Conversion to tacrolimus alone compared to full immunosuppression following cardiac transplantation (TACTFUL).

BACKGROUND: Cardiac transplantation requires lifelong immunosuppressant medications to prevent rejection. However, some patients may not tolerate multiple immunosuppressants due to adverse effects. At our institution, patients may be converted to monotherapy with tacrolimus if unable to tolerate a combination regimen. This study evaluated the outcomes among patients converted to tacrolimus monotherapy compared with those maintained on combination immunosuppression. METHODS: This single-center, retrospective cohort study included patients who received heart transplants at Sentara Norfolk General Hospital between January 2015 and July 2021. Patients were classified as receiving tacrolimus monotherapy (Mono) or combination immunosuppression (Combo). The primary outcome was all-cause mortality with key secondary outcomes including incidence of 2R/3R rejection, necessity for renal replacement therapy, and infection. RESULTS: 112 patients were included (Mono = 25, Combo = 87). Median age at transplant was 53.8 years (Mono) and 52.1 years (Combo). The most common reasons for conversion to monotherapy were leukopenia, infection, and gastrointestinal (GI) distress. There was no difference in mortality (0 in Mono, 11 in Combo; p = .09) or percentage of patients with 2R/3R rejection (24% in Mono, 32.2% in Combo; p = .43). No Mono group patients experienced rejection after converting from combination therapy. 24% of Mono group patients resumed at least one additional immunosuppressive medication during the study period. Median time to monotherapy was 9.0 months, with a total median duration on monotherapy of 16.0 months. A median of 3.3 years of follow-up was observed for patients in Mono and 3.4 years in Combo (p = .29). CONCLUSION: Selected patients who do not tolerate combination immunosuppression can be safely transitioned to tacrolimus monotherapy as a means of controlling adverse events without an increased risk of mortality or rejection.

Retrospective Cohort Study of the Incidence of Acute Kidney Injury with Vancomycin Area under the Curve-Based Dosing with Concomitant Piperacillin-Tazobactam Compared to Meropenem or Cefepime.

Acute kidney injury (AKI) is a complication associated with vancomycin. Previous studies demonstrated that the combination of vancomycin and piperacillin-tazobactam increases the risk of AKI compared to vancomycin with meropenem or cefepime. These studies did not utilize area under the curve (AUC)-based dosing, which reduces vancomycin exposure and may decrease nephrotoxicity compared with trough-based dosing. This study evaluated the incidence of AKI in patients receiving AUC-dosed vancomycin with either concomitant piperacillin-tazobactam (VPT) or meropenem or cefepime (VMC). This retrospective cohort study included patients admitted to Sentara Norfolk General Hospital between October 2019 and September 2020 who received AUC-dosed vancomycin and concomitant piperacillin-tazobactam, meropenem, or cefepime for at least 48 h. The primary outcome was the incidence of AKI during treatment or within 24 h of discontinuation. A total of 435 patients (VPT, n = 331; VMC, n = 104) who received a median duration of 4 days of treatment were included. The incidence of AKI was significantly higher with VPT than with VMC (13.6% versus 4.8% [P = 0.014]). Multivariable analysis showed VPT to be an independent risk factor for the development of AKI (odds ratio [OR], 3.00 [95% confidence interval {CI}, 1.15 to 7.76]). VPT was associated with more frequent AKI than VMC, even with the relatively short courses of antimicrobial therapy administered in this population. In comparison with the precedent in the literature for trough-based vancomycin dosing, our results suggest that the use of AUC-based vancomycin dosing in combination with piperacillin-tazobactam, meropenem, or cefepime may result in a lower overall incidence of AKI.

The utilization and safety of apixaban for therapeutic anticoagulation in heart transplant population requiring routine endomyocardial biopsies.

PURPOSE: Routine endomyocardial (EM) biopsies pose a challenge in the management of heart transplant recipients requiring anticoagulation. Apixaban is a direct-acting oral anticoagulant (DOAC) with a short half-life allowing for brief interruptions of anticoagulation for procedures. The study objective was to determine the safety and efficacy of apixaban in heart transplant patients undergoing EM biopsies. METHODS: This retrospective case series evaluated patients with a heart transplant from April 1, 2017 to July 30, 2020 who were treated with apixaban within 90 days post-transplant. The primary outcome was the occurrence of a bleeding or thrombotic event. RESULTS: A total of 12 patients with >100 biopsies were included. The median age was 54 years (IQR 37-59) with a mean weight of 91 ± 20 kg. There were no bleeding or thrombotic events. During therapy, patients underwent an average of eight biopsies. The median time from transplant to initiation of apixaban was 39.5 days (range 9-77). Therapy was maintained without any need for reversal for a median of 276 days (IQR 45-245). CONCLUSIONS: Apixaban is safe to use for anticoagulation of heart transplant recipients undergoing routine biopsies. Using apixaban allows for a short interruption of therapeutic anticoagulation to accommodate a biopsy without increased risk of bleeding.

Impact of time in therapeutic range after left ventricular assist device placement: a comparison between thrombus and thrombus-free periods.

The association between time in therapeutic range (TTR) and clinical outcomes in patients with left ventricular assist devices (LVADs) on chronic warfarin therapy is not well understood. This study assessed TTR using the Rosendaal Method prior to suspected or confirmed pump thrombosis or ischemic stroke. Each patient served as their own control. Characteristics and TTR in 1, 2, and 3 months prior to thrombus (thrombus period) were compared to a thrombus-free period during 6 months to 3 months prior to thrombus (control period). There were 30 thrombus events observed in 25 patients for a rate of 0.06 events per LVAD day. Average TTR (target INR = 2-3) over 3 months for patients combined in both the thrombus and control time period was 53.4%. TTR (target INR = 2-3) was 11.4% lower 1 month prior to thrombus than the comparable month in the control period (p = 0.029). The TTR (target INR = 1.8-2.5) was 11.8% lower in the thrombus time period compared to the control time period 2 months prior to thrombus (p = 0.032). Our study found an increased risk of thrombosis with lower TTR in months leading up to thrombus compared to a thrombus-free period.

Low vitamin D exposure is associated with higher risk of infection in renal transplant recipients.

BACKGROUND: Vitamin D is a steroid hormone with multiple vital roles within the immune system. Various studies evaluated the influence of vitamin D on infections postrenal transplantation and found contrasting results. This study aimed to assess the relationship between vitamin D status and the incidence of infection in renal transplant recipients. METHODS: This is a retrospective cohort study of adult renal transplant recipients at the University of Pittsburgh Medical Center between 2005 and 2012. Patients were grouped as vitamin D sufficient (≥30 ng/mL) or deficient (<30 ng/mL) based on total serum 25-hydroxyvitamin D concentrations. The association between vitamin D levels collected at any point post-transplantation and incidence of infection within ±90 days of the vitamin D levels were assessed using logistic and Poisson's regression models. RESULTS: Vitamin D sufficiency at any point post-transplantation was significantly associated with a 66% lower odds (OR: 0.34; 95% CI: 0.22-0.52; P<.001) and 43% lower rate of infections (incident rate ratio (IRR): 0.57; 95% CI: 0.46-0.71; P<.001) within ±90 days of the vitamin D level. Baseline vitamin D level was also associated with lower incidence and risk for infections within the first year post-transplantation. CONCLUSION: Adequate levels of vitamin D in kidney transplant recipients are associated with lower infection risk in the first year and at any time post-transplantation.

An ISHLT consensus statement on strategies to prevent and manage hemocompatibility related adverse events in patients with a durable, continuous-flow ventricular assist device.

Life expectancy of patients with a durable, continuous-flow left ventricular assist device (CF-LVAD) continues to increase. Despite significant improvements in the delivery of care for patients with these devices, hemocompatability-related adverse events (HRAEs) are still a concern and contribute to significant morbility and mortality when they occur. As such, dissemination of current best evidence and practices is of critical importance. This ISHLT Consensus Statement is a summative assessment of the current literature on prevention and management of HRAEs through optimal management of oral anticoagulant and antiplatelet medications, parenteral anticoagulant medications, management of patients at high risk for HRAEs and those experiencing thrombotic or bleeding events, and device management outside of antithrombotic medications. This document is intended to assist clinicians caring for patients with a CF-LVAD provide the best care possible with respect to prevention and management of these events.

Safety and Feasibility Assessment of a Pharmacy-Driven AUC/MIC Vancomycin Dosing Protocol in a Multicenter Hospital System.

Vancomycin is used for Gram-positive infections, including methicillin-resistant Staphylococcus aureus. The 2020 vancomycin guidelines described by M. J. Rybak, J. Le, T. P. Lodise, D. P. Levine, et al. (Am J Health Syst Pharm 77:835-864, 2020, https://doi.org/10.1093/ajhp/zxaa036) provided an update on vancomycin dosing, which recommended an optimal area under the concentration-time curve over 24 h to MIC (AUC/MIC) target of 400 to 600. In 2021, a pharmacy-driven AUC/MIC vancomycin dosing protocol was implemented across 12 Sentara Health System hospitals. The primary objective of this study was to assess if the pharmacy-driven AUC/MIC vancomycin dosing protocol led to fewer acute kidney injury (AKI) events than trough-based dosing. Secondary objectives included vancomycin duration, hospital length of stay, administered vancomycin dose during admission, vancomycin labs drawn during standard lab times, and cost. AKI was assessed in two separate ways: (i) modified AKIN (Acute Kidney Injury Network) criteria and (ii) a modified version from the vancomycin guidelines. Inferential statistics were used to analyze the results of this retrospective study. Per the AKIN definition, the rates of AKI were 13.9% (349/2,507) in the trough-based group and 14.9% (369/2,471) in the AUC/MIC-based group (P = 0.309). Per the definition of the vancomycin guidelines, the rates of AKI were 6.7% (169/2,507) in the trough-based group and 7.6% (187/2,471) in the AUC/MIC-based group (P = 0.258). A total of 52% (2,679/5,151) of vancomycin labs were obtained during standard lab times in the AUC group and 24% (1,144/4,766) in the trough group (P < 0.05). There was no difference in AKI events between AUC and trough dosing. Use of contrast dye may confound these results. AUC/MIC dosing was associated with more lab draws during standard times, a larger number of labs drawn per person, and less total use of vancomycin. IMPORTANCE In this article, we report that there were no differences in rates of acute kidney injury between trough-based vancomycin dosing and AUC/MIC-based vancomycin dosing across 12 hospitals. AUC/MIC dosing resulted in more vancomycin lab draws during standard lab draw times compared to trough dosing, thus making it more convenient for health care personnel. This study includes all uses for vancomycin, including empirical use, and all patient severity levels. Therefore, this research reflects real-world use of vancomycin in hospitals. AUC/MIC dosing is supported by various infectious disease societies. However, the feasibility of incorporating AUC/MIC dosing in hospitals is undetermined. This study is unique in that it includes hospitals of various sizes (small community hospitals and an academic teaching hospital), and it includes a feasibility component. Therefore, this study has broad applicability to other hospitals across the United States. This original research includes the clinical application of vancomycin in a multicenter health system.

Withdrawn as duplicate: Evaluation of discharge prescribing after rescheduling of gabapentin as a controlled substance.

This article has been withdrawn due to a publisher error that caused the article to be duplicated. The definitive version of this article is published under DOI 10.1093/ajhp/zxab293.

A retrospective evaluation of heparin product reactions in patients with alpha-gal allergies.

BACKGROUND: Alpha-gal allergy, also known as red meat allergy or alpha-gal syndrome, can present after bites of certain tick species that contain galactose-alpha-1,3-galactose (alpha-gal) carbohydrate. Following this exposure, patients may develop an allergic reaction after mammalian meat consumption. Some heparin products are derived from porcine intestinal tissue, and it is therefore possible that administering these medications to a patient with an alpha-gal allergy may trigger a reaction. OBJECTIVE: The purpose of this study was to evaluate the incidence of reactions to porcine heparin products in patients with an alpha-gal allergy. METHODS: A retrospective case series was conducted by review of electronic medical record data. Patients included were between the ages of 18 and 89 years, with a documented alpha-gal or red meat allergy and an admission to a hospital in the Sentara Healthcare system. The primary outcome was the incidence of allergic reactions upon exposure to heparin products in patients with a documented alpha-gal allergy. RESULTS: Patients with a documented alpha-gal allergy received a heparin product in 57 of 158 hospital visits (36.1%). Heparin products were tolerated in 56 of the 57 visits (98.3%). The incidence of an alpha-gal reaction to unfractionated heparin was 2.6% (1/39) while the incidence of an alpha-gal reaction to enoxaparin was 0% (0/22). CONCLUSION AND RELEVANCE: Heparin products were associated with a low incidence of alpha-gal reactions among patients with documented alpha-gal allergy. It is possible that enoxaparin poses less of a risk for reaction in these patients compared to unfractionated heparin.

Single-Dose Anti-Thymocyte Globulin Compared With Divided-Dose for Induction Therapy in Kidney Transplantation in a Predominantly Black Population.

BACKGROUND: The aim of this study was to compare single-dose rabbit anti-thymocyte globulin (rATG) with a divided dose in kidney transplant recipients within a majority Black patient population. METHODS: We analyzed the outcomes before and after a change in protocol from divided-dose (1.5 mg/kg/day over 4 days) to single-dose (6 mg/kg over 24 hours) rATG in a retrospective cohort study. All patients who received rATG for kidney transplant induction between December 2015 and July 2018 were included. RESULTS: A total of 197 patients (n = 98 in the divided-dose group, n = 99 in the single-dose group) received rATG. There was no difference in time to rejection at 1 year (P = .82) or incidence of rejection (P = .80). There was also no difference in delayed graft function, serum creatinine, or survival at 1 year. Patients in the single-dose group were more likely to leave the hospital by postoperative day 3 (12% vs 2%, P = .006). The cytomegalovirus infection rate was higher in the single-dose group (P = .031). CONCLUSIONS: Use of a single-dose rATG regimen is an acceptable accelerated induction compared with the standard divided dose for induction therapy in kidney transplant in a predominantly Black population.

Protocol-based anticoagulation management for mechanical circulatory support patients can be safe and efficient.

BACKGROUND: Achieving optimal anticoagulation remains a significant challenge in managing patients on left ventricular assist device (LVAD) support. Maintaining tight control of anticoagulation can be time-consuming but essential in preventing serious complications such as pump thrombosis and bleeding. OBJECTIVES: The efficacy and safety of a nurse coordinator-driven outpatient protocol (NCDOP) was evaluated for managing anticoagulation for LVAD patients. METHODS: A retrospective analysis was performed as part of a single-center quality improvement project. The primary outcome was time in therapeutic range (TTR), a measure of anticoagulation target efficacy before and after the implementation of the protocol. RESULTS: Among 47 patients, who served as their own control, there was no significant change in TTR or proportion of hospitalizations following institution of the protocol. Pre-NCDOP, there were six major bleeding and two thrombotic events, and none during the post-NCDOP period. CONCLUSIONS: A NCDOP is a reliable method to manage anticoagulation in LVAD patients and facilitates efficient care delivery. Future multicenter studies with larger patient cohorts are warranted to expand on the findings outlined in this manuscript.

Evaluation of discharge prescribing after rescheduling of gabapentin as a controlled substance.

PURPOSE: Gabapentin has increasingly been identified as a drug of abuse, especially when used concurrently with opioids. Rescheduling gabapentin as a schedule V controlled substance may strengthen monitoring and prescribing restrictions. The purpose of this study was to characterize the impact of rescheduling gabapentin from a nonscheduled to a schedule V substance in Virginia on discharge prescribing patterns in a health system. METHODS: This was a retrospective, pre-post, multicenter chart review conducted at 4 sites. Data from 3 months before gabapentin rescheduling (prerescheduling group) and 3 months after gabapentin rescheduling (postrescheduling group) were evaluated. The primary outcome was the percentage of newly prescribed gabapentin prescriptions upon discharge, which was compared between the pre- and postrescheduling groups. RESULTS: A similar percentage of gabapentin prescriptions were newly prescribed in the prerescheduling group as compared to the postrescheduling group (55.0% vs 50.0%, P = 0.479). Gabapentin prescribing characteristics did not differ between the groups for new gabapentin prescriptions (n = 55 in the prerescheduling group, n = 50 in the postrescheduling group). Concomitant discharge prescribing of benzodiazepines (5.5% vs 2.0%, P = 0.619) and opioids (45.5% vs 60.0%, P = 0.136) did not differ significantly between the postrescheduling group and prerescheduling group for new gabapentin prescriptions. However, fewer opioid prescriptions exceeded 90 daily morphine milligram equivalents (MME) in the postrescheduling group as compared to the prerescheduling group for new gabapentin prescriptions (36.0% vs 20.0%, P = 0.020). CONCLUSION: Gabapentin prescribing practices did not differ before and after rescheduling of gabapentin as a controlled substance. There was a trend toward dosages with reduced daily MME for concomitant opioid prescriptions after rescheduling. However, additional investigation with larger studies over longer periods of time is needed to discover whether gabapentin rescheduling significantly changes prescribing practices.

A Comparison of Two Regimens for Managing Sickle Cell Pain and Reducing Readmissions.

This was a multicenter retrospective analysis comparing intravenous push (IVP) analgesia versus patient-controlled analgesia (PCA) in patients admitted for sickle cell pain crisis. The primary objective was to compare the analgesic management, measured in total daily morphine milligram equivalents (MME). Secondary objectives included length of hospitalization, 30-day hospital readmissions and pain scores. Of the 98 patients identified between August 2017 and August 2018, 68 patients were included in this study. There were 51% (n = 35) in the IVP group and 49% (n = 33) in the PCA group. The majority of patients were on 90 or more daily MME prior to admission. The average total daily MME was significantly higher in patients on PCA compared to IVP on the first three days of hospitalization (289 vs 146, p < 0.01). Length of hospitalization was not different between patients on IVP and PCA (7.14 vs. 6.39 days, p = 0.53). There was no difference in 30-day readmissions, average pain scores on days 1-3 of hospitalization and adverse side effects between the groups. This study showed patients on IVP had significantly lower total daily MME requirements compared to PCA within the first three calendar days of admission.

Gastrointestinal Bleeding Rates in Left Ventricular Assist Device Population Reduced with Octreotide Utilization.

Patients with continuous-flow left ventricular assist devices have a high risk of gastrointestinal bleeding (GIB) and recurrent bleeding. Studies have shown octreotide can reduce the risk of GIB. This retrospective, case-crossover study, evaluated the efficacy of octreotide for the prevention of recurrent GIB in patients with left ventricular assist devices between August 2008 and October 2018. A total of 32 patients received octreotide and were included in the study. Hospital admission for GIB was evaluated before and after the initiation of octreotide. Each case served as his/her own control. Most patients were on a reduced aspirin dose (56.2%) and had a reduced international normalized ratio goal (59.4%) before starting monthly octreotide. The most common dose of long-acting octreotide was 30 mg every 28 days. Overall, octreotide decreased the frequency of GIB (4.3 vs. 0.9 events/year, p < 0.001). Nineteen (59.4%) patients did not have a subsequent gastrointestinal bleed. Of the 13 patients who rebled after initiation of octreotide, the frequency of events decreased by 2.6 bleeds per patient per year (4.8 vs. 2.2; p = 0.043). In high-risk patients who have failed conventional therapy, octreotide can be useful for the prevention of recurrent GIB.

Successful Treatment of UL97 Mutation Ganciclovir-Resistant Cytomegalovirus Viremia in a Renal Transplant Recipient With Letermovir and Adjunct Hyperimmune Cytomegalovirus Immunoglobulin: A Case Report.

Letermovir is an antiviral agent indicated for primary prophylaxis of cytomegalovirus (CMV) infection and disease in adult allogeneic hematopoietic stem cell transplant recipients. In this case, UL97 mutation that conferred resistance to ganciclovir was seen in a patient 8 months after renal transplant. We report the off-label use of letermovir with adjunct hyperimmune CMV immunoglobulin in the successful treatment of CMV disease. This report is the first to use this combination for treatment of CMV infection with a high viral load. It contributes to the limited available literature supporting the use of letermovir in the treatment of resistant CMV, where current therapeutic options can be suboptimal due to adverse effects and the risk of cross-resistance.

4-Factor Prothrombin Complex Concentrate (PCC4, Kcentra®) Protocol Reduces Blood Requirements for Heart Transplantation: A Novel Protocol.

BACKGROUND All patients with a ventricular assist device (VAD) awaiting heart transplantation are anticoagulated with warfarin to prevent thromboembolism. The use of 4 factor prothrombin complex concentrate (PCC4, Kcentra®) for anticoagulation reversal prior to surgery may include benefits such as quicker reversal, longer duration of action, and a reduction in total volume of blood products used compared to other reversal practices. The study objective is to evaluate benefits of using an anticoagulation reversal protocol featuring PCC4, over standard of care in heart transplant patients requiring anticoagulation. MATERIAL AND METHODS This is a single center, combined retrospective and prospective, time-matched cohort study compared 12 patients transplanted pre-protocol and 11 patients transplanted post-protocol. The primary outcome was the total volume of blood and blood products used. Secondary outcomes included length of hospital and ICU stay, safety and adverse events, primary chest closure, and a cost comparison. RESULTS The PCC4 reversal protocol showed a significant reduction in total blood volume received with an overall decrease of 1.76L (4.20L pre-protocol, 2.45L post-protocol, P=0.037), total units of blood products infused (20 units pre, 12 units post, P=0.033), and units of packed red blood cells (7 units pre, 3 units post, P=0.033). All heart transplant recipients were listed Status 1A with the primary indication being infection (n=12; 52%). Baseline characteristics, survival, and cost were not different between the two groups. There were no thrombotic events or patient that experienced serious reactions to PCC4. Secondary outcomes were only significant to time to INR reversal. CONCLUSIONS Patients treated with the PCC4 protocol demonstrated a significant decrease in volume of blood and units of blood products required prior to chest closure for heart transplant patients. PCC4 was found to be a safe and beneficial agent in anticoagulation reversal for patients on anticoagulation prior to heart transplantation.

Fanconi's syndrome and nephrogenic diabetes insipidus in an adult treated with ifosfamide.

Fanconi's syndrome is a serious condition characterized by type II proximal renal tubular dysfunction, with urinary loss of glucose, amino acids, phosphate, bicarbonate, and potassium. Ifosfamide-induced Fanconi's syndrome is reported in about 1.4-5% of children being treated for solid tumors, yet only a few cases have been reported in adults. We describe a 54-year-old man who came to the hospital with symptoms of neutropenic fever 4 days after his fourth cycle of ifosfamide and doxorubicin treatment for recurrent sarcoma with metastases to the lung. During admission, he was noted to have severe renal tubular dysfunction; ifosfamide-induced nephrogenic diabetes insipidus and Fanconi's syndrome were suspected. He received supportive therapy that resulted in incomplete resolution of signs and symptoms. The patient was discharged after a 5-day hospital stay when his white blood cell count increased from 0.1-2.5 × 10(3) /mm(3) and his fever had resolved. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship (score of 7) between the patient's development of diabetes insipidus and Fanconi's syndrome and his use of ifosfamide. This dual diagnosis of diabetes insipidus and Fanconi's syndrome in an adult makes this case unusual, as well as therapeutically challenging. We conducted a review of the existing literature regarding ifosfamide-induced Fanconi's syndrome and describe the proposed mechanisms and therapeutic options. This case suggests that patients treated with ifosfamide should be monitored closely for renal function to identify, and perhaps prevent, these rare adverse events. Preliminary animal models show promise for adding N-acetylcysteine to ifosfamide treatment, but more research is necessary before using this drug as a therapeutic option.