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Article ; Online: HBV reactivation and clinical resolution in an isolated anti-HBc-positive patient during immune checkpoint inhibition.

Baumert, Lukas S / Shih, Angela R / Chung, Raymond T

Med (New York, N.Y.)

2024 Volume 5, Issue 2, Page(s) 126–131.e1

Abstract: Background: Immune checkpoint inhibitor (ICI)-related liver injury is a growing concern as ICIs are increasingly used in cancer treatment regimens. Interestingly, ICIs have exhibited antiviral effects among patients with chronic hepatitis B virus (HBV). ...

Abstract	Background: Immune checkpoint inhibitor (ICI)-related liver injury is a growing concern as ICIs are increasingly used in cancer treatment regimens. Interestingly, ICIs have exhibited antiviral effects among patients with chronic hepatitis B virus (HBV). However, the underlying mechanisms remain unclear, and clinical data on patients with previous HBV infection/exposure and isolated anti-HBV core antibodies (IAHBcs) are lacking. Methods: We report a case illustrating the dual effects of ICIs in a patient experiencing panlobular hepatitis and concurrent HBV reactivation. Findings: A 68-year-old male patient positive for IAHBcs was admitted with panlobular hepatitis and HBV reactivation after receiving systemic chemotherapy (several months before admission) and ICI treatment (4 weeks before admission) subsequent to metastatic primary lung cancer (NSCLC stage IV). This was followed by a rapid and significant decrease of HBV DNA viral load before and during antiviral treatment. Conclusions: This unique case sheds light on the dynamics of ICI therapy in IAHBc-positive patients experiencing HBV reactivation during chemotherapy and underscores the dual impact of ICIs. Moreover, it emphasizes the need for assessment of HBV serology and prophylaxis in IAHBc-positive patients undergoing chemotherapy and ICI treatment. Funding: R.T.C. was supported by the MGH Research Scholars Program.
MeSH term(s)	Male ; Humans ; Aged ; Hepatitis B virus/physiology ; Immune Checkpoint Inhibitors/adverse effects ; Hepatitis B, Chronic/complications ; Hepatitis B, Chronic/drug therapy ; Hepatitis B Surface Antigens/pharmacology ; Hepatitis B Surface Antigens/therapeutic use ; Neoplasms ; Antiviral Agents/therapeutic use ; Antiviral Agents/adverse effects
Chemical Substances	Immune Checkpoint Inhibitors ; Hepatitis B Surface Antigens ; Antiviral Agents
Language	English
Publishing date	2024-02-10
Publishing country	United States
Document type	Case Reports ; Journal Article
ISSN	2666-6340
ISSN (online)	2666-6340
DOI	10.1016/j.medj.2024.01.002
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Article ; Online: COVID-19: gastrointestinal and hepatobiliary manifestations.

Shih, Angela R / Misdraji, Joseph

Human pathology

2022 Volume 132, Page(s) 39–55

Abstract: SARS-CoV-2 is the viral agent of COVID-19, a pandemic that surfaced in 2019. Although predominantly a respiratory ailment, patients with COVID-19 can have gastrointestinal (GI) and hepatobiliary manifestations. These manifestations are often mild and ... ...

Abstract	SARS-CoV-2 is the viral agent of COVID-19, a pandemic that surfaced in 2019. Although predominantly a respiratory ailment, patients with COVID-19 can have gastrointestinal (GI) and hepatobiliary manifestations. These manifestations are often mild and transient, but they can be severe and consequential. In the GI tract, ischemic enterocolitis is the most common and significant consequence of COVID-19. In the liver, the reported pathologic findings may often be related to consequences of severe systemic viral infection, but reports of hepatitis presumed to be due to SARS-CoV-2 suggest that direct viral infection of the liver may be a rare complication of COVID-19. In both the GI tract and liver, lingering symptoms of GI or hepatic injury after resolution of pulmonary infection may be part of the evolving spectrum of long COVID.
MeSH term(s)	Humans ; COVID-19/complications ; SARS-CoV-2 ; Gastrointestinal Diseases/diagnosis ; Gastrointestinal Diseases/etiology ; Post-Acute COVID-19 Syndrome ; Gastrointestinal Tract
Language	English
Publishing date	2022-07-16
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	207657-3
ISSN	1532-8392 ; 0046-8177
ISSN (online)	1532-8392
ISSN	0046-8177
DOI	10.1016/j.humpath.2022.07.006
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Zs.A 722: Show issues

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Article ; Online: Management of liver disease and portal hypertension in common variable immunodeficiency (CVID).

Baumert, Lukas S / Shih, Angela / Chung, Raymond T

JHEP reports : innovation in hepatology

2023 Volume 5, Issue 11, Page(s) 100882

Abstract: Patients with common variable immunodeficiency (CVID) frequently develop liver disease and associated complications, which represent an increasingly prevalent unmet medical need. The main hepatic manifestation of CVID is nodular regenerative hyperplasia ( ...

Abstract	Patients with common variable immunodeficiency (CVID) frequently develop liver disease and associated complications, which represent an increasingly prevalent unmet medical need. The main hepatic manifestation of CVID is nodular regenerative hyperplasia (NRH), resulting in non-cirrhotic portal hypertension (NCPH). Liver disease is often underdiagnosed, leading to poor outcomes and decreased survival. The increasing numbers of patients with CVID who are diagnosed late with progressive liver disease underscores the importance of appropriate clinical management and treatment of liver complications. At the same time, specific guidelines for the clinical management of CVID-related liver disease are still lacking. Here, we review the epidemiology of CVID-related liver disease, reveal new insights into NRH and NCPH biology and highlight recently uncovered opportunities for NCPH diagnostics in CVID. Finally, we focus on current management of liver disease, portal hypertension and its complications - the key challenge in patients with CVID. Specifically, we review recent data regarding the role of transjugular intrahepatic portosystemic shunt and liver transplantation in clinical management. The role for anticoagulants and immunosuppressants targeting the pathogenesis of NRH will also be discussed. We propose an updated algorithm for the diagnostic work-up and treatment of NCPH in CVID. Finally, we consider future needs and therapeutic opportunities for CVID-related liver disease.
Language	English
Publishing date	2023-08-13
Publishing country	Netherlands
Document type	Journal Article ; Review
ISSN	2589-5559
ISSN (online)	2589-5559
DOI	10.1016/j.jhepr.2023.100882
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Article ; Online: Advances and Annoyances in Anus Pathology.

Shih, Angela R / Zukerberg, Lawrence

Surgical pathology clinics

2020 Volume 13, Issue 3, Page(s) 557–566

Abstract: Anal lesions are commonly mistaken clinically for prolapse or hemorrhoids but span a wide spectrum of disorders. Anal lesions include squamous, glandular, melanocytic, infectious, and lymphoid tumors. This article provides a broad overview of anal ... ...

Abstract	Anal lesions are commonly mistaken clinically for prolapse or hemorrhoids but span a wide spectrum of disorders. Anal lesions include squamous, glandular, melanocytic, infectious, and lymphoid tumors. This article provides a broad overview of anal disorders and highlights specific issues that may hinder diagnosis.
MeSH term(s)	Anal Canal/pathology ; Anus Diseases/diagnosis ; Anus Diseases/pathology ; Anus Neoplasms/diagnosis ; Anus Neoplasms/pathology ; Humans
Language	English
Publishing date	2020-07-11
Publishing country	United States
Document type	Journal Article ; Review
ISSN	1875-9157
ISSN (online)	1875-9157
DOI	10.1016/j.path.2020.06.002
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Article ; Online: Malignant mesothelioma in Lynch syndrome: A report of two cases and a review of the literature.

Shih, Angela R / Kradin, Richard L

American journal of industrial medicine

2019 Volume 62, Issue 5, Page(s) 448–452

Abstract: Malignant mesothelioma is a rare and aggressive cancer most typically associated with prior asbestos exposure. The nature of the relationship between asbestos exposure and hereditary familial syndromes predisposing to malignancy has not been determined. ... ...

Abstract	Malignant mesothelioma is a rare and aggressive cancer most typically associated with prior asbestos exposure. The nature of the relationship between asbestos exposure and hereditary familial syndromes predisposing to malignancy has not been determined. We report two Lynch syndrome patients with paraoccupational asbestos exposure who developed diffuse malignant mesothelioma of the pleura or peritoneum. Interestingly, one showed a separate focus of pleural well-differentiated papillary mesothelioma. It is likely that Lynch syndrome patients are at increased risk for the development of mesothelioma in the setting of exposure to asbestos, even at what is generally considered to be low levels. In the presence of a documented history of low-level asbestos exposure, patients with genetic predisposition disorders (including Lynch syndrome) should be considered to have an independent risk factor modifying the effects of asbestos exposure.
MeSH term(s)	Aged ; Asbestos/adverse effects ; Colorectal Neoplasms, Hereditary Nonpolyposis/genetics ; Female ; Genetic Predisposition to Disease ; Humans ; Lung Neoplasms/chemically induced ; Lung Neoplasms/genetics ; Mesothelioma/chemically induced ; Mesothelioma/genetics ; Mesothelioma, Malignant ; Middle Aged ; Occupational Exposure/adverse effects ; Risk Factors
Chemical Substances	Asbestos (1332-21-4)
Language	English
Publishing date	2019-04-29
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	604538-8
ISSN	1097-0274 ; 0271-3586
ISSN (online)	1097-0274
ISSN	0271-3586
DOI	10.1002/ajim.22968
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Zs.A 1605: Show issues

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Jg. 1995 - 2021: Lesesall (1.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Case 3-2022: A 14-Year-Old Boy with Fever, Joint Pain, and Abdominal Cramping.

Zanger, Kerstin / Nimkin, Katherine / Israel, Esther J / Shih, Angela R

The New England journal of medicine

2022 Volume 386, Issue 4, Page(s) 375–383

MeSH term(s)	Abdominal Pain/etiology ; Adolescent ; Arthralgia/etiology ; Crohn Disease/complications ; Crohn Disease/diagnosis ; Crohn Disease/drug therapy ; Crohn Disease/pathology ; Diagnosis, Differential ; Diarrhea/etiology ; Fever/etiology ; Humans ; Ileum/diagnostic imaging ; Ileum/pathology ; Male ; Stomach/pathology ; Tomography, X-Ray Computed
Language	English
Publishing date	2022-01-24
Publishing country	United States
Document type	Case Reports ; Clinical Conference ; Journal Article
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMcpc2115850
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Ua VI Zs.34: Show issues

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Article ; Online: Decreased Lung Metastasis in Triple Negative Breast Cancer Following Locally Delivered Supratherapeutic Paclitaxel-Loaded Polyglycerol Carbonate Nanoparticle Therapy.

Sabatelle, Robert C / Chu, Ngoc-Quynh / Blessing, William / Kharroubi, Hussein / Bressler, Eric / Tsai, Lillian / Shih, Angela / Grinstaff, Mark W / Colson, Yolonda

Biomacromolecules

2024 Volume 25, Issue 3, Page(s) 1800–1809

Abstract: Breast cancer is among the most prevalent malignancies, accounting for 685,000 deaths worldwide in 2020, largely due to its high metastatic potential. Depending on the stage and tumor characteristics, treatment involves surgery, chemotherapy, targeted ... ...

Abstract	Breast cancer is among the most prevalent malignancies, accounting for 685,000 deaths worldwide in 2020, largely due to its high metastatic potential. Depending on the stage and tumor characteristics, treatment involves surgery, chemotherapy, targeted biologics, and/or radiation therapy. However, current treatments are insufficient for treating or preventing metastatic disease. Herein, we describe supratherapeutic paclitaxel-loaded nanoparticles (81 wt % paclitaxel) to treat the primary tumor and reduce the risk of subsequent metastatic lesions in the lungs. Primary tumor volume and lung metastasis are reduced by day 30, compared to the paclitaxel clinical standard treatment. The ultrahigh levels of paclitaxel afford an immunotherapeutic effect, increasing natural killer cell activation and decreasing NETosis in the lung, which limits the formation of metastatic lesions.
MeSH term(s)	Humans ; Female ; Paclitaxel ; Breast Neoplasms/drug therapy ; Breast Neoplasms/pathology ; Triple Negative Breast Neoplasms/drug therapy ; Triple Negative Breast Neoplasms/pathology ; Lung Neoplasms/drug therapy ; Nanoparticles ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Neoplasm Metastasis ; Glycerol ; Polymers
Chemical Substances	Paclitaxel (P88XT4IS4D) ; polyglycerol (25618-55-7) ; Glycerol (PDC6A3C0OX) ; Polymers
Language	English
Publishing date	2024-02-21
Publishing country	United States
Document type	Journal Article
ISSN	1526-4602
ISSN (online)	1526-4602
DOI	10.1021/acs.biomac.3c01258
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Article ; Online: Case 24-2023: A 43-Year-Old Man with a Pulmonary Nodule.

Frank, Angela J / Shepard, Jo-Anne O / Lennes, Inga T / Schumacher, Lana Y / Shih, Angela R

The New England journal of medicine

2023 Volume 389, Issue 6, Page(s) 550–558

MeSH term(s)	Adult ; Humans ; Male ; Precancerous Conditions ; Solitary Pulmonary Nodule/etiology
Language	English
Publishing date	2023-08-17
Publishing country	United States
Document type	Case Reports ; Journal Article
ZDB-ID	207154-x
ISSN	1533-4406 ; 0028-4793
ISSN (online)	1533-4406
ISSN	0028-4793
DOI	10.1056/NEJMcpc2300911
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Ua VI Zs.34: Show issues

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Article ; Online: Definition and Clinical Evaluation for Trimethoprim-Sulfamethoxazole Severe Acute Respiratory Failure.

Miller, Jenna / Khan, Hason / Mino-Kenudson, Mari / Taylor, Martin / Shih, Angela / Goldman, Jennifer

Critical care medicine

2023 Volume 51, Issue 12, Page(s) e264–e268

Abstract: Objectives: Trimethoprim-sulfamethoxazole (TMP-SMX)-associated severe acute respiratory distress syndrome (ARDS) has gone underrecognized. We propose the first disease definition and clinical evaluation for a novel adverse drug reaction (ADR) based on a ...

Abstract	Objectives: Trimethoprim-sulfamethoxazole (TMP-SMX)-associated severe acute respiratory distress syndrome (ARDS) has gone underrecognized. We propose the first disease definition and clinical evaluation for a novel adverse drug reaction (ADR) based on a series of recently identified rare cases of life-threatening ADRs. Design: A retrospective study was conducted. All medical records were evaluated. Available pathology samples were sent to Massachusetts General for clinical consultation. Blood samples from surviving patients were obtained and human leukocyte antigen (HLA) analysis was performed by the Children's Mercy Hospital Genomic Center and Vanderbilt University Medical Center. Setting: U.S. ICUs, 1996-2021. Patients: Nineteen young patients (10-37) were identified. Patients were previously healthy, with no preexisting pulmonary disease, no other cause for respiratory failure, and no chronic history of smoking/vaping. Interventions: None. Measurements and main results: Through our retrospective analysis, we analyzed clinical characteristics associated with TMP-SMX. Pathology samples were reviewed, and HLA analysis was performed on available samples by the study team or as standard of care at treatment hospitals in some cases. In 19 critically ill patients, we identified a pattern of severe respiratory failure requiring ICU admission, mechanical ventilation, and frequent extracorporeal membrane oxygenation use. We describe the first three-part clinical diagnosis and evaluation strategy: 1) Clinical definition: Unexplained severe respiratory failure in a patient receiving greater than or equal to 6 days of TMP-SMX at treatment dose (not prophylaxis). TMP-SMX ARDS is a diagnosis of exclusion. 2) Genetic association: One hundred percent of currently available TMP-SMX respiratory failure patient genomic data, ( n = 11) have been carriers of both HLA-B07:02 and HLA-C07:02 alleles. HLA allele evaluation could be considered in patients with suspected TMP-SMX respiratory failure. 3) Lung pathology: A unique pulmonary pathologic pattern of lung injury termed diffuse alveolar injury with delayed epithelialization has been observed in these cases. In suspected cases, surgical lung biopsy early in the clinical course could be considered. Conclusions: TMP-SMX is a commonly prescribed antibiotic. However, we find it imperative to share this relatively rare but life-threatening condition with clinicians as the mortality rate approaches 40%.
MeSH term(s)	Child ; Humans ; Trimethoprim, Sulfamethoxazole Drug Combination/adverse effects ; Retrospective Studies ; Anti-Bacterial Agents/adverse effects ; Respiratory Distress Syndrome/drug therapy ; Respiratory Insufficiency/chemically induced ; Respiratory Insufficiency/drug therapy
Chemical Substances	Trimethoprim, Sulfamethoxazole Drug Combination (8064-90-2) ; Anti-Bacterial Agents
Language	English
Publishing date	2023-07-14
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	197890-1
ISSN	1530-0293 ; 0090-3493
ISSN (online)	1530-0293
ISSN	0090-3493
DOI	10.1097/CCM.0000000000006002
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Zs.A 1261: Show issues

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Article ; Online: Updates on spread through air spaces (STAS) in lung cancer.

Shih, Angela R / Mino-Kenudson, Mari

Histopathology

2020 Volume 77, Issue 2, Page(s) 173–180

Abstract: Air space invasion of tumours, particularly spread through air spaces (STAS), is a relatively recent concept that has been identified as a novel mechanism of invasion. It has predominantly been described in lung adenocarcinoma, although it may be seen in ...

Abstract	Air space invasion of tumours, particularly spread through air spaces (STAS), is a relatively recent concept that has been identified as a novel mechanism of invasion. It has predominantly been described in lung adenocarcinoma, although it may be seen in other primary lung malignancies as well. STAS in lung cancer has been reported to have numerous associations with poor survival. The objective of this article was to review the concept of air space invasion, update findings regarding its clinical impact, and discuss controversies in the field. With this aim, we performed a PubMed search of the English-language literature. STAS has been introduced as a novel mechanism of invasion that is important for pathologists to recognise. There is a compelling body of evidence associating the presence of STAS with lower survival and suggesting that STAS is an independent prognostic factor, regardless of the stage of tumour. The standard of care for lung adenocarcinomas with STAS irrespective of size of tumour and nodal metastasis may be lobectomy rather than sublobar resection, owing to the risk of locoregional recurrence. Emerging data suggest that more work should be performed to improve consensus on and identification of STAS, including at frozen section.
MeSH term(s)	Adenocarcinoma of Lung/pathology ; Adenocarcinoma of Lung/surgery ; Humans ; Lung Neoplasms/pathology ; Lung Neoplasms/surgery ; Neoplasm Invasiveness/pathology ; Neoplasm Metastasis/pathology ; Neoplasm Recurrence, Local/pathology ; Neoplasm Staging ; Prognosis ; Retrospective Studies
Language	English
Publishing date	2020-07-01
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	131914-0
ISSN	1365-2559 ; 0309-0167
ISSN (online)	1365-2559
ISSN	0309-0167
DOI	10.1111/his.14062
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Zs.A 1328: Show issues

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