Rates and modulators of SARS‐CoV‐2 vaccine nonresponse and breakthrough infections remain unclear in serially vaccinated transplant recipients. In a prospective, mono‐centric, observational study, ...1878 adult solid organ and hematopoietic cell transplant recipients, with prior SARS‐CoV‐2 vaccination, were included between March 2021 and February 2022. SARS‐CoV‐2 anti‐spike IgG antibodies were measured at inclusion and details on SARS‐CoV‐2 vaccine doses and infection were collected. No life‐threatening adverse events were reported after a total of 4039 vaccine doses. In transplant recipients without prior SARS‐CoV‐2 infection (n = 1636), antibody response rates ranged widely, from 47% in lung transplant to 90% in liver transplant and 91% in hematopoietic cell transplant recipients after third vaccine dose. Antibody positivity rate and levels increased after each vaccine dose in all types of transplant recipients. In multivariable analysis, older age, chronic kidney disease and daily dose of mycophenolate and corticosteroids were negatively associated with antibody response rate. Overall rate of breakthrough infections was 25.2% and mainly (90.2%) occurred after third and fourth vaccine dose. Lung transplant recipients had the highest rates of severe breakthrough infection (10.5%) and death (2.5%). In multivariable analysis, older age, daily dose of mycophenolate and corticosteroids were associated with severe breakthrough infection. Transplant recipients with infection before first vaccine dose (n = 160) had higher antibody response rates and levels after each vaccine dose, and a significantly lower overall rate of breakthrough infections compared to those without prior infection. Antibody response after SARS‐CoV‐2 vaccination and rate of severe breakthrough infections vary largely between different transplant types and are modulated by specific risk factors. The observed heterogeneity supports a tailored approach against COVID‐19 in transplant recipients.
It is unclear whether the model for end-stage liver disease-sodium (MELD-Na) score captures the clinical severity of acute-on-chronic liver failure (ACLF). We compared observed 90-day mortality in ...patients with ACLF with expected mortality based on the calculated MELD-Na and examined the consequences of underestimating clinical severity.
We identified patients with ACLF during hospitalization for cirrhosis in 127 VA hospitals between 01/01/2004 and 12/31/2014. We examined MELD-Na scores by ACLF presence and grade. We used actual and observed 90-day mortality to estimate a standardized mortality ratio (SMR) by ACLF presence and grade. We used transplant center-specific median MELD-Na at transplantation (MMaT) to estimate the proportion likely to receive priority for liver transplantation (LT) based on MELD-Na alone.
Of 71,894 patients hospitalized for decompensated cirrhosis, 18,979 (26.4%) patients met the criteria for ACLF on admission. The median (P25-P75) MELD-Na on admission was 26 (22–30) for ACLF compared to 15 (12–20) for patients without ACLF; it was 24 (21–27), 27 (23–31), and 32 (26–37) for ACLF-1, 2 and 3, respectively. At 90 days, 40.0% of patients with ACLF died (30.8%, 41.6% and 68.8% with ACLF-1, 2 and 3, respectively) compared to 21.3% of patients without ACLF. Compared to the expected death rate based on MELD-Na, mortality risk was higher for patients with ACLF, SMR (95% CI): 1.52 (1.48–1.52), 1.46 (1.41–1.51), 1.50 (1.44–1.55), 1.66 (1.58–1.74) for overall ACLF, ACLF-1, -2 and -3, respectively. Only 9.1% of patients with ACLF reached the national median MELD-Na of 35 and between 17.3% to 35.1% exceeded the MMaT at any center. During index admission, 589 (0.8%) patients with ACLF were considered for LT evaluation and 16 (0.1%) were listed for LT.
In a US cohort of hospitalized patients with decompensated cirrhosis, MELD-Na did not capture 90-day mortality risk in patients with ACLF. Patients with ACLF are at a disadvantage in the current MELD-Na-based system.
Acute-on-chronic liver failure (ACLF) is a condition marked by multiple organ failures in patients with cirrhosis and is associated with a high risk of death. Liver transplantation may be the only curative treatment for these patients. A score called model for end-stage liver disease-sodium (MELD-Na) helps guide donor liver allocation for transplantation in the United States. The higher the MELD-Na score in a patient, the more likely that a patient receives a liver transplant. Our study data showed that MELD-Na score underestimates the risk of dying at 90 days in patients with ACLF. Thus, physicians need to start liver transplant evaluation early instead of waiting for a high MELD-Na number.
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•MELD-Na underestimates the 90-day mortality risk in patients with ACLF, particularly in those with MELD-Na less than 30.•Compared to other ACLF studies, this study's cohort is not restricted to waitlisted patients.•This is the first study of a large and geographically diverse population of patients with ACLF seen in routine clinical practice.•We suggest initiating early discussions about liver transplant for patients with ACLF, regardless of their MELD-Na score.
Direct‐acting antiviral medications (DAAs) have revolutionized care for hepatitis C positive (HCV+) liver (LT) and kidney (KT) transplant recipients. Scientific Registry of Transplant Recipients ...registry data were integrated with national pharmaceutical claims (2007‐2016) to identify HCV treatments before January 2014 (pre‐DAA) and after (post‐DAA), stratified by donor (D) and recipient (R) serostatus and payer. Pre‐DAA, 18% of HCV+ LT recipients were treated within 3 years and without differences by donor serostatus or payer. Post‐DAA, only 6% of D‐/R+ recipients, 19.8% of D+/R+ recipients with public insurance, and 11.3% with private insurance were treated within 3 years (P < .0001). LT recipients treated for HCV pre‐DAA experienced higher rates of graft loss (adjusted hazard ratio aHR 1.341.852.10, P < .0001) and death (aHR 1.471.681.91, P < .0001). Post‐DAA, HCV treatment was not associated with death (aHR 0.340.671.32, P = .25) or graft failure (aHR 0.320.641.26, P = .20) in D+R+ LT recipients. Treatment increased in D+R+ KT recipients (5.5% pre‐DAA vs 12.9% post‐DAA), but did not differ by payer status. DAAs reduced the risk of death after D+/R+ KT by 57% (0.190.430.95, P = .04) and graft loss by 46% (0.270.541.07, P = .08). HCV treatment with DAAs appears to improve HCV+ LT and KT outcomes; however, access to these medications appears limited in both LT and KT recipients.
Examination of integrated US transplant registry data and records from a nationwide pharmacy claims warehouse demonstrates patterns of improved patient and graft survival in HCV‐positive liver and kidney transplant recipients treated after introduction of direct‐acting antiviral medications, but relatively limited access to these expensive medications among patients most likely to benefit. Brown offers comments in his editorial on page 2382.
Cardiac allograft vasculopathy (CAV) is an obliterative and diffuse form of vasculopathy affecting almost 50% of patients after 10 years from heart transplant and represents the most common cause of ...long-term cardiovascular mortality among heart transplant recipients. The gold standard diagnostic technique is still invasive coronary angiography, which however holds potential for complications, especially contrast-related kidney injury and procedure-related vascular lesions. Non-invasive and contrast-sparing imaging techniques have been advocated and investigated over the past decades, in order to identify those that could replace coronary angiography or at least reach comparable accuracy in CAV detection. In addition, they could help the clinician in defining optimal timing for invasive testing. This review attempts to examine the currently available non-invasive imaging techniques that may be used in the follow-up of heart transplant patients, spanning from echocardiography to nuclear imaging, cardiac magnetic resonance and cardiac computed tomography angiography, weighting their advantages and disadvantages.
Assessing the accuracy of the lung allocation score Parker, William F; Dussault, Nicole E; Jablonski, Renea ...
The Journal of heart and lung transplantation,
02/2022, Letnik:
41, Številka:
2
Journal Article
Recenzirano
Odprti dostop
The United States (US) Lung Allocation Score (LAS) relies on the performance of 2 survival models that estimate waitlist and post-transplant survival. These models were developed using data from 2005 ...to 2008, and it is unknown if they remain accurate.
We performed an observational cohort study of US lung transplantation candidates and recipients greater than 12 years of age between February 19, 2015 and February 19, 2019. We evaluated the LAS waitlist and post-transplant models with the concordance probability estimate and by comparing predicted vs observed 1-year restricted mean survival times by risk decile. We then compared a nonparametric estimate of the observed LAS with the predicted LAS for each percentile of recipients.
The waitlist model ranked candidates (N = 11,539) in the correct risk order 72% of the time (95% CI 71%-73%), and underestimated candidate one-year survival by 136 days for the highest risk decile (p < 0.001). The post-transplant model ranked recipients (N = 9,377) in the correct risk order 57% of the time (95% CI 55-58%), and underestimated recipient one-year survival by 70 days for the highest risk decile (p < 0.001). Overall, the LAS at transplant explained only 56% of the variation in observed outcomes, and was increasingly inaccurate at higher predicted values.
The waitlist and the post-transplant models that constitute the LAS are inaccurate, limiting the ability of the system to rank candidates on the waitlist in the correct order. The LAS should therefore be updated and the underlying models should be modernized.
Antibodies against PD1 have been used to treat progressive multifocal leukoencephalopathy (PML), a rare brain disease caused by JC virus. We used these antibodies (nivolumab) to treat PML in 3 kidney ...transplant recipients. All died within 8 weeks of diagnosis. Hence, nivolumab did not improve PML outcome after solid organ transplantation.
This study investigates the incidence and clearance of cervical and anal high-risk human papillomavirus (hrHPV) infection in kidney transplant recipients (KTRs) compared to immunocompetent controls. ...During 2016-2017, we enrolled 125 female KTRs and 125 female controls. Liquid-based cervical and anal cytology samples collected at enrollment and follow-up were tested for human papillomavirus (HPV) DNA using the CLART HPV2 test. All participants answered a questionnaire on lifestyle and sexual behavior at both examinations. KTRs had an increased age-adjusted risk of incident cervical hrHPV infection compared to controls (hazard ratio HR = 3.6, 95% CI = 1.2-11.2). Probability of cervical hrHPV clearance at 18 months was lower among KTRs (8.3%) than controls (66.7%). There was no statistically significant difference in anal hrHPV incidence between KTRs and controls (HR = 0.9, 95% CI = 0.4-2.0). Clearance of anal hrHPV was similar between KTRs and controls at 18 months. During the total follow-up, a lower anal hrHPV clearance, although not statistically significant, was observed among KTRs (HR = 0.3, 95% CI = 0.06-1.2). KTRs had higher incidence of cervical hrHPV and lower probability of clearance, especially of cervical hrHPV infections, than controls. Our findings support that KTRs are at increased risk of HPV infection and point to the need for targeted HPV prevention strategies, such as cervical cancer screening.
Patients with end-stage renal disease and iliocaval venous obstruction are normally nonviable recipients of kidney transplantation. We report a case of a 34-year-old male patient who has been ...receiving hemodialysis as renal replacement therapy for 6 years due to immunoglobulin A nephropathy. Past medical history included multiple central venous catheter infections and catheter-associated thrombosis. Iliac confluence and inferior vena cava occlusion previously excluded the patient from the renal transplantation list. The exhaustion of venous access sites was already documented. After multidisciplinary discussion, the patient was proposed for endovascular iliocaval reconstruction aiming for a future kidney transplant. Iliocaval recanalization was achieved through bilateral femoral access. Inferior vena cava and iliac angioplasty were performed. A dedicated venous stent was deployed in the inferior vena cava, followed by a double-barrel reconstruction of the iliac confluence. Successful iliocaval recanalization was accomplished. Five months after kidney transplantation was performed with a deceased donor graft in the right iliac fossa. The postoperative period was uneventful. After 12 months, the patient remained free from kidney replacement therapies with a serum creatinine level of 1.3 mg/dL. To the best of our knowledge, this is the first clinical description of a successful kidney transplant in a patient with a previous iliocaval reconstruction.
Inquilinus limosus is an environmental bacterium associated with respiratory tract colonization in cystic fibrosis patients. We report a case of I. limosus bacteremia in a patient in France who ...received a lung transplant and experienced chronic graft dysfunction and SARS-CoV-2 infection. This case suggests I. limosus displays virulence factors associated with invasion.
Background
We reviewed the scientific literature to gain insight on the epidemiology and outcome of Strongyloides stercoralis infections after transplantation.
Methods
CINAHL, PUBMED, and ...OVID/MEDLINE were reviewed from inception through March 31, 2022 using key words Strongyloides and transplantation.
Results
Our review identified 108 episodes of Strongyloides infection among 91 solid organ transplant (SOT) and 15 hematopoietic cell transplant (HCT) recipients. Median time to infection was 10.8 (range, .14–417) and 8.8 (range, 0–208) weeks after SOT and HCT, respectively. Gastrointestinal symptoms were frequent (86/108 79.6%), while skin rash (22/108 20.3%) and fever (31/103 30%) were less common. Peripheral eosinophilia was observed in half of patients (41/77 53.2%). Bacteremia (31/59 52.5%) was frequently due to Gram‐negative organisms (24/31 77.4%). Abnormal chest radiologic findings were reported in half (56/108 51.9%). The majority had hyperinfection syndrome (97/108 89.8%) while disseminated strongyloidiasis was less common (11/108 10.2%). Thirty‐two cases were categorized as donor‐derived infection (DDI), with donors (23/24 95.8%) who had traveled to or lived in endemic areas. Median time to DDI was 8 weeks (range .5–34.3 weeks) after transplantation. Treatment consisted of ivermectin (n = 26), a benzimidazole (n = 27), or both drugs (n = 28). There was high all‐cause mortality (48/107, 44.9%) and a high Strongyloides‐attributable mortality (32/49, 65.3%).
Conclusions
Strongyloidiasis should be strongly considered among recipients with epidemiologic risk factors for infection, even in the absence of eosinophilia or rash. A policy that provides guidance on pro‐active screening is needed, to ensure preventive measures are provided to recipients at increased risk.
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