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Article ; Online: Validation of the Integrity of the OPTN/UNOS Transplantation Registry Data.

Malamon, John Stephen / Kaplan, Bruce

2023 Volume 107, Issue 12, Page(s) e324–e325

MeSH term(s)	Humans ; United States ; Routinely Collected Health Data ; Kidney Transplantation ; Living Donors ; Tissue and Organ Procurement ; Registries
Language	English
Publishing date	2023-09-20
Publishing country	United States
Document type	Journal Article
ZDB-ID	208424-7
ISSN	1534-6080 ; 0041-1337
ISSN (online)	1534-6080
ISSN	0041-1337
DOI	10.1097/TP.0000000000004793
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Article ; Online: Living-Donor Liver Transplant for Patients With End-stage Liver Disease-Reply.

Jackson, Whitney E / Malamon, John S

JAMA surgery

2023 Volume 158, Issue 4, Page(s) 428–429

MeSH term(s)	Humans ; Liver Transplantation ; End Stage Liver Disease/complications ; End Stage Liver Disease/surgery ; Living Donors ; Treatment Outcome ; Retrospective Studies
Language	English
Publishing date	2023-05-03
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	2701841-6
ISSN	2168-6262 ; 2168-6254
ISSN (online)	2168-6262
ISSN	2168-6254
DOI	10.1001/jamasurg.2022.7003
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Article ; Online: AI-enhanced Information Navigation: Insights From Information Theory in Transplantation Data.

Goncalves, Carlos / Bhagwandin, Bryon / Malamon, John / Kaplan, Bruce

Transplantation

2024

Language	English
Publishing date	2024-03-12
Publishing country	United States
Document type	Journal Article
ZDB-ID	208424-7
ISSN	1534-6080 ; 0041-1337
ISSN (online)	1534-6080
ISSN	0041-1337
DOI	10.1097/TP.0000000000004990
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Article ; Online: Patient years lost due to cytomegalovirus serostatus mismatching in the scientific registry of transplant recipients.

Abidi, Maheen Z / Schold, Jesse D / Kaplan, Bruce / Weinberg, Adriana / Erlandson, Kristine M / Malamon, John S

Frontiers in immunology

2024 Volume 14, Page(s) 1292648

Abstract: Background: The cytomegalovirus (CMV) mismatch rate in deceased donor kidney transplant (DDKT) recipients in the US remains above 40%. Since CMV mismatching is common in DDKT recipients, the cumulative effects may be significant in the context of ... ...

Abstract	Background: The cytomegalovirus (CMV) mismatch rate in deceased donor kidney transplant (DDKT) recipients in the US remains above 40%. Since CMV mismatching is common in DDKT recipients, the cumulative effects may be significant in the context of overall patient and graft survival. Our primary objective was to describe the short- and long-term risks associated with high-risk CMV donor positive/recipient negative (D+/R-) mismatching among DDKT recipients with the explicit goal of deriving a mathematical mismatching penalty. Methods: We conducted a retrospective, secondary analysis of the Scientific Registry of Transplant Recipients (SRTR) database using donor-matched DDKT recipient pairs (N=105,608) transplanted between 2011-2022. All-cause mortality and graft failure hazard ratios were calculated from one year to ten years post-DDKT. All-cause graft failure included death events. Survival curves were calculated using the Kaplan-Meier estimation at 10 years post-DDKT and extrapolated to 20 years to provide the average graft days lost (aGDL) and average patient days lost (aPDL) due to CMV D+/R- serostatus mismatching. We also performed an age-based stratification analysis to compare the relative risk of CMV D+ mismatching by age. Results: Among 31,518 CMV D+/R- recipients, at 1 year post-DDKT, the relative risk of death increased by 29% (p<0.001), and graft failure increased by 17% (p<0.001) as compared to matched CMV D+/R+ group (N=31,518). Age stratification demonstrated a significant increase in the risk associated with CMV mismatching in patients 40 years of age and greater. The aGDL per patient due to mismatching was 125 days and the aPDL per patient was 100 days. Conclusion: The risks of CMV D+/R- mismatching are seen both at 1 year post-DDKT period and accumulated throughout the lifespan of the patient, with the average CMV D+/R- recipient losing more than three months of post-DDKT survival time. CMV D+/R- mismatching poses a more significant risk and a greater health burden than previously reported, thus obviating the need for better preventive strategies including CMV serodirected organ allocation to prolong lifespans and graft survival in high-risk patients.
MeSH term(s)	Humans ; Adult ; Transplant Recipients ; Cytomegalovirus ; Retrospective Studies ; Registries ; Cytomegalovirus Infections
Language	English
Publishing date	2024-01-09
Publishing country	Switzerland
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2023.1292648
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Erosion of Gene Co-expression Networks Reveal Deregulation of Immune System Processes in Late-Onset Alzheimer's Disease.

Malamon, John Stephen / Kriete, Andres

Frontiers in neuroscience

2020 Volume 14, Page(s) 228

Abstract: We have applied a novel and integrative analysis framework for next-generation sequencing (NGS) data to 503 human subjects provided by the Religious Orders Study and Memory and Aging Project (ROSMAP) to examine changes in transcriptomic organization and ... ...

Abstract	We have applied a novel and integrative analysis framework for next-generation sequencing (NGS) data to 503 human subjects provided by the Religious Orders Study and Memory and Aging Project (ROSMAP) to examine changes in transcriptomic organization and common variants in association with late-onset Alzheimer's disease (LOAD). Our framework identified seven reproducible, co-regulated modules after quality control (QC), clinical segregation, preservation filtering, and functional ontology analysis. These modules were specifically enriched in several innate and adaptive immune system processes, the synaptic vesicle cycle, and Hippo signaling. Topological and functional erosion of these modules due to shedding of genes and loss of in-module connectivity was diagnostic of disease progression. Perturbation analysis revealed that only 1% of eQTLs overlapped genes participating in these co-regulated modules. Common variants nevertheless identified components of the immune systems like human leukocyte antigen (HLA) complex and microtubule-associated protein tau (MAPT) regions in association with LOAD. Our results implicate microglial function, adaptive immune response, and the structural degeneration of neurons as contributors to the transcriptional deregulation observed along with common genetic variants in the progression of LOAD.
Language	English
Publishing date	2020-03-20
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2411902-7
ISSN	1662-453X ; 1662-4548
ISSN (online)	1662-453X
ISSN	1662-4548
DOI	10.3389/fnins.2020.00228
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Article ; Online: Preliminary safety and efficacy of laser stricturotomy for treatment of refractory biliary anastomotic strictures following liver transplantation.

Trivedi, Premal / Saben, Jessica L / Liu, Lisa / Malamon, John S / Pomfret, Elizabeth / Pshak, Thomas

American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons

2023 Volume 23, Issue 4, Page(s) 573–576

Abstract: Biliary anastomotic stricture (BAS) is a frequent complication of liver transplantation and is associated with reduced graft survival and patient morbidity. Existing treatments for BAS involve dilation of the stricture though placement of 1 or more ... ...

Abstract	Biliary anastomotic stricture (BAS) is a frequent complication of liver transplantation and is associated with reduced graft survival and patient morbidity. Existing treatments for BAS involve dilation of the stricture though placement of 1 or more catheters for 6 to 24 months yielding limited effectiveness in transplant patients. In this case series, we present preliminary safety and efficacy of a novel percutaneous laser stricturotomy treatment in a cohort of 5 posttransplant patients with BAS refractory to long-term large bore catheterization. In all patients, holmium or thulium laser was used to excise the stricture and promote biliary re-epithelization. There were no periprocedural complications. Technical success was 100% and at mean follow-up time of 22 months, there have been no recurrences. In conclusion, percutaneous laser stricturotomy demonstrates preliminary safety and efficacy in treatment of refractory BAS following liver transplantation.
MeSH term(s)	Humans ; Liver Transplantation/adverse effects ; Cholestasis/etiology ; Cholestasis/surgery ; Constriction, Pathologic/etiology ; Constriction, Pathologic/surgery ; Treatment Outcome ; Catheterization/adverse effects ; Retrospective Studies
Language	English
Publishing date	2023-01-04
Publishing country	United States
Document type	Case Reports
ZDB-ID	2060594-8
ISSN	1600-6143 ; 1600-6135
ISSN (online)	1600-6143
ISSN	1600-6135
DOI	10.1016/j.ajt.2022.12.020
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Article: Integrated Systems Approach Reveals Sphingolipid Metabolism Pathway Dysregulation in Association with Late-Onset Alzheimer's Disease.

Malamon, John Stephen / Kriete, Andres

Biology

2018 Volume 7, Issue 1

Abstract: Late-onset Alzheimer's disease (LOAD) and age are significantly correlated such that one-third of Americans beyond 85 years of age are afflicted. We have designed and implemented a pilot study that combines systems biology approaches with traditional ... ...

Abstract	Late-onset Alzheimer's disease (LOAD) and age are significantly correlated such that one-third of Americans beyond 85 years of age are afflicted. We have designed and implemented a pilot study that combines systems biology approaches with traditional next-generation sequencing (NGS) analysis techniques to identify relevant regulatory pathways, infer functional relationships and confirm the dysregulation of these biological pathways in LOAD. Our study design is a most comprehensive systems approach combining co-expression network modeling derived from RNA-seq data, rigorous quality control (QC) standards, functional ontology, and expression quantitative trait loci (eQTL) derived from whole exome (WES) single nucleotide variant (SNV) genotype data. Our initial results reveal several statistically significant, biologically relevant genes involved in sphingolipid metabolism. To validate these findings, we performed a gene set enrichment analysis (GSEA). The GSEA revealed the sphingolipid metabolism pathway and regulation of autophagy in association with LOAD cases. In the execution of this study, we have successfully tested an integrative approach to identify both novel and known LOAD drivers in order to develop a broader and more detailed picture of the highly complex transcriptional and regulatory landscape of age-related dementia.
Language	English
Publishing date	2018-02-09
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2661517-4
ISSN	2079-7737
ISSN	2079-7737
DOI	10.3390/biology7010016
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Article: Integrated Systems Approach Reveals Sphingolipid Metabolism Pathway Dysregulation in Association with Late-Onset Alzheimer’s Disease

Malamon, John Stephen / Kriete, Andres

Biology. 2018 Feb. 09, v. 7, no. 1

2018

Abstract: Late-onset Alzheimer’s disease (LOAD) and age are significantly correlated such that one-third of Americans beyond 85 years of age are afflicted. We have designed and implemented a pilot study that combines systems biology approaches with traditional ... ...

Abstract	Late-onset Alzheimer’s disease (LOAD) and age are significantly correlated such that one-third of Americans beyond 85 years of age are afflicted. We have designed and implemented a pilot study that combines systems biology approaches with traditional next-generation sequencing (NGS) analysis techniques to identify relevant regulatory pathways, infer functional relationships and confirm the dysregulation of these biological pathways in LOAD. Our study design is a most comprehensive systems approach combining co-expression network modeling derived from RNA-seq data, rigorous quality control (QC) standards, functional ontology, and expression quantitative trait loci (eQTL) derived from whole exome (WES) single nucleotide variant (SNV) genotype data. Our initial results reveal several statistically significant, biologically relevant genes involved in sphingolipid metabolism. To validate these findings, we performed a gene set enrichment analysis (GSEA). The GSEA revealed the sphingolipid metabolism pathway and regulation of autophagy in association with LOAD cases. In the execution of this study, we have successfully tested an integrative approach to identify both novel and known LOAD drivers in order to develop a broader and more detailed picture of the highly complex transcriptional and regulatory landscape of age-related dementia.
Keywords	Alzheimer disease ; Americans ; autophagy ; experimental design ; genes ; genotype ; high-throughput nucleotide sequencing ; lipid metabolism ; quality control ; quantitative trait loci ; sphingolipids ; systems biology ; transcription (genetics)
Language	English
Dates of publication	2018-0209
Publishing place	Multidisciplinary Digital Publishing Institute
Document type	Article
ZDB-ID	2661517-4
ISSN	2079-7737
ISSN	2079-7737
DOI	10.3390/biology7010016
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Reassessing the survival benefit of deceased donor liver transplantation: retrospective cohort study.

Malamon, John S / Kaplan, Bruce / Jackson, Whitney E / Saben, Jessica L / Schold, Jesse D / Pomfret, Elizabeth A / Pomposelli, James J

International journal of surgery (London, England)

2023 Volume 109, Issue 9, Page(s) 2714–2720

Abstract: Introduction: Currently in the United States, deceased donor liver transplant (DDLT) allocation priority is based on the model for end-stage liver disease including sodium (MELD-Na) score. The United Network for organ sharing's 'Share-15' policy states ... ...

Abstract	Introduction: Currently in the United States, deceased donor liver transplant (DDLT) allocation priority is based on the model for end-stage liver disease including sodium (MELD-Na) score. The United Network for organ sharing's 'Share-15' policy states that candidates with MELD-Na scores of 15 or greater have priority to receive local organ offers compared to candidates with lower MELD-Na scores. Since the inception of this policy, major changes in the primary etiologies of end-stage liver disease have occurred and previous assumptions need to be recalibrated. Methods: The authors retrospectively analyzed the Scientific Registry of Transplant Recipients database between 2012 and 2021 to determine life years saved by DDLT at each interval of MELD-Na score and the time-to-equal risk and time-to-equal survival versus remaining on the waitlist. The authors stratified our analysis by MELD exception points, primary disease etiology, and MELD score. Results: On aggregate, compared to remaining on the waitlist, a significant 1-year survival advantage of DDLT at MELD-Na scores as low as 12 was found. The median life years saved at this score after a liver transplant was estimated to be greater than 9 years. While the total life years saved were comparable across all MELD-Na scores, the time-to-equal risk and time-to-equal survival decreased exponentially as MELD-Na scores increased. Conclusion: Herein, the authors challenge the perception as to the timing of DDLT and when that benefit occurs. The national liver allocation policy is transitioning to a continuous distribution framework and these data will be instrumental to defining the attributes of the continuos allocation score.
MeSH term(s)	Humans ; United States/epidemiology ; Liver Transplantation/adverse effects ; End Stage Liver Disease/surgery ; Retrospective Studies ; Tissue and Organ Procurement ; Living Donors ; Severity of Illness Index ; Waiting Lists
Language	English
Publishing date	2023-09-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2212038-5
ISSN	1743-9159 ; 1743-9191
ISSN (online)	1743-9159
ISSN	1743-9191
DOI	10.1097/JS9.0000000000000498
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Article ; Online: A model for calculating the long-term estimated post-transplant survival of deceased donor liver transplant patients.

Malamon, John S / Jackson, Whitney E / Saben, Jessica L / Conzen, Kendra / Schold, Jesse D / Pomposelli, James J / Pomfret, Elizabeth A / Kaplan, Bruce

EBioMedicine

2023 Volume 90, Page(s) 104505

Abstract: Background: The estimated long-term survival (EPTS) score is used for kidney allocation. A comparable prognostic tool to accurately quantify EPTS benefit in deceased donor liver transplant (DDLT) candidates is nonexistent.: Methods: Using the ... ...

Abstract	Background: The estimated long-term survival (EPTS) score is used for kidney allocation. A comparable prognostic tool to accurately quantify EPTS benefit in deceased donor liver transplant (DDLT) candidates is nonexistent. Methods: Using the Scientific Registry of Transplant Recipients (SRTR) database, we developed, calibrated, and validated a nonlinear regression equation to calculate liver-EPTS (L-EPTS) for 5- and 10-year outcomes in adult DDLT recipients. The population was randomly split (70:30) into two discovery (N = 26,372 and N = 46,329) and validation cohorts (N = 11,288 and N = 19,859) for 5- and 10-year post-transplant outcomes, respectively. Discovery cohorts were used for variable selection, Cox proportional hazard regression modeling, and nonlinear curve fitting. Eight clinical variables were selected to construct the L-EPTS formula, and a five-tiered ranking system was created. Findings: Tier thresholds were defined and the L-EPTS model was calibrated (R Interpretation: L-EPTS has high applicability and clinical utility because it uses easily obtained pre-transplant patients characteristics to accurately discriminate between those who are likely to receive a prolonged survival benefit and those who are not. It is important to evaluate medical urgency alongside survival benefit and placement efficiency when considering the allocation of a scarce resource. Funding: There are no funding sources related to this project.
MeSH term(s)	Adult ; Humans ; Liver Transplantation/adverse effects ; Kidney Transplantation ; Living Donors ; Prognosis ; Liver ; Retrospective Studies ; Graft Survival ; Transplant Recipients
Language	English
Publishing date	2023-03-02
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2851331-9
ISSN	2352-3964
ISSN (online)	2352-3964
DOI	10.1016/j.ebiom.2023.104505
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