Intravenous Levothyroxine for Unstable Brain-Dead Heart Donors.

BACKGROUND: Hemodynamic instability and myocardial dysfunction are major factors preventing the transplantation of hearts from organ donors after brain death. Intravenous levothyroxine is widely used in donor care, on the basis of observational data suggesting that more organs may be transplanted from donors who receive hormonal supplementation. METHODS: In this trial involving 15 organ-procurement organizations in the United States, we randomly assigned hemodynamically unstable potential heart donors within 24 hours after declaration of death according to neurologic criteria to open-label infusion of intravenous levothyroxine (30 µg per hour for a minimum of 12 hours) or saline placebo. The primary outcome was transplantation of the donor heart; graft survival at 30 days after transplantation was a prespecified recipient safety outcome. Secondary outcomes included weaning from vasopressor therapy, donor ejection fraction, and number of organs transplanted per donor. RESULTS: Of the 852 brain-dead donors who underwent randomization, 838 were included in the primary analysis: 419 in the levothyroxine group and 419 in the saline group. Hearts were transplanted from 230 donors (54.9%) in the levothyroxine group and 223 (53.2%) in the saline group (adjusted risk ratio, 1.01; 95% confidence interval [CI], 0.97 to 1.07; P = 0.57). Graft survival at 30 days occurred in 224 hearts (97.4%) transplanted from donors assigned to receive levothyroxine and 213 hearts (95.5%) transplanted from donors assigned to receive saline (difference, 1.9 percentage points; 95% CI, -2.3 to 6.0; P<0.001 for noninferiority at a margin of 6 percentage points). There were no substantial between-group differences in weaning from vasopressor therapy, ejection fraction on echocardiography, or organs transplanted per donor, but more cases of severe hypertension and tachycardia occurred in the levothyroxine group than in the saline group. CONCLUSIONS: In hemodynamically unstable brain-dead potential heart donors, intravenous levothyroxine infusion did not result in significantly more hearts being transplanted than saline infusion. (Funded by Mid-America Transplant and others; ClinicalTrials.gov number, NCT04415658.).

Pancreas transplantation perceptions and practice: Results from a national US survey.

BACKGROUND: Due to a substantial decline in pancreas transplantation (PT) across the United States over the past 15 years, we sought to understand the perceptions and practices of US PT programs. METHODS: Surveys were sent to members of the American Society of Transplantation Surgeons and the American Society of Transplantation by email and professional society postings between August 2019 and November 2019. RESULTS: One hundred twenty three responses were recorded from 56 unique programs. Program characteristics were obtained from the Scientific Registry of Transplant Recipients. Respondents were transplant surgeons (71%), transplant nephrologists (17%), trainees (9%), and allied professionals (3%). Programs were defined according to annual volume as: low (<5 PT/year), intermediate (6-20), or high (>20). High-volume programs reported that these factors were most important for increased PT: expansion of recipient selection, more aggressive donor utilization, and hiring of PT program-specific personnel. At both the program and national level, the vast majority (82% and 79%, respectively) felt the number of PTs currently performed are not in balance with patients' needs. CONCLUSIONS: Overall, programs reported that the option of PT is not offered adequately to diabetic patients and that strategies to maintain higher PT volume are most evident at intermediate, and especially, high-volume programs.

Intensive Care Unit Enhanced Recovery Pathway for Patients Undergoing Orthotopic Liver Transplants Recipients: A Prospective, Observational Study.

BACKGROUND: Liver transplant recipients continue to have high perioperative resource utilization and prolonged length of stay despite improvements in perioperative care. Enhanced recovery pathways have been shown in other surgical populations to produce reductions in hospital resource utilization. METHODS: A prospective, observational study was performed to examine the effect of an enhanced recovery pathway for postoperative care after liver transplantation. Outcomes from patients undergoing liver transplantation from November 1, 2013, to October 31, 2014, managed by the pathway were compared to transplant recipients from the year before pathway implementation. Multivariable regression analysis was used to assess the association of the clinical pathway on clinical outcomes. RESULTS: The intervention and control groups included 141 and 106 patients, respectively. There were no demographic differences between the control and intervention group including no differences between the length of surgery and cold ischemic time. Median intensive care unit length of stay was reduced from 4.4 to 2.6 days (P < .001). The intervention group had a higher likelihood of earlier discharge (hazard ratio [95% CI], 2.01 [1.55-2.62]; P < .001), and a 69% and 65% lower odds of receiving a plasma (P < .001) or packed red blood cell (P < .001) transfusion. There was no significant effect on hospital mortality (P = .40), intensive care unit readmission rates (P = .75), or postoperative infections (urinary traction infections: P = .09; pneumonia: P = .27). CONCLUSIONS: An enhanced recovery pathway focused on milestone-based elements of intensive care unit management and predetermined management triggers including hemodynamic goals, fluid therapy, perioperative antibiotics, glycemic control, and standardized transfusion triggers led to reductions in intensive care unit length of stay without an increase in perioperative complications.

Combined In Silico and In Vitro Approach Predicts Low Wall Shear Stress Regions in a Hemofilter that Correlate with Thrombus Formation In Vivo.

A major challenge in developing blood-contacting medical devices is mitigating thrombogenicity of an intravascular device. Thrombi may interfere with device function or embolize from the device to occlude distant vascular beds with catastrophic consequences. Chemical interactions between plasma proteins and bioengineered surface occur at the nanometer scale; however, continuum models of blood predict local shear stresses that lead to platelet activation or aggregation and thrombosis. Here, an iterative approach to blood flow path design incorporating in silico, in vitro, and in vivo experiments predicted the occurrence and location of thrombi in an implantable hemofilter. Low wall shear stress (WSS) regions identified by computational fluid dynamics (CFD) predicted clot formation in vivo. Revised designs based on CFD demonstrated superior performance, illustrating the importance of a multipronged approach for a successful design process.

An Outcome-Based Approach to Assign MELD Exception Points for Patients With Hepatocellular Cancer.

BACKGROUND: Current Model for End-Stage Liver Disease (MELD) exception points provided to patients with hepatocellular cancer (HCC) are not based on outcome data and advantage these patients compared to those listed based on laboratory values (LABMELD). We sought to develop a data-based assignment for exception points for patients with HCC that equalizes outcomes among HCC and LABMELD patients. METHODS: We used Scientific Registry of Transplant Recipients data to compare patients listed with HCC who received exception points versus patients listed with LABMELD. Nation- and region-specific data were examined for (1) a composite outcome for adverse events of death, delisting, or becoming ineligible for transplant; and (2) transplant rate. We also determined MELD progression rates for LABMELD patients. Candidates listed with LABMELD scores were compared with those listed with 22 exception points for HCC (HCC22) to determine the LABMELD for which statistical parity was achieved for our composite outcome. RESULTS: HCC22 candidates time to adverse event were comparable to LABMELD scores of 16 (LABMELD16) candidates (range, 15-19), whereas time to transplant was comparable to LABMELD22 candidates (range, 21-23). LABMELD22 candidates had 2.1 times greater risk of adverse event compared with HCC22 (95% confidence interval, 1.9-2.4; range, 1.5-2.4). Progression among LABMELD16 candidates whose scores did not improve was similar across regions and averaged 0.94 points/month (95% confidence interval, 0.88-0.99, range 0.80-1.04). CONCLUSIONS: To equalize the occurrence of an adverse outcome, the proper listing MELD for patients with HCC is 16, with approximately 1 additional point/month. These results provide a data-driven algorithm to increase fairness in listing priority.

Longitudinal assessment of cardiac morphology and function following kidney transplantation.

BACKGROUND: Abnormal cardiac morphology is a risk factor for cardiovascular complications in kidney transplant patients. A supraphysiologic level of fibroblast growth factor 23 (FGF-23) has been associated with myocardial hypertrophy in this patient population. Our aim was to evaluate the change in cardiac morphology and function following kidney transplantation and to evaluate the association between the change in FGF-23 concentrations and cardiac morphology. METHODS: We performed a longitudinal, prospective cohort study of 143 kidney transplant recipients (73% male, 75% white) measuring left ventricular (LV) mass index, left atrial (LA) volume index, and ejection fraction (EF) by echocardiography at months 1, 12, and 24 post-transplant. FGF-23 levels were measured at months 1 and 24 post-transplant. RESULTS: Unadjusted and adjusted linear mixed-effects models were used to examine changes in outcomes over time. In the adjusted model, LV mass index (P<.001) and LA volume index (P<.001) decreased and EF (P=.009) increased significantly over time. There was a significant association between decreasing FGF-23 levels and improving LV mass index following transplant (P=.036) in the unadjusted model; however, there was no significant relationship in the adjusted model (0.195). CONCLUSION: Understanding the progression of unique cardiovascular risk factors associated with kidney transplantation may provide potential opportunities to improve survival.

Long term evolution of endothelial function during kidney transplantation.

BACKGROUND: Endothelial dysfunction is an important precursor to the development of atherosclerosis, and has been suggested to play a role in the increased cardiovascular risk in patients with end stage renal disease. Endothelial function improves rapidly following post kidney transplantation, but the long term change remains unclear. Hypothesizing that endothelial function would remain improved long term post kidney transplantation, we evaluated the longitudinal change of endothelial function, measured by flow-mediated dilation (FMD) of the brachial artery, from months 1 to 24 post transplantation. Given the previously reported association of fibroblast growth factor 23 (FGF-23) with endothelial dysfunction, we also examined changes in the association between FGF-23 levels and the change in FMD following kidney transplantation. METHODS: We performed a prospective cohort study of 149 kidney transplant recipients, measuring endothelial function by FMD at months 1, 12, and 24 post-transplant. FGF-23 levels were measured at months 1 and 24 post-transplant. Linear mixed effects models were used to assess both the unadjusted and adjusted outcomes. RESULTS: The cohort (mean age 49 ± 13 years) was 74 % male and 75 % white. The median FMD was 6.3 % (IQR: 3.4, 10.2), 5.4 % (IQR: 3.1, 8.5), and 5.6 % (IQR: 3.5, 9.1) at 1, 12, and 24 months, respectively. After adjustment for covariates, compared to month 1, no change occurred in FMD at 12 months (-0.66 %; 95 % CI: -1.81 %, 0.49 %; P = 0.262) or 24 months (-0.25 %; 95%CI: -1.76 %, 1.26 %; P = 0.746). FGF-23 decreased significantly over time (P = 0.024), but there was no significant association between FGF-23 and FMD (P = 0.799). CONCLUSION: Endothelial function remained stable at 12 and 24 months from 1 month post-kidney transplant, indicating that the improved endothelial function seen with transplant is maintained up to 2 years post transplantation. There was also no significant association between FGF-23 and endothelial function following kidney transplantation.

A comparison of patency and interventions in thigh versus Hemodialysis Reliable Outflow grafts for chronic hemodialysis vascular access.

OBJECTIVE: With improvements in medical management and survival of patients with end-stage renal disease, maintaining durable vascular access is increasingly challenging. This study compared primary, assisted primary, and secondary patency, and procedure-specific complications, and evaluated whether the number of interventions to maintain or restore patency differed between prosthetic femoral-femoral looped inguinal access (thigh) grafts and Hemodialysis Reliable Outflow (HeRO; Hemosphere Inc, Minneapolis, Minn) grafts. METHODS: A single-center, retrospective, intention-to-treat analysis was conducted of consecutive thigh and HeRO grafts placed between May 2004 and June 2015. Medical history, interventions to maintain or restore patency, and complications were abstracted from the electronic medical record. Data were analyzed using parametric and nonparametric statistical tests, Kaplan-Meier survival methods, and multivariable proportional hazards regression and logistic regression. RESULTS: Seventy-six (43 thigh, 33 HeRO) grafts were placed in 61 patients (54% male; age 53 [standard deviation, 13] years). Median follow-up time in the intention-to-treat analysis was 21.2 months (min, 0.0; max, 85.3 months) for thigh grafts and 6.7 months (min, 0.0; max, 56.3 months) for HeRO grafts (P = .02). The groups were comparable for sex, age, coronary artery disease, diabetes mellitus, peripheral vascular disease, and smoking history (all P ≥ .12). One thigh graft (2%) and five HeRO (15%) grafts failed primarily. In the intention-to-treat analysis, patency durations were significantly longer in the thigh grafts (all log-rank P ≤ .01). Point estimates of primary patency at 6 months, 1 year, and 3 years were 61%, 46%, and 4% for the thigh grafts and 25%, 15%, and 6% for the HeRO grafts. Point estimates of assisted primary patency at 6 months, 1 year, and 3 years were 75%, 66%, and 54% for the thigh grafts and 41%, 30%, and 10% for the HeRO grafts. Point estimates of secondary patency at 6 months, 1 year, and 3 years were 88%, 88%, and 70% for the thigh grafts and 53%, 43%, and 12% for the HeRO grafts. There were no differences in ischemic (P = .63) or infectious (P = .79) complications between the groups. Multivariable logistic regression demonstrated that after adjusting for follow-up time, HeRO grafts were associated with an increased number of interventions (P = .03). CONCLUSIONS: Thigh grafts have significantly better primary, assisted primary, and secondary patency compared with HeRO grafts. There is no significant difference between thigh grafts and HeRO grafts in ischemic or infectious complications. Our logistic regression model demonstrated an association between HeRO grafts and an increased number of interventions to maintain or restore patency. Although HeRO grafts may extend the use of the upper extremity, thigh grafts provide a more durable option for chronic hemodialysis.

Patient-reported outcomes in liver transplant recipients with hepatocellular carcinoma.

BACKGROUND: The effect of awarding MELD exception points for hepatocellular carcinoma (HCC) on patient-reported outcomes (PROs) is unknown. We evaluated the physical and mental health-related quality of life (HRQOL) and symptoms of anxiety and depression in liver transplant recipients with HCC compared to patients without HCC. METHODS: The single-center sample measured PROs before and after transplant, which included 1521 multisurvey measurement points among 502 adults (67% male, 28% HCC, follow-up time: <1-131 months). Data were analyzed using multivariable mixed-effects models. RESULTS: Longitudinal PRO values did not differ between persons who received HCC exception points and those who did not have HCC. Patients with HCC who did not receive exception points had reduced physical HRQOL (P=.016), a late decline in mental HRQOL, and delayed reduction in anxiety (time-by-outcome interaction P<.050) compared to patients with HCC who received exception points. CONCLUSION: Transplant recipients who received HCC exception points had PROs that were comparable to those of patients without HCC, and reported better physical HRQOL and reduced symptoms of anxiety compared to patients with HCC who did not receive exception points. These analyses demonstrate the impact of HCC exception points on PROs, and may help inform policy regarding HCC exception point allocation.

First Implantation of Silicon Nanopore Membrane Hemofilters.

An implantable hemofilter for the treatment of kidney failure depends critically on the transport characteristics of the membrane and the biocompatibility of the membrane, cartridge, and blood conduits. A novel membrane with slit-shaped pores optimizes the trade-off between permeability and selectivity, enabling implanted therapy. Sustained (3-8) day function of an implanted parallel-plate hemofilter with minimal anticoagulation was achieved by considering biocompatibility at the subnanometer scale of chemical interactions and the millimeter scale of blood fluid dynamics. A total of 400 nm-thick polysilicon flat sheet membranes with 5-8 nm × 2 micron slit-shaped pores were surface-modified with polyethylene glycol. Hemofilter cartridge geometries were refined based on computational fluid dynamics models of blood flow. In an uncontrolled pilot study, silicon filters were implanted in six class A dogs. Cartridges were connected to the cardiovascular system by anastamoses to the aorta and inferior vena cava and filtrate was drained to collection pouches positioned in the peritoneum. Pain medicine and acetylsalicylic acid were administered twice daily until the hemofilters were harvested on postoperative days 3 (n = 2), 4 (n = 2), 5 (n = 1), and 8 (n = 1). No hemofilters were thrombosed. Animals treated for 5 and 8 days had microscopic fractures in the silicon nanopore membranes and 20-50 ml of transudative (albumin sieving coefficient θalb ~ 0.5 - 0.7) fluid in the collection pouches at the time of explant. Shorter experimental durations (3-4 days) resulted in filtration volumes similar to predictions based on mean arterial pressures and membrane hydraulic permeability and (θalb ~ 0.2 - 0.3), similar to preimplantation measurements. In conclusion, a detailed mechanistic and materials science attention to blood-material interactions allows implanted hemofilters to resist thrombosis. Additional testing is needed to determine optimal membrane characteristics and identify limiting factors in long-term implantation.

Characterizing the Clamor: An In-Depth Analysis of Inpatient Paging Communication.

PURPOSE: Communication failures contribute to adverse clinical events and health care inefficiencies. Paged messaging remains a predominant communication mechanism at many academic medical centers. An interprofessional, institutionally sponsored initiative to improve inpatient care team communication sought to understand the content and quantity of paged messages. METHOD: A retrospective analysis at Vanderbilt University Medical Center was performed for messages delivered to the 15 highest-volume pagers carried by inpatient medical, surgical, and pediatric residents over two monthlong periods of data collection between November 2013 and February 2014. An interprofessional team defined message content categories a priori. Descriptive statistics were used to demonstrate message volume and distribution by content category. Team members and stakeholder groups discussed common message themes during and after categorization to identify targets for improving care efficiency. RESULTS: During the data collection period, 10,928 messages were paged (median 38 messages per pager per shift). The most common primary content categories were bedside nursing (2,570; 30%) and medication (2,285; 26%). Common bedside nursing communications included notification of vital signs (915; 36%), patient activity (481; 19%), and diet (444; 18%). Most medication messages were requests to start (1,253; 55%) or change (694; 30%) a common medication. The team recommended implementing anticipatory orders for common medications and routine nursing staff needs using computerized order algorithms to reduce the volume of noncritical messages. CONCLUSIONS: An interprofessional assessment of the content and volume of paged communication identified high volumes of noncritical messages that could be eliminated through better anticipation of patient care needs.

Residents as Educators: A Modern Model.

Education during surgical residency has changed significantly. As part of the shifting landscape, the importance of an organized and structured curriculum has increased. However, establishing this is often difficult secondary to clinical demands and pressure both on faculty and residents. We present a peer-assisted learning model for academic institutions without professional non-clinical educations. The "resident as educator" (RAE) model empowers residents to be the organizers of the education curriculum. RAE is built on a culture of commitment to education, skill development and team building, allowing the upper level residents to develop and execute the curriculum. Several modules designed to address junior level residents and medical students' educational needs have been implemented, including (1) intern boot camp, (2) summer school, (3) technical skill sessions, (4) trauma orientation, (5) weekly teaching conferences, and (4) a fourth year medical student surgical preparation course. Promoting residents as educators leads to an overall benefit for the program by being cost-effective and time-efficient, while simultaneously promoting professional development of residents and a culture of education.

Multidisciplinary team approach to end-stage dialysis access patients.

BACKGROUND: The hemodialysis reliable outflow (HeRO) access device is a permanent dialysis graft used in patients with central venous obstruction. Given the complexity of care related to end-stage dialysis access (ESDA) patients, a multidisciplinary approach has been used to achieve operative success of HeRO graft placement. METHODS: The single-center retrospective review included adult patients that were seen in ESDA clinic who underwent a HeRO graft placement from September 2010-September 2014 under the care of a team consisting of a nephrologist, an interventional radiologist, and a surgeon. The effectiveness of the multidisciplinary approach was evaluated using outcome variables including successful HeRO graft placement, operative complications, the rate of obtaining central venous access, and advanced endovascular maneuvers performed by interventional radiology to obtain central venous access. RESULTS: A multidisciplinary approach has been used in 33 ESDA patients. Access to the right atrium was achieved in 100% of cases. Fifty-eight percent of patients required advanced endovascular maneuvers in the interventional radiology suite to obtain central venous access. Successful HeRO graft placement was achieved in 94% (31 of 33) of the study population. No intraoperative complications were encountered. Median primary and secondary patency rates were 83 d (interquartile range: 45-170) and 345 d (interquartile range: 146-579) per HeRO graft placement, respectively. Primary and secondary patency rates at 60 d were 70% (23 of 33) and 79% (26 of 33), respectively. CONCLUSIONS: In this difficult patient population, a multidisciplinary team can provide a unique and collaborative approach to HeRO graft placement in patients with complex central venous outflow obstruction.

Accuracy of FDG-PET to diagnose lung cancer in areas with infectious lung disease: a meta-analysis.

IMPORTANCE: Positron emission tomography (PET) combined with fludeoxyglucose F 18 (FDG) is recommended for the noninvasive diagnosis of pulmonary nodules suspicious for lung cancer. In populations with endemic infectious lung disease, FDG-PET may not accurately identify malignant lesions. OBJECTIVES: To estimate the diagnostic accuracy of FDG-PET for pulmonary nodules suspicious for lung cancer in regions where infectious lung disease is endemic and compare the test accuracy in regions where infectious lung disease is rare. DATA SOURCES AND STUDY SELECTION: Databases of MEDLINE, EMBASE, and the Web of Science were searched from October 1, 2000, through April 28, 2014. Articles reporting information sufficient to calculate sensitivity and specificity of FDG-PET to diagnose lung cancer were included. Only studies that enrolled more than 10 participants with benign and malignant lesions were included. Database searches yielded 1923 articles, of which 257 were assessed for eligibility. Seventy studies were included in the analysis. Studies reported on a total of 8511 nodules; 5105 (60%) were malignant. DATA EXTRACTION AND SYNTHESIS: Abstracts meeting eligibility criteria were collected by a research librarian and reviewed by 2 independent reviewers. Hierarchical summary receiver operating characteristic curves were constructed. A random-effects logistic regression model was used to summarize and assess the effect of endemic infectious lung disease on test performance. MAIN OUTCOME AND MEASURES: The sensitivity and specificity for FDG-PET test performance. RESULTS: Heterogeneity for sensitivity (I2 = 87%) and specificity (I2 = 82%) was observed across studies. The pooled (unadjusted) sensitivity was 89% (95% CI, 86%-91%) and specificity was 75% (95% CI, 71%-79%). There was a 16% lower average adjusted specificity in regions with endemic infectious lung disease (61% [95% CI, 49%-72%]) compared with nonendemic regions (77% [95% CI, 73%-80%]). Lower specificity was observed when the analysis was limited to rigorously conducted and well-controlled studies. In general, sensitivity did not change appreciably by endemic infection status, even after adjusting for relevant factors. CONCLUSIONS AND RELEVANCE: The accuracy of FDG-PET for diagnosing lung nodules was extremely heterogeneous. Use of FDG-PET combined with computed tomography was less specific in diagnosing malignancy in populations with endemic infectious lung disease compared with nonendemic regions. These data do not support the use of FDG-PET to diagnose lung cancer in endemic regions unless an institution achieves test performance accuracy similar to that found in nonendemic regions.