Delphi Panel Consensus Statement Generation: COVID-19 Vaccination Recommendations for Immunocompromised Populations in the European Union.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) pandemic has caused unprecedented pressure on healthcare systems globally. The lack of quality guidelines on the management of COVID-19 in rheumatologic disease, renal disease, hematological malignancy, and solid organ transplant recipients has resulted in a wide variation in clinical practice. METHODS: Using a Delphi process, a panel of 16 key opinion leaders developed clinical practice statements regarding vaccine recommendations in areas where standards are absent or limited. Agreement among practicing physicians with consensus statements was also assessed via an online physician survey. The strength of the consensus was determined by the following rating system: a strong rating was defined as all four key opinion leaders (KOLs) rating the statement ≥ 8, a moderate rating was defined as three out of four KOLs rating the statement ≥ 8, and no consensus was defined as less than three out of four KOLs provided a rating of ≤ 8. Specialists voted on agreement with each consensus statement for their disease area using the same ten-point scoring system. RESULTS: Key opinion leaders in rheumatology, nephrology, and hematology achieved consensuses for all nine statements pertaining to the primary and booster series with transplant physicians reaching consensus on eight of nine statements. Experts agreed that COVID-19 vaccines are safe, effective, and well tolerated by patients with rheumatological conditions, renal disease, hematologic malignancy, and recipients of solid organ transplants. The Delphi process yielded strong to moderate suggestions for the use of COVID-19 messenger ribonucleic acid (mRNA) vaccines and the necessity of the COVID-19 booster for the immunocompromised population. The expert panel had mixed feelings concerning the measurement of antibody titers, higher-dose mRNA vaccines, and the development of disease-specific COVID-19 guidance. CONCLUSIONS: These results confirmed the necessity of COVID-19 vaccines and boosters in immunocompromised patients with rheumatologic disease, renal disease, hematological malignancy, and solid organ transplant recipients. Statements where consensus was not achieved were due to absent or limited evidence.

Recurrent Clostridioides difficile infections in solid organ transplant recipients: The international CALIPSO study.

OBJECTIVE: To evaluate the risk of recurrent Clostridioides difficile infection (CDI) in solid-organ transplant (SOT) recipients. METHODS: Retrospective multicenter study including SOT recipients with a first CDI episode in the year after transplantation (Jan 2017-June 2020). The primary outcome measure was recurrence, defined as a new CDI ≤56 days from the first episode. A competing risk analysis was performed using the sub-distribution hazard model multivariable analysis. RESULTS: 191 SOT recipients were included: 101 (52.9%) were kidney, 66 (34.6%) liver, 11 (5.8%) lung, 8 (4.2%) simultaneous pancreas-kidney, 4 (2.1%) heart and 1 (0.5%) pancreas alone recipients. Treatment for the first CDI were: vancomycin (n = 114,59.7%), vancomycin+metronidazole (n = 39,20.4%), metronidazole (n = 26,13.6%), fidaxomicin (n = 9,4.7%), 3 patients did not receive any therapy. After the first CDI, 17/191 (8.9%) patients died within 56-day mortality without having a recurrence, while 23/191 (12%) patients had a recurrence. Among patients with recurrent CDI, 56-day mortality rate was 30.4% (7/23 patients). On multivariable analysis, severe CDI (sHR4.01, 95% CI 1.77-9.08, p < .001) and metronidazole monotherapy (sHR 3.65, 95% CI 1.64-8.14, p = .001) were factors independently associated with recurrence. CONCLUSIONS: Metronidazole monotherapy is associated with increased risk of recurrent CDI in SOT recipients. Therapeutic strategies aimed to reduce the risk of recurrence should be implemented in this setting.

COVID-19 Vaccination Recommendations for Immunocompromised Patient Populations: Delphi Panel and Consensus Statement Generation in the United States.

INTRODUCTION: The United States Advisory Committee on Immunization Practices (ACIP) and the Centers for Disease Control (CDC) recommend COVID-19 vaccines for all immunocompromised individuals. Certain disease groups are at increased risk of comorbidity and death for which disease-specific recommendations should be considered. The objective of the Delphi panel of experts was to summarize expert consensus on COVID-19 vaccinations for patients with rheumatologic disease, renal disease, hematologic malignancy and solid organ transplant (SOT) in the US. METHODS: A two-stage Delphi panel method was employed, starting with qualitative interviews with key opinion leaders (KOLs) in the four disease areas (n = 4 KOLs, n = 16 total) followed by three rounds of iterative revision of disease-specific COVID-19 vaccine recommendations. Final consensus was rated after the third round. Statements addressed primary and booster dosing (e.g., number and frequency) and other considerations such as vaccine type or heterologous messenger ribonucleic acid (mRNA) vaccination. Following the Delphi Panel, an online survey was conducted to assess physician agreement within the disease areas (n = 50 each, n = 200 total) with the consensus statements. RESULTS: Moderate to strong consensus was achieved for all primary series vaccination statements across disease groups, except one in hematology. Similarly, moderate to strong consensus was achieved for all booster series statements in all disease areas. However, statements on antibody titer measurements for re-vaccination considerations and higher dosages for immunocompromised patients did not reach agreement. Overall, approximately 62%-96% of physicians strongly agreed with the primary and booster vaccine recommendations. However, low agreement (29%-69%) was found among physicians for time interval between disease-specific treatment and vaccination, recommendations for mRNA vaccines, heterologous mRNA vaccination, antibody titer measurement and higher vaccine dosage for immunocompromised groups. CONCLUSION: Consensus was achieved for disease-specific COVID-19 vaccine recommendations concerning primary and booster series vaccines and was generally well accepted by practicing physicians.

Incidence and risk factors of de novo hepatitis E virus infection after receiving liver transplantation.

Organ transplant recipients with hepatitis E virus (HEV) infection bears high risk to develop chronic hepatitis, which is generally associated with immunosuppressive therapies. This study aimed to identify the incidence and predictors of de novo HEV infection in patients after receiving transplantation. We performed a large retrospective study to investigate the prevalence of anti-HEV at baseline, incidence of de novo HEV infection after transplantation, and the risk factors of HEV infection among patients with liver transplant in China. A total of 407 liver transplant recipients were examined for the presence of anti-HEV immunoglobulin G, IgM antibodies, and HEV RNA in serum. Basal indexes in individuals with evidence of post-transplant HEV infection were compared with those without evidence of that, and risk factors associated with HEV infection were assessed. The prevalence of anti-HEV at pretransplant in liver transplant recipients was 25.8% (105/407). Serum-negative conversion occurred in 34 (32.38%) of 105 liver transplant patients. Sixty-five out of 302 patients had de novo HEV infection after transplantation, with a cumulative incidence of 42.74% during follow-up. After transplantation, HEV infection was associated with liver failure (p = 0.012), hypoproteinemia (p = 0.030) and higher level of r-glutamyl transferase (GGT) (p = 0.022) before transplantation. Graft rejection (OR = 0.075; p = 0.045) was negatively associated with serum-negative conversion in patients who had positive anti-HEV antibody before transplantation. The incidence of de novo HEV infection after transplantation were higher in China. Liver failure, hypoproteinemia, and GGT elevation may be associated with HEV infection after liver transplantation. This study suggests that prevention and control of HEV infection after liver transplantation should be paid attention in patients bearing these risk factors.

Pre-transplant Loco-Regional Therapy for Hepatocellular Carcinoma and Post-transplant Outcomes: A National Study.

The ultimate preferred treatment for hepatocellular carcinoma (HCC) complicated with cirrhosis and portal hypertension is an orthotopic liver transplant (OLT). Loco regional therapy (LRT) has emerged to prevent tumor growth and progression of disease beyond the Milan criteria to achieve transplant. There is a paucity of data regarding safety, posttransplant survival benefits, and tumor recurrence rate achieved by these LRT modalities. We aim to assess and compare the five-year survival rate and tumor recurrence rate with or without LRT in patients after OLT with diagnosed HCC utilizing the nation's largest dataset. This is a retrospective observational study approved by Saint Louis University institutional review board. We utilized the largest dataset from the years 2003-2013 where pertaining data were gathered from Organ Procurement Transplant Network (OPTN) standard analysis and research files (STAR) through novel linkages with Medicare bills. Descriptive and comparative statistics were performed. 2412 (51.6%) patients received any form of locoregional therapy (single or combination) out of 4669 total study sample size. The overall five-year survival in the study sample was 76.1%. There was statistically no significant improvement seen in five-year posttransplant survival in the group that received one mode of LRT (adjusted hazard ratio (aHR) 0.97, P<0.64) or a combination of LRT (aHR 0.94, P<0.58) in comparison to those that received none after adjusting donor and recipient clinical characteristics. However, five-year survival trended higher among those treated with combination therapy over those treated with single LRT or none. Overall HCC recurrence was 4.8%, while no significant difference was noted when comparing above-mentioned groups. Five-year posttransplant survival and HCC recurrence rate were also found to have no difference when compared between above-mentioned groups after adjusting explant pathology. This is the largest retrospective study comparing liver transplant patients with HCC who received LRT to none. Although it did not show any statistically significant benefit of single or combination of LRT on survival or tumor recurrence after liver transplant for HCC patients, the outcomes encourage the safe and feasible use of LRT as a bridging therapy. Our study also suggests an observed pattern of improved posttransplant survival and tumor recurrence rate with combination loco-regional therapy. Larger multicenter prospective studies will be required to achieve the effect size to determine the best therapies for maximizing patient survival cost-effectively.

Cutaneous squamous cell carcinoma in solid organ transplant recipients: Current therapeutic and screening strategies.

Solid organ transplant recipients (SOTRs) are particularly prone to developing malignancies, often manifesting multiple tumors and tumors with a heightened susceptibility to metastasis, resulting in much lower survival rates when compared to the general population. Among these, cutaneous squamous cell carcinoma (CSCC) respresent a major challenge in terms of morbidity and mortality following organ transplantation. The management of post-transplant CSCC requires expertise from various disciplines, including dermatology, maxillofacial surgery, transplant medicine, radiation oncology, and medical oncology. Furthermore, the unique behaviors and prevalence of tumors in SOTRs necessitate tailored pathways for screening and treatment, distinct from those designed for immunocompetent patients. Despite the proven efficacy of immune checkpoint inhibitors (ICIs) in several cancers, SOTRs have often been systematically excluded from clinical trials due to concerns about potential allograft rejection and loss. Consequently, most data on the safety and efficacy of ICIs in SOTRs are derived from case series and reports. Given the significant risks involved, alternative therapeutic options should be thoroughly discussed with patients before considering ICI therapy. This literature review aims to provide an overview of CSCC in SOTRs, with a specific emphasis on therapeutic and screening strategies, particularly highlighting immunotherapy.

Vaccinations in Paediatric Solid Organ Transplant Candidates and Recipients.

Solid organ transplant (SOT) candidates and recipients are a fragile population, in which the presence of a pre-transplant disease leading to organ insufficiency and the post-transplant immunosuppressive treatment expose them to an increased risk of infectious diseases. The best intervention to guarantee efficient prevention of infections, with optimal cost-benefit ratio, is represented by vaccination programs; however, the response to vaccines needs that the immune system maintains a good function. This is even more relevant at paediatric age, when specific immunological conditions make transplant candidates and recipients particularly vulnerable. Paediatric patients may be naïve to most infections and may have incomplete immunization status at the time of transplant listing due to their age. Moreover, the unaccomplished development of a mature immune system and the immunosuppressive regimen adopted after transplant might affect the efficacy of post-transplant vaccinations. Therefore, every effort should be made to obtain the widest vaccination coverage before the transplantation, whenever possible. This review reports the most relevant literature, providing information on the current approach to the vaccinations in paediatric SOT candidates and recipients.

A case controlled study of risk factors for metastatic squamous cell carcinoma in organ transplant recipients: single academic medical center.

Solid organ transplant recipients (SOTRs) are at high risk of cutaneous squamous cell carcinoma (cSCC) metastasis. Despite prior studies identifying risk factors, mortality remains high. Understanding additional risk factors may aid in reducing mortality in this population. This study aimed to investigate risk factors and predictive variables for metastatic cSCC in SOTRs. The primary goal was to accurately identify transplant patients at increased risk of metastatic cSCC. A retrospective case-control study in a single institution of 3576 cases of organ transplants were identified from January 1991 to July 2022. A cohort of metastatic cancer patients and two randomly generated age and organ matched control cohorts were identified. 16 SOTR patients developed metastatic cSCC. The majority were male, with high-risk tumor sites. Tumor depth varied and half exhibited perineural invasion. Cylex® (p = 0.05) and white blood cell counts (p = 0.04) were significantly lower in these patients compared to control. Lung transplants were at highest risk relative to other solid organ transplants. Voriconazole exposure was also associated with increased metastatic risk (p = 0.04). Small sample size at a single institution. Close monitoring of SOTR, especially those with lung transplants given their increased risk, reducing immunosuppression, and limiting exposure to voriconazole can improve outcomes in SOTRs with metastatic cSCC.

Diagnosis and Prevention of Invasive Fungal Infections in the Immunocompromised Host.

TOPIC IMPORTANCE: The prevalence of invasive fungal infections (IFIs) has risen in the past 3 decades, attributed to advancements in immune-modulatory therapies used in transplantation, rheumatology, and oncology. REVIEW FINDINGS: Organisms that cause IFI evade the host's natural defenses or at opportunities of immunologic weakness. Infections occur from inhalation of potentially pathogenic organisms, translocation of commensal organisms, or reactivation of latent infection. Organisms that cause IFI in immunocompromised populations include Candida species, Cryptococcus species, environmental molds, and endemic fungi. Diagnosis of these infections is challenging due to slow organism growth and fastidious culture requirements. Moreover, fungal biomarkers tend to be nonspecific and can be negatively impacted by prophylactic antifungals. Antibody-based tests are not sensitive in immunocompromised hosts making antigen-based testing necessary. Risk reduction of IFI is guided by pathogen avoidance, removal or minimization of immune-suppressing factors, and pharmacologic prophylaxis in select hosts. SUMMARY: Understanding the complex interplay between the immune system and opportunistic fungal pathogens plays a key role in early diagnosis and prevention.

Management of resistant and refractory cytomegalovirus infections after transplantation.

INTRODUCTION: Cytomegalovirus (CMV) is a classic opportunistic infection in transplant recipients. Treatment-refractory CMV infections are of concern, with growing identification of strains that have developed genetic mutations which confer resistance to standard antiviral therapy. Resistant and refractory CMV infections are associated with worse patient outcomes, prolonged hospitalization, and increased healthcare costs. AREAS COVERED: This article provides a comprehensive practical overview of resistant and refractory CMV infections in transplant recipients. We review the updated definitions for these infections, antiviral pharmacology, mechanisms of drug resistance, diagnostic workup, management strategies, and host-related factors including immune optimization. EXPERT OPINION: Resistant and refractory CMV infections are a significant contributor to post-transplant morbidity and mortality. This is likely the result of a combination of prolonged antiviral exposure and active viral replication in the setting of intensive pharmacologic immunosuppression. Successful control of resistant and refractory infections in transplant recipients requires a combination of immunomodulatory optimization and appropriate antiviral drug choice with sufficient treatment duration.

Cutaneous Squamous Cell Carcinoma in Patients with Solid-Organ-Transplant-Associated Immunosuppression.

The management of advanced cutaneous squamous cell carcinoma (CSCC) has been revolutionized by the introduction of immunotherapy. Yet, successful treatment with immunotherapy relies on an adequate antitumor immune response. Patients who are solid-organ transplant recipients (SOTRs) have a higher incidence of CSCC compared to the general population. This review discusses the current knowledge of epidemiology, pathophysiology, and management of patients with CSCC who are immunocompromised because of their chronic exposure to immunosuppressive medications to prevent allograft rejection. First, we discuss the prognostic impact of immunosuppression in patients with CSCC. Next, we review the risk of CSCC development in immunosuppressed patients due to SOT. In addition, we provide an overview of the biological immune disruption present in transplanted immunosuppressed CSCC patients. We discuss the available evidence on the use of immunotherapy and provide a framework for the management approach with SOTRs with CSCC. Finally, we discuss potential novel approaches that are being investigated for the management of immunosuppressed patients with CSCC.

Antibody-Mediated Rejection in Liver Transplantation: Immuno-Pathological Characteristics and Long-Term Follow-Up.

The diagnosis of liver antibody-mediated rejection (AMR) is challenging and likely under-recognized. The association of AMR with donor-specific antibodies (DSA), and its clinical course in relation to pathologic findings and treatment are ill defined. We identified cases of liver AMR by following the criteria outlined by the 2016 Banff Working Group. Patient demographics, native liver disease, histopathologic findings, treatment type, clinical outcome, and transaminase levels during AMR diagnosis, treatment, and resolution were determined. Patients (n = 8) with AMR average age was 55.2 years (range: 19-68). Seven of eight cases met the Banff criteria for AMR. Personalized treatment regimens consisted of optimization of immunosuppression, intravenous pulse steroids, plasmapheresis, IVIG, rituximab, and bortezomib. Five patients experienced complete resolution of AMR, return of transaminases to baseline, and decreased DSA at long-term follow-up. One patient developed chronic AMR and two patients required re-transplantation. Follow-up after AMR diagnosis ranged from one to 11 years. Because AMR can present at any time, crossmatch, early biopsy, and routine monitoring of DSA levels should be implemented following transaminase elevation to recognize AMR. Furthermore, treatment should be immediately implemented to reverse AMR and prevent graft failure, chronic damage, re-transplantation, and possibly mortality.

Solid organ transplant in recipients with ongoing SARS-CoV-2 infection: A systematic review of case reports and series.

BACKGROUND: Whether solid organ transplant (SOT) can be safely performed in recipients with ongoing SARS-CoV-2 infection is still a debated question. METHODS: A systematic review of the literature on recipients with ongoing SARS-CoV-2 infection at the time of surgery and the associated outcomes. RESULTS: From 29 studies, we identified 54 recipients; their median age was 47.5 years, and over half (23/54, 54.85%) were affected by fewer than two comorbidities. Kidney was the most common transplanted organ (24/54, 44.4%). SOT was performed without knowing the ongoing infection in 11.1% (6/54) of patients. On average, 16.1 (SD 23.2) days elapsed between SARS-CoV-2 infection and SOT, with a mean Ct value at diagnosis and transplantation of 29 and 31.9, respectively. Most patients (25/39,64.1%) had received previous COVID-19 vaccinations. Twenty-four patients (45.3%) received an anti-SARS-CoV-2 therapy. Ten patients (18.5%) required oxygen support, while seven (13.7%) were admitted to the intensive care unit. There were two reported cases (3.7%) of all-cause death, while there were no cases of COVID-19-related death. CONCLUSIONS: Deliberate SOT of recipients with ongoing SARS-CoV-2 is performed worldwide in candidates of nonlung transplant who are fit, immunized against the virus, and displaying a nonsevere disease course. No COVID-19-related deaths were recorded.

Transcatheter Versus Surgical Aortic Valve Replacement in Recipients of Solid Organ Transplants and Liver Cirrhosis: A Propensity-Matched Analysis of National Readmission Data.

Transcatheter aortic valve replacement (TAVR) continues to grow in the United States. There are limited data on recipients of solid organ transplant (SOT) and patients with liver cirrhosis who undergo aortic valve replacement (AVR). Our study aims to evaluate outcomes in these populations. Using the national readmission database (2016 to 2020), we identified recipients of SOT and patients with liver cirrhosis without previous liver transplants who were admitted for severe aortic stenosis and underwent either TAVR or surgical AVR (SAVR). We used multivariable regression for adjusted analysis and the propensity score matching model, implementing complete Mahalanobis distance matching within the Propensity Score Caliper (0.2) to match TAVR and SAVR cohorts for outcomes. Of 3,394 hospitalizations for AVR in recipients of SOT, 2,181 underwent TAVR, and 1,213 underwent SAVR. On propensity-matched analysis, SAVR was associated with more adverse events than was TAVR, including in-hospital mortality (5.2% vs 1.1%, adjusted odds ratio [aOR] 4.49, p <0.001), acute kidney injury (43.7% vs 10.2%, p <0.001), cardiogenic shock (9.0% vs 1.6%, p <0.001), sudden cardiac arrest (15.9 vs 6.0%, p <0.001), major adverse cardiac and cerebrovascular events (28% vs 10.4%, p <0.001), and net adverse events (72.8 vs 37.6%, p <0.001). A greater median length of stay (10 vs 2 days, p <0.001) and adjusted cost ($80,842 vs $57,014, p <0.001) were also observed. The readmission rates were the same for both cohorts after a 6-month follow-up. Similarly, in 14,763 hospitalizations for AVR in liver cirrhosis, 7,109 patients underwent TAVR, and 7,654 underwent SAVR. In propensity-matched cohorts (n = 2,341), SAVR was found to be associated with greater adverse events, including in-hospital mortality (19.8% vs 10%), stroke (6.7% vs 2%), acute kidney injury (67.7% vs 30.3%), cardiogenic shock (41.9% vs 19.9%), sudden cardiac arrest (31.8% vs 13.2%, aOR 2.89), major adverse cardiac and cerebrovascular events (66.2% vs 35.7%), and net adverse events (86% vs 59.5%) (p <0.001). A greater median length of stay (16 vs 3 days) and cost ($500,218 vs $263,383) were also observed (p <0.001). However, the rate of readmissions at 30-day (9% vs 11.1%) and 180-day intervals (33.4% vs 39.8%) was lower for the SAVR cohort (p <0.05). In recipients of SOT and patients with liver cirrhosis, SAVR is associated with greater short-term mortality, adverse events, and healthcare burden than is TAVR. TAVR is a relatively safer alternative to SAVR in these patient populations, although further studies are warranted to compare the long-term outcomes.

Predictors for Development of Chronic Rhinosinusitis in Transplant Recipients.

OBJECTIVES: Studies suggest that transplant patients are at a higher risk of developing chronic rhinosinusitis (CRS). However, there is a dearth of studies describing the factors that may be linked to the development of CRS in this population. Our objective is to identify the risk factors associated with the development of CRS in transplant recipients. STUDY DESIGN: Retrospective cohort. SETTING: Tertiary care center. METHODS: This cohort included 3347 transplant recipients seen between 2017 and 2022. Of these, 2128 patients met the inclusion criteria and were grouped according to whether they were diagnosed with CRS during the post-transplant period. The analysis included both univariate and multivariate analysis to ascertain the odds ratio (OR) and predictive factors. RESULTS: Of the 2128 patients, 649/2128 (30.4%) had CRS. CRS patients had an increased prevalence of previous endoscopic sinus surgery, allergic rhinitis, and recurrent acute rhinosinusitis in the pre-transplant period compared to the non-CRS group. According to the multivariate analysis, patients with primary immunodeficiency and additional transplant were 1.9 and 3.1 times more likely to develop CRS during the posttransplant period (95% CI: 1.3-2.6, p < .0001), (95% CI: 1.3 -7.3, p = .01), respectively. Sirolimus use was also associated with the development of CRS (OR = 1.4, 95% CI: 1.1-1.9, p = .01). CONCLUSION: This study is the largest cohort aimed at determining the predictive factors associated with the development of CRS. Patients with pretransplant rhinologic conditions, hematologic deficiencies, and the utilization of specific immunosuppressants were found to have a higher likelihood of developing CRS following transplantation.

Daptomycin treatment for persistent bacteremia in a pediatric solid organ transplant recipient: Case report and literature review.

INTRODUCTION: Information on the clinical utility of daptomycin in patients with persistent bacteremia and daptomycin's pharmacokinetic data in pediatric patients has been sparse. In addition, reports on the experience of using daptomycin in children undergoing solid organ transplantation have been extremely limited. The authors describe a pediatric case of persistent bacteremia after solid organ transplantation successfully treated by daptomycin. Blood daptomycin concentrations were measured by liquid chromatography-mass spectrometry and pharmacokinetic analysis was performed. We also conducted a literature review on the use of daptomycin in children with persistent bacteremia. CASE REPORT: An eight-year-old girl who underwent small bowel and liver transplantation experienced persistent bacteremia due to Staphylococcus epidermidis. The bacteremia persisted despite standard therapy; however, it finally resolved with the addition of daptomycin. The patient had renal dysfunction and the initial dosing resulted in excessive drug exposure. The dosage was adjusted based on the pharmacokinetic analysis. The dosage of administrated teicoplanin was also adjusted according to trough concentration values. In the literature review, we identified 12 cases of neonates and 24 cases of post-neonatal children with the experience of using daptomycin for persistent bacteremia; however, no solid organ transplant recipient was identified. Similar trends in blood concentrations and dose ratios of teicoplanin and daptomycin were observed over time. DISCUSSION: More information is required regarding the clinical utility and pharmacokinetics of daptomycin in pediatric patients with persistent bacteremia. Referring to the exposure to renally excreted drugs that are routinely measured and pharmacokinetic analysis of daptomycin may be useful in optimizing the dose of daptomycin in special patient populations, including those with renal impairment.

Angiotensin II as a Vasopressor for Perioperative Hypotension in Solid Organ Transplant.

During the perioperative period of transplantation, patients experience hypotension secondary to the side effects of anesthesia, surgical stress, inflammatory triggering, and intraoperative fluid shifts, among others causes. Vasopressor support, in this context, must reverse systemic hypotension, but ideally, the agents used should benefit allograft function and avoid the adverse events commonly seen after transplantation. Traditional therapies to reverse hypotension include catecholamine vasopressors (norepinephrine, epinephrine, dopamine, and phenylephrine), but their utility is limited when considering allograft complications and adverse events such as arrhythmias with agents with beta-adrenergic properties. Synthetic angiotensin II (AT2S-[Giapreza]) is a novel vasopressor indicated for distributive shock with a unique mechanism of action as an angiotensin receptor agonist restoring balance to an often-disrupted renin angiotensin aldosterone system. Additionally, AT2S provides a balanced afferent and efferent arteriole vasoconstriction at the level of the kidney and could avoid the arrhythmic complications of a beta-adrenergic agonist. While the data, to date, are limited, AT2S has demonstrated safety in case reports, pilot studies, and small series in the kidney, liver, heart, and lung transplant populations. There are physiologic and hemodynamic reasons why AT2S could be a more utilized agent in these populations, but further investigation is warranted.

Sulfonamide allergy label and the risk of opportunistic infections in solid organ transplant recipients - A retrospective matched cohort study.

BACKGROUND: While a penicillin allergy label has been linked to various negative clinical outcomes, limited studies have specifically characterized the implication of sulfonamide allergy labels (SAL) on clinical outcomes. We examined the impact of SAL on clinical outcomes of solid organ transplant recipients. METHODS: In this retrospective matched cohort study, we utilized the TriNetX US collaborative Network, a multicenter de-identified US database, and identified solid organ transplant recipients with and without SAL. The 1-year probability of developing Pneumocystis jirovecii pneumonia (PJP), toxoplasmosis, and nocardiosis was estimated and contrasted between the two study groups. The hazard ratio (HR) and the 95% confidence interval (CI) quantified the strength and direction of the association between SAL and these outcomes. RESULTS: When comparing 1571 solid organ transplant recipients with SAL to an equal number of matched controls, patients with SAL had a higher probability of developing nocardiosis (HR 3.85; 95% CI, 1.44-10.30; p = .004; corrected p = .04), and toxoplasmosis (HR, 1.87; 95% CI, 1.10-3.17; p = .019; corrected p = .19), but no difference in the risk of developing PJP (HR, 1.64; 95% CI, 0.68-3.95; p = .27). There was no mortality difference (HR, 1.31; 95% CI, 0.99-1.75; p = .061; corrected p = .6). SAL influenced antibiotic prescription with overutilization of dapsone, atovaquone, and pentamidine and underutilization of trimethoprim and sulfamethoxazole. CONCLUSION: SAL is associated with an increased risk of opportunistic infections following solid organ transplantation. Measures to evaluate and de-label sulfonamide allergy prior to transplantation or desensitizing shortly after transplantation are advisable.

Ehrlichiosis and anaplasmosis in solid organ transplantation: A case series and review of the literature.

Ehrlichiosis and anaplasmosis are rising tickborne infections posing significant risks to solid-organ transplant (SOT) patients. We present three cases highlighting clinical presentations, diagnostic challenges, and the benefits of microbial cell-free DNA (mcfDNA) sequencing. Emphasizing early diagnosis and preventive measures, we advocate for advanced diagnostic modalities to improve outcomes in this vulnerable population.

The Adolescent Transplant Recipient: An Overview of Neurocognitive Functioning and Implications for Long-Term Outcomes.

BACKGROUND: Solid organ transplantation (SOT) offers improved long-term survival for youth with end-stage organ disease. From a neurodevelopmental, cognitive, and academic perspective, children with solid organ transplant have a number of unique risk factors. While cognitive functioning may improve post-transplantation, it is important to understand the trajectory of neurocognitive development starting in transplant candidacy to evaluate the implications of early deficits. AIM: The aim of this paper is to describe the neurocognitive risks and long-term implications for adolescent transplant recipients. METHOD: This paper provides an overview of neurocognitive functioning in youth with end-stage organ dysfunction with discussion of implications for adolescent transplant recipients. RESULTS: Post-transplant, adolescent, and young adult solid organ transplant recipients exhibit significant levels of executive dysfunction, with implications for decision-making, regimen adherence, and transition to adult transplant care. CONCLUSION: Transplantation may reduce the risk for poor long-term neurocognitive effects, yet adolescent transplant recipients remain at increased risk, particularly in executive functioning, which has implications for adherence and transition to adulthood. Baseline and follow-up assessments for youth with end-stage organ disease and transplant are important for the monitoring of neurocognitive development and may be used to mitigate risk for low adherence to post-transplantation treatment regimens and reduce barriers to transitioning to adult transplant care.