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Systemic light chain (AL) amyloidosis is a multisystem disorder characterized by extracellular deposition of misfolded insoluble amyloid fibrils resulting in progressive organ dysfunction. AL. amyloidosis most commonly affects the heart, kidneys, gastrointestinal tract and peripheral nerves. Early mortality is chiefly determined by the degree of cardiac involvement. The aim of therapy is to rapidly reduce amyloidogenic light chain production by targeting the underlying clonal plasma or lymphoma cell population. High dose therapy with melphalan followed by autologous peripheral blood stem cell transplant (ASCT) continues to remain a highly effective treatment and is considered a standard of care for transplant eligible patients, which offers long term disease control in patients with AL amyloidosis. In recent years, several new therapeutic options have emerged (including anti-CD38 monoclonal antibodies) which are very effective alone or in combination in eradicating clonal plasma cells. In this review, we discuss the role of ASCT in the current setting of a rapidly evolving treatment landscape for patients with AL amyloidosis and provide our practice recommendations., (Published by Elsevier Inc.)

Background: The Global increase in colonization by multidrug-resistant (MDR) bacteria poses a significant concern. The precise impact of MDR colonization in solid organ transplant recipients (SOTR) remains not well established., Objectives: To assess the impact of MDR colonization on SOTR's mortality, infection, or graft loss., Methods and Data Sources: Data from PROSPERO, OVID Medline, OVID EMBASE, Wiley Cochrane Library, ProQuest Dissertations, Theses Global, and SCOPUS were systematically reviewed, spanning from inception until 20 March 2023. The study protocol was registered with PROSPERO (CRD42022290011) and followed the PRISMA guidelines. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, INTERVENTIONS, AND ASSESSMENT OF RISK OF BIAS: Cohorts and case-control studies that reported on adult SOTR colonized by Methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), extended-spectrum β-lactamase (ESBL) or carbapenem-resistant Enterobacteriaceae. (CRE), or MDR-pseudomonas, and compared to noncolonized, were included. Two reviewers assessed eligibility, conducted a risk of bias evaluation using the Newcastle-Ottawa Scale, and rated certainty of evidence using the GRADE approach., Methods of Data Synthesis: We employed RevMan for a meta-analysis, using random-effects models to compute pooled odds ratios (OR) and 95% confidence intervals (CI). Statistical heterogeneity was determined using the I 2 statistic., Results: 15,202 SOTR (33 cohort, six case-control studies) were included, where liver transplant and VRE colonization (25 and 14 studies) were predominant. MDR colonization significantly increased posttransplant 1-year mortality (OR, 2.35; 95% CI, 1.63-3.38) and mixed infections (OR, 10.74; 95% CI, 7.56-12.26) across transplant types (p < 0.001 and I 2  = 58%), but no detected impact on graft loss (p 0.41, I 2  = 0). Subgroup analysis indicated a higher association between CRE or ESBL colonization with outcomes (CRE: death OR, 3.94; mixed infections OR, 24.8; ESBL: mixed infections OR, 10.3; no mortality data) compared to MRSA (Death: OR, 2.25; mixed infection: OR, 7.75) or VRE colonization (Death: p 0.20, mixed infections: OR, 5.71)., Conclusions: MDR colonization in SOTR, particularly CRE, is associated with increased mortality. Despite the low certainty of the evidence, actions to prevent MDR colonization in transplant candidates are warranted., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Bartonella quintana infection is rarely described to be transmitted through solid organ transplant (SOT). We report a cluster of using donor-derived B quintana infection and the attack rate from Bartonella seropositive donors. In this retrospective study of SOT recipients that received an organ from an unhoused deceased donor (UDD) in Alberta in 2022-2023, serology testing for Bartonella was performed indirect immunofluorescent assay on UDDs and recipients of UDDs with positive serology. Titers ≥1:64 were considered positive. During the study period, 31/32 UDDs were tested for immunoglobulin G to Bartonella (20 negative, 11 positive for B quintana and/or B henselae). Thirty-two organs were transplanted from the 11 seropositive donors. Six SOT recipients developed bartonellosis secondary to B quintana (4 SOT recipients received organs from 3 seropositive donors, and 2 SOT recipients from 1 UDD with no stored sample for testing). The attack rate for clinical disease from positive donors was 12.5% (4/32). The main presentation was skin nodules/papules (median 5.5 months) with bacillary angiomatosis in 4/6. Bartonella serology was positive in 5/6 SOT recipients (initially negative in 2) and blood B quintana quantitative polymerase chain reaction in 1. None had visceral involvement. All donors had history of substance use. This outbreak of bartonellosis reinforces the potential for unexpected donor-transmitted infections. Clinicians should be aware of high transmission of B quintana through transplant from infected UDDs., Competing Interests: Declaration of competing interest The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objectives: Post-marketing surveillance of sotrovimab's effect during implementation in the Canadian population is limited., Methods: The study used a propensity score-matched retrospective cohort design. Follow-up began between the periods of December 15, 2021 and April 30 2022. The study assessed any severe outcome defined as all-cause hospital admission or mortality within 30 days of a confirmed COVID-19-positive test. Covariate-adjusted odds ratios between sotrovimab treatment and the severe outcome was conducted using logistic regression., Results: There were 22,289 individuals meeting the treatment criteria for sotrovimab. There were 1603 treated and 6299 untreated individuals included in the analysis. The outcome occurrence in the study was 5.49% (treated) and 4.21% (untreated), with a median time from diagnosis to treatment of 1.00 days (interquartile range 2.00 days). In the propensity-matched cohort, sotrovimab was not associated with lower odds of a severe outcome (odds ratio 1.20, 95% confidence interval 0.91-1.58), adjusting for confounding variables., Conclusions: After adjusting for confounding variables, sotrovimab treatment was not associated with lower odds of a severe outcome within 30-days of COVID-19-positive date., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Palliative care is integral to symptom management, and we examined its relationship with income, education, and Medicaid expansion in acute myeloid leukemia. This was a retrospective cross-sectional study using the National Cancer Database that included patients with acute myeloid and monocytic leukemias > 18 years of age treated at Commission on Cancer facilities from 2004 to 2016. Univariate and multivariate models were adjusted for demographic variables and facility characteristics. There were 124,988 patients, but only 106,495 had palliative care data, and of this 4111 (3%) received palliative care. The most educated had the highest odds of receiving palliative care (odds ratio, OR 1.23, 95% CI 1.08-1.41; P = 0.002), but the highest income bracket (≥ $63,333) had the lowest odds (OR 0.82, 95% CI 0.72-0.93; P = 0.003). Residence in states with Medicaid expansion (January 2014 onward) had greater palliative care utilization. Palliative care use was associated with higher education but underutilized with higher incomes. Increased access with Medicaid expansion suggests the importance of public insurance., (Copyright © 2024 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Current policies in organ and tissue donation and transplantation (OTDT) systems in Canada and the United States unnecessarily restrict access to donation for sexual and gender minorities (SGMs) and pose safety risks to transplant recipients. We compare SGM-relevant policies between the Canadian and United States systems. Policy domains include the risk assessment of living and deceased organ and tissue donors, physical examination considerations, viral testing recommendations, and informed consent and communication. Identified gaps between current evidence and existing OTDT policies along with differences in SGM-relevant policies between systems, represent an opportunity for improvement. Specific recommendations for OTDT system policy revisions to achieve these goals include the development of behavior-based, gender-neutral risk assessment criteria, a reduction in current SGM no-sexual contact period requirements pending development of inclusive criteria, and destigmatization of sexual contact with people living with human immunodeficiency virus. OTDT systems should avoid rectal examinations to screen for evidence of receptive anal sex without consent and mandate routine nucleic acid amplification test screening for all donors. Transplant recipients must receive enhanced risk-to-benefit discussions regarding decisions to accept or decline an offer of an organ classified as increased risk. These recommendations will expand the donor pool, enhance equity for SGM people, and improve safety and outcomes for transplant recipients., Competing Interests: Declaration of interests The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Murdoch Leeies reports a relationship with Canadian Blood Services that includes: funding grants., (Copyright © 2023 American Society of Transplantation & American Society of Transplant Surgeons. Published by Elsevier Inc. All rights reserved.)

Background & Aims: Canadian clinical practice guidelines currently recommend risk-based screening for HCV in pregnant individuals. However, no provinces or territories have ever compared the effectiveness of risk-based vs. universal screening for the prenatal diagnosis of HCV. We aimed to evaluate and compare HCV screening programs after implementing a universal population-level pilot program among prenatal patients in Alberta, Canada., Methods: The Alberta Prenatal Screening Program for Select Communicable Diseases was amended to include universal HCV antibody screening. Cohorts of pregnant individuals screened for HCV through risk-based or universal programs were generated over 1-year periods. HCV screening rates and prevalence were analyzed and compared between cohorts to evaluate the effectiveness of screening methods. Social and demographic risk factors for HCV-positive individuals were compared between screening cohorts to identify which populations may be overlooked with risk-based guidelines., Results: HCV antibody screening rates were 11.9% and 99.9% among pregnant individuals in the risk-based and universal cohorts, respectively. HCV prevalence among the cohorts was 0.07% and 0.11% (difference = 0.04%, p = 0.032), with an average of 21 additional HCV-positive pregnant individuals identified annually with universal screening. HCV-positive pregnant patients diagnosed through universal screening were more likely to engage in high-risk sexual behaviours/sex work compared to those diagnosed through risk-based screening (47.6% vs. 12.5%, respectively p = 0.035), suggesting that these high-risk cases are being missed by risk-based screening., Conclusions: Universal HCV screening diagnoses significantly higher numbers of pregnant individuals infected with HCV compared to risk-based screening. Universal HCV screening or amending risk-based guidelines to incorporate more proxy variables for risk factors should be considered to improve prenatal HCV screening guidelines in Canada and help achieve HCV elimination in the next decade., Impact and Implications: HCV is a bloodborne pathogen that can cause severe liver disease and be vertically transmitted from a mother to her baby during pregnancy. Pregnant individuals in Alberta are currently only tested for HCV if they disclose engaging in activities that put them at risk of acquiring the infection (risk-based screening). Using a population-wide universal prenatal HCV screening program, our work shows that testing based on patient disclosed risk alone leads to the significant underdiagnosis of HCV in pregnant individuals and suggests individuals engaging in sex work or risky sexual behaviours are being overlooked by the current risk-based program. Our outcomes represent the first province-wide study to evaluate and compare prenatal HCV risk-based and universal screening programs in Canada and provide evidence to support the update of prenatal HCV screening policies across the country and in similar jurisdictions., (Copyright © 2023 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Although antiviral prophylaxis has reduced cytomegalovirus (CMV) DNAemia and disease in seronegative solid organ transplant (SOT) recipients (R-) receiving seropositive donor organs (D+), its impact on CMV transmission is uncertain. Transmission, defined as CMV antigenemia/CMV DNAemia and/or seroconversion by year 2, and associated demographic risk factors were studied retrospectively in 428 D+/R- and 429 D-/R- patients receiving a SOT at our center. The cumulative transmission incidence was higher for lung (90.5%) and liver recipients (85.1%) than heart (72.7%), kidney (63.9%), and pancreas (56.2%) recipients (p < .001) and was significantly lower in living (50.1%) versus deceased donor (77.4%, p < .001) kidney recipients despite identical antiviral prophylaxis. In multivariate analysis, only allograft type predicted transmission risk (HR [CI] lung 1.609 [1.159, 2.234] and liver 1.644 [1.209, 2.234] vs kidney). For 53 D+ donating to >1 R- with adequate follow-up, 43 transmitted to all, three transmitted to none, and seven transmitted inconsistently with lungs and livers always transmitting but donor-matched heart, kidney or kidney-pancreas allografts sometimes not. Kidney pairs transmitted concordantly. CMV transmission risk is allograft-specific and unchanged despite antiviral prophylaxis. Tracking transmission and defining donor factors associated with transmission escape may provide novel opportunities for more targeted CMV prevention and improve outcome analysis in antiviral and vaccine trials., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Significant practice-changing developments have occurred in the care of heart transplantation candidates and recipients over the past decade. This Canadian Cardiovascular Society/Canadian Cardiac Transplant Network Position Statement provides evidence-based, expert panel recommendations with values and preferences, and practical tips on: (1) patient selection criteria; (2) selected patient populations; and (3) post transplantation surveillance. The recommendations were developed through systematic review of the literature and using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. The evolving areas of importance addressed include transplant recipient age, frailty assessment, pulmonary hypertension evaluation, cannabis use, combined heart and other solid organ transplantation, adult congenital heart disease, cardiac amyloidosis, high sensitization, and post-transplantation management of antibodies to human leukocyte antigen, rejection, cardiac allograft vasculopathy, and long-term noncardiac care. Attention is also given to Canadian-specific management strategies including the prioritization of highly sensitized transplant candidates (status 4S) and heart organ allocation algorithms. The focus topics in this position statement highlight the increased complexity of patients who undergo evaluation for heart transplantation as well as improved patient selection, and advances in post-transplantation management and surveillance that have led to better long-term outcomes for heart transplant recipients., (Copyright © 2020 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Currently many but not all centers transplant hepatitis C virus (HCV) viremic positive (+) donor kidneys into HCV+ recipients. Directed donation of HCV+ organs reduces the wait time to transplantation for HCV+ patients. Direct-acting antiviral (DAA) therapy can cure HCV in virtually all who are infected. Some have suggested that treatment of HCV+ waitlisted patients be deferred with the hope that earlier transplantation will provide better outcomes than early DAA therapy. However, there are not enough organs to guarantee prompt transplantation for the current waitlist of infected candidates. A Markov medical decision analysis model was created to compare the overall outcomes of delayed DAA therapy (Option 1) to immediate DAA therapy (Option 2) in waitlisted HCV+ patients. Option 1 patients were modeled to be transplanted 1 year earlier, with a higher cumulative transplant incidence (54% at 5 years post-listing vs 45% for Option 2). Despite this, Option 2 provided 0.43 (95% confidence interval [CI] 0.38-0.49) more life years than Option 1. However, Option 1 was preferred for regions with much greater access to HCV+ organs or in patients with very low HCV+-associated mortality. The best option from an individual patient's perspective will differ by region and candidate., (© 2018 The American Society of Transplantation and the American Society of Transplant Surgeons.)

A 67-year-old man with significant smoking history presented with fever, unintentional weight loss, night sweats, productive cough, and progressive dyspnea. Multiple respiratory specimens grew Mycobacterium branderi. Computed tomography scanning of the chest revealed a cavitary right upper lung lesion. Bronchoscopy and thoracoscopic biopsy were negative for malignancy but showed necrotizing granulomatous inflammation, which was culture negative. Due to clinical and radiologic progression despite therapy with clarithromycin, ethambutol and moxifloxacin, the lesion was surgically resected and the patient's symptoms resolved. Mycobacteria were seen in histopathology but did not grow from resected tissue. The patient received an additional 6 months of medical therapy and remains asymptomatic 1 month after completing antimicrobials. Cases of M. branderi causing human infection are very rarely reported. This is a novel case of multi-drug resistant M. branderi pulmonary infection in an apparently immunocompetent patient, progressive despite medical therapy and requiring surgical resection for definitive management., (Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Hepatitis C virus (HCV) infection negatively impacts patient and graft survival following nonhepatic solid organ transplantation. Most data, however, are in kidney transplant, where despite modest impact on outcomes, transplantation is recommended for those with mild to moderate hepatic fibrosis given overall benefit compared to remaining on dialysis. In lung transplantation (LuTx), there is little data on outcomes and international guidelines are vague on the criteria under which transplant should be considered. The University of Alberta Lung Transplant Program routinely considers patients with HCV for lung transplant based on criteria extrapolated from the kidney transplant literature. Here we describe the outcomes of 27 HCV-positive, compared to 443 HCV-negative LuTx recipients. Prior to transplant, five patients were treated for HCV and cured. At the time of transplant, 14 patients remained HCV RNA positive. The 1-, 3-, and 5-year survival were similar in HCV RNA-positive versus -negative recipients at 93%, 77%, and 77% versus 86%, 75%, and 66% (p = 0.93), respectively. Long-term follow-up in eight patients demonstrated no significant progression of fibrosis. In our cohort, HCV did not impact LuTx outcomes and in the era of interferon-free HCV therapies this should not be a barrier to LuTx., (© Copyright 2016 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Use of organs from donors testing positive for hepatitis B virus (HBV) may safely expand the donor pool. The American Society of Transplantation convened a multidisciplinary expert panel that reviewed the existing literature and developed consensus recommendations for recipient management following the use of organs from HBV positive donors. Transmission risk is highest with liver donors and significantly lower with non-liver (kidney and thoracic) donors. Antiviral prophylaxis significantly reduces the rate of transmission to liver recipients from isolated HBV core antibody positive (anti-HBc+) donors. Organs from anti-HBc+ donors should be considered for all adult transplant candidates after an individualized assessment of the risks and benefits and appropriate patient consent. Indefinite antiviral prophylaxis is recommended in liver recipients with no immunity or vaccine immunity but not in liver recipients with natural immunity. Antiviral prophylaxis may be considered for up to 1 year in susceptible non-liver recipients but is not recommended in immune non-liver recipients. Although no longer the treatment of choice in patients with chronic HBV, lamivudine remains the most cost-effective choice for prophylaxis in this setting. Hepatitis B immunoglobulin is not recommended., (© Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.)

As the disparity between the number of candidates listed for transplant and the number of donors continues to grow, marginal organ donors are increasingly utilized. This includes bacteremic donors which may carry an increased risk of transmission of infection. It is recommended that recipients of organs from bacteremic donors receive antibiotic prophylaxis based on the susceptibilities of the donor isolate to prevent transmission. Here, we present four cases of donor-derived bacteremia, despite appropriate antimicrobial prophylaxis, in four liver transplant recipients. Transmitted pathogens included Staphylococcus aureus in two cases, and Escherichia coli and Group B Streptococcus each in one case. Interestingly, none of the nonhepatic organs (n=10) utilized from these bacteremic donors resulted in transmissions. These cases highlight the fact that risk of transmission from bacteremic donors is not eliminated with antimicrobial therapy in the donor and recipient. As no transmissions occurred in recipients of nonhepatic organs from these donors, these cases also suggest that liver recipients may be at higher risk of donor transmitted bacteremia., (© Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Screening for latent tuberculosis infection (LTBI) is recommended prior to organ transplantation. The Quantiferon-TB Gold assay (QFT-G) may be more accurate than the tuberculin skin test (TST) in the detection of LTBI. We prospectively compared the results of QFT-G to TST in patients with chronic liver disease awaiting transplantation. Patients were screened for LTBI with both the QFT-G test and a TST. Concordance between test results and predictors of a discordant result were determined. Of the 153 evaluable patients, 37 (24.2%) had a positive TST and 34 (22.2%) had a positive QFT-G. Overall agreement between tests was 85.1% (kappa= 0.60, p < 0.0001). Discordant test results were seen in 12 TST positive/QFT-G negative patients and in 9 TST negative/QFT-G positive patients. Prior BCG vaccination was not associated with discordant test results. Twelve patients (7.8%), all with a negative TST, had an indeterminate result of the QFT-G and this was more likely in patients with a low lymphocyte count (p = 0.01) and a high MELD score (p = 0.001). In patients awaiting liver transplantation, both the TST and QFT-G were comparable for the diagnosis of LTBI with reasonable concordance between tests. Indeterminate QFT-G result was more likely in those with more advanced liver disease.

Background: Rejection remains a significant cause of morbidity and mortality after lung transplantation. The purpose of this study was to test the efficacy and safety of daclizumab (DZM) vs anti-thymocyte globulin (ATG) as a component of induction therapy., Methods: Fifty adults undergoing lung transplantation were randomized to receive either ATG or DZM during induction therapy. Patients were followed for 1 year after transplant., Results: Although there was no significant difference in the number of acute or chronic rejections between groups, there was a trend toward a delay in time to first acute rejection with DZM induction. Average absolute lymphocytes and average platelet count were significantly higher in the DZM group. Cytomegalovirus (CMV) serology mismatch was higher in the DZM group (7 vs 1, p = 0.05). The DZM group had a greater number of infections (83 vs 47, p = 0.02); however, the number of CMV infections was also significantly greater (18 vs 6, p = 0.03), corresponding to a higher incidence of CMV mismatch. A cost analysis revealed no difference between total drug costs, intensive-care unit (ICU) costs and total hospital costs. One-year survival was 96% in the DZM group and 88% in the ATG group., Conclusions: DZM is a safe component of induction therapy in lung transplantation. In addition, DZM may prolong freedom from acute rejection. Significant infections were more frequent in the DZM group, but this was likely due to a higher incidence of CMV mismatch. Both methods of induction therapy worked well, with excellent 1-year survival.

Background: Little is known about adenovirus infections in adult lung transplant recipients. Because the virus can establish latency, re-activation may be relatively common after transplantation., Methods: We assessed adenovirus infection in 80 adult lung transplant recipients. Adenovirus polymerase chain reaction (real-time PCR assay; limit of detection approximately 25 copies/ml plasma) was done on plasma samples collected at regular intervals until 1 year post-transplant., Results: Adenovirus DNA was detected in 18 of 80 patients (22.5%) and in 19 of 595 (3.4%) plasma samples up to 12 months post-transplant. Median time to detection of viremia was 134 days post-transplant (range 1 to 370 days). Median viral load was 180 copies/ml plasma (range 50 to 360 copies/ml). Symptoms were evaluated at the time of adenovirus detection: 14 of 18 (78%) patients were asymptomatic; 4 of 18 (22%) patients had otherwise unexplained febrile/flu-like illness that resolved spontaneously. Adenovirus was not found to be a trigger for acute rejection. No detrimental effect on pulmonary function was seen immediately after adenovirus infection., Conclusions: Adenovirus viremia is common in adult lung transplant recipients. In contrast to findings on adenoviral pneumonitis in lung transplant recipients, isolated episodes of low-level viremia are self-limited and do not trigger acute rejection or a decline in pulmonary function.

Background/aims: Occult hepatitis B virus (HBV) infection [HBV-DNA detection in hepatitis B surface antigen (HBsAg)-negative individuals] may cause acute and/or chronic liver disease. The objective of this study was to document the prevalence of occult HBV in an isolated, North American Inuit community., Methods: Four hundred and eighty seven HBsAg negative sera (61% of the community population) were available for HBV-DNA testing by real time PCR. Of these, 80 (Group 1) had serologic evidence of resolved HBV infection and 407 (Group 2) were HBV-seronegative., Results: HBV-DNA was detected in 14/80 (18%) and S-variants in 12/14 (86%) samples from Group 1. In Group 2, HBV-DNA was detected in 33/407 (8.1%) and S-variants in 17/33 (52%). In all cases (Groups 1 and 2) viral loads were low (<10(5) viral copies/ml) and clinical or biochemical features did not distinguish HBV-DNA positive from negative individuals. However, S-variants were more common (P<0.0001) in older age groups., Conclusions: The results of this study indicate that in this community-based population; (1) the prevalence of occult HBV infection is 18% in those with serologic evidence of previous HBV infection and 8.1% in HBV seronegative individuals, (2) age, gender and liver biochemistry findings do not identify those with occult HBV and (3) S-variants are present in the majority of individuals with occult HBV.