial therapy guided by conventional microbiological cultures and standardized procalcitonin protocol. Choice of antimicrobial agent is based on use of the narrowest-spectrum antimicrobial agent possible according to culture sensitivity. Current standard investigations for any patient mechanically ventilated for suspected pneumonia in our ICU includes two sets of blood cultures, daily procalcitonin, respiratory specimen of tracheal aspirate or bronchoalveolar lavage for bacterial gram stain and cultures, respiratory viral PCR and urine streptococcus and legionella antigen. FA Pneumonia Panel will be performed from concurrent respiratory samples in the standard care group at the end of the study and the results will not be used by the treating clinical team for treatment decisions. Blinded results will only be available to the antimicrobial review panel for outcome assessment.

Participants who are heterozygous for the SERPINA1 'Z' allele with either 0 or 2+ exacerbations in the previous year, and have not received pneumococcal vaccination within 5 years will be given PCV20.

20-valent pneumococcal conjugate vaccine

LaFon

David C LaFon, MD

subcutaneous injection of 20 mg ofatumumab every 4 weeks

Ofatumumab

0.5mL Vial/Syringe Containing 5 limit of flocculation (LF) tetanus toxoid

Tetanus toxoid (TT) containing vaccine (Td, Tdap)

13-valent pneumococcal conjugate vaccine (13-PCV)

23-valent pneumococcal polysaccharide vaccine (23-PPV)

Seasonal 2020-2021 0.5mL Vial/Syringe (trivalent may be used where quadrivalent is not available)

메타게놈 차세대 시퀀싱, 폐렴에 대한 표준 검사

접합 폐렴구균 백신 20(PCV20)

생체 검체 채취, 골수 흡인, 골수 생검, 컴퓨터 단층촬영, 레날리도마이드, 폐렴구균 다가 백신

제넨텍 제논 MRI 특발성 폐섬유증

폐렴구균 13가 복합백신 디프테리아 CRM197 단백질, 다가 폐렴구균 백신

폐렴구균 접합백신(PCV13), CD19 표적 CAR T 세포 치료

디프테리아 톡소이드/파상풍 톡소이드/무세포 백일해 흡착 백신, 이브루티닙, 실험실 바이오마커 분석, 약리학 연구, 폐렴구균 13가 접합 백신, 삶의 질 평가, 3가 인플루엔자 백신

FA 폐렴 패널

20가 폐렴구균 접합백신

오파투무맙, 파상풍 톡소이드(TT) 함유 백신(Td, Tdap), 13가 폐렴구균 접합 백신(13-PCV), 23가 폐렴구균 다당류 백신(23-PPV), 계절성 4가 인플루엔자 백신, 키홀림펫 헤모시아닌(KLH) 신항원