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Background: Black heart transplant recipients have higher risk of mortality than White recipients. Better understanding of this disparity, including subgroups most affected and timing of the highest risk, is necessary to improve care of Black recipients. We hypothesize that this disparity may be most pronounced among young recipients, as barriers to care like socioeconomic factors may be particularly salient in a younger population and lead to higher early risk of mortality. Methods: We studied 22 997 adult heart transplant recipients using the Scientific Registry of Transplant Recipients data from January 2005 to 2017 using Cox regression models adjusted for recipient, donor, and transplant characteristics. Results: Among recipients aged 18 to 30 years, Black recipients had 2.05-fold (95% CI, 1.67–2.51) higher risk of mortality compared with non-Black recipients ( P P P P =0.4). This association was attenuated among recipients aged 31 to 40 and 41 to 60 years, in whom Black recipients had 1.53-fold ([95% CI, 1.25–1.89] P P P =0.1). Conclusions: Young Black recipients have a high risk of mortality in the first year after heart transplant, which has been masked in decades of research looking at disparities in aggregate. To reduce overall racial disparities, clinical research moving forward should focus on targeted interventions for young Black recipients during this period.

Dystonias are a heterogenous group of often disabling movement disorders characterized by uncontrollable simultaneous contraction of agonist and antagonist muscles. Secondary dystonias are often caused by injuries to the central nervous system such as stroke, trauma, or Parkinson Disease. Primary dystonia, on the other hand, presents idiopathically without clear structural lesions or other neurological symptoms. Symptoms may be present in one body region, as in focal dystonia, or include large regions of the body, as in generalized dystonia. Existing therapies for dystonia are limited and often cause undesirable side effects or require surgery. A significant barrier to improving therapies for dystonia is a lack of understanding of its pathophysiology. Both genetic and extragenetic factors are believed to contribute, as evidenced by endophenotypes in both symptomatic and non-symptomatic carriers of dystonia-causing genes. These endophenotypes include loss of intracortical inhibition, maladaptive plasticity, and abnormal sensorimotor integration. However, most mouse behavioral assays are implemented independently of cortex. It is therefore important to identify dystonia mouse models in which motor cortex-dependent behaviors are altered in ways relevant to human disease. I implemented several behavioral paradigms with the goal of characterizing cortically-dependent behaviors in the recently developed Dlx-CKO mouse model of dystonia. I found that Dlx-CKO mice develop abnormal movements during a manual skilled reaching task and that these abnormal movements respond to antimuscarinics, which are used to treat human dystonia. Additional testing on an automated skilled reaching task failed to replicate these results, suggesting that task demands may influence development of abnormal movements. Automated skilled reaching also revealed that Dlx-CKO mice exhibit a primary motor deficit. This finding is supported by results in a pasta handling task showing that Dlx-CKO mice exhibit more frequent pasta drops. Lastly, grooming was used to assess innate motor sequence performance independently of cortex. Dlx-CKO mice exhibited normal syntactic chain sequences, but reduced chain initiation. This result parallels abnormalities in motor sequencing identified in genetic carriers of DYT1. This work establishes cortically-dependent motor abnormalities in a genetic mouse model of dystonia. These results support the use of a wider variety of behavioral assays to characterize dystonia models. The motor abnormalities identified in this work may facilitate determination of the interplay between genetic and extragenetic factors in the development of dystonia, and allow identification of physiologic changes that lead directly to impaired motor function.

BACKGROUND AND AIMS: In February 2020, the Organ Procurement and Transplantation Network replaced donor service area-based allocation of livers with acuity circles, a system based on three homogeneous circles around each donor hospital. This system has been criticized for neglecting to consider varying population density and proximity to coast and national borders. APPROACH AND RESULTS: Using Scientific Registry of Transplant Recipients data from July 2013 to June 2017, we designed heterogeneous circles to reduce both circle size and variation in liver supply/demand ratios across transplant centers. We weighted liver demand by Model for End-Stage Liver Disease (MELD)/Pediatric End-Stage Liver Disease (PELD) because higher MELD/PELD candidates are more likely to be transplanted. Transplant centers in the West had the largest circles; transplant centers in the Midwest and South had the smallest circles. Supply/demand ratios ranged from 0.471 to 0.655 livers per MELD-weighted incident candidate. Our heterogeneous circles had lower variation in supply/demand ratios than homogeneous circles of any radius between 150 and 1,000 nautical miles (nm). Homogeneous circles of 500 nm, the largest circle used in the acuity circles allocation system, had a variance in supply/demand ratios 16 times higher than our heterogeneous circles (0.0156 vs. 0.0009) and a range of supply/demand ratios 2.3 times higher than our heterogeneous circles (0.421 vs. 0.184). Our heterogeneous circles had a median (interquartile range) radius of only 326 (275–470) nm but reduced disparities in supply/demand ratios significantly by accounting for population density, national borders, and geographic variation of supply and demand. CONCLUSIONS: Large homogeneous circles create logistical burdens on transplant centers that do not need them, whereas small homogeneous circles increase geographic disparity. Using carefully designed heterogeneous circles can reduce geographic disparity in liver supply/demand ratios compared with homogeneous circles of radius ranging from 150 to 1,000 nm.

In our first survey of transplant centers in March 2020, >75% of kidney and liver programs were either suspended or operating under restrictions. To safely resume transplantation, we must understand the evolving impact of COVID-19 on transplant recipients and center-level practices. We therefore conducted a six-week follow-up survey May 7-15, 2020, and linked responses to the COVID-19 incidence map, with a response rate of 84%. Suspension of live donor transplantation decreased from 72% in March to 30% in May for kidneys and from 68% to 52% for livers. Restrictions/suspension of deceased donor transplantation decreased from 84% to 58% for kidneys and from 73% to 42% for livers. Resuming transplantation at normal capacity was envisioned by 83% of programs by August 2020. Exclusively using local recovery teams for deceased donor procurement was reported by 28%. Respondents reported caring for a total of 1166 COVID-19-positive transplant recipients; 25% were critically ill. Telemedicine challenges were reported by 81%. There was a lack of consensus regarding management of potential living donors or candidates with SARS-CoV-2. Our findings demonstrate persistent heterogeneity in center-level response to COVID-19 even as transplant activity resumes, making ongoing national data collection and real-time analysis critical to inform best practices.

Patients with liver cirrhosis (LC) are at an increased risk for postoperative complications after open inguinal hernia repair (OIHR). It is possible that orthotopic liver transplant (OLT) recipients may have better outcomes, given reversal of liver failure pathophysiology. Therefore, we sought to compare mortality risk, complications, length of stay (LOS), and cost associated with OIHR in OLT recipients versus LC.From the National Inpatient Sample (NIS), using ICD-9 codes, we found 83 OLT recipients and 764 patients with LC who underwent OIHR between 2002 and 2014. We used logistic, negative binomial, and multiple linear regression models to compare peri-operative mortality risk, postoperative complications, and LOS, and cost associated with OIHR in OLT recipients versus LC patients. Models were adjusted for patient demographic and clinical characteristics, and hospital factors.OLT recipients were younger (58 vs 61, p = 0.02), more likely to be privately insured (42.0% vs 24.6%, p = 0.006), less likely to have ascites at time of surgery (5.1% vs 18.9%, p = 0.003), and have surgery at large (84.3% vs 65.2%, p = 0.01) and teaching hospitals (84.2% vs 47.9%, p 0.001). There were no mortalities among OLT recipients, but 19 (2.5%) deaths among LC patients. OLT recipients had a similar risk of overall complications (adjusted odds ratio aOR = 0.71 1.30 2.41) and hospital-associated costs (adjusted cost ratio = 0.71 0.88 1.09). However, LOS was significantly different with OLT recipients having shorter LOS (adjusted LOS ratio = 0.56 0.70 0.89).Delaying OIHR in patients with LC until after OLT decreases LOS and may carry decreased mortality.

In March 2020, coronavirus disease 2019 (COVID-19) spread rapidly nationally, causing widespread emergent changes to the health system. Our goal was to understand the impact of the epidemic on kidney transplantation (KT), at both the national and center levels, accounting statistically for waitlist composition. Using Scientific Registry of Transplant Recipients data, we compared data on observed waitlist registrations, waitlist mortality, and living-donor and deceased-donor kidney transplants (LDKT/DDKT) March 15-April 30, 2020 to expected events calculated from preepidemic data January 2016-February 2020. There were few changes before March 15, at which point the number of new listings/DDKT/LDKT dropped to 18%/24%/87% below the expected value (all P&nbsp

Background The early effects of coronavirus disease 2019 (COVID-19) on transplantation are dramatic: >75% of kidney and liver programs are either suspended or operating under major restrictions. To resume transplantation, it is important to understand the prevalence of COVID-19 among transplant recipients, donors, and healthcare workers (HCWs) and its associated mortality. Methods To investigate this, we studied severe acute respiratory syndrome coronavirus 2 diagnostic test results among patients with end-stage renal disease or kidney transplants from the Johns Hopkins Health System (n = 235), and screening test results from deceased donors from the Southwest Transplant Alliance Organ Procurement Organization (n = 27), and donors, candidates, and HCWs from the National Kidney Registry and Viracor-Eurofins (n = 253) between February 23 and April 15, 2020. Results We found low rates of COVID-19 among donors and HCWs (0%-1%) who were screened, higher rates of diagnostic tests among patients with end-stage renal disease or kidney transplant (17%-20%), and considerable mortality (7%-13%) among those who tested positive. Conclusions These findings suggest the threat of COVID-19 for the transplant population is significant and ongoing data collection and reporting is critical to inform transplant practices during and after the pandemic.

COVID‐19 is a novel, rapidly changing pandemic: consequently, evidence‐based recommendations in solid organ transplantation (SOT) remain challenging and unclear. To understand the impact on transplant activity across the United States, and center‐level variation in testing, clinical practice, and policies, we conducted a national survey between March 24, 2020 and March 31, 2020 and linked responses to the COVID‐19 incidence map. Response rate was a very high 79.3%, reflecting a strong national priority to better understand COVID‐19. Complete suspension of live donor kidney transplantation was reported by 71.8% and live donor liver by 67.7%. While complete suspension of deceased donor transplantation was less frequent, some restrictions to deceased donor kidney transplantation were reported by 84.0% and deceased donor liver by 73.3%; more stringent restrictions were associated with higher regional incidence of COVID‐19. Shortage of COVID‐19 tests was reported by 42.5%. Respondents reported a total of 148 COVID‐19 recipients from 10 years posttransplant: 69.6% were kidney recipients, and 25.0% were critically ill. Hydroxychloroquine (HCQ) was used by 78.1% of respondents; azithromycin by 46.9%; tocilizumab by 31.3%, and remdesivir by 25.0%. There is wide heterogeneity in center‐level response across the United States; ongoing national data collection, expert discussion, and clinical studies are critical to informing evidence‐based practices.

Recently, the Organ Procurement and Transplant Network approved a plan to allocate kidneys within 250-nm circles around donor hospitals. These homogeneous circles might not substantially reduce geographic differences in transplant rates because deceased donor kidney supply and demand differ across the country. Using Scientific Registry of Transplant Recipients data from 2016-2019, we used an integer program to design unique, heterogeneous circles with sizes between 100 and 500 nm that reduced supply/demand ratio variation across transplant centers. We weighted demand according to wait time because candidates who have waited longer have higher priority. We compared supply/demand ratios and average travel distance of kidneys, using heterogeneous circles and 250 and 500-nm fixed-distance homogeneous circles. We found that 40% of circles could be 250 nm or smaller, while reducing supply/demand ratio variation more than homogeneous circles. Supply/demand ratios across centers for heterogeneous circles ranged from 0.06 to 0.13 kidneys per wait-year, compared to 0.04 to 0.47 and 0.05 to 0.15 kidneys per wait-year for 250-nm and 500-nm homogeneous circles, respectively. The average travel distance for kidneys using heterogeneous, and 250-nm and 500-nm fixed-distance circles was 173 nm, 134 nm, and 269 nm, respectively. Heterogeneous circles reduce geographic disparity compared to homogeneous circles, while maintaining reasonable travel distances.

Identification and inactivation of hybrid lethality genes can be used to expand the available gene pool for improvement of a cultivated crop species. Hybrid lethality is one genetic mechanism that contributes to reproductive isolation in plants and serves as a barrier to use of diverse germplasm for improvement of cultivated species. A classic example is the seedling lethality exhibited by progeny from the Nicotiana tabacum × N. africana interspecific cross. In order to increase the body of knowledge on mechanisms of hybrid lethality in plants, and to potentially develop tools to circumvent them, we utilized a transposon tagging strategy to identify a candidate gene involved in the control of this reaction. N. tabacum gene Nt6549g30 was identified to code for a class of coiled-coil nucleotide-binding site-leucine-rich repeat (CC-NBS-LRR) proteins, the largest class of plant defense proteins. Gene editing, along with other experiments, was used to verify that Nt6549g30 is the gene at the N. tabacum Hybrid Lethality 1 (NtHL1) locus controlling the hybrid lethality reaction in crosses with N. africana. Gene editing of Nt6549g30 was also used to reverse interspecific seedling lethality in crosses between N. tabacum and eight of nine additional tested species from section Suaveolentes. Results further implicate the role of disease resistance-like genes in the evolution of plant species and demonstrate the possibility of expanding the gene pool for a crop species through gene editing.

Infections remain a major threat to successful kidney transplantation (KT). To characterize the landscape and impact of post-KT infections in the modern era, we used United States Renal Data System (USRDS) data linked to the Scientific Registry of Transplant Recipients (SRTR) to study 141 661 Medicare-primary kidney transplant recipients from January 1, 1999 to December 31, 2014. Infection diagnoses were ascertained by International Classification of Diseases, Ninth Revision (ICD-9) codes. The cumulative incidence of a post-KT infection was 36.9% at 3 months, 53.7% at 1 year, and 78.0% at 5 years. The most common infections were urinary tract infection (UTI; 46.8%) and pneumonia (28.2%). Five-year mortality for kidney transplant recipients who developed an infection was 24.9% vs 7.9% for those who did not, and 5-year death-censored graft failure (DCGF) was 20.6% vs 10.1% (P < .001). This translated to a 2.22-fold higher mortality risk (adjusted hazard ratio [aHR]: 2.15 2.222.29 , P < .001) and 1.92-fold higher DCGF risk (aHR: 1.84 1.911.98 , P < .001) for kidney transplant recipients who developed an infection, although the magnitude of this higher risk varied across infection types (for example, 3.11-fold higher mortality risk for sepsis vs 1.62-fold for a UTI). Post-KT infections are common and substantially impact mortality and DCGF, even in the modern era. Kidney transplant recipients at high risk for infections might benefit from enhanced surveillance or follow-up to mitigate these risks.

Loeys-Dietz syndrome is a rare connective tissue disorder with widespread arterial tortuosity and aneurysms. This syndrome is most notable for its aortic disease, including aortic root dilation and aortic dissection or rupture. Although not as well studied, peripheral artery aneurysms are a prevalent concurrent manifestation and have previously been repaired with both open and endovascular approaches. There are minimal data about the durability and technical considerations of endovascular repair in this disease. We report a case of a patient who developed an extremely tortuous recurrent femoral-popliteal artery aneurysm secondary to aneurysmal degeneration around previously placed stents that was treated with an endovascular approach.

Recently, surgeon scientists have started to grapple with structural racism’s effect on health and prior academic failures in codifying and promoting institutionalized racism in research and clinical practice. In this Surgical Perspective, we hope to describe our journey of being humbled by the vast work of social epidemiologists on racism and health, and we will offer our reflections on how to apply this work to future research and practice.

It's Been Beautiful: “Soul!” and Black Power Television , by Gayle Wald. Photographs by Chester Higgins. Durham, NC: Duke University Press, 2015. x, 278 pp. Disconcerting, peculiar, provocative, and transformational are words that describe the history of the engagement between television, black America, and black music culture. Television, more than any other form of media, has historically been valued for its potential as an effective tool in fostering public sentiment. While the first generation of dramatic and comedic shows featuring black characters did not challenge the racial and ethnic stereotypes that had been advanced through popular culture, this changed with the highlighting of black music and black musicians on television during the 1950s and 1960s. Programs such as Ed Sullivan's Toast of the Town (later called The Ed Sullivan Show ), Steve Allen's Tonight Show , and Shindig! provided important platforms for the promotion of black music, black artistry, and racial pride. One needs only look to the countless baby boomers who recall seeing the Supremes or the Temptations on Ed Sullivan during the early 1960s for evidence. In the late 1960s, however, the relationship between black America and television changed significantly. In the wake of riots and racial unrest in a number of major cities, in 1967 President Lyndon B. Johnson charged the Kerner Commission with studying race relations in America. An entire section of the Commission's findings was devoted to the role of the media in perpetuating inflammatory representations of the black community. Although the commercial networks were …

Prioritization of highly sensitized (HS) candidates under the kidney allocation system (KAS) and growth of large, multicenter kidney-paired donation (KPD) clearinghouses have broadened the transplant modalities available to HS candidates. To quantify temporal trends in utilization of these modalities, we used SRTR data from 2009 to 2017 to study 39 907 adult HS (cPRA ≥ 80%) waitlisted candidates and 19 003 recipients. We used competing risks regression to quantify temporal trends in likelihood of DDKT, KPD, and non-KPD LDKT for HS candidates (Era 1: January 1, 2009-December 31, 2011; Era 2: January 1, 2012-December 3, 2014; Era 3: December 4, 2014-December 31, 2017). Although the likelihood of DDKT and KPD increased over time for all HS candidates (adjusted subhazard ratio [aSHR] Era 3 vs 1 for DDKT: (1.74)1.85(1.97), P < .001 and for KPD: (1.70)2.20(2.84), P < .001), the likelihood of non-KPD LDKT decreased (aSHR: (0.69)0.82(0.97), P = .02). However, these changes affected HS recipients differently based on cPRA. Among recipients, more cPRA 98%−99.9% and 99.9%+ recipients underwent DDKT (96.2% in Era 3% vs 59.1% in Era 1 for cPRA 99.9%+), whereas fewer underwent non-KPD LDKT (1.9% vs 30.9%) or KPD (2.0% vs 10.0%). Although KAS increased DDKT likelihood for the most HS candidates, it also decreased the use of non-KPD LDKT to transplant cPRA 98%+ candidates.

Rodent skilled reaching is commonly used to study dexterous skills, but requires significant time and effort to implement the task and analyze the behavior. Several automated versions of skilled reaching have been developed recently. Here, we describe a version that automatically presents pellets to rats while recording high-definition video from multiple angles at high frame rates (300 fps). The paw and individual digits are tracked with DeepLabCut, a machine learning algorithm for markerless pose estimation. This system can also be synchronized with physiological recordings, or be used to trigger physiologic interventions (e.g., electrical or optical stimulation).

A chromosome segment designated as Wz found to positively affect resistance of to black shank disease caused by Phytophthora nicotianae was previously introgressed from Nicotiana rustica into cultivated tobacco (N. tabacum). DNA markers associated with this region can aid in efforts to pyramid multiple mechanisms of black shank resistance into single new tobacco cultivars. In order to identify DNA markers associated with Wz, we generated RNA-seq data from roots of nearly isogenic lines (NILs) differing for the presence/absence of the alien genomic region. Analysis of SNPs, INDELs, and differentially expressed genes that distinguished the NILs suggested that the N. rustica Wz introgression replaced an approximately 65 Mb region of N. tabacum chromosome 19. The utility of a subset of derived Kompetitive Allele Specific PCR (KASP) and Cleaved Amplified Polymorphic Sequence (CAPS) markers for predicting the presence of Wz was verified using segregating populations and F3:4 families that were evaluated for field black shank resistance. The new markers are useful for overall efforts to develop tobacco cultivars containing novel gene combinations affecting soil-borne pathogen resistance.

Importance Initial hemodialysis access with arteriovenous fistula (AVF) is associated with superior clinical outcomes compared with arteriovenous graft (AVG) and should be the procedure of choice whenever possible. To address the national underuse of AVF in the United States, the Centers for Medicare & Medicaid has established an AVF goal of 66% or greater in 2009. Objective To explore contemporary practice patterns and physician characteristics associated with high AVG use compared with AVF use. Design, Setting, and Participants This review of 100% Medicare Carrier claims between January 1, 2016, and December 31, 2017, includes both inpatient and outpatient Medicare claims data. All patients undergoing initial permanent hemodialysis access placement with an AVF or AVG were included. All surgeons performing more than 10 hemodialysis access procedures during the study period were analyzed. Exposures Placement of an AVF or AVG for initial permanent hemodialysis access. Main Outcomes and Measures A surgeon-level AVG (vs AVF) use rate was calculated for all included surgeons. Hierarchical logistic regression modeling was used to identify patient-level and surgeon-level factors associated with AVG use. Results A total of 85 320 patients (median age, 70 [range, 18-103] years; 47 370 men [55.5%]) underwent first-time hemodialysis access placement, of whom 66 489 (77.9%) had an AVF and 18 831 (22.1%) had an AVG. Among the 2397 surgeons who performed more than 10 procedures per year, the median surgeon level AVG use rate was 18.2% (range, 0.0%-96.4%). However, 498 surgeons (20.8%) had an AVG use rate greater than 34%. After accounting for patient characteristics, surgeon factors that were independently associated with AVG use included more than 30 years of clinical practice (vs 21-30 years; odds ratio, 0.85 [95% CI, 0.75-0.96]), metropolitan setting (odds ratio, 1.25 [95% CI, 1.02-1.54]), and vascular surgery specialty (vs general surgery; odds ratio, 0.77 [95% CI, 0.69-0.86]). Surgeons in the Northeast region had the lowest rate of AVG use (vs the South; odds ratio, 0.83 [95% CI, 0.73-0.96]). First-time hemodialysis access benchmarking reports for individual surgeons were created for potential distribution. Conclusions and Relevance In this study, one-fifth of surgeons had an AVG use rate above the recommended best practices guideline of 34%. Although some of these differences may be explained by patient referral practices, sharing benchmarked performance data with surgeons could be an actionable step in achieving more high-value care in hemodialysis access surgery.