Physical Frailty Predicts Outcomes in Patients Undergoing Evaluation for Kidney Transplantation.

INTRODUCTION: An increasing number of older patients are undergoing evaluation for kidney transplantation; however, older patients experience increased rates of complications compared with younger patients, leading to the study of frailty assessments. Although many centers have evaluated the Fried Frailty Phenotype (FFP), less is known about the ability of the Short Performance Physical Battery (SPPB) to predict outcomes. METHODS: Frailty assessment by FFP and SPPB was introduced into routine outpatient evaluation for patients aged 55 years and older referred for transplantation. Transplant rate, length of stay, readmission up to 3 months posttransplant, and death were reviewed. Patients were evaluated in an initial cohort followed by a validation cohort by FFP and SPPB. Multivariate analysis correcting for demographic characteristics was applied. RESULTS: Patient cohorts reflected the racial and ethnic diversity of our population, including approximately 40% Hispanic patients. The first cohort of 514 patients demonstrated a significant association between frailty as measured by SPPB and transplantation (odds ratio [OR], 2.27; 95% CI, 1.38-3.83; p = .002). The second cohort of 1408 patients validated the association between frailty measured by SPPB and transplantation (OR, 2.81; 95% CI, 1.83-4.48; p < .001). In addition, there was a significant association between nonfrail status measured by SPPB and death (OR, 0.16; 95% CI, 0.04-0.62; p = .006). CONCLUSIONS: Frailty assessment is a potentially useful approach for the assessment of transplant candidates. Our real-world study examined the performance of 2 methods of frailty evaluation methods in a diverse population, demonstrating that SPPB but not FFP was predictive of clinical outcomes. Incorporation of frailty assessments into transplant evaluation may improve risk stratification and optimize outcomes for older patients.

CPR in correctional facilities: a missed opportunity?

In the incarcerated population, the largest ethnic and racial group is Black people. Heart disease is known as the leading causes of death in the United States which can lead to cardiac arrest. Layperson cardiopulmonary resuscitation (CPR) has been shown to provide a benefit and increase likelihood of return of spontaneous circulation (ROSC). Recent research shows that in witnessed out of hospital cardiac arrests, the likelihood of receiving bystander CPR was found to be less among Black or Hispanic people when compared to White persons. One neglected area for layperson CPR training are these correctional facilities. This population is known to have higher rates of diabetes, high blood pressure and coronary artery disease, all of which contribute to an increased risk of acute coronary syndrome.A search was performed of the NEMSIS database. When comparing witnessed cardiac arrest, incidents without bystander interventions occurred more frequently than expected if the arrest was witnessed by a family member or other lay person. These interventions included bystander CPR or AED placement with or without defibrillation.The data presented shows that there is an unmet need of additional lay person CPR training in correctional facilities which could be implemented for little cost.

A Covid -19 Virtual Ward Model: A Preliminary Retrospective Clinical Evaluation From a UK District General Hospital.

OBJECTIVE: This study aims to evaluate the safety, utilization, ability to reduce length of hospitalization and overall outcomes of a COVID-19 virtual ward providing ongoing treatment at home. METHOD: A retrospective single-center study of patients discharged to the COVID-19 virtual "step down" ward between January 27th 2021 and March 2nd 2021. The referral process, length of hospitalization, length of stay on the virtual ward, readmissions, and ongoing treatment requirements including supplemental oxygen, antibiotics, and/or steroids were all noted. RESULTS: A total of 50 patients were referred to the virtual ward. 43 referrals were accepted, 39 of which were from the respiratory ward. Four patients were readmitted, all due to hypoxia. All readmissions occurred within 5 days of discharge. 72% (n = 31) were discharged home with an ongoing oxygen requirement. 14.3% of patients were discharged with antibiotics only, 9.5% with steroids only and 23.8% with both antibiotics and steroids. The mean length of hospital stay for patients discharged to the virtual ward was 10.3 ± 9.7 days and 11.9 ± 11.6 days for all covid positive patients during this time. On average, patients spent 13.7 ± 7.3 days on the virtual ward. The average number of days spent on oxygen on the virtual ward was 11.6 ± 6.0 days. CONCLUSION: The virtual ward model exemplifies the potential benefits of collaborative working between primary and secondary care services, relieving pressure on hospitals whilst providing ongoing treatments at home such as supplemental oxygen. It also facilitates an early supported discharge of clinically stable patients with an improving clinical trajectory by managing them in the community.

Spectrum of Coronavirus Disease 2019 Outcomes in Kidney Transplant Recipients: A Single-Center Experience.

PURPOSE: We reviewed the clinical experience of kidney transplant recipients diagnosed with severe acute respiratory syndrome coronavirus 2 infection in order to understand the impact of the current coronavirus disease 2019 (COVID-19) pandemic infection on transplant recipients. Given that early reports from heavily affected areas demonstrated a very high mortality rate amongst kidney transplant recipients, ranging between 30% and 40%, we sought to evaluate outcomes at a center with a high burden of cases but not experiencing acute crisis due to COVID-19. PROCEDURES: In this single center retrospective observational study, medical records of all kidney transplant recipients at the UCLA Medical Center were reviewed for a diagnosis of COVID-19 by polymerase chain reaction, followed by chart review to determine kidney transplant characteristics and clinical course. MAIN FINDINGS: A total of 41 kidney transplant recipients were identified with COVID-19 positive polymerase chain reaction. Recipients had been transplanted for a median of 47 months before diagnosis. The large proportion of infected individuals were minorities (Hispanic 65.9%, black 14.6%), on prednisone, tacrolimus, and mycophenolate mofetil (95.1%, 87.8%, and 87.8%, respectively), and had excellent allograft function (median 1.25 mg/dL). The most common presenting symptoms were fever, dyspnea, or cough. Most patients were hospitalized (63.4%); mortality was 9.8% and occurred only in patients in the intensive care unit. The most common treatment was reduction or removal of antimetabolite (77.8%). Approximately 26.9% presented with AKI. CONCLUSIONS: COVID-19 infection in kidney transplant recipients results in a higher rate of hospitalization and mortality than in the general population. In an area with a high number of infections, the mortality rate was lower compared with earlier reports from areas experiencing early surge and strain on the medical system. Minorities were disproportionately affected. Future studies are needed to determine optimal approach to treatment and management of immunosuppression in kidney transplant recipients with COVID-19 infection.

Vicarious resilience in sexual assault and domestic violence advocates.

OBJECTIVE: There is little research related to sexual assault and domestic violence advocates' experiences, with the bulk of the literature focused on stressors and systemic barriers that negatively impact efforts to assist survivors. However, advocates participating in these studies have also emphasized the positive impact they experience consequent to their work. This study explores the positive impact. METHOD: Vicarious resilience, personal trauma experiences, peer relational quality, and perceived organizational support in advocates (n = 222) are examined. Also, overlap among the conceptual components of vicarious resilience is explored. RESULTS: The first set of multiple regressions showed that personal trauma experiences and peer relational health predicted compassion satisfaction and vicarious posttraumatic growth, with organizational support predicting only compassion satisfaction. The second set of multiple regressions showed that (a) there was significant shared variance between vicarious posttraumatic growth and compassion satisfaction; (b) after accounting for vicarious posttraumatic growth, organizational support accounted for significant variance in compassion satisfaction; and (c) after accounting for compassion satisfaction, peer relational health accounted for significant variance in vicarious posttraumatic growth. CONCLUSIONS: Results suggest that it may be more meaningful to conceptualize advocates' personal growth related to their work through the lens of a multidimensional construct such as vicarious resilience. Organizational strategies promoting vicarious resilience (e.g., shared organizational power, training components) are offered, and the value to trauma-informed care of fostering advocates' vicarious resilience is discussed. (PsycINFO Database Record

Perioperative Analgesic Management of Newborn Bladder Exstrophy Repair Using a Directly Placed Tunneled Epidural Catheter with 0.1% Ropivacaine.

Effective multimodal analgesia and sedation reduce the postoperative morbidity and mortality associated with newborn bladder exstrophy repair. Epidural analgesia is safe and effective for major surgery in neonates and infants, reducing the need for muscle relaxants, opioids, and ventilator support postoperatively. The risk of epidural catheter colonization typically dictates removal after 3 to 5 days. Tunneling the catheter subcutaneously reduces the risk of colonization, providing prolonged analgesia for patients requiring an extended immobilization to prevent compromise of the repair. In this report, we describe the postoperative analgesic management of an infant undergoing bladder exstrophy repair using a directly placed tunneled epidural catheter with ropivacaine 0.1% infusion. Because of the prolonged infusion, we also monitored plasma ropivacaine levels to preclude systemic toxicity from local anesthetic overdose.

Outcomes of simultaneous liver and kidney transplantation in relation to a high level of preformed donor-specific antibodies.

BACKGROUND: The protective effect of the liver allograft when simultaneously transplanted with a kidney in the setting of allosensitization is unclear. METHODS: We analyzed the significance of sensitization, defined based on positive cytotoxicity crossmatches, positive flow cytometry crossmatches, and/or the presence of high levels of donor-specific antibodies, on the outcomes of simultaneous liver and kidney (SLK) transplantation. We reviewed 56 SLK performed at our center through December 31, 2011 and identified 13 patients who met high sensitization criteria. RESULTS: Median patient survival was not significantly different: 86 months (95% confidence interval [CI], 47-135) for nonsensitized patients versus 151 months (95% CI, 4 to ∞) for sensitized patients (P=0.5). The 5-year survival was 67% (95% CI, 0.5-0.8) in the nonsensitized group and 64% (95% CI, 0.3-0.9) in the sensitized group. There were six renal allograft failures in the nonsensitized group but none in the sensitized group. The adjusted hazard ratios associated with the risk of death or the combined risk of death or renal allograft failure were 0.7 (95% CI, 0.1-3.8) and 0.4 (95% CI, 0.1-2.2) for sensitized versus nonsensitized patients. There were significantly more renal allograft rejections in the sensitized group (5 vs. 1; P=0.002) in the first year after transplantation, only one showing C4d positivity. Creatinine levels at 1 year after transplantation were similar: 1.5 mg/dL in the nonsensitized group versus 1.36 mg/dL in the sensitized group (P=0.6). CONCLUSION: Sensitization does not appear to have a significant negative impact on the survival of SLK patients.

Continuous intraoperative TEE monitoring for a child with Fontan pathway undergoing post spinal fusion.

The following case report describes a very challenging surgical case where the use of intraoperative, continuous TEE monitoring in the prone position was crucial for the anesthetic management (diagnosis and treatment) of a patient with single ventricle physiology. The use of TEE monitoring enabled the anesthesia team to continuously assess hemodynamic stability and respond immediately to hypotension and bradycardia in our patient, thereby providing optimal anesthetic care of the intraoperative spinal fusion patient with Fontan physiology.

Donor-recipient size matching influences early but not late graft function after pediatric en-bloc kidney transplantation.

BACKGROUND: Pediatric en-bloc kidney transplantation into adult recipients is an accepted technique to expand the donor pool. Concerns about adequate "nephron dosing" have traditionally favored placing these kidneys into smaller recipients. METHODS: We reviewed 20 pediatric en-bloc transplants performed at our institution between 2002 and 2008. We examined the impact of donor age, donor weight, recipient sex, combined kidney length, recipient weight, recipient-to-donor weight ratio, and recipient weight gain on serum creatinine over time using regression analysis. RESULTS: Patient survival was 100%. Two grafts were lost early from vascular thrombosis. Of the remaining 18 recipients, all had immediate and excellent long-term function with average creatinine of 0.91+/-0.38 mg/dL at a mean follow-up of 1257+/-656 days. For 17 patients with 1 year follow-up, recipient weight, recipient-to-donor weight ratio, and recipient male sex negatively influenced renal function at 1 month. However, this relationship was lost by 1 year with increasing function in the smallest donors and largest size mismatches. Between 1 month and 1 year posttransplant, estimated creatinine clearance improved from 59+/-13 mL/min at 1 month posttransplant to 88+/-41 mL/min (P<0.015). Weight gain after transplant was associated with improved creatinine clearance, suggesting continued adaptation over time. CONCLUSIONS: We conclude that donor or recipient size matching up to a recipient-to-donor weight ratio of 7.5 does not significantly impact later renal function after pediatric en-bloc kidney transplantation into adults.

Combination of peritubular c4d and transplant glomerulopathy predicts late renal allograft failure.

The histologic associations and clinical implications of peritubular capillary C4d staining from long-term renal allografts are unknown. We identified 99 renal transplant patients who underwent an allograft biopsy for renal dysfunction at least 10 yr after transplantation, 25 of whom were C4d-positive and 74 of whom were C4d-negative. The average time of the index biopsy from transplantation was 14 yr in both groups. Compared with C4d-negative patients, C4d-positive patients were younger at transplantation (29 +/- 13 versus 38 +/- 12 yr; P < 0.05) and were more likely to have received an allograft from a living donor (65 versus 35%; P < 0.001). C4d-positive patients had more inflammation, were more likely to have transplant glomerulopathy, and had worse graft outcome. The combined presence of C4d positivity, transplant glomerulopathy, and serum creatinine of >2.3 mg/dl at biopsy were very strong predictors of rapid graft loss. C4d alone did not independently predict graft loss. Retrospective staining of historical samples from C4d-positive patients demonstrated C4d deposition in the majority of cases. In summary, these data show that in long-term renal allografts, peritubular capillary staining for C4d occurs in approximately 25% of biopsies, can persist for many years after transplantation, and strongly predicts graft loss when combined with transplant glomerulopathy.

Care home medicine in the UK--in from the cold.

The quality of care within care homes comes under frequent media scrutiny, and is underpinned by the medical support to the staff. In the UK, medical care to care homes is provided by general practitioners. A GP is likely to have patients in many homes, and each home relates to many GPs. The growing complexity of patients in care requires proactive models of care delivered by those with an understanding of care home medicine. A range of innovative models of medical care are emerging across the UK which have the potential to improve the standard of care in homes, and reduce inappropriate use of secondary care admissions. These models are described, and the need for them to be subjected to evaluation.

Higher levels of leflunomide are associated with hemolysis and are not superior to lower levels for BK virus clearance in renal transplant patients.

BACKGROUND AND OBJECTIVES: Leflunomide use in renal transplantation has been increasing. Outcome correlation and safety data are still to be refined. The goals of this study were to report one center's experience with leflunomide, specifically the correlation of leflunomide levels with the outcomes of BK nephropathy and the observed toxic effects during the treatment with leflunomide. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Leflunomide was used in 21 patients with BK nephropathy. These patients were divided into two groups on the basis of the leflunomide levels achieved: Low-level group (<40 microg/ml) and high-level group (>40 microg/ml). RESULTS: During 13 mo of follow-up, there was no difference in the rate of serum BK viral clearance between the groups. There were three graft losses in the low-level group and one in the high-level group; however, creatinine levels were higher at the time of starting leflunomide in the low-level group. Leflunomide was also used in six patients with chronic allograft injury. No graft loss was observed during the follow-up period of 16 mo. Treatment with leflunomide seemed to be associated with a new toxicity, hemolysis, seen in four of the 27 patients so treated. Patients with hemolysis had high leflunomide levels (81.4 +/- 14 microg/ml) and worsening allograft function. Two patients had histologic evidence of thrombotic microangiopathy, which led to graft loss in one patient. CONCLUSIONS: The clinical correlation between leflunomide levels and outcomes needs to be further refined. This study described a possible association of leflunomide with thrombotic microangiopathy, especially at higher levels.

Development of posttransplant antidonor HLA antibodies is associated with acute humoral rejection and early graft dysfunction.

BACKGROUND: The goal of this study was to determine whether the production of posttransplant antibodies directed against donor HLA mismatches (donor specific antibody; DSA) is associated with renal allograft rejection and early graft dysfunction. METHODS: Forty-nine adult renal allograft recipients with increased risk of rejection were enrolled during the period of October 2001 through May 2003 and were prospectively monitored for the development of anti-HLA antibodies. RESULTS: Of 49 patients, eight (16.3 %) patients were diagnosed with acute humoral rejection (AHR) and 11/49 (22.4%) patients were diagnosed with acute cellular rejection (ACR). A strong association between pretransplant HLA sensitization and AHR was found (P=0.005). Of the eight patients diagnosed with AHR, the majority developed DSA before or concomitant with episodes of rejection (P<0.001). Only 3 of 41 patients (7.3%) without AHR developed DSA. The pathogenic role of alloantibodies was further substantiated by analyzing their association with graft function as measured by serum creatinine levels. The average serum creatinine after the third month posttransplantation in DSA producers was 2.24+/-1.01 mg/dL, while in non-DSA patients the average serum creatinine was 1.41+/-0.37 mg/dL (P<0.01). CONCLUSION: This study reveals a strong association between the production of DSA, AHR, and early graft dysfunction. Our findings indicate that prospective monitoring for anti-HLA antibodies following transplantation is a useful test for the diagnosis and classification of AHR for identifying patients at risk of early graft dysfunction.

Managing the failing allograft.

Managing the failing allograft juxtaposes immunosuppressive management and routine chronic kidney disease care. The complications of immunosuppression can be more pronounced in those with renal failure (infection, anemia, bone disease). The withdrawal of immunosuppression may be associated with acute allograft rejection, arthralgias, and the development of antidonor antibodies. Likewise depression is prevalent. Improving well-being and overall survival necessitates proper titration of immunosuppressive medications and control of blood pressure, anemia, lipids, and glucose along with attention to treatment of depression.

Sirolimus-associated pulmonary toxicity.

BACKGROUND: Pulmonary toxicity has recently been recognized as a potentially serious complication associated with sirolimus therapy. We further detail this condition on the basis of our own cases and those reported in the literature. METHODS: We report three cases of suspected sirolimus-induced pulmonary toxicity that occurred in three renal transplant recipients and searched PubMed for all previously reported cases. RESULTS: Including our current cases, 43 patients with sirolimus-induced pulmonary toxicity have now been reported. Clinical data were incomplete in 28 cases. Analysis of available data for 15 patients revealed that the most commonly presenting symptoms were dyspnea on exertion and dry cough followed by fatigue and fever. Chest radiographs and high-resolution computed tomography scans commonly revealed bilateral patchy or diffuse alveolo-interstitial infiltrates. Bronchoalveolar fluid analysis and lung biopsy in selected case reports revealed several distinct histologic features, including lymphocytic alveolitis, lymphocytic interstitial pneumonitis, bronchoalveolar obliterans organizing pneumonia, focal fibrosis, pulmonary alveolar hemorrhage, or a combination thereof. The diagnosis of sirolimus-associated pulmonary toxicity was made after an exhaustive work-up to exclude infectious causes and other pulmonary disease. Sirolimus discontinuation or dose reduction resulted in clinical and radiologic improvement in all 15 patients within 3 weeks. CONCLUSION: The temporal relationship between sirolimus exposure and onset of pulmonary symptoms in the absence of infectious causes and other alternative pulmonary disease and the associated clinical and radiologic improvement after its cessation suggests a causal relationship. Because the use of sirolimus in organ transplantation has become more widespread, clinicians must remain vigilant to its potential pulmonary complication.

Inhibitors of ADAMTS13: a potential factor in the cause of thrombotic microangiopathy in a renal allograft recipient.

BACKGROUND: Thrombotic microangiopathy (TMA) is a well-known complication after renal allograft transplantation. In most cases, calcineurin inhibitor is believed to play a role in the development of this disorder. Recent studies have shown that a deficiency in the activity of the von Willebrand factor-cleaving metalloprotease ADAMTS13 causes thrombotic thrombocytopenic purpura. A similar mechanism occurring in patients who develop TMA after renal transplantation has not been described. METHODS: Analysis of plasma samples from a patient who developed TMA after receiving a cadaveric renal allograft revealed undetectable ADAMTS13 activity and the presence of its inhibitors. RESULTS: Discontinuation of cyclosporine and daily plasma exchange increased the ADAMTS13 activity, which was followed by resolution of the microangiopathic hemolysis and improvement of the graft function. At 3-month follow-up, the ADAMTS13 activity remained in the normal range and no inhibitors were detected. CONCLUSIONS: This is the first case to demonstrate a correlation between the presence of ADAMTS13 inhibitors and transplant-associated TMA. Autoimmune inhibitors of ADAMTS13 should be considered in patients with transplant-associated thrombotic microangiopathy. The role of calcineurin inhibitor in the formation of autoantibodies to ADAMTS13 remains to be explored.

Kidney transplantation at UCLA.

The demand for renal transplantation continues to increase. Combined organ transplantation currently accounts for approximately 10% of the kidney transplants at UCLA. As the demand for renal transplantation has increased, living kidney donation has become more common and achieves excellent results. Thirty-five percent of the 1,307 renal transplants at UCLA during the past 5 years were from living donors. The donor morbidity has been reduced with improvements in postoperative analgesia and laparoscopic nephrectomy techniques. Management of the patients waiting for cadaveric renal transplantation is becoming increasingly complex, since this population now exceeds 1,000 patients and the median waiting time is approaching 5 years. Improved immunosuppressive, antibiotic, and antiviral medications have significantly reduced the rate of acute rejection and serious infections. As long-term graft survival improves, the side effect profiles of newer medications are increasingly important. The one- and 3-year graft survival rates during the past 5 years were 98% and 90% for adult recipients of living donor kidneys and were 91% and 82% for recipients of cadaveric grafts, respectively. The results for pediatric transplants were 100% and 97% for living donor kidneys and 97% and 85% for cadaveric grafts at one and 3 years, respectively. We are pleased with our excellent results and the manner in which our program has responded to changes in the organ transplant environment.