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Article ; Online: Novel Noninvasive Biomarkers in Liver Transplantation: A Tool on the Doorstep of Clinical Utilization.

Merola, Jonathan / Emond, Jean C / Levitsky, Josh

2023 Volume 107, Issue 10, Page(s) 2120–2125

Abstract: Biomarkers have the potential to transform the detection, treatment, and outcomes of liver transplant complications, though their application is limited because of the lack of prospective validation. Although many genetic, proteomic, and immune markers ... ...

Abstract	Biomarkers have the potential to transform the detection, treatment, and outcomes of liver transplant complications, though their application is limited because of the lack of prospective validation. Although many genetic, proteomic, and immune markers correlating with allograft rejection and graft dysfunction have been described, evaluation of these markers in combination and validation among a broad liver transplant recipient population remain understudied. In this review, we present evidence supporting biomarker applications in 5 clinical liver transplant scenarios: (i) diagnosis of allograft rejection, (ii) prediction of allograft rejection, (iii) minimization of immunosuppression, (iv) detection of fibrosis and recurrent disease, and (v) prediction of renal recovery following liver transplantation. Current limitations for biomarker utilization and opportunities for further investigation are discussed. Accurate risk assessment, diagnosis, and evaluation of treatment responses using such noninvasive tools will pave the way for a more personalized and precise approach to management of the liver transplant patients that has profound potential to reduce morbidity and improve graft and patient longevity.
MeSH term(s)	Humans ; Liver Transplantation/adverse effects ; Proteomics ; Graft Rejection/diagnosis ; Graft Rejection/prevention & control ; Graft Rejection/genetics ; Transplantation, Homologous ; Biomarkers
Chemical Substances	Biomarkers
Language	English
Publishing date	2023-04-05
Publishing country	United States
Document type	Review ; Journal Article
ZDB-ID	208424-7
ISSN	1534-6080 ; 0041-1337
ISSN (online)	1534-6080
ISSN	0041-1337
DOI	10.1097/TP.0000000000004580
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Article ; Online: Invited Commentary.

Merola, Jonathan / Yoo, Peter S

Journal of the American College of Surgeons

2020 Volume 230, Issue 6, Page(s) 861–862

MeSH term(s)	Hepatitis C ; Humans ; Kidney Transplantation
Language	English
Publishing date	2020-05-22
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	1181115-8
ISSN	1879-1190 ; 1072-7515
ISSN (online)	1879-1190
ISSN	1072-7515
DOI	10.1016/j.jamcollsurg.2020.02.039
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Article ; Online: Update on immunosuppressive strategies in intestinal transplantation.

Merola, Jonathan / Shamim, Abrar / Weiner, Joshua

Current opinion in organ transplantation

2022 Volume 27, Issue 2, Page(s) 119–125

Abstract: Purpose of review: The intestine is the most immunologically complex solid organ allograft with the greatest risk of both rejection and graft-versus-host disease (GVHD). High levels of immunosuppression are required, further increasing morbidity. Due to ...

Abstract	Purpose of review: The intestine is the most immunologically complex solid organ allograft with the greatest risk of both rejection and graft-versus-host disease (GVHD). High levels of immunosuppression are required, further increasing morbidity. Due to low volume of transplants and few centers with experience, there is paucity of evidence-based, standardized, and effective therapeutic regimens. We herein review the most recent data about immunosuppression, focusing on novel and emerging therapies. Recent findings: Recent data are moving the field toward increasing use of basilixumab and consideration of alemtuzumab for induction and inclusion of mammalian target of rapamycin inhibitors and antimetabolites for maintenance. For rejection, we highlight novel roles for tumor necrosis factor-α inhibition, α4β7 integrin inhibition, microbiome modulation, desensitization protocols, and tolerance induction strategies. We also highlight emerging novel therapies for GVHD, especially the promising role of Janus kinase inhibition. Summary: New insights into immune pathways associated with rejection and GVHD in intestinal allografts have led to an evolution of therapies from broad-based immunosuppression to more targeted strategies that hold promise for reducing morbidity from infection, rejection, and GVHD. These should be the focus of further study to facilitate their widespread use.
MeSH term(s)	Graft Rejection/prevention & control ; Graft vs Host Disease/prevention & control ; Humans ; Immunosuppression Therapy ; Immunosuppressive Agents/adverse effects ; Intestines/transplantation ; Transplantation, Homologous
Chemical Substances	Immunosuppressive Agents
Language	English
Publishing date	2022-02-25
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1390429-2
ISSN	1531-7013 ; 1087-2418
ISSN (online)	1531-7013
ISSN	1087-2418
DOI	10.1097/MOT.0000000000000958
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Article ; Online: Venous Thromboembolism in Patients With Bullous Pemphigoid.

Schneeweiss, Maria C / Merola, Joseph F / Wyss, Richard / Silverberg, Jonathan I / Mostaghimi, Arash

JAMA dermatology

2023 Volume 159, Issue 7, Page(s) 750–756

Abstract: Importance: Studies have linked bullous pemphigoid (BP) with venous thromboembolism (VTE) across several data sources finding 6-fold to 15-fold increased incidence rates.: Objective: To determine the incidence of VTE in patients with BP compared with ...

Abstract	Importance: Studies have linked bullous pemphigoid (BP) with venous thromboembolism (VTE) across several data sources finding 6-fold to 15-fold increased incidence rates. Objective: To determine the incidence of VTE in patients with BP compared with similar controls. Design, setting, and participants: This cohort study used insurance claims data from a nationwide US health care database from January 1, 2004, through January 1, 2020. Patients with dermatologist-recorded BP were identified (≥2 diagnoses of BP [International Classification of Diseases, Ninth Revision (ICD-9) 694.5 and ICD-10 L12.0] recorded by dermatologists within 1 year). Risk-set sampling identified comparator patients without BP and free of other chronic inflammatory skin diseases. Patients were followed-up until the first of the following events occurred: VTE, death, disenrollment, or end of data stream. Exposures: Patients with BP compared with those without BP and free of other chronic inflammatory skin diseases (CISD). Main outcome: Venous thromboembolism events were identified and incidence rates were computed before and after propensity-score (PS) matching to account for VTE risk factors. Hazard ratios (HRs) compared the incidence of VTE in BP vs non-CISD. Results: Overall, 2654 patients with BP and 26 814 comparator patients without BP or another CISD were identified. The mean (SD) age in the BP group was 73.0 (12.6) years and 55.0 (18.9) years in the non-CSID group. With a median follow-up time was 2 years, the unadjusted incidence rate (per 1000 person-years) of outpatient or inpatient VTE was 8.5 in the BP group compared with 1.8 in patients without a CISD. Adjusted rates were 6.7 in the BP group compared with 3.0 in the non-CISD group. Age-specific adjusted incidence rates (per 1000 person-years) in patients aged 50 to 74 years was 6.0 (vs 2.9 in the non-CISD group) and in those aged 75 years or older was 7.1 (vs 4.53 in the non-CISD group). After 1:1 propensity-score matching including 60 VTE risk factors and severity markers, BP was associated with a 2-fold increased risk of VTE (2.24 [1.26-3.98]) vs those in the non-CISD group. When restricting to patients aged 50 years or older, the adjusted relative risk of VTE was 1.82 (1.05-3.16) for the BP vs non-CISD groups. Conclusions: In this nationwide US cohort study, BP was associated with a 2-fold increased incidence of VTE after controlling for VTE risk factors in a dermatology patient population.
MeSH term(s)	Humans ; Venous Thromboembolism/etiology ; Venous Thromboembolism/complications ; Cohort Studies ; Pemphigoid, Bullous/epidemiology ; Pemphigoid, Bullous/complications ; Risk Factors ; Incidence
Language	English
Publishing date	2023-06-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2701761-8
ISSN	2168-6084 ; 2168-6068
ISSN (online)	2168-6084
ISSN	2168-6068
DOI	10.1001/jamadermatol.2023.1461
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Article ; Online: The Impact of COVID-19 on Organ Donation, Procurement, and Liver Transplantation in the United States.

Merola, Jonathan / Schilsky, Michael L / Mulligan, David C

Hepatology communications

2020 Volume 5, Issue 1, Page(s) 5–11

Abstract: The coronavirus disease 2019 pandemic has had an impact on all facets of our health care system, including life-saving procedures like organ transplantation. Concerns for potential exposure to the causative severe acute respiratory syndrome coronavirus ... ...

Abstract	The coronavirus disease 2019 pandemic has had an impact on all facets of our health care system, including life-saving procedures like organ transplantation. Concerns for potential exposure to the causative severe acute respiratory syndrome coronavirus type 2 have profoundly altered the process of organ donation and recovery that is vital to the execution of organ transplantation. Issues regarding adequate donor evaluation and consent, organ recovery, organ procurement organization, and donor hospital resources as well as the transplant center's acceptance of organ offers for their candidates have all required new practice paradigms. Consequently, the ability to treat patients with organ failure, in particular patients with end-stage liver disease in whom no temporizing treatments exist, and to obtain expected excellent outcomes for new liver transplant recipients has been challenged during this time.
Keywords	covid19
Language	English
Publishing date	2020-10-18
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2471-254X
ISSN (online)	2471-254X
DOI	10.1002/hep4.1620
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Article ; Online: The Impact of COVID‐19 on Organ Donation, Procurement and Liver Transplantation in the United States

Merola, Jonathan / Schilsky, Michael L. / Mulligan, David C.

Hepatology Communications ; ISSN 2471-254X 2471-254X

2020

Keywords	covid19
Language	English
Publisher	Wiley
Publishing country	us
Document type	Article ; Online
DOI	10.1002/hep4.1620
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Article: Changes in united network for organ sharing policy for simultaneous liver-kidney allocation.

Merola, Jonathan / Formica, Richard N / Mulligan, David C

Clinical liver disease

2017 Volume 9, Issue 1, Page(s) 21–24

Language	English
Publishing date	2017-02-03
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2657644-2
ISSN	2046-2484
ISSN	2046-2484
DOI	10.1002/cld.609
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Article: 3D bioprinting of an implantable xeno-free vascularized human skin graft.

Baltazar, Tania / Jiang, Bo / Moncayo, Alejandra / Merola, Jonathan / Albanna, Mohammad Z / Saltzman, W Mark / Pober, Jordan S

Bioengineering & translational medicine

2022 Volume 8, Issue 1, Page(s) e10324

Abstract: Bioengineered tissues or organs produced using matrix proteins or components derived from xenogeneic sources pose risks of allergic responses, immune rejection, or even autoimmunity. Here, we report successful xeno-free isolation, expansion, and ... ...

Abstract	Bioengineered tissues or organs produced using matrix proteins or components derived from xenogeneic sources pose risks of allergic responses, immune rejection, or even autoimmunity. Here, we report successful xeno-free isolation, expansion, and cryopreservation of human endothelial cells (EC), fibroblasts (FBs), pericytes (PCs), and keratinocytes (KCs). We further demonstrate the bioprinting of a human skin substitute with a dermal layer containing xeno-free cultured human EC, FBs, and PCs in a xeno-free bioink containing human collagen type I and fibronectin layered in a biocompatible polyglycolic acid mesh and subsequently seeded with xeno-free human KCs to form an epidermal layer. Following implantation of such bilayered skin grafts on the dorsum of immunodeficient mice, KCs form a mature stratified epidermis with rete ridge-like structures. The ECs and PCs form human EC-lined perfused microvessels within 2 weeks after implantation, preventing graft necrosis, and eliciting further perfusion of the graft by angiogenic host microvessels. As proof-of-concept, we generated 12 individual grafts using a single donor of all four cell types. In summary, we describe the fabrication of a bioprinted vascularized bilayered skin substitute under completely xeno-free culture conditions demonstrating feasibility of a xeno-free approach to complex tissue engineering.
Language	English
Publishing date	2022-04-21
Publishing country	United States
Document type	Journal Article
ISSN	2380-6761
ISSN	2380-6761
DOI	10.1002/btm2.10324
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Article ; Online: Incidence of Bacterial and Nonbacterial Conjunctivitis in Patients With Atopic Dermatitis Treated With Dupilumab: A US Multidatabase Cohort Study.

Schneeweiss, Maria C / Wyss, Richard / Chin, Kristyn / Merola, Joseph F / Silverberg, Jonathan I / Mostaghimi, Arash / Schneeweiss, Sebastian

Dermatitis : contact, atopic, occupational, drug

2022 Volume 33, Issue 6S, Page(s) S73–S82

Abstract: Background: Dupilumab-associated conjunctivitis in patients with atopic dermatitis (AD) is not fully characterized.: Objective: The aim of the study was to characterize the incidence of bacterial and nonbacterial conjunctivitis among patients with AD ...

Abstract	Background: Dupilumab-associated conjunctivitis in patients with atopic dermatitis (AD) is not fully characterized. Objective: The aim of the study was to characterize the incidence of bacterial and nonbacterial conjunctivitis among patients with AD who initiated dupilumab. Methods: Pooling longitudinal claims data from 2 US databases, we identified AD patients who newly filled either dupilumab or methotrexate, mycophenolate or cyclosporine, between March 2017 and January 2020. Outcomes were conjunctivitis and its subtypes, bacterial, allergic, and keratoconjunctivitis. Patient follow-up lasted 6 months and 1:1 propensity score (PS) matching-controlled confounding. Results: Within 6 months of treatment initiation, the incidence of conjunctivitis was 6.6% in 3744 dupilumab initiators; bacterial conjunctivitis, 1.5%; allergic conjunctivitis, 2.2%; keratoconjunctivitis, 0.8%; and conjunctivitis requiring ophthalmic medication, 2.7%. After PS matching, dupilumab doubled the risk of conjunctivitis compared with methotrexate (relative risk [RR] 2.12; 1.56-2.91), mycophenolate (RR = 2.43; 1.32-4.47), or cyclosporine (RR = 1.83; 1.05-3.20). Risk of bacterial conjunctivitis was 1.6- to 4.0-fold increased with wide confidence intervals, and allergic conjunctivitis was increased 2.7- to 7-fold. There was no increased risk of keratoconjunctivitis. Patients with comorbid asthma had a further increased risk of conjunctivitis. Conclusions: One in 15 patients treated with dupilumab developed conjunctivitis driven by bacterial and allergic conjunctivitis and not keratoconjunctivitis. This risk was further increased with comorbid asthma.
MeSH term(s)	Humans ; Dermatitis, Atopic/drug therapy ; Dermatitis, Atopic/epidemiology ; Dermatitis, Atopic/complications ; Cohort Studies ; Incidence ; Conjunctivitis, Allergic/drug therapy ; Conjunctivitis, Allergic/epidemiology ; Conjunctivitis, Allergic/complications ; Methotrexate/adverse effects ; Conjunctivitis/chemically induced ; Conjunctivitis/epidemiology ; Asthma/complications ; Immunosuppressive Agents/therapeutic use ; Cyclosporine/adverse effects ; Conjunctivitis, Bacterial/complications
Chemical Substances	dupilumab (420K487FSG) ; Methotrexate (YL5FZ2Y5U1) ; Immunosuppressive Agents ; Cyclosporine (83HN0GTJ6D)
Language	English
Publishing date	2022-03-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	2144723-8
ISSN	2162-5220 ; 1532-8163 ; 1710-3568
ISSN (online)	2162-5220 ; 1532-8163
ISSN	1710-3568
DOI	10.1097/DER.0000000000000843
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Article: The Impact of COVID-19 on Organ Donation, Procurement and Liver Transplantation in the United States

Merola, Jonathan / Schilsky, Michael L / Mulligan, David C

Abstract: The Coronavirus Disease 2019 (COVID-19) pandemic has had an impact on all facets of our health care system, including life-saving procedures like organ transplantation. Concerns for potential exposure to the causative severe acute respiratory syndrome ... ...

Abstract	The Coronavirus Disease 2019 (COVID-19) pandemic has had an impact on all facets of our health care system, including life-saving procedures like organ transplantation. Concerns for potential exposure to the causative severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) have profoundly altered the process of organ donation and recovery that is vital to the execution of organ transplantation. Issues regarding adequate donor evaluation and consent, organ recovery, organ procurement organization (OPO) and donor hospital resources as well as the transplant center's acceptance of organ offers for their candidates have all required new practice paradigms. Consequently, the ability to treat patients with organ failure, in particular patients with end stage liver disease where no temporizing treatments exist, and to obtain expected excellent outcomes for new liver transplant recipients has been challenged during this time. We summarize some of the negative effects of the current pandemic on organ recovery and liver transplantation as well as offer considerations and strategies for their mitigation that could have a lasting impact on the field even after COVID-19 has waned.
Keywords	covid19
Publisher	WHO
Document type	Article
Note	WHO #Covidence: #802274
Database	COVID19

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