Solid Organ Transplant Recipients Research Articles

Remdesivir in solid organ transplant recipients with COVID-19: a systematic review and meta-analysis.

The use of remdesivir in solid organ transplant recipients (SOTRs) with coronavirus disease 2019 (COVID-19) has been studied. The present systematic review and analysis aimed to assess its effectiveness in this population. A comprehensive search of PubMed, Cochrane Library, Web of Science, Embase, medRxiv, and Google Scholar was conducted to identify relevant articles published up to April 2024. The quality of the included studies was evaluated using the Cochrane assessment tool. Data analysis was performed using the Comprehensive Meta-Analysis software ver. 3.0. The meta-analysis included seven eligible retrospective studies, involving a total of 574 SOTRs. The findings indicated no significant differences in mortality rate (odds ratio [OR], 1.19; 95% confidence interval [CI], 0.59-2.39), hospitalization rate (OR, 0.69; 95% CI, 0.10-4.79), need for mechanical ventilation (OR, 0.98; 95% CI, 0.44-2.18), or need for oxygen therapy (OR, 3.73; 95% CI, 0.75-18.34) between the groups that received remdesivir and those that did not. However, a statistically significant difference was observed in the rate of intensive care unit admissions between the two groups (OR, 2.39; 95% CI, 1.24-4.57). Our meta-analysis found that remdesivir offers no clinical benefits to SOTRs infected with COVID-19. Additional high-quality research is required to assess the potential clinical advantages of remdesivir for SOTRs with COVID-19.

Dynamics and Evolution of Donor-derived Cytomegalovirus Infection in 3 Solid Organ Transplant Recipients With the Same Multiorgan Donor.

Cytomegalovirus (CMV) infection poses a significant risk to immunosuppressed transplant recipients, manifesting through primary infection, reinfection, or reactivation. We analyzed the emergence of drug resistance in CMV infection in 3 patients who were later found to have received an allograft from a shared, deceased donor. The seronegative transplant recipients developed symptomatic CMV infections after bowel/pancreas, kidney, or lung transplantation. Prospective Sanger sequencing was used to identify mutations in the viral DNA polymerase (DP) and protein kinase (PK). DP and PK variants were retrospectively quantified by targeted next-generation sequencing. The impact of the novel DP-A505G substitution on drug susceptibility was assessed using a recombinant virus. Whole-genome sequencing of clinical CMV samples was enabled through target DNA enrichment. The DP-A505G substitution was found in all patient samples and could be associated with a natural polymorphism. A subsequent review of the patients' clinical histories revealed that they had all received organs from a single donor. The CMV infection exhibited divergent evolution among the patients: patient 1 developed resistance to ganciclovir and foscarnet because of 2 DP mutations (V715M and V781I), patient 2 showed no genotypic resistance, and patient 3 developed ganciclovir (PK-L595S) and maribavir resistance (PK-T409M). Interpatient variation across the entire CMV genome was minimal, with viral samples clustering in phylogenetic analysis. All 3 transplant recipients were infected with the same donor-derived CMV strain and readily developed different drug susceptibility profiles. This underscores the importance of judicious antiviral drug use and surveillance in preventing antiviral resistance emergence.

Characterization of Ganciclovir Dosing for the Management of Cytomegalovirus in Solid Organ Transplant Recipients Receiving Sustained Low-Efficiency Dialysis.

The optimal dosing of intravenous ganciclovir in patients receiving sustained low-efficiency dialysis (SLED) remains unclear. The primary objective is to characterize the dosing of ganciclovir for treating and preventing cytomegalovirus (CMV) in Solid Organ Transplant Recipients receiving SLED. The secondary objective is to evaluate the safety and efficacy of the dosing practices described in this study. Retrospective review of electronic medical records from solid organ transplant recipients (SOTRs) admitted to the Medical Surgical Intensive Care Unit at the Toronto General Hospital (TGH) between November 28, 2016, and September 1, 2021, was conducted. Patients concurrently receiving ganciclovir and SLED were included. Among the 27 encounters for CMV prevention, 18 patients underwent 8-hour SLED, 6 underwent 24-hour SLED, and 3 received other SLED durations. Most patients (80%) on 8-hour SLED began ganciclovir at 2.5 mg/kg/d, whereas 80% of those on 24-hour SLED started at 5 mg/kg/d. No breakthrough viremia occurred at 5 mg/kg/d, with 1 instance at 2.5 mg/kg/d. Cytopenia rates were higher at 5 mg/kg/d (33% vs 20%). For treatment (n = 20), 16 patients underwent 8-hour SLED, 2 underwent 24-hour SLED, and 2 underwent 12-hour SLED. Most (75%) on 8-hour SLED started at 2.5 mg/kg/d, whereas all on 24-hour SLED began at 5 mg/kg/d. Viral eradication rates were 75% and 60% at 2.5 and 5 mg/kg/d, respectively, with higher cytopenia rates at 5 mg/kg/d (37.5% vs 0%). Dose adjustments were primarily in response to refractory disease or cytopenia. At our institution, ganciclovir dosing patterns suggest that for patients requiring 8-hour SLED, there is clinician comfort in using 2.5 mg/kg/d for prevention and 5 mg/kg/d for treatment. In 24-hour SLED, 5 mg/kg/d may be considered for prevention. Higher doses may be considered for CMV treatment; however, we found greater variability in the dosing practices for these patients. Further research with larger sample sizes and ganciclovir drug-level assessments is needed to optimize dosing strategies for CMV treatment.

Clinical Characteristics and Risk Factors for Cryptococcal Meningitis in Diverse Patient Populations in New York City.

Cryptococcal meningitis (CM) is responsible for 15%-20% of human immunodeficiency virus (HIV)-associated mortalities. CM prevalence has also increased in other immunocompromised populations of transplant recipients, patients with cancer, and individuals on immunomodulatory medication. This retrospective review included 51 definitive patients with CM hospitalized at a tertiary academic medical center in New York City between 2010 and 2023. We assessed clinical features and outcomes of CM, with additional analysis of factors related to antiretroviral therapy (ART) adherence in HIV-infected cases and immunomodulatory medication history of HIV-negative cases. The cohort had a mean (standard deviation) age of 47.1 ± 15.1 years, and was predominantly male (37, 72.5%). Of 32 patients with HIV, 3 (9.4%) were newly diagnosed with HIV at the time of CM hospitalization, 5 (15.6%) had recurrent CM, and 2 (6.3%) had a CM relapse. The majority (30, 93.8%) of patients with HIV were ART nonadherent. Of 19 HIV-negative patients, 8 (42.1%) were solid-organ transplant recipients, 5 (26.3%) had autoimmune conditions of sarcoidosis or systemic lupus erythematosus, and 3 (15.8%) had chronic lymphocytic leukemia. Six (11.8%) patients died during hospitalization, 4 of whom had HIV. The burden of CM in people with HIV and immunocompromised patients continues even in settings with accessible standard antifungal treatment though interventions of increased ART adherence for those with HIV and antifungal prophylaxis may improve morbidity and mortality.

A limited sampling model to estimate the area under the curve of mycophenolic acid in hematopoietic stem cell transplantation recipients.

Relationship between the areas under the curve (AUC) of mycophenolic acid (MPA) and the likelihood of rejection is well-established in solid organ transplantation recipients. In hematopoietic stem cell transplantation (HSCT), MPA AUC is also linked to graft versus host disease. This study aimed to develop a simplified method to estimate MPA AUC0-12 in Chinese patients undergoing allogeneic HSCT (allo-HSCT). Intensive sampling was conducted in 22 patients who were orally administered mycophenolate mofetil. Plasma concentrations of total MPA were measured, and a model predicting AUC0-12 using data from these 22 patients was constructed through regression analysis. The accuracy of the most suitable model was assessed in an additional 20 patients. None of the individual MPA concentrations showed a strong correlation with AUC0-12 (r2<0.7). Models utilizing 4 or more concentrations were found to effectively estimate MPA AUC0-12 (r2>0.87). The most operationally feasible model demonstrated good predictive performance with a mean absolute percentage error (APE%)<20%. Single MPA concentrations showed poor correlation with MPA AUC0-12. A model utilizing 4 oral concentrations (0, 0.5, 1, and 4h postdose) over a 12-h period could effectively estimate MPA AUC0-12 with precise results and minimal bias.

The Outcome of Solid Organ Transplant Recipients with COVID-19 Depends not only on a few but on a Large Number of Influencing Factors

The Outcome of Solid Organ Transplant Recipients with COVID-19 Depends not only on a few but on a Large Number of Influencing Factors

The impact of high intensity training and sports on recipients of solid organ transplants: a narrative review.

High intensity exercise in individuals post solid organ transplant (SOT) remains a largely understudied phenomenon, with potential risks and benefits. Additionally, the optimal training protocols are still unclear. This narrative review aimed to explore the impact of high-intensity exercise training and strenuous sports on solid organ transplant recipients (SOTRs). We conducted a narrative review of intervention studies of any design that included high-intensity exercise training and cross-sectional studies of strenuous sports and activities. Additionally, we reviewed individual reports documenting post-SOT performance at highly competitive or physiological levels. We used MEDLINE to search for relevant articles followed by a manual search for additional articles. Data were extracted and results were summarized. High-intensity and strenuous exercise appears to be safe among stable SOTRs. High-intensity protocols consistently demonstrated improvements in VO2peak and a reduction in coronary artery disease prevalence, though findings related to body composition, health-related quality of life outcomes, and cardiovascular exercise variables were inconsistent. Pre-transplant athletes showcase notable achievements and physiological adaptations post-transplantation, highlighting the capacity for athletic performance among this population. However, caution is warranted in interpreting the findings from these studies due to limitations in generalizability and other methodological limitations. As evidenced by current literature, high intensity exercise emerges as a promising exercise method for safely improving various physiological parameters, and reducing the prevalence of coronary heart disease in SOTRs. It can induce similar or greater effects to moderate intensity exercise, however follow-up studies indicate low retention. Further research of higher methodological rigor is warranted in this field to advance understanding, and to guide evidence-based practice.

Musculoskeletal infections associated with Nocardia species: a case series.

Background: Nocardia is an uncommon pathogen that has been reported to infect musculoskeletal structures. However, studies are largely limited to case reports, and little is known regarding management and outcomes of these infections. Methods: We performed a multicenter retrospective cohort study of adults with culture-confirmed musculoskeletal Nocardia infections at three Mayo Clinic centers in Arizona, Florida, and Minnesota from November 2011 through April2022. Results: Nine cases of Nocardia musculoskeletal infection were identified. Seven (78 %) occurred in men, and the median age was 57.3 years (range 32.6-79.0). Specific infections included native joint septic arthritis with or without associated osteomyelitis ( ), hardware-associated infection ( ), sternal osteomyelitis ( ), pyomyositis ( ), bursitis ( ), and tenosynovitis ( ). Three cases (33 %) were associated with disseminated disease, all three occurring in solid organ transplant recipients. Surgical intervention was performed in all but the bursitis case. Length of treatment varied from 21 d for tenosynovitis to 467 d for osteomyelitis. The 1-year mortality was 22 %, and all fatal cases involved disseminated disease. Conclusion: Patients with localized nocardiosis affecting musculoskeletal structures generally have good outcomes, as opposed to those with disseminated infection. Management often required operative intervention, with one patient experiencing recurrence within 1year.

Model-Informed Precision Dosing of Tacrolimus: A Systematic Review of Population Pharmacokinetic Models and a Benchmark Study of Software Tools.

Tacrolimus is an immunosuppressant commonly administered after solid organ transplantation. It is characterized by a narrow therapeutic window and high variability in exposure, demanding personalized dosing. In recent years, population pharmacokinetic models have been suggested to guide model-informed precision dosing of tacrolimus. We aimed to provide a comprehensive overview of population pharmacokinetic models and model-informed precision dosing software modules of tacrolimus in all solid organ transplant settings, including a simulation-based investigation of the impact of covariates on exposure and target attainment. We performed a systematic literature search to identify population pharmacokinetic models of tacrolimus in solid organ transplant recipients. We integrated selected population pharmacokinetic models into an interactive software tool that allows dosing simulations, Bayesian forecasting, and investigation of the impact of covariates on exposure and target attainment. We conducted a web survey amongst model-informed precision dosing software tool providers and benchmarked publicly available tools in terms of models, target populations, and clinical integration. We identified 80 population pharmacokinetic models, including 44 one-compartment and 36 two-compartment models. The most frequently retained covariates on clearance and distribution parameters were cytochrome P450 3A5 polymorphisms and body weight, respectively. Our simulation tool, hosted at https://lpmx.shinyapps.io/tacrolimus/ , allows thorough investigation of the impact of covariates on exposure and target attainment. We identified 15 model-informed precision dosing software tool providers, of which ten offer a tacrolimus solution and nine completed the survey. Our work provides a comprehensive overview of the landscape of available tacrolimus population pharmacokinetic models and model-informed precision dosing software modules. Our simulation tool allows an interactive thorough exploration of covariates on exposure and target attainment.

Management of cytomegalovirus infection after liver transplantation.

Cytomegalovirus (CMV) infection is one of the primary causes of morbidity and mortality following liver transplantation (LT). Based on current worldwide guidelines, the most effective strategies for avoiding post-transplant CMV infection are antiviral prophylaxis and pre-emptive treatment. CMV- IgG serology is the established technique for pretransplant screening of both donors and recipients. The clinical presentation of CMV infection and disease exhibits variability, prompting clinicians to consistently consider this possibility, particularly within the first year post-transplantation or subsequent to heightened immunosuppression. At annual symposia to discuss CMV prevention and how treatment outcomes can be improved, evidence on the incorporation of immune functional tests into clinical practice is presented, and the results of studies with new antiviral treatments are evaluated. Although there are ongoing studies on the use of letermovir and maribavir in solid organ transplantation, a consensus reflected in the guidelines has not been formed. Determining the most appropriate strategy at the individual level appears to be the key to enhancing outcomes. Although prevention strategies reduce the risk of CMV disease, the disease can still occur in up to 50% of high-risk patients. A balance between the risk of infection and disease development and the use of immunosuppressants must be considered when talking about the proper management of CMV in solid organ transplant recipients. The objective of this study was to establish a comprehensive framework for the management of CMV in patients who have had LT.

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.

Individualized dosing parameters for tacrolimus in the presence of voriconazole: a real-world PopPK study.

Significant increase in tacrolimus exposure was observed during co-administration with voriconazole, and no population pharmacokinetic model exists for tacrolimus in renal transplant recipients receiving voriconazole. To achieve target tacrolimus concentrations, an optimal dosage regimen is required. This study aims to develop individualized dosing parameters through population pharmacokinetic analysis and simulate tacrolimus concentrations under different dosage regimens. We conducted a retrospective study of renal transplant recipients who were hospitalized at the Second Xiangya Hospital of Central South University between January 2016 and March 2021. Subsequently, pharmacokinetic analysis and Monte Carlo simulation were employed for further analysis. Nineteen eligible patients receiving tacrolimus and voriconazole co-therapy were included in the study. We collected 167 blood samples and developed a one-compartment model with first-order absorption and elimination to describe the pharmacokinetic properties of tacrolimus. The final typical values for tacrolimus elimination rate constant (Ka), apparent volume of distribution (V/F), and apparent oral clearance (CL/F) were 8.39h-1, 2690L, and 42.87L/h, respectively. Key covariates in the final model included voriconazole concentration and serum creatinine. Patients with higher voriconazole concentration had lower tacrolimus CL/F and V/F. In addition, higher serum creatinine levels were associated with lower tacrolimus CL/F. Our findings suggest that clinicians can predict tacrolimus concentration and estimate optimal tacrolimus dosage based on voriconazole concentration and serum creatinine. The effect of voriconazole concentration on tacrolimus concentration was more significant than serum creatinine. These findings may inform clinical decision-making in the management of tacrolimus and voriconazole therapy in solid organ transplant recipients.

Current Advances and Challenges in the Management of Cutaneous Squamous Cell Carcinoma in Immunosuppressed Patients.

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin malignancy and poses a significant risk to immunosuppressed patients, such as solid organ transplant recipients and those with hematopoietic malignancies, who are up to 100 times more likely to develop cSCC compared with the general population. This review summarizes the current state of treatment for cSCC in immunosuppressed patients, focusing on prevention, prophylaxis, surgical and non-surgical treatments, and emerging therapies. Preventative measures, including high-SPF sunscreen and prophylactic retinoids, are crucial for reducing cSCC incidence in these patients. Adjusting immunosuppressive regimens, particularly favoring mTOR inhibitors over calcineurin inhibitors, has been shown to lower cSCC risk. Surgical excision and Mohs micrographic surgery remain the primary treatments, with adjuvant radiation therapy recommended for high-risk cases. Traditional chemotherapy and targeted therapies like EGFR inhibitors have been utilized, though their efficacy varies. Immunotherapy, particularly with agents like cemiplimab and pembrolizumab, has shown promise, but its use in immunosuppressed patients requires further investigation due to potential risks of organ rejection and exacerbation of underlying conditions. Treatment of cSCC in immunosuppressed patients is multifaceted, involving preventive strategies, tailored surgical approaches, and cautious use of systemic therapies. While immunotherapy has emerged as a promising option, its application in immunosuppressed populations necessitates further research to optimize safety and efficacy. Future studies should focus on the integration of personalized medicine and combination therapies to improve outcomes for this vulnerable patient group.

Analysis of Indeterminate QuantiFERON Assay Results in Solid Organ Transplant Candidates and Proposed Management Algorithm.

Identification and treatment of latent tuberculosis infection (LTBI) mitigate the risk of tuberculosis (TB) reactivation after transplantation. TB reactivation is higher in those with indeterminate QuantiFERON (QFT) than those with negative results. Management of indeterminate QFT results in the pretransplant period remains unclear. We conducted a retrospective study of solid organ transplant (SOT) recipients, 18 y and older, who were screened with QFT assay pretransplantation at Mayo Clinic between January 2010 and June 2023. We examined the frequency of indeterminate QFT results, results of repeat LTBI screening, treatment decisions, and rate of posttransplant TB infection. Of 13 008 patients screened for LTBI before SOT, 736 (6%) patients had indeterminate QFT results. Among these, 247 (34%) underwent a second LTBI screening test, and 39 (5%) received LTBI treatment. Among 247 patients with a repeat LTBI screening test, 185 (75%), 48 (19%), and 14 (6%) were tested by QFT, T-SPOT.TB, or TST, respectively. The repeat QFT remained indeterminate in 160 (86%) patients, whereas all T-SPOT.TB results were negative. Posttransplant TB infection occurred in 2 (0.3%) patients; neither had a second TB screening test pretransplant nor received LTBI treatment. In SOT recipients with indeterminate QFT results at pretransplant evaluation, opting for T-SPOT.TB as a second test may be preferable over repeat QFT. TB infection after transplantation in patients with a pretransplant indeterminate QFT result was rare. Patient management and LTBI treatment in those with indeterminate QFT pretransplant should account for epidemiological risk factors, and shared decision-making is recommended.

Multiple indicators of gut dysbiosis predict all-cause and cause-specific mortality in solid organ transplant recipients

ObjectiveGut microbiome composition is associated with multiple diseases, but relatively little is known about its relationship with long-term outcome measures. While gut dysbiosis has been linked to mortality risk in...

Characterization of the Antibody Response to SARS-CoV-2 Infection in COVID-19 Transplant versus Nontransplant Recipients by Ig-MS.

Solid organ transplant recipients with immunosuppressant regimens to prevent rejection are less able to mount effective immune responses to pathogenic infection. Here, we apply a recently reported mass spectrometry-based serological approach known as Ig-MS to characterize immune responses against infection with SARS-CoV-2 in cohorts of transplant recipients and immunocompetent controls, both at a single early time point following COVID-19 diagnosis as well as over the course of one-month postdiagnosis. We found that the antibody repertoires generated by transplant recipients against SARS-CoV-2 do not differ significantly compared to immunocompetent individuals with regard to repertoire titer, clonality, or glycan composition. Importantly, our study is the first to characterize the evolution of antibody glycan profiles in transplant recipients with COVID-19 disease, presenting evidence that the evolution of glycan composition in these immunocompromised individuals is similar to that in immunocompetent people.

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.

Engagement With Sports After Solid Organ Transplant.

Introduction Transplant Games lend a unique opportunity not only by providing a platform for donors and recipients to engage in sports but also to counter the negativity surrounding organ donation and showcase to the world that transplant recipients can lead active lives. When the Transplant Games were held in Kochi, Kerala, India, for the first time, it provided a venue to engage with transplant recipients, donors, and the families of deceased donors. We aimed to understand the impact that engagement in sports brings on the lives of donors and recipients. Methods After obtaining permission from the organizers, we explained the objectives of the survey to the participants and encouraged them to participate. A survey, covering basic demographic information, transplantation details, and questions related to sports engagement was formulated. Participants could complete the survey electronically via a quick response code or in hard copy. They were fully informed about the objectives of the survey and had the right to withdraw at any stage without consequences. The survey was available for five hours during the games. The study received institutional ethics committee approval (ECASM-AIMS-2024-059). Results Among the approximate 150 participants, we received 78 respondents (52%). After the nine who withdrew consent were removed, we had a full response from 69 participants. Of these, 59 were males (85.5%), and 10 (14.5%) were females. The average age of the participants was 45 ± 13 years. Self-motivation was the most common factor in taking up sports for 30.4% of the responders, followed by family and friends in 23.2% and transplant doctors in 5.8%. Liver Foundation of Kerala (LIFOK), a self-help group of transplant recipients, played a major role in 4.3% of the responders. Bowling was the most popular sport with 23 mentions, followed by carroms and badminton with 27 and 20 mentions, respectively. Donors started to take an active role in sports earlier than recipients, 3.1 ± 1.89 vs. 5.7 ± 5.5 months. The most common reason cited for taking up sports was to become part of the transplant community, followed by a desire to embrace a healthier lifestyle and improve fitness levels. Although none had a personalized coach, most intensified their training and improved nutrition as part of their preparation for the games. Conclusion Our survey is limited by its small and self-selected sample size. Our study highlights the significant role of self-motivation, family support, and self-help groups in encouraging solid organ transplant recipients and donors to engage in sports after surgery. It also highlights the need for more proactive encouragement from doctors and better availability of sports facilities and support staff to help transplant recipients and donors engage in physical activities, which are crucial for their physical and emotional well-being.

Multidrug-resistant organism bloodstream infections in solid organ transplant recipients and impact on mortality: a systematic review.

Bloodstream infections (BSIs) cause significant morbidity and mortality in solid organ transplant (SOT) recipients. There are few data regarding the contribution of MDR organisms (MDROs) to these infections. We evaluated the resistance percentage of MDRO BSIs in SOT recipients and the associated mortality. A systematic review of MEDLINE and Embase databases up to January 2024, for studies of adult SOT recipients that quantified MDRO BSI resistance percentage and/or associated crude mortality. MDROs studied were carbapenem-resistant Enterobacterales (CRE), Acinetobacter baumannii (CRAB) and Pseudomonas aeruginosa (CRPA), third-generation cephalosporin-resistant Enterobacterales (3GCR-E), MRSA and VRE. Resistance percentage and mortality outcomes were reported as median (IQR) and crude mortality (%), respectively. Of 945 studies identified, 52 were included. Most were retrospective (41/52) and/or single centre (37/52), and liver transplantation was the most frequently studied SOT type (22/52). High resistance percentages of BSIs were noted, ranging from 13.6% CRE for Enterobacterales to 59.2% CRAB for A. baumannii. Resistance percentage trends decreased over time, but these changes were not statistically significant. Asia had the highest resistance percentages for MRSA [86.2% (IQR 77.3%-94.6%)], 3GCR-E [59.5% (IQR 40.5%-66.7%)] and CRE [35.7% (IQR 8.3%-63.1%)]. North America had the highest VRE resistance percentages [77.7% (IQR 54.6%-94.7%)]. Crude mortality was 15.4%-82.4% and was consistently higher than for non-MDRO BSIs. MDRO BSI resistance percentages were high for all pathogens studied (IQR 24.6%-69.4%) but there was geographical and temporal heterogeneity. MDRO BSIs were associated with high mortality in SOT recipients. Microbiological and clinical data in this vulnerable population were incomplete, highlighting the need for robust international multicentre studies.

Impact of Hyponatremia on COVID-19-Related Outcomes: A Retrospective Analysis.

Sodium disturbances are observed in one-third of patients with COVID-19 and result from multifaceted mechanisms. Notably, hyponatremia is associated with disease progression and mortality. We aimed to analyze the impact of hyponatremia on COVID-19 outcomes and its correlation with clinical and laboratory parameters during the first wave. We evaluated the sodium levels of 558 patients with COVID-19 between 21 March 2020, and 31 July 2020, at a single center. We performed linear regression analyses to explore the correlation of sodium levels with COVID-19-related outcomes, demographic data, signs and symptoms, and laboratory parameters. Next, we conducted Pearson correlation analyses. A p-value < 0.05 was considered significant. Hyponatremia was found in 35.3% of hospitalized patients with COVID-19. This was associated with the need for intensive care transfer (B = -1.210, p = 0.009) and invasive mechanical ventilation (B = -1.063, p = 0.032). Hyponatremia was frequently found in oncologic patients (p = 0.002) and solid organ transplant recipients (p < 0.001). Sodium was positively associated with diastolic blood pressure (p = 0.041) and productive cough (p = 0.022) and negatively associated with dry cough (p = 0.032), anorexia (p = 0.004), and nausea/vomiting (p = 0.007). Regarding the correlation of sodium levels with other laboratory parameters, we observed a positive correlation with hematocrit (p = 0.011), lymphocytes (p = 0.010), pCO2 (p < 0.0001), bicarbonate (p = 0.0001), and base excess (p = 0.008) and a negative correlation with the neutrophil-to-lymphocyte ratio (p = 0.009), the platelet-to-lymphocyte ratio (p = 0.033), and arterial blood glucose (p = 0.016). Hyponatremia is a risk factor for adverse outcomes in COVID-19 patients. It is associated with demographic data and clinical and laboratory parameters. Therefore, hyponatremia is an important tool for risk stratification in COVID-19 patients.