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Article ; Online: Risk factors for renal dysfunction after isolated intestinal transplantation.

von Ahrens, Dagny / Santeusanio, Andrew D / Weinberg, Alan D / Moon, Jang / Iyer, Kishore R

2024 Volume 38, Issue 1, Page(s) e15228

Abstract: Introduction: Kidney dysfunction is a known complication of intestinal transplantation; however, the rate of development and risk factors for chronic kidney disease (CKD) remain poorly defined.: Methods: This was a single-center retrospective review ... ...

Abstract	Introduction: Kidney dysfunction is a known complication of intestinal transplantation; however, the rate of development and risk factors for chronic kidney disease (CKD) remain poorly defined. Methods: This was a single-center retrospective review of isolated adult intestinal allograft recipients from 2011 to 2019. Patients who died or experienced graft loss within 1-year or had a prior transplant were excluded. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-EPI equation at 0-, 6- and 12-months post-transplant, and multivariable linear regression was performed to identify variables associated with adjusted eGFR at 1-year. Independent variables included age, ethnicity, BMI, history of diabetes/hypertension, vasopressor use, TPN and stoma days, urinary or bloodstream infections, intravenous contrast exposure, rejection, concomitant immunosuppression, and time above the therapeutic range of tacrolimus. Variables with a p < .1 in univariate analysis were considered for multivariable modeling. Results: Thirty-three patients were included with a mean age of 43.9 ± 13.0. A mean 42.3% decline in eGFR was observed at 1-year post-transplant, with 15.2% of patients developing new stage 4/5 CKD. Factors associated with a greater decline in adjusted eGFR in the univariate model included increasing age, decreased BMI, stoma days, and vasopressor use. In the adjusted multivariable model patient age (β = -.77, p < .01) and stoma days (β = -.06, p < .01) remained significant. Tacrolimus and sirolimus exposure were not associated with decline in eGFR at 1 year. Conclusions: Renal dysfunction is common following intestinal transplantation. The need for stoma creation should be carefully considered, and reversal should be performed when feasible for renal protection.
MeSH term(s)	Adult ; Humans ; Middle Aged ; Infant ; Tacrolimus/adverse effects ; Immunosuppressive Agents/therapeutic use ; Kidney Transplantation/adverse effects ; Risk Factors ; Glomerular Filtration Rate ; Renal Insufficiency, Chronic/etiology ; Kidney Failure, Chronic/etiology ; Graft Rejection/etiology ; Graft Rejection/prevention & control ; Retrospective Studies
Chemical Substances	Tacrolimus (WM0HAQ4WNM) ; Immunosuppressive Agents
Language	English
Publishing date	2024-01-30
Publishing country	Denmark
Document type	Journal Article
ZDB-ID	639001-8
ISSN	1399-0012 ; 0902-0063
ISSN (online)	1399-0012
ISSN	0902-0063
DOI	10.1111/ctr.15228
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Article ; Online: Pediatric Fungal Ventriculoperitoneal Shunt Infection Due to Paecilomyces.

Li, Adam Y / Stephen, Tyler / Jay, Catherine / D George, Derek / Furst, Taylor / Cameron, Andrew / Weinberg, Geoffrey A / Silberstein, Howard J

The Pediatric infectious disease journal

2023

Language	English
Publishing date	2023-12-27
Publishing country	United States
Document type	Journal Article
ZDB-ID	392481-6
ISSN	1532-0987 ; 0891-3668
ISSN (online)	1532-0987
ISSN	0891-3668
DOI	10.1097/INF.0000000000004161
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Article ; Online: Mortality differences by race over 20 years in individuals with peripheral artery disease.

Dicks, Andrew B / Lakhter, Vladimir / Elgendy, Islam Y / Schainfeld, Robert M / Mohapatra, Abhisekh / Giri, Jay / Weinberg, Mitchell D / Weinberg, Ido / Parmar, Gaurav

Vascular medicine (London, England)

2023 Volume 28, Issue 3, Page(s) 214–221

Abstract: Introduction: Racial disparities exist in patients with peripheral artery disease (PAD), with Black individuals having worse PAD-specific outcomes. However, mortality risk in this population has been mixed. As such, we sought to evaluate all-cause ... ...

Abstract	Introduction: Racial disparities exist in patients with peripheral artery disease (PAD), with Black individuals having worse PAD-specific outcomes. However, mortality risk in this population has been mixed. As such, we sought to evaluate all-cause mortality by race among individuals with PAD. Methods: We analyzed data from the National Health and Nutrition Examination Survey (NHANES). Baseline data were obtained from 1999 to 2004. Patients with PAD were grouped according to self-reported race. Multivariable Cox proportional hazards regression was performed to calculate adjusted hazard ratios (HR) by race. A separate analysis was performed to study the effect of burden of social determinants of health (SDoH) on all-cause mortality. Results: Of 647 individuals identified, 130 were Black and 323 were White. Black individuals had more premature PAD (30% vs 20%, Conclusions: In a nationally representative sample, Black individuals with PAD and CAD had higher rates of mortality compared to their White counterparts. These findings add further proof to the ongoing racial disparities among Black individuals with PAD and highlight the necessity to identify ways to mitigate these differences.
MeSH term(s)	Humans ; Black or African American ; Nutrition Surveys ; Peripheral Arterial Disease/ethnology ; Peripheral Arterial Disease/mortality ; Risk Factors ; White
Language	English
Publishing date	2023-04-03
Publishing country	England
Document type	Journal Article
ZDB-ID	1311628-9
ISSN	1477-0377 ; 1358-863X
ISSN (online)	1477-0377
ISSN	1358-863X
DOI	10.1177/1358863X231159947
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Article: Characterization of hyperpolarization-activated cyclic nucleotide-gated channels in oligodendrocytes.

Lyman, Kyle A / Han, Ye / Robinson, Andrew P / Weinberg, Samuel E / Fisher, Daniel W / Heuermann, Robert J / Lyman, Reagan E / Kim, Dong Kyu / Ludwig, Andreas / Chandel, Navdeep S / Does, Mark D / Miller, Stephen D / Chetkovich, Dane M

Frontiers in cellular neuroscience

2024 Volume 18, Page(s) 1321682

Abstract: Mature oligodendrocytes (OLG) are the myelin-forming cells of the central nervous system. Recent work has shown a dynamic role for these cells in the plasticity of neural circuits, leading to a renewed interest in voltage-sensitive currents in OLG. ... ...

Abstract	Mature oligodendrocytes (OLG) are the myelin-forming cells of the central nervous system. Recent work has shown a dynamic role for these cells in the plasticity of neural circuits, leading to a renewed interest in voltage-sensitive currents in OLG. Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and their respective current (I
Language	English
Publishing date	2024-02-26
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2452963-1
ISSN	1662-5102
ISSN	1662-5102
DOI	10.3389/fncel.2024.1321682
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Article ; Online: Cardiac-Specific Deletion of Scn8a Mitigates Dravet Syndrome-Associated Sudden Death in Adults.

King, D Ryan / Demirtas, Mustafa / Tarasov, Mikhail / Struckman, Heather L / Meng, Xiaolei / Nassal, Drew / Moise, Nicolae / Miller, Alec / Min, Dennison / Soltisz, Andrew M / Anne, Midhun N K / Alves Dias, Patrícia A / Wagnon, Jacy L / Weinberg, Seth H / Hund, Thomas J / Veeraraghavan, Rengasayee / Radwański, Przemysław B

JACC. Clinical electrophysiology

2024

Abstract: Background: Sudden unexpected death in epilepsy (SUDEP) is a fatal complication experienced by otherwise healthy epilepsy patients. Dravet syndrome (DS) is an inherited epileptic disorder resulting from loss of function of the voltage-gated sodium ... ...

Abstract	Background: Sudden unexpected death in epilepsy (SUDEP) is a fatal complication experienced by otherwise healthy epilepsy patients. Dravet syndrome (DS) is an inherited epileptic disorder resulting from loss of function of the voltage-gated sodium channel, Na Objectives: In this study the authors sought to provide evidence implicating remodeling of Na Methods: The authors undertook scanning ion conductance microscopy (SICM)-guided patch clamp, super-resolution microscopy, confocal Ca Results: DS promotes I Conclusions: These data demonstrate that Na
Language	English
Publishing date	2024-02-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	2846739-5
ISSN	2405-5018 ; 2405-500X ; 2405-500X
ISSN (online)	2405-5018 ; 2405-500X
ISSN	2405-500X
DOI	10.1016/j.jacep.2024.01.003
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Article ; Online: Unraveling Impacts of Chamber-Specific Differences in Intercalated Disc Ultrastructure and Molecular Organization on Cardiac Conduction.

Struckman, Heather L / Moise, Nicolae / King, D Ryan / Soltisz, Andrew / Buxton, Andrew / Dunlap, Izabella / Chen, Zhenhui / Radwański, Przemysław B / Weinberg, Seth H / Veeraraghavan, Rengasayee

JACC. Clinical electrophysiology

2023 Volume 9, Issue 12, Page(s) 2425–2443

Abstract: Background: Propagation of action potentials through the heart coordinates the heartbeat. Thus, intercalated discs, specialized cell-cell contact sites that provide electrical and mechanical coupling between cardiomyocytes, are an important target for ... ...

Abstract	Background: Propagation of action potentials through the heart coordinates the heartbeat. Thus, intercalated discs, specialized cell-cell contact sites that provide electrical and mechanical coupling between cardiomyocytes, are an important target for study. Impaired propagation leads to arrhythmias in many pathologies, where intercalated disc remodeling is a common finding, hence the importance and urgency of understanding propagation dependence on intercalated disc structure. Conventional modeling approaches cannot predict changes in propagation elicited by perturbations that alter intercalated disc ultrastructure or molecular organization, because of lack of quantitative structural data at subcellular through nano scales. Objectives: This study sought to quantify intercalated disc structure at these spatial scales in the healthy adult mouse heart and relate them to chamber-specific properties of propagation as a precursor to understanding the effects of pathological intercalated disc remodeling. Methods: Using super-resolution light microscopy, electron microscopy, and computational image analysis, we provide here the first ever systematic, multiscale quantification of intercalated disc ultrastructure and molecular organization. Results: By incorporating these data into a rule-based model of cardiac tissue with realistic intercalated disc structure, and comparing model predictions of electrical propagation with experimental measures of conduction velocity, we reveal that atrial intercalated discs can support faster conduction than their ventricular counterparts, which is normally masked by interchamber differences in myocyte geometry. Further, we identify key ultrastructural and molecular organization features underpinning the ability of atrial intercalated discs to support faster conduction. Conclusions: These data provide the first stepping stone to elucidating chamber-specific effects of pathological intercalated disc remodeling, as occurs in many arrhythmic diseases.
MeSH term(s)	Mice ; Animals ; Heart Rate ; Myocardium ; Myocytes, Cardiac/physiology ; Arrhythmias, Cardiac
Language	English
Publishing date	2023-07-26
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2846739-5
ISSN	2405-5018 ; 2405-500X ; 2405-500X
ISSN (online)	2405-5018 ; 2405-500X
ISSN	2405-500X
DOI	10.1016/j.jacep.2023.05.042
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Article: Unraveling Chamber-specific Differences in Intercalated Disc Ultrastructure and Molecular Organization and Their Impact on Cardiac Conduction.

Struckman, Heather L / Moise, Nicolae / King, D Ryan / Soltisz, Andrew / Buxton, Andrew / Dunlap, Izabella / Chen, Zhenhui / Radwański, Przemysław B / Weinberg, Seth H / Veeraraghavan, Rengasayee

bioRxiv : the preprint server for biology

2023

Abstract: During each heartbeat, the propagation of action potentials through the heart coordinates the contraction of billions of individual cardiomyocytes and is thus, a critical life process. Unsurprisingly, intercalated discs, which are cell-cell contact sites ...

Abstract	During each heartbeat, the propagation of action potentials through the heart coordinates the contraction of billions of individual cardiomyocytes and is thus, a critical life process. Unsurprisingly, intercalated discs, which are cell-cell contact sites specialized to provide electrical and mechanical coupling between adjacent cardiomyocytes, have been the focus of much investigation. Slowed or disrupted propagation leads to potentially life-threatening arrhythmias in a wide range of pathologies, where intercalated disc remodeling is a common finding. Hence, the importance and urgency of understanding intercalated disc structure and its influence on action potential propagation. Surprisingly, however, conventional modeling approaches cannot predict changes in propagation elicited by perturbations that alter intercalated disc ultrastructure or molecular organization, owing to lack of quantitative structural data at subcellular through nano scales. In order to address this critical gap in knowledge, we sought to quantify intercalated disc structure at these finer spatial scales in the healthy adult mouse heart and relate them to function in a chamber-specific manner as a precursor to understanding the impacts of pathological intercalated disc remodeling. Using super-resolution light microscopy, electron microscopy, and computational image analysis, we provide here the first ever systematic, multiscale quantification of intercalated disc ultrastructure and molecular organization. By incorporating these data into a rule-based model of cardiac tissue with realistic intercalated disc structure, and comparing model predictions of electrical propagation with experimental measures of conduction velocity, we reveal that atrial intercalated discs can support faster conduction than their ventricular counterparts, which is normally masked by inter-chamber differences in myocyte geometry. Further, we identify key ultrastructural and molecular organization features underpinning the ability of atrial intercalated discs to support faster conduction. These data provide the first stepping stone to elucidating chamber-specific impacts of pathological intercalated disc remodeling, as occurs in many arrhythmic diseases.
Language	English
Publishing date	2023-03-24
Publishing country	United States
Document type	Preprint
DOI	10.1101/2023.02.13.528369
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Article ; Online: Tacrolimus time-in-therapeutic range is associated with freedom from acute rejection and graft failure following intestinal transplantation.

Santeusanio, Andrew D / Gu, Alan / Weinberg, Alan D / Moon, Jang / Iyer, Kishore R

Clinical transplantation

2021 Volume 35, Issue 6, Page(s) e14291

Abstract: Background: Trough-adjusted tacrolimus is commonly prescribed following intestinal transplantation to prevent allograft rejection. Despite established practice, there remains limited direct evidence linking tacrolimus levels with improved clinical ... ...

Abstract	Background: Trough-adjusted tacrolimus is commonly prescribed following intestinal transplantation to prevent allograft rejection. Despite established practice, there remains limited direct evidence linking tacrolimus levels with improved clinical outcomes. Methods: This was a single-center review of all adult non-liver containing intestinal allograft recipients from 2011 to 2018. Patients received lymphocyte depleting induction and maintenance immunosuppression consisting of tacrolimus and a corticosteroid taper. Tacrolimus time-in-therapeutic range (TAC-TTR) was calculated for all patients from the date of transplant until 1-year post-transplant using Rosendaal's method. Cox-Proportional hazards modeling was utilized to assess freedom from acute rejection and graft failure stratified by TAC-TTR quartile. Results: 47 patients were included in the review. Mean TAC-TTR for the cohort was 30.2% ± 11.4. Fifteen episodes of acute rejection were observed, 8 of which were severe. Patients in the highest TAC-TTR quartile >36% had a lower incidence of acute rejection and graft failure relative to patients with a TAC-TTR <20%. Cox-Proportional hazards modeling found a 10% decrease in TAC-TTR was associated with an increased hazard for acute rejection (2.03), severe acute rejection (2.19), and graft loss (3.33). Conclusion: The results of this study suggest that decreasing TAC-TTR is a risk factor for both acute rejection as well as intestinal allograft failure.
MeSH term(s)	Adult ; Freedom ; Graft Rejection/drug therapy ; Graft Rejection/etiology ; Graft Survival ; Humans ; Immunosuppressive Agents/therapeutic use ; Kidney Transplantation ; Tacrolimus/therapeutic use
Chemical Substances	Immunosuppressive Agents ; Tacrolimus (WM0HAQ4WNM)
Language	English
Publishing date	2021-04-03
Publishing country	Denmark
Document type	Journal Article
ZDB-ID	639001-8
ISSN	1399-0012 ; 0902-0063
ISSN (online)	1399-0012
ISSN	0902-0063
DOI	10.1111/ctr.14291
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Article ; Online: Safety of direct-acting oral anticoagulants relative to warfarin in a matched cohort of liver transplant recipients.

Santeusanio, Andrew D / Weinberg, Alan D / Florman, Sander S / Schiano, Thomas D

Clinical transplantation

2019 Volume 34, Issue 1, Page(s) e13756

Abstract: Despite increasingly widespread utilization of direct-acting oral anticoagulants (DOACs), there remains limited experience with the use of these agents following liver transplantation. We performed a single-center, retrospective review of liver ... ...

Abstract	Despite increasingly widespread utilization of direct-acting oral anticoagulants (DOACs), there remains limited experience with the use of these agents following liver transplantation. We performed a single-center, retrospective review of liver transplant recipients prescribed DOACs or warfarin between January 2014 and January 2018. Patients receiving DOACs were matched with warfarin-treated controls based on discrete clinical parameters and followed from the time of anticoagulant prescription, until treatment discontinuation or study conclusion. The primary endpoint for this review was the incidence of clinically relevant major or non-major bleeding among the treatment groups. Twenty-seven patients prescribed DOACs were identified for inclusion in the review, of which 20 could be matched with suitable warfarin controls. At the conclusion of the study, warfarin-treated patients had a significantly higher incidence of clinically relevant bleeding (45% vs 15%; P = .01). No statistically significant differences were found in the rate of new or recurrent thrombotic events. Multivariable logistic regression demonstrated that warfarin treatment was associated with a significantly higher odds of a bleeding event compared to treatment with a DOAC (OR = 6.9; 95% CI, 1.1-44.6). DOAC use appears relatively safe compared with warfarin in select liver transplant recipients. Patient-specific factors still bear consideration when selecting between the various anticoagulant options.
MeSH term(s)	Administration, Oral ; Anticoagulants/therapeutic use ; Atrial Fibrillation/drug therapy ; Factor Xa Inhibitors/therapeutic use ; Humans ; Liver Transplantation ; Retrospective Studies ; Warfarin/therapeutic use
Chemical Substances	Anticoagulants ; Factor Xa Inhibitors ; Warfarin (5Q7ZVV76EI)
Language	English
Publishing date	2019-12-12
Publishing country	Denmark
Document type	Journal Article ; Review
ZDB-ID	639001-8
ISSN	1399-0012 ; 0902-0063
ISSN (online)	1399-0012
ISSN	0902-0063
DOI	10.1111/ctr.13756
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Article ; Online: Clinical characteristics, treatment and outcomes of patients with spontaneous renal artery dissections.

Dicks, Andrew B / Elgendy, Islam Y / Thondapu, Vikas / Ghoshhajra, Brian / Waller, Harold D / Rubio, Manolo / Schainfeld, Robert M / Weinberg, Ido

Journal of nephrology

2022 Volume 36, Issue 2, Page(s) 377–384

Abstract: Objectives: The natural history and optimal management of spontaneous renal artery dissections (SRADs) are poorly understood. We compared baseline characteristics, presentation, management, and outcomes between patients with symptomatic versus ... ...

Abstract	Objectives: The natural history and optimal management of spontaneous renal artery dissections (SRADs) are poorly understood. We compared baseline characteristics, presentation, management, and outcomes between patients with symptomatic versus asymptomatic SRADs. Methods: We performed a retrospective review of medical charts for patients diagnosed with SRAD at a single, tertiary care center. Patients were identified using billing codes. Patient demographics, medical history, clinical presentation, treatment, and follow up were recorded. We compared patients based on presence or absence of symptoms at the time of SRAD diagnosis. Results: A total of 125 patients were included; 73 (58.4%) patients had symptoms at the time of SRAD diagnosis. Symptomatic patients were younger at the time of diagnosis (47.4 vs. 54.3 years, p = 0.008) and more likely male (74.0% vs. 44.2%, p = 0.005). Most patients received medical therapy (93.2% vs. 82.6%, p = 0.32). Endovascular therapy utilization was low in both groups (8.2% vs. 7.7%, p = 0.9). Outcomes between the two groups were comparable; renal function remained stable, and mortality was rare. Conclusion: Most patients who presented with SRAD were treated with medical therapy alone and usually experienced a benign course. Further studies are needed to understand the pathophysiology and natural history of renal artery dissections.
MeSH term(s)	Humans ; Male ; Renal Artery/diagnostic imaging ; Retrospective Studies ; Treatment Outcome
Language	English
Publishing date	2022-09-30
Publishing country	Italy
Document type	Journal Article
ZDB-ID	1093991-x
ISSN	1724-6059 ; 1120-3625 ; 1121-8428
ISSN (online)	1724-6059
ISSN	1120-3625 ; 1121-8428
DOI	10.1007/s40620-022-01444-4
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