Population Based Time Trends in the Epidemiology and Mortality of Gastroesophageal Junction and Esophageal Adenocarcinoma.

BACKGROUND: Limited data are available on the epidemiology of gastroesophageal junction adenocarcinoma (GEJAC), particularly in comparison to esophageal adenocarcinoma (EAC). With the advent of molecular non-endoscopic Barrett's esophagus (BE) detection tests which sample the esophagus and gastroesophageal junction, early detection of EAC and GEJAC has become a possibility and their epidemiology has gained importance. AIMS: We sought to evaluate time trends in the epidemiology and survival of patients with EAC and GEJAC in a population-based cohort. METHODS: EAC and GEJAC patients from 1976 to 2019 were identified using ICD 9 and 10 diagnostic codes from the Rochester Epidemiology Project (REP). Clinical data and survival status were abstracted. Poisson regression was used to calculate incidence rate ratios (IRR). Survival analysis and Cox proportional models were used to assess predictors of survival. RESULTS: We included 443 patients (287 EAC,156 GEJAC). The incidence of EAC and GEJAC during 1976-2019 was 1.40 (CI 1.1-1.74) and 0.83 (CI 0.61-1.11) per 100,000 people, respectively. There was an increase in the incidence of EAC (IRR = 2.45, p = 0.011) and GEJAC (IRR = 3.17, p = 0.08) from 2000 to 2004 compared to 1995-1999, plateauing in later time periods. Most patients had associated BE and presented at advanced stages, leading to high 5-year mortality rates (66% in EAC and 59% in GEJAC). Age and stage at diagnosis were predictors of mortality. CONCLUSION: The rising incidence of EAC/GEJAC appears to have plateaued somewhat in the last decade. However, both cancers present at advanced stages with persistently poor survival, underscoring the need for early detection.

ROAR ED-SANE: A Retrospective Observational Assessment Review of an Emergency Department Sexual Assault Nurse Examiner Program's Adherence to Centers for Disease Control and Prevention Guidelines for Sexually Transmitted Infections.

BACKGROUND: Sexual assault survivors are at increased risk for sexually transmitted infections. Sexual Assault Nurse Examiner programs guide sexually transmitted infection treatment, monitoring, and follow-up scheduling according to guidelines by the Centers for Disease Control and Prevention (CDC). Reported low rates of provider adherence to CDC treatment guidelines and patient adherence to follow-up necessitate a review of medication prescribing and follow-up scheduling practices, especially at smaller community hospitals in the United States. METHODS: A retrospective medical record review was conducted to assess adherence rates to CDC guidelines for prescribing practices, scheduling, and follow-up of sexual assault survivors. We included pediatric and adult patients presenting to the emergency department (ED) and participating in the ED Sexual Assault Nurse Examiner program at a rural, community-based teaching hospital in La Crosse, WI, from January 2018 to December 2021. Descriptive statistics were used to evaluate results. RESULTS: Analysis included 103 patients. Prescribing adherence to CDC guidelines was >80% for all except human immunodeficiency virus (53.4%), trichomoniasis (68.1%), and hepatitis B (69%). Of the 38 patients who had a follow-up scheduled during their ED encounter, 78.9% attended their scheduled follow-up and 94.7% of those appointments were scheduled within the CDC-recommended time frame, leading to an overall adherence of 40%. CONCLUSIONS: Adherence rates were high for most prescribing practices, and attendance of scheduled follow-up was higher than expected. Opportunities to improved adherence to CDC guidelines were identified in prescribing for 3 disease states (human immunodeficiency virus, trichomoniasis, and hepatitis B) and in scheduling of follow-up.

Magnetic resonance elastography for prediction of long-term progression and outcome in chronic liver disease: A retrospective study.

BACKGROUND AND AIMS: Although magnetic resonance elastography (MRE) has been well-established for detecting and staging liver fibrosis, its prognostic role in determining outcomes of chronic liver disease (CLD) is mostly unknown. APPROACH AND RESULTS: This retrospective study consisted of 1269 subjects who underwent MRE between 2007 and 2009 and followed up until death or last known clinical encounter or end of study period. Charts were reviewed for cirrhosis development, decompensation, and transplant or death. The cohort was split into baseline noncirrhosis (group 1), compensated cirrhosis (group 2), and decompensated cirrhosis (group 3). Cox-regression analysis with age, sex, splenomegaly, CLD etiology, Child-Pugh Score (CPS), Fibrosis-4 Index (FIB-4) score, and Model for End-Stage Liver Disease (MELD)-adjusted HR for every 1-kPa increase in liver stiffness measurement (LSM) were used to assess the predictive performance of MRE on outcomes. Group 1 (n = 821) had baseline median LSM of 2.8 kPa, and cirrhosis developed in 72 (8.8%) subjects with an overall rate of about 1% cirrhosis/year. Baseline LSM predicted the future cirrhosis with multivariable adjusted HR of 2.38 (p < 0.0001) (concordance, 0.84). In group 2 (n = 277) with baseline median LSM of 5.7 kPa, 83 (30%) subjects developed decompensation. Baseline LSM predicted the future decompensation in cirrhosis with FIB-4 and MELD-adjusted HR of 1.22 (p < 0.0001) (concordance, 0.75). In group 3 (n = 171) with median baseline LSM of 6.8 kPa (5.2, 8.4), 113 (66%) subjects had either death or transplant. Baseline LSM predicted the future transplant or death with HR of 1.11 (p = 0.013) (concordance 0.53) but not in CPS and MELD-adjusted models (p = 0.08). CONCLUSION: MRE-based LSM is independently predictive of development of future cirrhosis and decompensation, and has predictive value in future transplant/death in patients with CLD.

Malignancy among adult heart transplant recipients following patient-tailored dosing of anti-thymocyte globulin: a retrospective, nested case-control study of individualized dosing.

Post-transplant malignancy is diagnosed in approximately 18% of heart transplant patients and is a leading cause of death post-transplant. One modifiable risk factor is the type and amount of immunosuppression received. Contemporary rabbit anti-thymocyte globulin (rATG) dosing strategy using T-cell-guided dosing, and its effect on malignancy in heart transplant patients is unclear. This was a single-center, retrospective chart review of heart transplant recipients receiving rATG for induction. Patients diagnosed with malignancy post-transplant were matched 1:2 to controls using a nested case-control design. The primary endpoint was to determine the relative risk of rATG exposure with the actual incidence of malignancy post-transplant. The secondary endpoint was the impact of maintenance immunosuppression on malignancy risk. Of the 126 patients included in the study, 25 developed malignancy and were matched to 50 control patients. The median cumulative rATG dose in milligrams (mg) between groups was 365 mg in malignancy cases and 480 mg in controls (OR 0.90, 95% CI 0.75-1.08, P = 0.28). In both the univariate and multivariable analysis, there was no statistically significant difference in malignancy risk found with any maintenance immunosuppressant. The results of this study showed that patient-tailored rATG dosing strategies may not be associated with malignancy development as previously thought.

Early, empiric high-dose leucovorin rescue in lymphoma patients treated with sequential doses of high-dose methotrexate.

BACKGROUND: In patients exposed to high-dose methotrexate (HDMTX; >1g/m2) with a history of elevated methotrexate (MTX) concentrations during previous doses, it is unclear whether prescribing high-dose leucovorin (HDLV) rescue limits future high levels or reduces the likelihood of acute kidney injury (AKI). METHODS: This retrospective, single-center study longitudinally followed adult lymphoma patients treated with HDMTX between 1/1/2011 and 10/31/2017 from diagnosis until 30 days after the last HDMTX dose. Endpoints included elevated MTX concentrations at 48 h (>1.0 µmol/L) and incident AKI after each HDMTX dose. RESULTS: The 321 included patients had a median (IQR) age of 65 (57, 72) years, 190 (59%) were male, and 293 (91%) were Caucasian. There were 1558 HDMTX doses [median (IQR) 3 (2, 6) doses per patient] prescribed with 265 (83%) patients receiving more than one MTX dose. Those receiving HDLV rescue were more likely to have an elevated MTX concentration after that dose (OR = 2.69, 95% CI: 1.75-4.11, p < 0.001). Receiving HDLV rescue was associated with a greater likelihood of AKI after MTX (OR = 2.18, 95% CI: 1.38-3.43, p < 0.001). Hospital LOS was longer in those prescribed empiric HDLV rescue after MTX than those prescribed standard leucovorin with an estimated difference of 1.1 days, (95% CI: 0.5-1.7, p < 0.001). CONCLUSION: Sequential HDMTX doses are associated with a significant incidence of elevated MTX levels and AKI during lymphoma management. HDLV rescue prescribed during subsequent MTX doses in patients with a previously elevated level was not associated with improved safety outcomes. The optimal supportive care strategy following HDMTX administration requires further investigation.

Outcomes of radiofrequency ablation by manual versus self-sizing circumferential balloon catheters for the treatment of dysplastic Barrett's esophagus: a multicenter comparative cohort study.

BACKGROUND AND AIMS: Radiofrequency ablation (RFA) is the preferred ablative modality for treating dysplastic Barrett's esophagus. The recently introduced self-sizing circumferential ablation catheter eliminates the need for a sizing balloon. Although it enhances efficiency, outcomes have not been compared with the previous manual-sizing catheter. We evaluated the comparative safety and efficacy of these 2 ablation systems in a large, multicenter cohort. METHODS: Patients undergoing RFA at 3 tertiary care centers from 2005 to 2018 were included. Circumferential RFA was performed in a standard fashion, followed by focal RFA as needed. Outcomes were compared between the self-sizing and manual-sizing groups. The primary outcome was the rate of adverse events, including strictures, perforation, and bleeding. Secondary outcomes were procedure time and treatment efficacy, as assessed by rates and time to complete eradication of dysplasia (CE-D) and intestinal metaplasia (CE-IM). RESULTS: Three hundred eighteen patients were included, 90 (28.3%) treated with the self-sizing catheter and 228 (71.7%) with the manual-sizing catheter. Twenty-one patients (6.6%) developed strictures (8 [8.9%] in the self-sizing group and 13 [5.7%] in the manual-sizing group, P = .32). Of the self-sizing strictures, 75% occurred at the 12J dose before widespread adoption of the current 10J treatment standard. One patient developed bleeding, and no perforations were encountered. Procedure time was significantly shorter in the self-sizing group. No significant differences were observed in rates of and time to CE-D and CE-IM. CONCLUSIONS: These findings suggest that both systems are comparable in safety and efficacy. The use of the self-sizing system may enhance the efficiency of RFA for treating dysplastic Barrett's esophagus.

Characteristics and Outcome of Periengraftment Respiratory Distress Syndrome after Autologous Hematopoietic Cell Transplant.

Rationale: The periengraftment respiratory distress syndrome (PERDS) is an early important cause of morbidity following autologous hematopoietic cell transplantation (HCT). There are few contemporary data describing PERDS. Objectives: To determine prevalence, risk factors, and outcomes of PERDS after autologous HCT. Methods: This was a historical cohort study of adults undergoing autologous HCT at Mayo Clinic, Rochester, Minnesota, between 2005 and 2016. PERDS was defined as 1) respiratory failure requiring supplemental oxygen within 5 days on either side of the neutrophil engraftment date, 2) new pulmonary opacities on chest imaging, and 3) exclusion of an infectious or cardiac etiology to explain the clinical presentation. Results: Of 3,473 patients undergoing autologous HCT, 167 (4.8%) developed PERDS. Radiographic changes preceded engraftment in 77% of cases. In a multivariable regression model, risk factors for PERDS included female sex (odds ratio [OR], 1.73; P = 0.001), the number of preengraftment platelet transfusions (OR, 1.22; P = 0.002), and more rapid engraftment (OR, 0.72 per day longer; P < 0.001). PERDS cases were more likely to be admitted to the intensive care unit (47.3% vs. 9.5%, P < 0.001) and require intubation (20.4% vs. 1.6%, P < 0.001). In an adjusted 100-day death analysis, those diagnosed with PERDS were more likely to die (hazard ratio, 3.1; 95% confidence interval, 1.5-6.2; P = 0.002). Conclusions: PERDS is a common complication of autologous HCT and is associated with increased mortality and healthcare use. Radiographic evidence of pulmonary involvement precedes hematopoietic recovery. A larger number of platelet transfusions and more rapid engraftment appear to increase risk for PERDS.

Provision of a Drug Deactivation System for Unused Opioid Disposal at Surgical Dismissal: Opportunity to Reduce Community Opioid Supply.

OBJECTIVE: To determine the impact of a drug deactivation system to post-surgical patients on the rate of opioid prescription disposal. PATIENTS AND METHODS: Two hundred post-operative patients discharged after inpatient surgery at a large academic medical center. This study was conducted August 20, 2018, through November 30, 2018. Patients were provided with a drug deactivation system (DDS) and instruction sheet along with their opioid prescription. Three to 4 weeks after dismissal, patients were surveyed about quantity of opioids remaining, use of DDS or other disposal methods, and satisfaction with DDS if used. RESULTS: One hundred forty-nine of 200 (74.5%) patients were surveyed. One hundred six reported leftover opioids and 29 (27.3%) had disposed of these medications. By the time of survey, 23 (21.2%) participants with leftover opioids had used the DDS to destroy their remaining supply and an additional 33 (31.1%) participants reported plans to use the disposal bag on a future date. Of the 23 participants who used the DDS, 22 (96.0%) reported that they were very satisfied with the disposal process. CONCLUSION: Participants are willing to use a DDS and are satisfied with the process; however, additional education is needed to ensure timely disposal.

A Prospective Survey of Outpatient Medication Adherence in Adult Allogeneic Hematopoietic Stem Cell Transplantation Patients.

Limited data exist regarding the prevalence and outcome of medication nonadherence in the adult allogeneic hematopoietic stem cell transplantation (allo-HSCT) population. The objective of this cross-sectional survey study is to determine the prevalence of medication nonadherence to immunosuppressant and nonimmunosuppressant medications in adult recipients of allo-HSCT. An electronic survey using previously validated medication adherence scales was distributed between December 2014 and April 2015 to 200 adult patients with at least 3 months of follow-up after allo-HSCT. Immunosuppressant serum drug levels and prescription refill records were retrospectively collected to assess correlation with survey responses. In the entire cohort, 51% of subjects (n = 102) reported nonadherence to nonimmunosuppressant medications (95% confidence interval [CI], 44.07% to 57.93%) on the Morisky Medication Adherence Scale. Of the 153 patients taking oral immunosuppressant medications at the time of the survey, 58 (37.9%) reported nonadherence to immunosuppressant therapy (95% CI, 30.22% to 45.6%), as measured by the Immunosuppressant Therapy Adherence Scale. Younger age and distress were associated with medication nonadherence. Nonadherence to immunosuppressant therapy was associated with mild chronic graft-vs-host disease (cGVHD), and a similar trend was observed for moderate cGVHD. Medication nonadherence was found to be highly prevalent for both immunosuppressant and nonimmunosuppressant medications in adult allo-HSCT recipient, and further study to identify interventions to improve adherence in these patients is warranted.

Outcomes of patients with submucosal (T1b) esophageal adenocarcinoma: a multicenter cohort study.

BACKGROUND AND AIMS: The treatment of submucosal (T1b) esophageal adenocarcinoma (EAC) remains in evolution, with some evidence supporting endoscopic management of low-risk lesions. Using a multicenter cohort, we evaluated outcomes of patients with T1b EAC and predictors of survival. METHODS: Patients diagnosed between 2001 and 2016 with T1b EAC were identified from 3 academic medical centers in the United States. Demographic, clinical, and outcome data were collected. Outcomes studied were overall and cancer-free survival. Cox proportional hazards models were constructed to assess independent predictors of survival. RESULTS: One hundred forty-one patients were included, of whom 68 (48%) underwent esophagectomy and 73 (52%) were treated endoscopically. Most patients (85.8%) had high-risk histologic features. Thirty-day operative mortality was 2.9%. Median follow-up in the esophagectomy and endoscopic cohorts was 49.4 and 43.4 months, respectively. Patients treated endoscopically were older with higher comorbidity scores, with 46 (63%) achieving histologic remission. Nineteen patients (26.0%) also received chemoradiation. Five-year overall survival rates in the surgical and endoscopic cohorts were 89% and 59%, respectively, whereas 5-year cancer-free survival rates were 92% and 69%. Presence of high-risk histologic features was associated with reduced overall survival. CONCLUSIONS: In this large multicenter study of patients with T1b EAC, esophagectomy was associated with improved overall but not cancer-free survival. High-risk histologic features were associated with poorer survival.

Iron deficiency anemia associated with extracorporeal photopheresis: A retrospective analysis.

BACKGROUND: Extracorporeal photopheresis (ECP) is associated with few adverse effects. We have anecdotally noted patients treated with long-term ECP develop iron deficiency anemia (IDA). METHODS: We performed a retrospective chart review of adult patients who received ECP for any indication at Mayo Clinic Rochester and Mayo Clinic Arizona. The primary objective was to describe the cumulative incidence of IDA at 1 year of ECP therapy. RESULTS: A total of 123 patients were eligible for analysis. Graft-vs-host disease was the most common indication for ECP (n = 76, 61.8%). At 1 year of ECP therapy, the cumulative incidence of IDA was 24.1% (95% CI, 14.2%-32.9%). At 5 years, the cumulative incidence of IDA was 68.3% (95% CI, 38%-83.8%). Risk factors for the development of IDA included: cumulative number of ECP sessions (HR 1.34, 95% CI, 1.05-1.73 per 10 additional sessions, P = .022), an indication for ECP of solid organ transplant rejection (compared to cutaneous T-cell lymphoma, HR 5.46, 95% CI, 2.06-14.49, P < .001), and proton pump inhibitor use at baseline (HR 2.15, 95% CI, 1.1-4.21, P = .03). Iron supplementation was initiated in 29 of 37 evaluable patients who developed IDA, with a cumulative incidence of supplementation in 77.2% patients within 3 months of recognition of IDA (95% CI, 55.8%-88.3%). Hemoglobin normalized in 50.1% of patients started on iron supplementation for IDA within 7 months (95% CI, 25.2%-66.7%). CONCLUSIONS: Iron deficiency anemia is common in patients receiving long-term ECP and occurs throughout ECP therapy. IDA resolved with iron supplementation in half of patients.

Warfarin-Induced Rapid Rise in INR Post-Cardiac Surgery Is Not Associated With Increased Bleeding Risk.

Background: Post-cardiac surgery bleeding can have devastating consequences, and it is unknown if warfarin-induced rapid international normalized ratio (INR) rise during the immediate postoperative period increases bleed risk. Objective: To determine the impact of warfarin-induced rapid-rise INR on post-cardiac surgery bleeding. Methods: This was a single-center, retrospective chart review of post-cardiac surgery patients initiated on warfarin at Mayo Clinic Hospital, Rochester. Patients were grouped based on occurrence or absence of rapid-rise INR (increase ≥1.0 within 24 hours). The primary outcome compared bleed events between groups. Secondary outcomes assessed hospital length of stay (LOS) and identified risk factors associated with bleed events and rapid rise in INR. Results: During the study period, 2342 patients were included, and 56 bleed events were evaluated. Bleed events were similar between rapid-rise (n = 752) and non-rapid-rise (n = 1590) groups in both univariate (hazard ratio [HR] = 1.22; P = 0.594) and multivariable models (HR = 1.24; P = 0.561). Those with rapid-rise INR had longer LOS after warfarin administration (discharge HR = 0.84; P = 0.0002). The most common warfarin dose immediately prior to rapid rise was 5 mg. Risk factors for rapid-rise INR were low body mass index, female gender, and cross-clamp time. Conclusion and Relevance: This represents the first report to assess warfarin-related rapid-rise INR in post-cardiac surgery patients and found correlation to hospital LOS but not bleed events. Conservative warfarin dosing may be warranted until further research can be conducted.

QT prolongation in patients with acute leukemia or high-risk myelodysplastic syndrome prescribed antifungal prophylaxis during chemotherapy-induced neutropenia.

Benefits of serial electrocardiographic (ECG) monitoring to detect QT prolongation in patients with hematological malignancies remain unclear. This retrospective, single-center, study evaluated 316 adult acute leukemia and high-risk MDS patients who received 11,775 patient-days of voriconazole prophylaxis during induction chemotherapy. Of these, 37 patients (16.2%) experienced QTc prolongation. Medications associated with QTc prolongation included furosemide, haloperidol, metronidazole, mirtazapine, prochlorperazine, and venlafaxine. Hypokalemia and hypomagnesemia were also significantly associated with QTc prolongation (HR 3.15; p = .003 and HR 6.47, p = .007, respectively). Management modifications due to QTc prolongation included discontinuation of QT prolonging medications (n = 25), more aggressive electrolyte repletion (n = 5), and enhanced ECG monitoring (n = 3). One patient with multiple QT prolonging factors experienced possible Torsades de Pointes. Overall mortality was 15% with no cardiac-related deaths. Serial ECG monitoring during induction chemotherapy can be tailored proportionally to QT-prolonging risk factors. Management should include aggressive electrolyte repletion and avoidance of concurrent QT prolonging medications.

Timeline and location of recurrence following successful ablation in Barrett's oesophagus: an international multicentre study.

OBJECTIVE: Surveillance interval protocols after complete remission of intestinal metaplasia (CRIM) post radiofrequency ablation (RFA) in Barrett's oesophagus (BE) are currently empiric and not based on substantial evidence. We aimed to assess the timeline, location and patterns of recurrence following CRIM to inform these guidelines. DESIGN: Data on patients undergoing RFA for BE were obtained from prospectively maintained databases of five (three USA and two UK) tertiary referral centres. RFA was performed until CRIM was confirmed on two consecutive endoscopies. RESULTS: 594 patients achieved CRIM as of 1 May 2017. 151 subjects developed recurrent BE over a median (IQR) follow-up of 2.8 (1.4-4.4) years. There was 19% cumulative recurrence risk of any BE within 2 years and an additional 49% risk over the next 8.6 years. There was no evidence of a clinically meaningful change in the recurrence hazard rate of any BE, dysplastic BE or high-grade dysplasia/cancer over the duration of follow-up, with an estimated 2% (95% CI -7% to 12%) change in recurrence rate of any BE in a doubling of follow-up time. 74% of BE recurrences developed at the gastro-oesophageal junction (GOJ) (24.1% were dysplastic) and 26% in the tubular oesophagus. The yield of random biopsies from the tubular oesophagus, in the absence of visible lesions, was 1% (BE) and 0.2% (dysplasia). CONCLUSIONS: BE recurrence risk following CRIM remained constant over time, suggesting that lengthening of follow-up intervals, at least in the first 5 years after CRIM, may not be advisable. Sampling the GOJ is critical to detecting recurrence. The requirement for random biopsies of the neosquamous epithelium in the absence of visible lesions may need to be re-evaluated.

Validation of the sarcopenia index to assess muscle mass in the critically ill: A novel application of kidney function markers.

BACKGROUND & AIMS: Adverse outcomes for hospitalized patients with sarcopenia are well documented, and identification of patients at risk remains challenging. The sarcopenia index (SI), previously defined as (serum creatinine/serum cystatin C) × 100, could be an inexpensive, readily accessible, objective tool to predict muscle mass and risk for adverse clinical outcomes. The aim of this study was to assess the validity of the SI as a predictor of muscle mass. METHODS: Retrospective study of critically ill adults admitted to Mayo Clinic from 2012 to 2015 with suspected sepsis and an available creatinine and serum cystatin C. Muscle surface area was quantified at the L3/4 vertebral level in patients with an abdominal CT scan (CTMSA). Multivariable regression modeling was used to assess the relationship between SI and CTMSA, as well as short-term clinical outcomes. RESULTS: The 171 included had a mean weight and body mass index (BMI) of 75.2 ± 16.4 kg and 26.0 ± 4.6 kg/m2 and abdominal CT scans were available for 81 (47%) patients. The SI correlated with CTMSA (r = 0.40). After adjustment for age, sex, severity of illness, and BMI, SI was independently associated with muscle mass (P = 0.001). A decrease in the SI (indicative of lower muscle mass) was also associated with frailty and worse short-term clinical outcomes. CONCLUSION: The SI, a simple calculation from kidney function markers, is a significant predictor of muscle mass in this validation cohort of ICU patients. A low SI was associated with longer hospital length of stay and frailty. Future studies could explore whether the use of SI assists with identifying patients likely to benefit from pharmacotherapy-, nutrition-, or physical therapy-based interventions.

Impact of Serum Cystatin C-Based Glomerular Filtration Rate Estimates on Drug Dose Selection in Hospitalized Patients.

STUDY OBJECTIVE: Serum creatinine (Scr ) concentration is used to calculate estimated glomerular filtration rate (eGFR) for medication dosing. Serum cystatin C (CysC) concentration has been proposed as an adjunct or alternative to Scr . This study sought to evaluate the possible impact of using CysC in eGFR equations on drug dose recommendations in hospitalized patients with infections. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Large academic tertiary care medical center. PATIENTS: A total of 308 adults with suspected or documented infections and stable kidney function who were hospitalized between 2012 and 2015. MEASUREMENTS AND MAIN RESULTS: Standardized Scr and CysC measured at the time of antibiotic dosing were used to estimate GFR from the three Chronic Kidney Disease Epidemiology Collaborative (CKD-EPI) equations using Scr (eGFRCr ), CysC(eGFRCysC ), or a combination of Scr and CysC (eGFRCr-CysC ), and these values were compared with estimated creatinine clearance (eClcr ) from the Cockcroft-Gault equation (standard of care for drug dosage adjustments). The eGFRs were categorized into five common dosage adjustment strata (lower than 20, 20-49, 50-79, 80-130, and higher than 130 ml/min), and agreement between equations was tested with the weighted κ statistic. Recommended drug doses varied considerably between the eClcr and the CKD-EPI equations (weighted κ [95% confidence interval]: eGFRCr 0.73 [0.68-0.79], eGFRCysC 0.42 [0.35-0.5], eGFRCr-CysC 0.65 [0.6-0.71]). If eGFRCr, eGFRCysC , or eGFRCr-CysC were used instead of eClcr to dose drugs, 11%, 12%, and 8% of doses, respectively, would be higher, and 12%, 38%, and 24% of doses, respectively, would be lower. CONCLUSION: Significant discordance in drug doses was observed when the CKD-EPI equations were used in place of eClcr . When CysC was included in eGFR equations, recommended doses were often lower. Further study is needed to develop and test drug-specific dosing guidelines that incorporate alternate renal biomarkers and/or more contemporary eGFR equations.

Comparison of Warfarin Requirements in Post-cardiac Surgery Patients: Valve Replacement Versus Non-valve Replacement.

INTRODUCTION: Anticoagulation with warfarin affects approximately 140,000 post-cardiac surgery patients every year, yet there remains limited published data in this patient population. Dosing remains highly variable due to intrinsic risk factors that plague cardiac surgery candidates and a lack of diverse literature that can be applied to those who have undergone a cardiac surgery alternative to heart valve replacement (HVR). In the present study, our aim was to compare the warfarin requirements between HVR and non-HVR patients. METHODS: This was a single-center, retrospective study of post-cardiac surgery patients initiated on warfarin at Mayo Clinic Hospital, Rochester, from January 1st, 2013 to October 31st, 2016. The primary outcome was the maintenance warfarin dose at the earliest of discharge or warfarin day 10 between patients with HVR and non-HVR cardiac surgeries. RESULTS: A total of 683 patients were assessed during the study period: 408 in the HVR group and 275 in the non-HVR group. The mean warfarin maintenance doses in the HVR and non-HVR groups were 2.55 mg [standard deviation (SD) 1.52] and 2.43 mg (SD 1.21), respectively (adjusted p = 0.65). A multivariable analysis was performed to adjust for gender, age, body mass index and drug interactions. CONCLUSIONS: This was the largest study to evaluate warfarin dose requirements in post-cardiac surgery patients and is the first to compare warfarin requirements between HVR and non-HVR patients during the immediate post-operative period. Both groups had similar warfarin requirements, which supports expanding the initial warfarin dosing recommendations of the 9th edition Chest guideline to include non-HVR patients as well as HVR patients.

Esophagorespiratory Fistulas: Survival and Outcomes of Treatment.

GOAL: The purpose of this study was to characterize outcomes of esophagorespiratory fistulas (ERF) by etiology and initial treatment strategy. BACKGROUND: ERF is a morbid condition for which optimal treatment strategies and outcomes are still in evolution. STUDY: Medical records and images were reviewed for all patients diagnosed with ERF at Mayo Clinic in Rochester, MN, between September 1, 2001 and January 1, 2012. Fistulas were classified as malignant or benign. Treatment strategies were classified as surgical or nonsurgical (typically esophageal stent placement). Technical and clinical success, survival, and survival free of second intervention were assessed. RESULTS: A total of 123 patients with acquired ERF were identified, of whom 65 (53%) were malignant and 58 (47%) benign. Initial treatment strategy was nonsurgical in 88 (72%) patients and surgical in 35 (28%); lower Charlson comorbidity scores were associated with increased likelihood of surgery. Technical and clinical success was seen in a majority of patients treated both surgically and nonsurgically. Patients with malignant ERF treated surgically survived longer than patients undergoing nonsurgical treatment (hazard ratio=5.6, P=0.005). In contrast, those with benign ERF had similar overall survival regardless of whether they received initial surgical or nonsurgical treatment; reintervention was more common in those who underwent nonsurgical treatment (hazard ratio=2.3, P=0.03). CONCLUSIONS: We conclude that survival in malignant ERF is better with surgical intervention in selected patients. Surgical and nonsurgical techniques achieve similar survival in benign ERF, but reintervention is more common in those treated endoscopically.

A comparison of levofloxacin and oral third-generation cephalosporins as antibacterial prophylaxis in acute leukaemia patients during chemotherapy-induced neutropenia.

BACKGROUND: There is demonstrated benefit with fluoroquinolones as infection prophylaxis in neutropenic patients; however, side effects, drug interactions and increasing resistance necessitate investigation of alternative therapies. OBJECTIVES: To compare the incidence of febrile neutropenia in high-risk patients with haematological malignancy receiving a fluoroquinolone with those receiving an oral third-generation cephalosporin (OTGC) as antibacterial prophylaxis during chemotherapy-induced neutropenia. METHODS: A retrospective, matched, single-centre study comparing clinical and microbiological outcomes in acute leukaemia patients receiving fluoroquinolones versus OTGCs as antibacterial prophylaxis after chemotherapy. RESULTS: A total of 120 patients (levofloxacin n = 80, OTGC n = 40) were included and matched. The 30 day incidence of febrile neutropenia was 89.7% (95% CI = 82.4-93.9). The rates of febrile neutropenia were similar between antimicrobials (OTGC versus levofloxacin HR = 0.90, 95% CI = 0.54-1.52, P = 0.70). The most frequent site of infection was the bloodstream (line related) (n = 24, 62%) and the majority (n = 28, 72%) of infections were caused by Gram-positive organisms. Groups were similar in terms of site of infection (P = 0.91) and morphology of recovered microorganisms (P = 0.74). There were significantly more cultures positive for Enterobacter spp. in the OTGC group (P = 0.043). Three patients died during follow-up (from first dose up to 30 days after the last dose) (30 day survival = 99.2%, 95% CI = 97.5-100), with only two of the reported deaths attributable to infection. CONCLUSIONS: These findings demonstrate comparable rates of febrile neutropenia and culture positivity with an increase in cultures positive for Enterobacter spp. when OTGCs are compared with levofloxacin for antibacterial prophylaxis during chemotherapy-induced neutropenia. Further prospective, randomized investigation is warranted.