Mara, Kristin C.

ABSTRACT Background Valganciclovir is the preferred antiviral agent for cytomegalovirus (CMV) prophylaxis in solid organ transplant (SOT) recipients; however, limited data exist to guide optimal dosing in patients requiring intermittent hemodialysis (iHD). This study evaluated the safety and efficacy of our institution's current dosing strategy of valganciclovir 450 mg three times weekly. Methods In this single‐center, retrospective study, adult liver, heart, lung, and kidney transplant recipients from January 2014 to November 2024 were included. Patients requiring ≥ 3 iHD sessions posttransplant and receiving valganciclovir 450 mg three times weekly were compared with recipients with normal renal function receiving 900 mg once daily. The primary outcomes were the risk of neutropenia, leukopenia, and thrombocytopenia within 3.5 months posttransplant. Results A total of 116 patients were included in the iHD cohort and were matched 1:2 to 232 patients in the normal renal function cohort. Rates of leukopenia and neutropenia were comparable between cohorts. However, thrombocytopenia occurred significantly more frequently in the iHD cohort (45.2% vs. 26.7%; p = 0.002). No significant differences were observed in rates of CMV infection between groups. Conclusion Valganciclovir 450 mg three times weekly appears safe and effective for CMV prophylaxis in SOT recipients requiring iHD, though it may be associated with an increased risk of thrombocytopenia. image

ABSTRACT Introduction Patients often receive propofol for sedation and clevidipine for hypertension in the intensive care unit. Both agents are formulated as a lipid emulsion, which may increase the risk of hypertriglyceridemia and acute pancreatitis with their coadministration. We aimed to determine the incidence of hypertriglyceridemia and acute pancreatitis with concurrent administration of propofol and clevidipine and identify patient risk factors for hypertriglyceridemia. Methods This was a multicenter retrospective study of adult patients (≥ 18 years old) receiving concurrent propofol and clevidipine infusions for ≥ 6 h. The primary outcome was the frequency of triglyceride levels greater than 400 mg/dL and acute pancreatitis. The secondary outcome was risk factors associated with hypertriglyceridemia during concurrent propofol and clevidipine infusions until both infusions had been discontinued. Univariable and multivariable logistic regression analyses were used to assess risk factors of hypertriglyceridemia in patients receiving concurrent propofol and clevidipine infusions. Results Across 1,226 patients, the median duration of infusion overlap was 12.4 [interquartile range (IQR) 8.3, 22.7] hours. The mean age of the cohort was 59.6 [standard deviation (SD) 14.9] years, and 59.4% were male. Assuming those without a triglyceride level drawn did not have hypertriglyceridemia, hypertriglyceridemia after initiation of propofol and clevidipine infusion was found in 7.7% [95% confidence interval (CI) 6.3% to 9.3%] of the entire cohort. Twenty‐six patients (2.1%) had a diagnosis of pancreatitis after initiation of lipid infusions, of which 12 cases were possibly infusion‐related, and one case was likely infusion‐related. After calculating the Naranjo Scale, all 13 cases of pancreatitis were possibly related to propofol or clevidipine infusions. Based on a multivariable logistic regression of those with a triglyceride level available, risk factors for hypertriglyceridemia included pancreatitis within the past 5 years [adjusted odds ratio (aOR) 2.77, 95% CI, 1.23 to 6.23] and statin use (aOR 1.94, 95% CI, 1.13 to 3.34). Conclusions In our cohort of patients receiving concurrent propofol and clevidipine, the frequency of hypertriglyceridemia and acute pancreatitis was low. Further comparative studies are warranted to assess the risk of pancreatitis with the addition of clevidipine to propofol.

Abstract Objective: Antibiotics are frequently prescribed for acute sinusitis despite national guidelines recommending antibiotics only if specific symptom criteria are met. We aimed to define the proportion of acute sinusitis encounters meeting criteria for antibiotic prescribing, characterize prescribing practices, and identify factors associated with guideline-discordant prescribing. Design: This retrospective cohort study included 1,000 randomly selected adult ambulatory encounters with a primary diagnosis of acute sinusitis between January 1, 2024 and March 31, 2024. Encounter notes were reviewed for appropriate antibiotic prescribing criteria as per national guidelines. Encounters were evaluated for drug selection and duration concordance based on local guidelines. A multivariable logistic regression analysis was performed to identify predictors of inappropriate antibiotic prescribing. Setting: Emergency departments, urgent care centers, and primary care clinics. Results: Antibiotic prescribing criteria were met for 67.6% of included encounters. Antibiotics were prescribed in 93.5% of encounters that met prescribing criteria, and 80.2% of encounters that did not. Both drug selection and duration were guideline-concordant in 49.2% of total encounters. On multivariable analysis, predictors of inappropriate antibiotic prescribing included cough (OR 2.15, 95% CI 1.08–4.29; P = 0.03) and symptom duration between 7 and 9 days (compared to <6 days; OR 7.70, 95% CI 3.24–18.31; P < 0.001). Electronic encounters were associated with lower odds of prescribing compared to in-person encounters (OR 0.03, 95% CI 0.01–0.09; P < 0.001). Conclusions: Most encounters for acute sinusitis result in an antibiotic prescription, despite prescribing criteria not being met. These findings may aid antimicrobial stewardship programs in benchmarking and optimizing antibiotic prescribing for acute sinusitis.

ABSTRACT Objective This study assessed the impact of sex and age on weight loss outcomes in patients receiving tirzepatide in real‐world clinical practice. Methods We conducted a retrospective cohort study of adults with overweight or obesity who initiated tirzepatide at Mayo Clinic between June 2022 and May 2024 and completed ≥ 12 months of continuous therapy. Primary outcome was total body weight loss percentage (TBWL%) at 15 months, stratified by sex and age groups (≤ 45, 46–59, ≥ 60 years). Results Among 1039 patients (57% women; mean age 56 ± 11 years), women achieved significantly greater TBWL% than men after 15 months of treatment (15.1% vs. 10.7%, p < 0.001). Patients aged ≤ 45 years had greater weight loss than those ≥ 60 years (15.1% vs. 12.3%, p = 0.024). In multivariable analyses, greater weight loss was independently associated with female sex, absence of type 2 diabetes, no prior obesity medication use, no concomitant weight gain‐promoting medications, and higher tirzepatide dosage. Age was not an independent predictor. Conclusions Sex, but not age, predicted weight loss with tirzepatide among individuals using the medication continuously for ≥ 12 months. These findings underscore the importance of incorporating sex‐specific considerations into personalized obesity treatment strategies.

Itraconazole is the recommended first-line antifungal agent in blastomycosis treatment. However, pharmacokinetic limitations and adverse drug events may necessitate the use of alternative antifungal agents. The primary objective of the study was to retrospectively describe a cohort of patients with blastomycosis who received voriconazole (as partial or complete therapy), for complete or partial treatment, compared to those who received itraconazole alone. Secondary objectives included rationale for voriconazole selection, treatment response, mortality, and adverse drug events. This retrospective multicenter cohort study included adult patients with proven/probable blastomycosis who received itraconazole or voriconazole. Treatment response was evaluated at one year or end of therapy, whichever came first. Mortality outcomes were assessed within 7 days of the last documented azole dose. Propensity score weighting and subgroup analysis were utilized to control confounding variables between cohorts. A total of 119 patients receiving itraconazole and 25 receiving voriconazole as complete or partial treatment were included. Voriconazole was often selected for CNS involvement or after intolerance to alternative azoles. After propensity score weighting, no significant difference in complete or partial treatment response was observed. Rates of all-cause mortality and blastomycosis-related mortality were numerically higher in the voriconazole cohort. Adverse drug event rates were similar between cohorts; however, discontinuation due to adverse events was more common in the voriconazole cohort. Voriconazole was most utilized for the treatment of blastomycosis in cases with CNS involvement or intolerance to other azoles. A statistically significant difference in response rate was not identified between voriconazole-containing or itraconazole-treated patients; however, given limited sample sizes, further data is needed to assess the equivalency of these agents in the treatment of blastomycosis.

ABSTRACT The COVID‐19 pandemic underscored the critical need to strengthen healthcare systems and optimize resource allocation planning during times of disruption and crisis. This retrospective, single‐center, cross‐sectional study included 33,158 admissions for patients ≤ 17 years old admitted to the Children's Hospital (CH) between January 1, 2017, and December 31, 2021. Data was abstracted using Vizient Clinical Data Base and the internal data warehouse. A Poisson regression model was implemented to compare admission diagnosis patterns during the pre‐ and intra‐pandemic phases. CH SARS‐CoV‐2 prevalence rate was 0.1% in 2020 and 0.5% in 2021. There was a decrease in overall admissions to the CH ( p < 0.01) and PICU ( p < 0.01) at the onset of the pandemic. There were significant and variable differences in admission patterns for certain infectious and seizure‐related diagnoses. The CH experienced an increase in certain specific mental health diagnoses. Seasonality was noted for viral bronchiolitis during the pre‐pandemic phase, but was disrupted during the intra‐pandemic phase. The COVID‐19 pandemic had a significant impact on the number and pattern of admissions, despite low prevalence of SARS‐CoV‐2 in our hospital. These changes may be secondary to COVID‐19 community mitigation strategies. Results can inform anticipated patterns during future pandemics.

Abstract Background Follow-up blood cultures (FUBCs) for streptococcal bacteremia are infrequently positive and may not provide sufficient clinical impact to justify the time and resources expended for their routine use. We aimed to evaluate the frequency of and risk factors for positive FUBCs in patients with streptococcal bacteremia and to compare clinical outcomes among patients with or without positive FUBCs. Methods We retrospectively reviewed hospitalized patients with streptococcal bacteremia from September 2023 to June 2024 within a multisite health system. Patients ≥18 years old with ≥1 positive blood culture for a Streptococcus species were included. Patients with polymicrobial bacteremia, those who died or were discharged to hospice within 48 hours of their index culture, and Minnesota residents who declined research authorization were excluded. Results We included 454 patients, with 48 (10.6%) having positive FUBCs. The rate of positivity ranged from 0% for Streptococcus pyogenes to 18.5% for Streptococcus anginosus. Endocarditis and osteomyelitis were more common in the positive than in the negative FUBC group (22.9% vs 12.1%, respectively, for endocarditis [P = .04] and 16.7% vs 5.4% [P = .005] for osteomyelitis). Positive FUBCs were associated with a higher incidence of infection relapse (8.5% vs 2.7%; P = .047) and longer duration of antibiotics (30 vs 16 days; P = .01), but no differences in mortality rate, length of stay, or infection-related readmission were observed. Conclusions Positive FUBCs were infrequent for S pyogenes, Streptococcus agalactiae, Streptococcus pneumoniae, and group C and G streptococci. It may be reasonable to forego FUBC for these streptococcal species if endocarditis or osteomyelitis are not clinically suspected.

Summary Recipients of haploidentical and unrelated haematopoietic cell transplants (HCTs) historically had a higher risk for graft‐versus‐host disease (GvHD). However, with improved GvHD prophylaxis, recent data suggest adult patients undergoing transplantation from unrelated or mismatched donors now experience the rates of GvHD similar to those receiving matched related donor grafts. This finding is not yet explored in paediatric patients. The objectives of this study were to: (1) compare acute and chronic GvHD incidence, mortality and GvHD‐free relapse‐free survival (GRFS) among matched related donor (MRD), matched unrelated donor (MUD) and haploidentical paediatric HCT recipients in the era of enhanced GvHD prophylaxis for high‐risk patients, (2) identify independent risk factors for GvHD and (3) evaluate the efficacy of various GvHD prophylactic regimens in our cohort. We conducted a retrospective, single‐centre medical record abstraction among patients aged 0–25 years who underwent allogeneic HCT for any indication. The results demonstrated that 5‐year cumulative incidence rates of any GvHD, all‐cause mortality and GRFS are similar across the haploidentical, MRD and MUD groups. Tacrolimus‐containing doublet/triplet regimens were associated with decreased GvHD, as compared to ciclosporin. Adding alemtuzumab also decreased risk for GvHD, without increasing relapse rates. Prospective studies with larger cohorts are warranted to further optimize outcomes for paediatric allogeneic HCT patients.

Introduction: Reversible and irreversible nephrotoxicity are known complications of tacrolimus. Approaches to reduce the incidence of nephrotoxicity include the reduction or avoidance of tacrolimus but must be weighed against risk of rejection. Infrequently, basiliximab has been used outside of the induction period to facilitate temporary tacrolimus cessation in the setting of acute kidney injury (AKI). Objective: The primary objective of this study was to describe renal recovery after temporary tacrolimus cessation with non-induction basiliximab (NIB) compared to a matched cohort. Methods: We conducted a single-center study of adult cardiothoracic transplant recipients that received basiliximab beyond post-operative day 7 for temporary tacrolimus cessation in the setting of AKI between January 2019 and November 2023 and matched them to acontrol cohort. Results: Twelve patients underwent temporary tacrolimus cessation with NIB. In total, 7 (58%) patients achieved initial renal recovery at tacrolimus resumption compared to 15 (42%) patients in the matched cohort at an equivalent time point. No difference between treated rejection (17% vs. 19%, p = 0.80) or infection (75% vs. 50%, p = 0.32) was observed between tacrolimus cessation and its matched cohort. Conclusions: The use of NIB for tacrolimus cessation can allow for potential renal recovery after an AKI or in patients at risk of AKI. This approach does not appear to significantly increase the risk of rejection but may increase the risk of infection in the long term.

ABSTRACT Background The association between transjugular intrahepatic portosystemic shunt TIPS and waitlist outcomes in simultaneous liver‐kidney (SLK) transplant recipients remains unclear. Methods Between 2003 and 2023, we examined the scientific registry of transplant recipients. All adult candidates with overlapping waiting lists for liver and kidney transplants ( N = 15 087) were analyzed (entire cohort). Candidates without TIPS ( n = 13 980) and with ( n = 1107) were followed through November 30, 2023, and the following outcomes were analyzed: death, SLK transplant, liver‐ or kidney‐alone transplant, or removal from the list. The Aalen–Johansen method was used to calculate the cumulative incidence rates of the outcomes, where the outcomes were considered competing risks. Mixed effects Cox proportional hazard models were used to compare the outcomes by TIPS status. We separately analyzed dialysis‐dependent candidates ( n = 10 370). Results In the entire cohort, the 1‐year cumulative incidence of death in those without TIPS was higher than in those with (12.5% vs. 9%). In the dialysis‐dependent cohort, the 1‐year death incidence was 13.3% versus 8.8% in those without TIPS and those with, respectively. In the multivariable Cox proportional hazard models, TIPS was associated with a 29% lower mortality risk in the entire cohort (HR = 0.71, 95% CI: 0.60–0.84, p < 0.001) and a 33% lower risk of mortality in the dialysis‐dependent cohort. The likelihood of receiving SLK was lower for recipients with TIPS in the univariable analysis. However, this association was attenuated after adjustment. The causes of removal were similar irrespective of TIPS status in both cohorts. Conclusion In this large cohort of SLK candidates, those with TIPS had a better waitlist survival, irrespective of their dialysis requirements before transplantation. Prospective studies are needed to validate these findings.