Publications by authors named "David Goldberg"

975 Publications

Decision-making Among Hepatitis C Virus-negative Transplant Candidates Offered Organs from Donors with HCV Infection.

Transplant Direct 2022 Aug 19;8(8):e1341. Epub 2022 Jul 19.

Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.

Background: Historically, many organs from deceased donors with hepatitis C virus (HCV) were discarded. The advent of highly curative direct-acting antiviral (DAA) therapies motivated transplant centers to conduct trials of transplanting HCV-viremic organs (nucleic acid amplification test positive) into HCV-negative recipients, followed by DAA treatment. However, the factors that influence candidates' decisions regarding acceptance of transplant with HCV-viremic organs are not well understood.

Methods: To explore patient-level perceptions, influences, and experiences that inform candidate decision-making regarding transplant with organs from HCV-viremic donors, we conducted a qualitative semistructured interview study embedded within 3 clinical trials investigating the safety and efficacy of transplanting lungs and kidneys from HCV-viremic donors into HCV-negative recipients. The study was conducted from June 2019 to March 2021.

Results: Among 44 HCV-negative patients listed for organ transplant who were approached for enrollment in the applicable clinical trial, 3 approaches to decision-making emerged: positivist, risk analyses, and instinctual response. Perceptions of risk contributed to conceptualizations of factors influencing decisions. Moreover, most participants relied on multiple decision-making approaches, either simultaneously or sequentially.

Conclusions: Understanding how different decisional models influence patients' choices regarding transplant with organs from HCV-viremic donors may promote shared decision-making among transplant patients and providers.
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http://dx.doi.org/10.1097/TXD.0000000000001341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9298473PMC
August 2022

Sociodemographic and georaphic differences in the US epidemiology of autoimmune hepatitis with and without cirrhosis.

Hepatology 2022 Jul 10. Epub 2022 Jul 10.

Division of Digestive Health and Liver Disease, University of Miami Miller School of Medicine, Miami, Florida, USA.

Background And Aims: Data on the epidemiology of autoimmune hepatitis (AIH) in the United States are limited. This study investigated the sociodemographic and geographic factors associated with AIH incidence and prevalence with and without cirrhosis.

Approach And Results: In a retrospective cohort of adults in the Optum Clinformatics Data Mart (2009-2018), we identified AIH cases using a validated claims-based algorithm. Incidence and prevalence were compared between sociodemographic subgroups. Logistic regression evaluated the association of US Census Division with AIH incidence and the factors associated with incident AIH with cirrhosis. From 2009 to 2018, the age- and sex-standardized prevalence of AIH in the Optum cohort was 26.6 per 100,000 persons with an incidence of 4.0 per 100,000 person-years. AIH incidence increased earlier among Hispanics (age 50-59 years) and later among Asians (≥80 years). Adjusted AIH incidence was higher in the Mountain Division (odds ratio [OR] 1.17) and lower in the Pacific (OR 0.68), Middle Atlantic (OR 0.81), and West North Central Divisions (OR 0.86 vs. East North Central; p < 0.001). Male sex (OR 1.31, p = 0.003), Black race (OR 1.32, p = 0.022), and Hispanic ethnicity (OR 1.37 vs. non-Hispanic White, p = 0.009) were associated with incident AIH with cirrhosis. Incident AIH with cirrhosis was greater in the West South Central Division (OR 1.30 vs. South Atlantic; p = 0.008).

Conclusions: AIH epidemiology differs according to sociodemographic and geographic factors in the United States. Studies are needed to determine the genetic, epigenetic, and environmental factors underlying the heterogeneity in AIH risk and outcomes.
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http://dx.doi.org/10.1002/hep.32653DOI Listing
July 2022

Center-level and region-level variations in liver transplantation practices following acuity circles policy change.

Am J Transplant 2022 Jun 27. Epub 2022 Jun 27.

Department of Gastroenterology, University of Miami Miller School of Medicine, Miami, Florida, USA.

Although early studies suggest the Acuity Circles (AC) allocation policy has increased access to deceased donor liver transplants (DDLTs) for patients with the highest MELD scores, changes in center- and region-level practices among patients with the highest MELD scores in response to AC are not well-characterized. OPTN/UNOS data were analyzed to compare center-level changes in the number of DDLTs based on allocation-MELD (aMELD) categories used for AC sharing performed in the 18-month periods before and after AC enactment on February 4, 2020. There was large center-level variation in the number and proportion of aMELD ≥ 37 DDLTs performed from pre-AC to AC period; 13 centers accounted for 196 of the 198 total net increase in aMELD ≥ 37 DDLTs performed after AC, 5 of these being from UNOS region 5. Similar center-level variation was seen for MELD 33-36 and MELD 29-32 DDLTs, with 17 centers and 14 centers, respectively, accounting for the entire net increase in DDLTs in the aMELD categories. In conclusion, AC increased access to livers for transplantation for high MELD patients nationally, but imbalances remain in transplant practice patterns at the center and regional levels. Longer-term study is necessary to assess effectiveness of AC in improving equitability of liver transplantations.
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http://dx.doi.org/10.1111/ajt.17131DOI Listing
June 2022

Recipient and Center Factors Associated With Immunosuppression Practice Beyond the First Year After Liver Transplantation and Impact on Outcomes.

Transplantation 2022 Jun 16. Epub 2022 Jun 16.

Division of Digestive Health and Liver Diseases, University of Miami Miller School of Medicine, Miami, FL.

Background: Immunosuppression is a critical aspect of post-transplant management, yet practices at intermediate and late time points after liver transplantation (LT) are poorly characterized.

Methods: A retrospective cohort of 11 326 adult first LT alone recipients between 2007 and 2016 was identified by linking United Network for Organ Sharing transplant data to Medicare administrative claims. The immunosuppression regimen was obtained from Medicarebilling claims. Factors associated with calcineurin inhibitor (CNI) monotherapy at 1-, 3-, and 5-y post-LT were investigated using mixed-effects logistic regression. Center practice heterogeneity was evaluated. The association of immunosuppression regimen (time-updating) with patient and graft survival was studied.

Results: CNI monotherapy was used in 51.9% at 1-y post-LT and 68.6% at 5-y post-LT. Center-specific rates ranged from 20.0%-79.9% to 15.4%-95.2%, respectively. CNI monotherapy at 1- and 3-y post-LT was less likely among Black recipients (P = 0.027 and P = 0.015 versus White, respectively). CNI plus antimetabolite was associated with improved adjusted patient (hazard ratio, 0.59; P < 0.001) and graft (hazard ratio, 0.62; P < 0.001) survival versus CNI monotherapy. The benefit of CNI plus antimetabolite on patient and graft survival increased with older age.

Conclusions: In this first longitudinal analysis of LT immunosuppression practices among Medicare beneficiaries, a CNI plus antimetabolite approach led to improved outcomes. Significant center heterogeneity in practice was observed.
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http://dx.doi.org/10.1097/TP.0000000000004209DOI Listing
June 2022

County-level Differences in Liver-related Mortality, Waitlisting, and Liver Transplantation in the United States.

Transplantation 2022 May 9. Epub 2022 May 9.

Division of Transplantation, Department of Surgery, University of Alabama at Birmingham, Birmingham, AL.

Background: Much of our understanding regarding geographic issues in transplantation is based on statistical techniques that do not formally account for geography and is based on obsolete boundaries such as donation service area.

Methods: We applied spatial epidemiological techniques to analyze liver-related mortality and access to liver transplant services at the county level using data from the Centers for Disease Control and Prevention and Scientific Registry of Transplant Recipients from 2010 to 2018.

Results: There was a significant negative spatial correlation between transplant rates and liver-related mortality at the county level (Moran's I, -0.319; P = 0.001). Significant clusters were identified with high transplant rates and low liver-related mortality. Counties in geographic clusters with high ratios of liver transplants to liver-related deaths had more liver transplant centers within 150 nautical miles (6.7 versus 3.6 centers; P < 0.001) compared with all other counties, as did counties in geographic clusters with high ratios of waitlist additions to liver-related deaths (8.5 versus 2.5 centers; P < 0.001). The spatial correlation between waitlist mortality and overall liver-related mortality was positive (Moran's I, 0.060; P = 0.001) but weaker. Several areas with high waitlist mortality had some of the lowest overall liver-related mortality in the country.

Conclusions: These data suggest that high waitlist mortality and allocation model for end-stage liver disease do not necessarily correlate with decreased access to transplant, whereas local transplant center density is associated with better access to waitlisting and transplant.
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http://dx.doi.org/10.1097/TP.0000000000004171DOI Listing
May 2022

A Path FORWARD: Development of a Comprehensive Multidisciplinary Clinic to Create Health and Wellness for the Child and Adolescent with a Fontan Circulation.

Pediatr Cardiol 2022 Aug 23;43(6):1175-1192. Epub 2022 May 23.

Division of Cardiology, Children's Hospital of Philadelphia, Philadelphia, USA.

Today, it is anticipated most individuals diagnosed with single-ventricle malformation will survive surgical reconstruction through a successful Fontan operation. As greater numbers of patients survive, so has the recognition that individuals with Fontan circulation face a variety of challenges. The goal of a normal quality and duration of life will not be reached by all. The hurdles fall into a variety of domains. From a cardiovascular perspective, the Fontan circulation is fundamentally flawed by its inherent nature of creating a state of chronically elevated venous pressure and congestion, accompanied by a relatively low cardiac output. Ventricular dysfunction, atrioventricular valve regurgitation, and arrhythmia may directly impact cardiac performance and can progress with time. Problems are not limited to the cardiovascular system. Fontan circulatory physiology impacts a multitude of biological processes and health parameters outside the heart. The lymphatic circulation is under strain manifesting as variable degrees of protein-rich lymph loss and immune system dysregulation. Organ system dysfunction develops through altered perfusion profiles. Liver fibrosis is ubiquitous, and a process of systemic fibrogenesis in response to circulatory stressors may affect other organs as well. Somatic growth and development can be delayed. Behavioral and mental health problems are common, presenting as clinically important levels of anxiety and depression. Most striking is the high variability in prevalence and magnitude of these complications within the population, indicating the likelihood of additional factors enhancing or mitigating their emergence. We propose that optimal care for the individual with single ventricle and a Fontan circulation is ideally offered in a comprehensive multidisciplinary manner, with attention to elements that are beyond cardiac management alone. In this report, we share the concepts, our experiences, and perspectives on development of a clinic model-the "Fontan rehabilitation, wellness and resilience development" or FORWARD program. We provide insights into the mechanics of our multidisciplinary model of care and the benefits offered serving our growing population of individuals with a Fontan circulation and their families.
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http://dx.doi.org/10.1007/s00246-022-02930-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9125546PMC
August 2022

Lost potential and missed opportunities for DCD liver transplantation in the United States.

Am J Surg 2022 May 13. Epub 2022 May 13.

Department of Surgery, Division of Transplantation, University of Alabama at Birmingham, Birmingham, AL, USA.

Background: Donation after cardiac death(DCD) has been proposed as an avenue to expand the liver donor pool.

Methods: We examined factors associated with nonrecovery of DCD livers using UNOS data from 2015 to 2019.

Results: There 265 non-recovered potential(NRP) DCD livers. Blood type AB (7.8% vs. 1.1%) and B (16.9% vs. 9.8%) were more frequent in the NRP versus actual donors (p < 0.001). The median driving time between donor hospital and transplant center was similar for NRP and actual donors (30.1 min vs. 30.0 min; p = 0.689), as was the percentage located within a transplant hospital (20.8% vs. 20.9%; p = 0.984).The donation service area(DSA) of a donor hospital explained 27.9% (p = 0.001) of the variability in whether a DCD liver was recovered.

Conclusion: A number of potentially high quality DCD donor livers go unrecovered each year, which may be partially explained by donor blood type and variation in regional and DSA level practice patterns.
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http://dx.doi.org/10.1016/j.amjsurg.2022.05.001DOI Listing
May 2022

Impact of major hepatocellular carcinoma policy changes on liver transplantation for hepatocellular carcinoma in the United States.

Liver Transpl 2022 May 18. Epub 2022 May 18.

Division of Digestive Health and Liver Diseases, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida, USA.

Since its inception in 2002, Model for End-Stage Liver Disease (MELD)-based allocation has undergone a series of revisions, especially with respect to exception points. Hepatocellular carcinoma (HCC) is the most common indication for MELD exceptions, and as a result of higher transplant proportions and lower waitlist mortality, a series of policy changes have been implemented to deprioritize HCC transplants. We examined the impact of HCC exception policy changes on transplant and waitlist mortality rates. We evaluated Organ Procurement and Transplantation Network/United Network for Organ Sharing data on adult patients from January 1, 2005, to June 4, 2021, focusing on waitlist mortality and deceased donor liver transplantation (DDLT) proportions. The data were divided into four policy eras: (1) MELD 22 points at waitlisting with an increase in points every 3 months (i.e., elevator) (January 2005-October 2015), (2) delay and cap at MELD 34 points (October 2015-May 2019), (3) delay and fixed exceptions based on donor service area (DSA) median MELD at transplantation minus three (MMaT-3; May 2019-February 2020), and (4) delay and fixed exceptions based on the MMaT-3 of centers within 250 nautical miles (i.e., acuity circles; February 2020-June 2021). We evaluated (a) changes in the proportions of DDLTs for patients with HCC exceptions within each era nationally and by DSA and (b) waitlist mortality in the three recent policy eras, focusing on mortality in the 6 months after the 6-month delay period. The percentage of adult DDLT with HCC exceptions decreased through the four eras: 22.9% (n = 14,049), 17.9% (n = 4598), 14.3% (n = 851), and 12.4% (n = 1425), respectively. Of the 51 DSAs analyzed, the annual percent change in DDLTs for patients with HCC exceptions was negative (i.e., decreased) in 47 (92.2%). Waitlist mortality remained stable. All HCC policy implementations led to a decrease in the percentage of transplants for HCC without an increase in waitlist mortality. The impact is not uniform across geographic areas.
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http://dx.doi.org/10.1002/lt.26509DOI Listing
May 2022

Association of the Liver Acuity Circle Allocation Policy With Timing of Donor Procurements in the US.

JAMA Surg 2022 07;157(7):631-633

Division of Digestive Health and Liver Disease, Miller School of Medicine, University of Miami, Miami, Florida.

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http://dx.doi.org/10.1001/jamasurg.2022.1058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9118054PMC
July 2022

What Drives Radical Halogenation versus Hydroxylation in Mononuclear Nonheme Iron Complexes? A Combined Experimental and Computational Study.

J Am Chem Soc 2022 06 10;144(24):10752-10767. Epub 2022 May 10.

Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester M1 7DN, United Kingdom.

Nonheme iron halogenases are unique enzymes in nature that selectively activate an aliphatic C-H bond of a substrate to convert it into C-X (X = Cl/Br, but not F/I). It is proposed that they generate an Fe(OH)(X) intermediate in their catalytic cycle. The analogous Fe(OH) intermediate in nonheme iron hydroxylases transfers OH to give alcohol product, whereas the halogenases transfer X to the carbon radical substrate. There remains significant debate regarding what factors control their remarkable selectivity of the halogenases. The reactivity of the complexes Fe(BNPAO)(OH)(X) (X = Cl, Br) with a secondary carbon radical (R) is described. It is found that X transfer occurs with a secondary carbon radical, as opposed to OH transfer with tertiary radicals. Comprehensive computational studies involving density functional theory were carried out to examine the possible origins of this selectivity. The calculations reproduce the experimental findings, which indicate that halogen transfer is not observed for the tertiary radicals because of a nonproductive equilibrium that results from the endergonic nature of these reactions, despite a potentially lower reaction barrier for the halogenation pathway. In contrast, halogen transfer is favored for secondary carbon radicals, for which the halogenated product complex is thermodynamically more stable than the reactant complex. These results are rationalized by considering the relative strengths of the C-X bonds that are formed for tertiary versus secondary carbon centers. The computational analysis also shows that the reaction barrier for halogen transfer is significantly dependent on secondary coordination sphere effects, including steric and H-bonding interactions.
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http://dx.doi.org/10.1021/jacs.2c01375DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9228086PMC
June 2022

Factors Associated With Geographic Disparities in Gastrointestinal Cancer Mortality in the United States.

Gastroenterology 2022 Aug 25;163(2):437-448.e1. Epub 2022 Apr 25.

Division of Digestive Health and Liver Diseases, Department of Medicine, University of Miami Miller School of Medicine, Miami, Florida.

Background & Aims: Significant geographic variability in gastrointestinal (GI) cancer-related death has been reported in the United States. We aimed to evaluate both modifiable and nonmodifiable factors associated with intercounty differences in mortality due to GI cancer.

Methods: Data from the Centers for Disease Control and Prevention's Wide-ranging Online Data for Epidemiologic Research platform were used to calculate county-level mortality from esophageal, gastric, pancreatic, and colorectal cancers. Multivariable linear regression models were fit to adjust for county-level covariables, considering both patient (eg, sex, race, obesity, diabetes, alcohol, and smoking) and structural factors (eg, specialist density, poverty, insurance prevalence, and colon cancer screening prevalence). Intercounty variability in GI cancer-related mortality explained by these covariables was expressed as the multivariable model R.

Results: There were significant geographic disparities in GI cancer-related county-level mortality across the US from 2010-2019 with the ratio of mortality between 90th and 10th percentile counties ranging from 1.5 (pancreatic) to 2.1 (gastric cancer). Counties with the highest 5% mortality rates for gastric, pancreatic, and colorectal cancer were primarily in the Southeastern United States. Multivariable models explained 43%, 61%, 14%, and 39% of the intercounty variability in mortality rates for esophageal, gastric, pancreatic, and colorectal cancer, respectively. Cigarette smoking and rural residence (independent of specialist density) were most strongly associated with GI cancer-related mortality.

Conclusions: Both patient and structural factors contribute to significant geographic differences in mortality from GI cancers. Our findings support continued public health efforts to reduce smoking use and improve care for rural patients, which may contribute to a reduction in disparities in GI cancer-related death.
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http://dx.doi.org/10.1053/j.gastro.2022.04.019DOI Listing
August 2022

Longitudinal assessment of vascular calcification in generalized arterial calcification of infancy.

Pediatr Radiol 2022 Apr 19. Epub 2022 Apr 19.

Department of Radiology, Children's Hospital of Philadelphia, 3401 Civic Center Blvd., Philadelphia, PA, 19104, USA.

Background: Generalized arterial calcification of infancy (GACI), also known as idiopathic infantile arterial calcification, is a very uncommon genetic disorder characterized by calcifications and stenoses of large- and medium-size arteries that can lead to end-organ damage.

Objective: To describe changes in imaging findings in 10 children with GACI at a single institution from 2010 to 2021.

Materials And Methods: In this retrospective study we reviewed initial and follow-up body imaging in children with genetic confirmation of GACI at our hospital. All initial images were analyzed for the presence and distribution of arterial calcifications, stenoses and wall thickening/irregularity within the chest, abdomen and pelvis. We compared available follow-up studies to the initial imaging findings. We extracted clinical information including prenatal and postnatal treatment from the children's medical records.

Results: We evaluated 10 children (five boys) with a diagnosis of GACI. Median age at first body imaging was 8 days (range: 1 day to 5 years). Six children were identified prenatally and four postnatally. Postnatal presentation included cardiac failure, seizures and hypertension. Images in newborns (n = 8) most commonly showed diffuse arterial calcifications (6/8; 75%), while stenoses were less common (2/8; 25%) during this period. Two children were diagnosed after the neonatal period - one in infancy and one during childhood. In total, half the children (5/10; 50%) had arterial stenoses - three cases visualized at first imaging and two identified on follow-up images during infancy. Stenoses had completely resolved in one child (1/5; 20%) at last follow-up. Eight children received prenatal or postnatal treatment or both. All children who received both prenatal and postnatal treatment (n = 4) had completely resolved calcifications at last follow-up.

Conclusion: Children with GACI might have characteristic vascular calcifications at birth that raise the suspicion of this disease. Arterial calcifications decrease or disappear spontaneously or after treatment, but arterial stenoses usually persist. Calcifications and arterial stenoses can be easily identified and followed with non-contrast CT and CT angiography.
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http://dx.doi.org/10.1007/s00247-022-05364-0DOI Listing
April 2022

Trends in the Incidence of Upper Gastrointestinal Cancers Show Changing Dynamics.

Clin Gastroenterol Hepatol 2022 Apr 2. Epub 2022 Apr 2.

Division of Gastroenterology and Hepatology, University of Miami Miller School of Medicine, Sylvester Comprehensive Cancer Center, University of Miami Health System, Miami, Florida.

Over the last 50 years, there have been shifts in the incidence of gastric and esophageal cancers in the United States, including a decline in noncardia gastric adenocarcinoma (NCGC), and increases in cardia gastric adenocarcinoma (CGC) and esophageal adenocarcinoma (EAC). Hypotheses for the changing incidences include eradication of Helicobacter pylori, the main causative agent of NCGC, and rising rates of reflux, obesity, and diet, which are risk factors associated with EAC and CGC..
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http://dx.doi.org/10.1016/j.cgh.2022.03.034DOI Listing
April 2022

Injury prevention for older adults: A dataset of safety concern narratives from online reviews of mobility-related products.

Data Brief 2022 Jun 15;42:108044. Epub 2022 Mar 15.

Bloomberg School of Public Health, Johns Hopkins University, 615N Wolfe St, Baltimore, MD 21205, USA.

Older adults are among the fastest-growing demographic groups in the United States, increasing by over a third this past decade. Consequently, the older adult consumer product market has quickly become a multi-billion-dollar industry in which millions of products are sold every year. However, the rapidly growing market raises the potential for an increasing number of product safety concerns and consumer product-related injuries among older adults. Recent manufacturer and consumer injury prevention efforts have begun to turn towards online reviews, as these provide valuable information from which actionable, timely intelligence can be derived and used to detect safety concerns and prevent injury. The presented dataset contains 1966 curated online product reviews from consumers, equally distributed between safety concerns and non-concerns, pertaining to product categories typically intended for older adults. Identified safety concerns were manually sub-coded across thirteen dimensions designed to capture relevant aspects of the consumer's experience with the purchased product, facilitate the safety concern identification and sub-classification process, and serve as a gold-standard, balanced dataset for text classifier learning.
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http://dx.doi.org/10.1016/j.dib.2022.108044DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8960888PMC
June 2022

Relationship Between Serum Brain-Type Natriuretic Peptide and Biomarkers of Growth in Infants With Shunt-Dependent Single Cardiac Ventricle.

Am J Cardiol 2022 05 11;171:146-150. Epub 2022 Mar 11.

Division of Cardiology, Department of Pediatrics, Children's Hospital of Philadelphia, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania.

For infants with shunt-dependent or ductal-dependent single ventricle heart disease, poor growth is common and associated with morbidity and impaired neurodevelopmental outcomes. Although attention has focused on nutrition to promote weight gain, little is known about the relation between heart failure and growth factors. A prospective observational pilot study was performed to assess the relation between heart failure, assessed by brain natriuretic peptide (BNP), and growth factors (insulin-like growth factor 1 [IGF-1] and insulin-like growth factor-binding protein 3) at 3 visits: (1) before discharge from neonatal intervention with the establishment of stable pulmonary blood flow, (2) immediately before superior cavopulmonary connection, and (3) before discharge after superior cavopulmonary connection operation. The relation between BNP and growth factors was analyzed using Spearman pairwise correlations at each visit and modeled over time with a linear mixed-effects model. Correlations were considered worthy of further exploration using a p <0.10, given the exploratory nature of the study. The study included 38 infants (66% male, 68% hypoplastic left heart syndrome). Median BNP was elevated at visit 1 and decreased over time (287 pg/dl [interquartile range 147 to 794], 85 pg/dl [52 to 183], and 90 pg/dl [70 to 138]). Median IGF-1 Z score was <0 at each visit but increased over time (-0.9 [interquartile range -1.1 to 0.1], -0.7 [-1.2 to 0.1], and -0.5 [-1.2 to 0]). Inverse correlations were found between BNP and IGF-1 at visit 1 (r = -0.40, p = 0.097), BNP and IGF-1 and insulin-like growth factor-binding protein 3 at visit 2 (r = -0.33, p = 0.080 and r = -0.33, p = 0.085, respectively) and BNP and IGF-1 Z score at visit 3 (r = -0.42, p = 0.049). Significant relations were likewise found between the change in BNP and the change in IGF-1 between visits 1 and 3 (p = 0.046) and between visits 2 and 3 (p = 0.048). In conclusion, this pilot study demonstrates an inverse correlation between BNP and growth factors, suggesting that the heart failure state associated with this physiology may play a mechanistic role in impaired growth.
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http://dx.doi.org/10.1016/j.amjcard.2022.01.052DOI Listing
May 2022

Accurate long-term prediction of death for patients with cirrhosis.

Hepatology 2022 Sep 1;76(3):700-711. Epub 2022 Apr 1.

Renal-Electrolye and Hypertension Division, Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, USA.

Background And Aims: Cirrhosis is a major cause of death and is associated with extensive health care use. Patients with cirrhosis have complex treatment choices due to risks of morbidity and mortality. To optimally counsel and treat patients with cirrhosis requires tools to predict their longer-term liver-related survival. We sought to develop and validate a risk score to predict longer-term survival of patients with cirrhosis.

Approach And Results: We conducted a retrospective cohort study of adults with cirrhosis with no major life-limiting comorbidities. Adults with cirrhosis within the Veterans Health Administration were used for model training and internal validation, and external validation used the OneFlorida Clinical Research Consortium. We used four model-building approaches including variables predictive of cirrhosis-related mortality, focused on discrimination at key time points (1, 3, 5, and 10 years). Among 30,263 patients with cirrhosis ≤75 years old without major life-limiting comorbidities and complete laboratory data during the baseline period, the boosted survival tree models had the highest discrimination, with 1-year, 3-year, 5-year, and 10-year survival rates of 0.77, 0.81, 0.84, and 0.88, respectively. The 1-year, 3-year, and 5-year discrimination was nearly identical in external validation. Secondary analyses with imputation of missing data and subgroups by etiology of liver disease had similar results to the primary model.

Conclusions: We developed and validated (internally and externally) a risk score to predict longer-term survival of patients with cirrhosis. This score would transform management of patients with cirrhosis in terms of referral to specialty care and treatment decision-making for non-liver-related care.
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http://dx.doi.org/10.1002/hep.32457DOI Listing
September 2022

Characterizing accident narratives with word embeddings: Improving accuracy, richness, and generalizability.

Authors:
David M Goldberg

J Safety Res 2022 02 29;80:441-455. Epub 2021 Dec 29.

San Diego State University, 5500 Campanile Drive, San Diego, CA 92182, United States. Electronic address:

Introduction: Ensuring occupational health and safety is an enormous concern for organizations, as accidents not only harm workers but also result in financial losses. Analysis of accident data has the potential to reveal insights that may improve capabilities to mitigate future accidents. However, because accident data are often transcribed textually, analyzing these narratives proves difficult. This study contributes to a recent stream of literature utilizing machine learning to automatically label accident narratives, converting them into more easily analyzable fields.

Method: First, a large dataset of accident narratives in which workers were injured is collected from the U.S. Occupational Safety and Health Administration (OSHA). Word embeddings-based text mining is implemented; compared to past works, this methodology offers excellent performance. Second, to improve the richness of analyses, each record is assessed across five dimensions. The machine learning models provide classifications of body part(s) injured, the source of the injury, the type of event causing the injury, whether a hospitalization occurred, and whether an amputation occurred. Finally, demonstrating generalizability, the trained models are deployed to analyze two additional datasets of accident narratives in the construction industry and the mining and metals industry (transfer learning). Practical Applications: These contributions improve organizations' capacities to rapidly analyze textual accident narratives.
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http://dx.doi.org/10.1016/j.jsr.2021.12.024DOI Listing
February 2022

Chromosome 22q11 copy number variants and single ventricle CHD.

Cardiol Young 2022 Feb 24:1-5. Epub 2022 Feb 24.

Children's Hospital of Philadelphia, Division of Cardiothoracic Surgery, Philadelphia, PA, USA.

Objectives: CHD is an important phenotypic feature of chromosome 22q11.2 copy number variants. Biventricular repair is usually possible, however there are rare reports of patients with chromosome 22q copy number variants and functional single ventricle cardiac disease.

Methods: This is a single centre retrospective review of patients with chromosome 22q copy number variants who underwent staged single ventricle reconstructive surgery between 1 July, 1984 and 31 December, 2020.

Results: Seventeen patients met inclusion criteria. The most common diagnosis was hypoplastic left heart syndrome (n = 8) and vascular anomalies were present in 13 patients. A microdeletion of the chromosome 22 A-D low-copy repeat was present in 13 patients, and the remaining had a duplication. About half of the patients had documented craniofacial abnormalities and/or hypocalcaemia, and developmental delay was very common. Fifteen patients had a Norwood operation, 10 patients had a superior cavopulmonary anastomosis, and 7 patients had a Fontan. Two patients had cardiac transplantation after Fontan. Overall survival is 64% at 1 year, and 58% at 5 and 10 years. Most deaths occurred following Norwood operation (n = 5).

Conclusions: CHD necessitating single ventricle reconstruction associated with chromosome 22q copy number variants is not common, but typically occurs as a variant of hypoplastic left heart syndrome with the usual cytogenetic microdeletion. The most common neonatal surgical intervention performed is the Norwood, where most of the mortality burden occurs. Associated anomalies and medical issues may cause additional morbidity after cardiac surgery, but survival is similar to infants with other types of single ventricle disease.
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http://dx.doi.org/10.1017/S1047951122000385DOI Listing
February 2022

One-Year Outcomes of the Multi-Center StudY to Transplant Hepatitis C-InfeCted kidneys (MYTHIC) Trial.

Kidney Int Rep 2022 Feb 1;7(2):241-250. Epub 2021 Dec 1.

Department of Biostatistics, Epidemiology and Informatics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Introduction: Transplanting kidneys from hepatitis C virus (HCV) viremic donors into HCV-negative patients (HCV D-RNA-positive/R-negative) has evolved from experimental to "standard-of-care" at many centers. Nevertheless, most data derive from single centers and provide only short-term follow-up.

Methods: The Multicenter Study to Transplant Hepatitis C-Infected Kidneys (MYTHIC) study was a multicenter (7 sites) trial of HCV D-RNA-positive/R-negative kidney transplantation (KT) followed by 8 weeks of glecaprevir/pibrentasvir (G/P) initiated 2 to 5 days post-KT. Prespecified outcomes included probability of KT (vs. matched waitlist comparators) and 1-year safety outcomes, allograft function, and survival.

Results: Among 63 enrolled patients, 1-year cumulative incidence of KT was approximately 3.5-fold greater for the MYTHIC cohort versus 2055 matched United Network for Organ Sharing (UNOS) comparators who did not opt-in to receive a kidney from an HCV-viremic donor (68% vs. 19%,  < 0.0001). Of 30 HCV D-RNA-positive/R-negative KT recipients, all achieved HCV cure. None developed clinically significant liver disease or HCV-related kidney injury. Furthermore, 1-year survival was 93% and 1-year graft function was excellent (median creatinine 1.17; interquartile range [IQR]: 1.02-1.38 mg/dl). There were 4 cases of cytomegalovirus (CMV) disease among 10 CMV-negative patients transplanted with a kidney from an HCV-viremic/CMV-positive donor.

Conclusion: The 1-year findings from this multicenter trial suggest that opting-in for HCV-viremic KT offers can increase probability of KT with excellent 1-year outcomes. Trial Registration: NCT03781726.
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http://dx.doi.org/10.1016/j.ekir.2021.11.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8820987PMC
February 2022

Examining the impact of the first wave of COVID-19 and associated control measures on interventions to prevent blood-borne viruses among people who inject drugs in Scotland: an interrupted time series study.

Drug Alcohol Depend 2022 Mar 31;232:109263. Epub 2022 Jan 31.

School of Health and Life Sciences, Glasgow Caledonian University, Cowcaddens Road, Glasgow, G4 0BA, UK; Public Health Scotland, Meridian Court, 5 Cadogan Street, Glasgow, G2 6QQ, UK.

Background: COVID-19 has likely affected the delivery of interventions to prevent blood-borne viruses (BBVs) among people who inject drugs (PWID). We examined the impact of the first wave of COVID-19 in Scotland on: 1) needle and syringe provision (NSP), 2) opioid agonist therapy (OAT) and 3) BBV testing.

Methods: An interrupted time series study design; 23rd March 2020 (date of the first 'lockdown') was chosen as the key date.

Results: The number of HIV tests and HCV tests in drug services/prisons, and the number of needles/syringes (N/S) distributed decreased by 94% (RR=0.062, 95% CI 0.041-0.094, p < 0.001), 95% (RR=0.049, 95% CI 0.034-0.069, p < 0.001) and 18% (RR = 0.816, 95% CI 0.750-0.887, p < 0.001), respectively, immediately after lockdown. Post-lockdown, an increasing trend was observed relating to the number of N/S distributed (0.6%; RR = 1.006, 95% CI 1.001-1.012, p = 0.015), HIV tests (12.1%; RR = 1.121, 95% CI 1.092-1.152, p < 0.001) and HCV tests (13.2%; RR = 1.132, 95 CI 1.106-1.158, p < 0.001). Trends relating to the total amount of methadone prescribed remained stable, but a decreasing trend in the number of prescriptions (2.4%; RR = 0.976, 95% CI 0.959-0.993, p = 0.006) and an increasing trend in the quantity prescribed per prescription (2.8%; RR = 1.028, 95% CI 1.013-1.042, p < 0.001) was observed post-lockdown.

Conclusions: COVID-19 impacted the delivery of BBV prevention services for PWID in Scotland. While there is evidence of service recovery; further effort is likely required to return some intervention coverage to pre-pandemic levels in the context of subsequent waves of COVID-19.
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http://dx.doi.org/10.1016/j.drugalcdep.2021.109263DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8802039PMC
March 2022

A highly virulent variant of HIV-1 circulating in the Netherlands.

Science 2022 02 3;375(6580):540-545. Epub 2022 Feb 3.

Laboratory of Experimental Virology, Department of Medical Microbiology and Infection Prevention, Amsterdam University Medical Centers, University of Amsterdam, Amsterdam, Netherlands.

We discovered a highly virulent variant of subtype-B HIV-1 in the Netherlands. One hundred nine individuals with this variant had a 0.54 to 0.74 log increase (i.e., a ~3.5-fold to 5.5-fold increase) in viral load compared with, and exhibited CD4 cell decline twice as fast as, 6604 individuals with other subtype-B strains. Without treatment, advanced HIV-CD4 cell counts below 350 cells per cubic millimeter, with long-term clinical consequences-is expected to be reached, on average, 9 months after diagnosis for individuals in their thirties with this variant. Age, sex, suspected mode of transmission, and place of birth for the aforementioned 109 individuals were typical for HIV-positive people in the Netherlands, which suggests that the increased virulence is attributable to the viral strain. Genetic sequence analysis suggests that this variant arose in the 1990s from de novo mutation, not recombination, with increased transmissibility and an unfamiliar molecular mechanism of virulence.
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http://dx.doi.org/10.1126/science.abk1688DOI Listing
February 2022

Discordance in categorization of acute-on-chronic liver failure in the United Network for Organ Sharing database.

J Hepatol 2022 05 21;76(5):1122-1126. Epub 2022 Jan 21.

University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, United States.

Background & Aims: Studies regarding acute-on-chronic liver failure (ACLF) among liver transplant (LT) candidates from the United Network for Organ Sharing (UNOS) database are being used to inform LT policy changes worldwide. We assessed the validity of identifying ACLF in UNOS.

Methods: We performed stratified random sampling among 3 US LT centers between 2013-2019 to obtain a representative patient sample across ACLF grades. We compared the concordance of ACLF classification by UNOS vs. blinded manual chart review, according to EASL-CLIF.

Results: Among 481 sampled LT registrants, 250 (52%) had no ACLF, 75 (16%) had ACLF grade 1, 79 (16%) had ACLF grade 2, and 77 (16%) had ACLF grade 3 per UNOS categorization. Concordance of ACLF grade by UNOS vs. chart review was: 72%, 64%, 56%, and 64% for no ACLF, grade 1, grade 2, and grade 3, respectively, with an overall Cohen's kappa coefficient of 0.48 (95% CI 0.42-0.54). Absence of acute decompensation was the most common reason for overestimation, and discordant brain and respiratory failure categorization were the most common reasons for underestimation of ACLF by UNOS.

Conclusions: In this retrospective multi-center study, ACLF categorization by UNOS showed weak agreement with manual chart review. These findings are informative for ongoing allocation policy discussions, highlight the importance of prospective studies regarding ACLF in LT, and should encourage UNOS reform.

Lay Summary: Acute-on-chronic-liver-failure (ACLF) is a specific and common form of liver failure associated with high death rates. Studies have been published using the United States transplant registry (UNOS) to identify and describe outcomes of transplant candidates and recipients with ACLF, and these data are driving policy changes for transplant allocation around the world, but nobody has shown whether these data are reliable. We found that UNOS was not categorizing ACLF in concordance or accurately when compared to chart review, which shows the need for UNOS reform and non-UNOS studies to appropriately inform policies regarding the transplantation of patients with ACLF.
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http://dx.doi.org/10.1016/j.jhep.2021.12.040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9018597PMC
May 2022

Statin exposure is associated with reduced development of acute-on-chronic liver failure in a Veterans Affairs cohort.

J Hepatol 2022 05 21;76(5):1100-1108. Epub 2022 Jan 21.

Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA; Department of Medicine, Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA, USA.

Backgrounds & Aims: There is a need to identify therapies that prevent the development of acute-on-chronic liver failure (ACLF) in patients with cirrhosis. This study sought to evaluate the association between statin exposure and the risk of developing ACLF in a large national cohort of patients with cirrhosis.

Methods: We performed a retrospective cohort study of patients diagnosed with cirrhosis within the Veterans Health Administration from 2008 and 2018. Patients were stratified into 3 groups based on statin exposure (statin naïve, existing statin user, and new statin initiator). Cox proportional hazards regression models with inverse probability treatment weighting and marginal structural models were utilized to comprehensively address potential confounding in estimating the association between time-updated statin exposure and first occurrence of high-grade ACLF.

Results: The cohort included 84,963 patients, of whom 26.9% were on a statin at baseline. A total of 8,558 (10.1%) patients with cirrhosis were hospitalized with high-grade ACLF over a median follow-up time of 51.6 months (IQR 27.5-81.4). Time-updated statin use was associated with a significant reduction in the hazard of developing ACLF (hazard ratio [HR] 0.62, 95% CI 0.59-0.65, p <0.001). Increasing doses of statin were associated with progressively reduced hazard of developing ACLF (HR 0.75, 95% CI 0.66-0.86, p <0.001 for <20 mg vs. 0 mg of time-updated statin exposure, in simvastatin equivalents; HR 0.61, 95%, CI 0.58-0.64, p <0.001 for >20 mg vs. 0 mg statin exposure). Furthermore, every additional 5 months of statin exposure was associated with a 9% reduced hazard of high-grade ACLF (HR 0.91, 95% CI 0.90-0.92, p <0.001).

Conclusions: In this large, retrospective, cohort study in patients with cirrhosis, statin use was significantly associated with reduced development of high-grade ACLF.

Lay Summary: Statin therapy has been shown to have numerous beneficial effects in patients with chronic liver disease. This study demonstrated a strong association between statin therapy and a reduced risk of acute-on-chronic liver failure development in patients with cirrhosis. The results of this study support the promising role that statins may play in future prevention of acute-on-chronic liver failure in patients with cirrhosis.
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http://dx.doi.org/10.1016/j.jhep.2021.12.034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9018495PMC
May 2022

Algorithms to Identify Alcoholic Hepatitis Hospitalizations in Patients with Cirrhosis.

Dig Dis Sci 2022 Sep 13;67(9):4395-4402. Epub 2022 Jan 13.

Division of Gastroenterology and Hepatology, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Boulevard, 4th Floor, South Pavilion, Philadelphia, PA, 19104, USA.

Background: Alcoholic hepatitis (AH) is a clinically diagnosed syndrome with high short-term mortality for which liver transplantation may be curative. A lack of validated algorithms to identify AH hospitalizations has hindered clinical epidemiology research.

Methods: This was a retrospective cohort study of patients with cirrhosis using Veterans Health Administration (VHA) data from 2008 to 2015. We randomly sampled hospitalizations based upon abnormal liver tests and administrative codes for acute hepatitis or alcohol-associated liver disease (ALD). Hospitalizations were manually adjudicated for AH per society guidelines. A priori algorithms were evaluated to compute positive predicted value (PPV) and positive likelihood ratio (LR+), and were tested in an external University of Pennsylvania Health System (UPHS) cohort.

Results: Of 368 hospitalizations, 142 (38.6%) were adjudicated as AH. AH patients were younger (55 vs. 58 years, p < 0.001), less likely to have prior cirrhosis decompensation (57% vs. 73.9%, p < 0.001), and had higher AST-to-ALT ratios (median 2.9 vs. 1.9 mg/dL, p < 0.001) and higher bilirubin levels (median 2.9 vs. 1.9 mg/dL, p < 0.001). Algorithms combining clinical laboratory criteria (AST > 85 U/L but < 450 U/L, AST-to-ALT ratio > 2, total bilirubin > 5 mg/dL) and administrative coding criteria yielded the highest PPV (96.4%, 95% CI 87.7-99.6) and the highest LR+ (43.0, 95% CI 10.6-173.5). Several algorithms demonstrated 100% PPV for definite AH in the UPHS external cohort.

Conclusion: We have identified algorithms for AH hospitalizations with excellent PPV and LR+. These high-specificity algorithms may be used in VHA datasets to identify patients with high likelihood of AH, but should not be used to study AH incidence.
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http://dx.doi.org/10.1007/s10620-021-07321-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9276834PMC
September 2022

Effect of Acuity Circles Allocation Policy on Local Use of Donation After Circulatory Death Donor Livers.

Liver Transpl 2022 06 27;28(6):1103-1107. Epub 2022 Jan 27.

Division of Digestive Health and Liver Diseases, Department of Medicine, University of Miami Miller School of Medicine, Miami, FL.

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http://dx.doi.org/10.1002/lt.26402DOI Listing
June 2022

The Relationship between Nurses' Training and Perceptions of Electronic Documentation Systems.

Nurs Rep 2021 Jan 1;11(1):12-27. Epub 2021 Jan 1.

Department of Business Education, North Carolina A&T State University, Greensboro, NC 27411, USA.

Electronic documentation systems have been widely implemented in the healthcare field. These systems have become a critical part of the nursing profession. This research examines how nurses' general computer skills, training, and self-efficacy affect their perceptions of using these systems. A sample of 248 nurses was surveyed to examine their general computer skills, self-efficacy, and training in electronic documentation systems in nursing programs. We propose a model to investigate the extent to which nurses' computer skills, self-efficacy, and training in electronic documentation influence perceptions of using electronic documentation systems in hospitals. The data supports a mediated model in which general computer skills, self-efficacy, and training influence perceived usefulness through perceived ease of use. The significance of these findings was confirmed through structural equation modeling. As the electronic documentation systems are customized for every organization, our findings suggest value in nurses receiving training to learn these specific systems in the workplace or during their internships. Doing so may improve patient outcomes by ensuring that nurses use the systems consistently and effectively.
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http://dx.doi.org/10.3390/nursrep11010002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8608127PMC
January 2021

Declining incidence of hepatitis C related hepatocellular carcinoma in the era of interferon-free therapies: A population-based cohort study.

Liver Int 2022 03 5;42(3):561-574. Epub 2022 Jan 5.

School of Health and Life Sciences, Glasgow Caledonian University, Glasgow, UK.

Background & Aims: The impact of interferon (IFN)-free therapies on the epidemiology of hepatitis C virus (HCV) related hepatocellular carcinoma (HCC) is not well understood at a population level. Our goal was to bridge this evidence gap.

Methods: This study included all patients in Scotland with chronic HCV and a diagnosis of cirrhosis during 1999-2019. Incident cases of HCC, episodes of curative HCC therapy, and HCC-related deaths were identified through linkage to nationwide registries. Three time periods were examined: 1999-2010 (pegylated interferon-ribavirin [PIR]); 2011-2013 (First-generation DAA); and 2014-2019 (IFN-free era). We used regression modelling to determine time trends for (i) number diagnosed and living with HCV cirrhosis, (ii) HCC cumulative incidence, (iii) HCC curative treatment uptake and (iv) post-HCC mortality.

Results: 3347 cirrhosis patients were identified of which 381 (11.4%) developed HCC. After HCC diagnosis, 140 (36.7%) received curative HCC treatment and there were 202 deaths from HCC. The average annual number of patients diagnosed and living with HCV cirrhosis was approximately seven times higher in the IFN-free versus the PIR era, whereas the number of incident HCCs was four times higher. However, the cumulative incidence of HCC was significantly lower in the IFN-free versus PIR era (sdHR: 0.65; 95%CI:0.47-0.88; P = .006). Among HCC patients, diagnosis in the IFN-free era was not associated with improved uptake of curative treatment (aOR:1.18; 95%CI:0.69-2.01; P = .54), or reduced post-HCC mortality (sdHR: 0.74; 95%CI:0.53-1.05; P = .09).

Conclusions: The cumulative incidence of HCC is declining in HCV cirrhosis patients, but uptake of curative HCC therapy and post-HCC survival remains suboptimal.
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http://dx.doi.org/10.1111/liv.15143DOI Listing
March 2022

Failure to Upregulate the RNA Binding Protein ZBP After Injury Leads to Impaired Regeneration in a Rodent Model of Diabetic Peripheral Neuropathy.

Front Mol Neurosci 2021 7;14:728163. Epub 2021 Dec 7.

Burke Neurological Institute, White Plains, NY, United States.

Most diabetes patients eventually suffer from peripheral nerve degeneration. Unfortunately, there is no treatment for the condition and its mechanisms are not well understood. There is, however, an emerging consensus that the inability of peripheral nerves to regenerate normally after injury contributes to the pathophysiology. We have previously shown that regeneration of peripheral axons requires local axonal translation of a pool of axonal mRNAs and that the levels and members of this axonal mRNA pool are altered in response to injury. Here, we show that following sciatic nerve injury in a streptozotocin rodent model of type I diabetes, this mobilization of RNAs into the injured axons is attenuated and correlates with decreased axonal regeneration. This failure of axonal RNA localization results from decreased levels of the RNA binding protein ZBP1. Over-expression of ZBP1 rescues the growth defect in injured dorsal root ganglion neurons from diabetic rodents. These results provide evidence that decreased neuronal responsiveness to injury in diabetes is due to a decreased ability to alter the pool of axonal mRNAs available for local translation, and may open new therapeutic opportunities for diabetic peripheral neuropathy.
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http://dx.doi.org/10.3389/fnmol.2021.728163DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8688773PMC
December 2021
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