Evaluation of the Safety of Slow IV Push Versus Slow IV Infusion Administration of 23.4% Sodium Chloride.

Background and Purpose: Increased intracranial pressure due to cerebral edema is a medical emergency in which 23.4% sodium chloride (23.4% NaCl) may be a lifesaving intervention. Currently, safety data is limited on slow IV push (IVP) administration. The purpose of this study was to evaluate the safety of IVP administration of 23.4% NaCl and determine the number of infusion-related adverse events (IRAEs) compared to slow IV infusion (SIV) administration. Methods: We performed a retrospective review of patients who received a dose of 23.4% NaCl at the (removed institution) from January 2015 to June 2020 as either SIV over 30 minutes or IVP over 2-5 minutes. Results: In total, 81 patients, 55 in the IVP group and 26 in the SIV group, were included in the analysis. There was a significantly faster time from order entry to dose completion (IVP 25 [13,58] vs SIV 73 [55,113] minutes, P < .001). There was no difference in IRAEs between the groups (IVP 17 [31%] vs SIV 6 [23%], P = .466). Hypotension was most common (IVP 13 [24%] vs SIV 5 [19%], P = .656) followed by bradycardia (IVP 6 [11%] vs SIV 1 [4%], P = .291). There were no extravasations reported. Conclusions: Overall, among a cohort of patients with cerebral edema, we found no difference in the incidence of IRAEs between SIV and IVP administration of 23.4% NaCl, and found a faster time to complete administration fssor the latter. In emergent scenarios where time may impact neurologic function, 23.4% NaCl administered IVP may be an alternative to SIV administration.

Evaluating the Use of Unfractionated Heparin with Intra-Aortic Balloon Counterpulsation.

BACKGROUND: Evidence supporting anticoagulation with unfractionated heparin (UFH) in patients with an intra-aortic balloon pump (IABP) to prevent limb ischaemia remains limited, while bleeding risks remain high. Monitoring heparin in this setting with anti-factor Xa (anti-Xa) is not previously described. OBJECTIVES: The study objective is to describe the incidence of thromboembolic and bleeding events with the use of UFH in patients with an IABP utilising monitoring with both anti-Xa and activated partial thromboplastin time (aPTT). METHODS: This is a retrospective study of adults who received an IABP and UFH for ≥24 hours. Electronic medical records were reviewed for pertinent data. The primary outcome was the incidence of limb ischaemia during IABP. Secondary outcomes included myocardial infarction, thrombus on IABP, or stroke. Exploratory outcomes included any venous thromboembolism and bleeding events. RESULTS: Of 159 patients, 88% received an IABP for cardiogenic shock and median duration of IABP support was 118 hours (interquartile range, 67-196). Limb ischaemia occurred in four of 159 patients (2.5%). Strokes occurred in 3.8% of the cohort, and bleeding events occurred in 33%. Despite anticoagulation use in all patients, 11% experienced a venous thromboembolism, with most identified upon asymptomatic screening with concern for heparin-induced thrombocytopenia. We found no differences in outcomes that occurred with a hybrid anti-Xa and aPTT versus aPTT monitoring alone. CONCLUSIONS: We observed a high rate of thrombotic and bleeding complications with the use of UFH in patients with an IABP. Use of anti-Xa versus aPTT for monitoring was not associated with complications. These data suggest safer anticoagulation strategies are needed in this setting.

Antithrombotic Stewardship: Evaluation of Platelet Reactivity-Guided Cangrelor Dosing Using the VerifyNow® Assay.

Cangrelor may be used as a bridge when temporary interruption of dual antiplatelet therapy (DAPT) is necessary. However, the optimal dose and monitoring of cangrelor in patients remains unknown, especially in the setting of mechanical circulatory support (MCS). We conducted an observational, single-center, retrospective cohort study of patients that had PCI within 3 months and received cangrelor while admitted to any intensive care unit. The primary outcome was the incidence of any major adverse cardiovascular event (MACE). Secondary outcomes included VerifyNow® platelet reactivity units (PRU) measured while on cangrelor and any bleeding events while on cangrelor. A total of 92 patients were included. The most common reason for cangrelor use was in the periprocedural setting, with or without MCS (42, 45%), followed by NPO status (26, 28%), and MCS alone (22, 24%). The primary outcome of MACE occurred in one patient (1.1%). Out of 92 patients, 77% had a P2Y12 level collected within 24 hours and 89% of the cohort was able to achieve the goal P2Y12 PRU of < 194. The median P2Y12 value was 115 PRU (40, 168 PRU). We observed a bleed event rate of 23% (21/92). We found a standardized protocol of cangrelor dosing in critically ill patients that received a DES in the past 3 months to be successful in achieving a goal P2Y12 PRU. Although the optimal PRU remains unknown, cardiovascular clinicians may monitor these levels to help guide decisions regarding cangrelor management. Future randomized controlled trials should evaluate the optimal PRU threshold to balance risks of ischemia and bleeding.

Robotic or open superficial inguinal lymph node dissection as staging procedures for clinically node negative high risk penile cancer.

OBJECTIVE: To evaluate perioperative and oncologic outcomes of a cohort of clinically node negative high-risk penile cancer patients undergoing robotic assisted inguinal lymph node dissection (RAIL) compared to patients undergoing open superficial inguinal lymph node dissection (OSILND). PATIENTS AND METHODS: We retrospectively reviewed the clinical characteristics and outcomes of clinically node negative high-risk penile cancer patients undergoing RAIL at MDACC from 2013-2019. We sought to compare this to a contemporary open cohort of clinically node negative patients treated from 1999 to 2019 at MDACC and Moffit Cancer Center (MCC) with an OSILND. Descriptive statistics were used to characterize the study cohorts. Comparison analysis between operative variables was performed using Fisher's exact test and Wilcoxon's rank-sum test. The Kaplan-Meier method was used to estimate survival endpoints. RESULTS: There were 24 patients in the RAIL cohort, and 35 in the OSILND cohort. Among the surgical variables, operative time (348.5 minutes vs. 239.0 minutes, P < 0.01) and the duration of operative drain (37 vs. 22 days P = 0.017) were both significantly longer in the RAIL cohort. Complication incidences were similar for both cohorts (34.3% for OSILND vs. 33.3% for RAIL), with wound complications making up 33% of all complications for RAIL and 31% of complications for OSILND. No inguinal recurrences were noted in either cohort. The median follow-up was 40 months for RAIL and 33 months for OSILND. CONCLUSIONS: We observed similar complication rates and surgical variable outcomes in our analysis apart from operative time and operative drain duration. Oncological outcomes were similar between the two cohorts. RAIL was a reliable staging and potentially therapeutic procedure among clinically node negative patients with penile squamous cell carcinoma with comparable outcomes to an OSILND cohort.

Anticoagulant prescribing patterns in patients with primary central nervous system malignancies and secondary metastases.

To evaluate the safety of direct oral anticoagulants (DOACs) versus low-molecular weight heparin (LMWH) in patients with central nervous system (CNS) malignancies and secondary metastases. All adult patients with CNS malignancies and secondary metastases who were treated with a DOAC or LMWH for any indication from 2018 to 2022 were included. The primary outcome was the incidence of any intracranial hemorrhage (ICH) after anticoagulation initiation. Secondary outcomes included non-ICH bleeding events and thromboembolic events. Tolerability was assessed by any changes in anticoagulant therapy during study period. 153 patients were included; 48 patients received enoxaparin and 105 received DOACs, of which apixaban was used most commonly. The population was predominantly White (74%) and male (59%) with a median age of 65. Data was censored for immortal time bias for outcomes evaluated beyond 3 months. ICH occurred in 7.7% of the population, more frequently in the enoxaparin group (DOACs 4, 4% vs. enoxaparin 7, 16%, p = 0.037). Non-ICH bleeds were predominantly minor and more common in the DOAC group (DOACs 13, 13% vs. enoxaparin 1, 2%, p = 0.037). Thromboembolic events were not different between groups (DOACs 9. 9% vs, enoxaparin 2, 4%, p = 0.503). Anticoagulant switches occurred more in the enoxaparin group (DOACs 12, 12.4% vs. enoxaparin, 37.8%, p < 0.001), primarily due to patient or provider preference. Our data supports DOACs to be preferred over LMWH for the treatment of VTE or for stroke prevention with AF to prevent ICH in patients with brain tumors or metastases.

The association of body mass index with tumor aggression among men undergoing radical prostatectomy.

OBJECTIVES: To evaluate the association of preoperative body mass index (BMI) on adverse pathology in peripheral (PZ) and transition zone (TZ) tumors at time of prostatectomy for localized prostate cancer. METHODS: Clinical and pathologic characteristics were obtained from up to 100 consecutive prostatectomy patients from 10 prostate surgeons. BMI groups included normal (18.5-24.9), overweight (25-29.9) and obese (> 29.9). "Aggressive" pathology was defined as the presence of Grade Group (GG) 3 or higher and/or pT3a or higher. Pathologic characteristics were evaluated for association with BMI using univariate analyses. Our primary outcome was the association of BMI with adverse pathology, which was assessed using logistic regression accounting for patient age. We hypothesized that obese BMI would be associated with aggressive TZ tumor. RESULTS: Among 923 patients, 140 (15%) were classified as "normal" BMI, 413 (45%) were "overweight", and 370 (40%) were "obese." 474 patients (51%) had aggressive PZ tumors while 102 (11%) had aggressive TZ tumors. "Obese" BMI was not associated with aggressive TZ tumor compared to normal weight. Increasing BMI group was associated with overall increased risk of aggressive PZ tumor (HR 1.56 [95CI 1.04-2.34]; P = 0.03). Among patients with GG1 or GG2, increasing BMI was associated with presence of pT3a or higher TZ tumor (P = 0.03). CONCLUSIONS: Increased BMI is associated with adverse pathology in PZ tumors. TZ adverse pathology risk may be increased among obese men with GG1 or GG2 disease, which has implications for future studies assessing behavioral change among men whose tumors are actively monitored.

Impact of oral vancomycin treatment duration on rate of Clostridioides difficile recurrence in patients requiring concurrent systemic antibiotics.

BACKGROUND: There is a paucity of data guiding treatment duration of oral vancomycin for Clostridiodes difficile infection (CDI) in patients requiring concomitant systemic antibiotics. OBJECTIVES: To evaluate prescribing practices of vancomycin for CDI in patients that required concurrent systemic antibiotics and to determine whether a prolonged duration of vancomycin (>14 days), compared to a standard duration (10-14 days), decreased CDI recurrence. METHODS: In this retrospective cohort study, we evaluated adult hospitalized patients with an initial episode of CDI who were treated with vancomycin and who received overlapping systemic antibiotics for >72 hours. Outcomes of interest included CDI recurrence and isolation of vancomycin-resistant Enterococcus (VRE). RESULTS: Among the 218 patients included, 36% received a standard duration and 64% received a prolonged duration of treatment for a median of 13 days (11-14) and 20 days (16-26), respectively. Patients who received a prolonged duration had a longer median duration of systemic antibiotic overlap with vancomycin (11 vs 8 days; P < .001) and significantly more carbapenem use and infectious disease consultation. Recurrence at 8 weeks (12% standard duration vs 8% prolonged duration; P = .367), recurrence at 6 months (15% standard duration vs 10% prolonged duration; P = .240), and VRE isolation (3% standard duration vs 9% prolonged duration; P = .083) were not significantly different between groups. Discontinuation of vancomycin prior to completion of antibiotics was an independent predictor of 8-week recurrence on multivariable logistic regression (OR, 4.8; 95% CI, 1.3-18.1). CONCLUSIONS: Oral vancomycin prescribing relative to the systemic antibiotic end date may affect CDI recurrence to a greater extent than total vancomycin duration alone. Further studies are needed to confirm these findings.

A Case Report of Cardiac Arrest After Intravenous Administration of Sulfur Hexafluoride (Lumason®) Ultrasound Enhancing Agent.

Ultrasound enhancing agents (UEAs) are medications that enable clear visualization of ultrasound images. While large studies have demonstrated the safety of these agents, case reports of life-threatening reactions temporally associated with their use have been published and reported to the Food and Drug Administration. Current literature describes the most serious adverse reactions due to UEAs to be allergic in nature; however, embolic phenomena may play a role as well. Here, we report a case of unexplained cardiac arrest following the administration of sulfur hexafluoride (Lumason®) in an adult inpatient undergoing echocardiography where resuscitative efforts were ultimately unsuccessful, and review possible mechanisms of cardiac arrest based on prior published literature.

Anti-factor Xa as the preferred assay to monitor heparin for the treatment of pulmonary embolism.

INTRODUCTION: The mainstay of acute pulmonary embolism (PE) treatment is anticoagulation. Timely anticoagulation correlates with decreased PE-associated mortality, but the ability to achieve a therapeutic activated partial thromboplastin time (aPTT) with unfractionated heparin (UFH) remains limited. Although some institutions have switched to a more accurate and reproducible test to assess for heparin's effectiveness, the anti-factor Xa (antiXa) assay, data correlating a timely therapeutic antiXa to PE-associated clinical outcomes remains scarce. We evaluated time to a therapeutic antiXa using intravenous heparin after PE response team (PERT) activation and assessed clinical outcomes including bleeding and recurrent thromboembolic events. METHODS: This was a retrospective cohort study at NYU Langone Health. All adult patients ≥18 years with a confirmed PE started on IV UFH with >2 antiXa levels were included. Patients were excluded if they received thrombolysis or alternative anticoagulation. The primary endpoint was the time to a therapeutic antiXa level of 0.3-0.7 units/mL. Secondary outcomes included recurrent thromboembolism, bleeding and PE-associated mortality within 3 months. RESULTS: A total of 330 patients with a PERT consult were identified with 192 patients included. The majority of PEs were classified as sub massive (64.6%) with 87% of patients receiving a bolus of 80 units/kg of UFH prior to starting an infusion at 18 units/kg/hour. The median time to the first therapeutic antiXa was 9.13 hours with 93% of the cohort sustaining therapeutic anticoagulation at 48 hours. Recurrent thromboembolism, bleeding and mortality occurred in 1%, 5% and 6.2%, respectively. Upon univariate analysis, a first antiXa <0.3 units/ml was associated with an increased risk of mortality [27.78% (5/18) vs 8.05% (14/174), p = 0.021]. CONCLUSION: We observed a low incidence of recurrent thromboembolism or PE-associated mortality utilizing an antiXa titrated UFH protocol. The use of an antiXa based heparin assay to guide heparin dosing and monitoring allows for timely and sustained therapeutic anticoagulation for treatment of PE.

Treatment of Piperacillin-Tazobactam-Nonsusceptible/Ceftriaxone-Susceptible Infections With Carbapenem Versus Carbapenem-Sparing Antimicrobials.

Background: Escherichia coli and Klebsiella pneumoniae with a piperacillin-tazobactam-nonsusceptible/ceftriaxone-susceptible (TZP-NS/CRO-S) phenotype have been increasingly identified, with limited available literature evaluating treatment strategies. Methods: This was a retrospective study of noncritically ill adults hospitalized between 2013 and 2021 and treated at least 48 hours for TZP-NS/CRO-S E coli or K pneumoniae infections. The primary composite endpoint included escalation to intensive care unit, infection- or treatment-related readmission, mortality, and infection recurrence. Outcomes were compared between groups who received carbapenem (CG) versus carbapenem-sparing agents (CSG) as targeted gram-negative therapy. Results: Of 1062 patients screened, 200 were included (CG, n = 51; CSG, n = 149). Baseline characteristics, including Charlson Comorbidity Index (CCI; median [interquartile range], 6 [3-9] vs 6 [4-9]; P = .704), were similar between groups, except for more immunocompromised CG patients (29% vs 11%, P = .001). The most common infection sources were urinary (31% vs 57%, P = .002) and bloodstream (18% vs 17%, P = .887). Eighty-eight percent of the CG received meropenem, while 58% of the CSG received ceftriaxone as targeted therapy. There was no statistical difference in the primary endpoint between overall groups (27% vs 17%, P = .123), nor when stratified by infection source. More patients in the CSG switched to oral therapy (15 [29%] vs 100 [67%], P < .001). In multivariate analysis, CCI was an independent predictor of the primary outcome (odds ratio [OR], 1.199 [95% confidence interval, 1.074-1.340]; P = .001), while treatment with carbapenem-sparing therapy was not. Conclusions: Our study did not find improved clinical outcomes with targeted carbapenem therapy for TZP-NS/CRO-S infections. Carbapenem-sparing agents may be considered to spare carbapenems in noncritically ill patients similar to those included in our cohort.

Evaluation of Parenteral Potassium Supplementation in Pediatric Patients.

OBJECTIVE: The primary objective was to evaluate the effect of parenteral potassium chloride (KCl) supplementation on potassium (K+) concentrations in a non-cardiac pediatric population. Secondary outcomes were to identify variables that may influence response to KCl supplementation (i.e., change in K+ concentration after KCl administration) and assess the incidence of hyperkalemia. METHODS: This single-center, retrospective study evaluated infants and children who received parenteral KCl supplementation of 0.5 or 1 mEq/kg between January 2017 and December 2019. RESULTS: The study included 102 patients with a median age of 1 year (IQR, 0.4-3.9) and weight of 9.1 kg (IQR, 4.9-14.2) who received 288 parenteral KCl administrations. One hundred seventy-three administrations were in the 1 mEq/kg group, and 115 administrations were in the 0.5 mEq/kg group. The median changes in K+ were 0.8 and 0.5 mEq/L in the 1 mEq/kg and 0.5 mEq/kg groups, respectively. Patients who had a repeat K+ concentration within 4 hours of the end of a 1 to 2-hour infusion had a higher median change in K+ compared with those who had a concentration drawn after this time frame (0.8 vs 0.6 mEq/L; p < 0.01). CONCLUSIONS: There is a paucity of data on the correlation between parenteral KCl supplementation and change in K+ concentrations in pediatric patients. Our study demonstrated an association between KCl supplementation doses of 1 and 0.5 mEq/kg and changes in K+ of 0.8 and 0.5 mEq/L, respectively, in non-cardiac pediatric patients, with low observed incidence of hyperkalemia.

Quetiapine for the Treatment of Pediatric Delirium.

BACKGROUND: Delirium is a common complication of critical illness, with a prevalence of 25% among pediatric intensive care unit (ICU) patients. Pharmacological treatment options for ICU delirium are limited to off-label use of antipsychotics, but their benefit remains uncertain. OBJECTIVE: The purpose of this study was to evaluate quetiapine effectiveness for the treatment of delirium in critically ill pediatric patients and to describe the safety profile of quetiapine. METHODS: A single-center, retrospective review of patients aged ≤ 18 years who screened positive for delirium via the Cornell Assessment of Pediatric Delirium (CAPD ≥ 9) and received ≥ 48 hours of quetiapine therapy was conducted. The relationship between quetiapine and deliriogenic medication doses was evaluated. RESULTS: This study included 37 patients who received quetiapine for the treatment of delirium. The change in sedation requirements before quetiapine initiation to 48 hours after the highest quetiapine dose demonstrated a downward trend; 68% of patients had a decrease in opioid requirements and 43% of patients had a decrease in benzodiazepine requirements. The median CAPD score at baseline was 17 and the median CAPD score at 48 hours after the highest dose was 16. Three patients experienced QTc prolongation (defined as a QTc ≥ 500), although none developed dysrhythmias. CONCLUSION AND RELEVANCE: Quetiapine did not have a statistically significant impact on deliriogenic medication doses. There were minimal changes in QTc and dysrhythmias were not identified. Therefore, quetiapine can be safe to use in our pediatric patients but further studies are needed to find an effective dose.

Novel Multidisciplinary Approach for Outpatient Antimicrobial Stewardship Using an Emergency Department Follow-Up Program.

Purpose: Outpatient antimicrobial stewardship programs (ASPs) are becoming increasingly prevalent in healthcare. Many programs have demonstrated the effectiveness of pharmacist-driven outpatient consultations or follow-up programs to ensure appropriate antimicrobial prescribing. However, there is a paucity of literature describing multidisciplinary approaches in large healthcare systems for patients discharged from the emergency department (ED). The objective of this study was to describe the feasibility and impact of a combined effort between ASP pharmacotherapy specialists and nurse practitioners (NPs) in managing an ED follow-up center. Methods: A retrospective analysis was conducted for patients discharged from the ED between January 2018 and June 2019. Patients were identified for inclusion based on documentation by ASP pharmacotherapy specialists in the electronic health record for patient-specific inquiries from ED follow-up center NPs. The primary outcome of this study was to describe the number and types of interventions made by ASP pharmacotherapy specialists. Results: A total of 1088 patients were included in the study, for 1114 documented ASP calls. The urinary tract was the most common source of positive culture (79%), and third-generation cephalosporins were the most frequent antibiotic associated with calls (20%). Out of total calls, 60% lead to ASP interventions. Among total calls, the most frequent interventions were to correct drug-bug mismatches (20%), initiate new therapy (10%), and discontinue therapy (7%). Conclusion: This report describes a novel initiative that combines the efforts of ED NPs and ASP pharmacotherapy specialists in managing an ED follow-up center at a large healthcare system.

The Use of High-Dose Corticosteroids Versus Low-Dose Corticosteroids With and Without Tocilizumab in COVID-19 Acute Respiratory Distress Syndrome.

BACKGROUND: Corticosteroids and tocilizumab have been shown to improve survival in patients who require supplemental oxygen from coronavirus disease 2019 (COVID-19) pneumonia. The optimal dose of immunosuppression for the treatment of COVID-19 acute respiratory distress syndrome (ARDS) is still unknown. OBJECTIVE: The objective of this study was to evaluate the effectiveness and safety of high- versus low-dose corticosteroids with or without tocilizumab for the treatment of COVID-19 ARDS. METHODS: This was a retrospective study of patients admitted to the intensive care unit (ICU) requiring mechanical ventilation who received high- versus low-dose corticosteroids with or without tocilizumab. The primary outcome was survival to discharge. Safety outcomes included infections and incidence of hyperglycemia. RESULTS: In this cohort, 110 (54%) and 95 (46%) patients received high-dose (≥10 mg dexamethasone equivalent) and low-dose (<10 mg dexamethasone equivalent) corticosteroids for more than 3 consecutive days, respectively. Thirty-five patients (32%) in the high-dose group and 33 patients (35%) in the low-dose group survived to hospital discharge (P = 0.85). There was no difference in 28-day mortality in patients who received high-dose corticosteroids without tocilizumab compared with those who received low-dose corticosteroids with tocilizumab (n = 38/82, 46% vs n = 19/40, 48% P = 0.99); however, there was a higher mortality if patients received low-dose corticosteroids without tocilizumab (n = 39/55, 71%, P = 0.01). The highest rate of a bacterial pneumonia was in patients who received high-dose corticosteroids with tocilizumab. CONCLUSIONS: In critically ill patients with COVID-19 ARDS requiring mechanical ventilation, we found no difference in high- versus low-dose corticosteroids with regard to survival to hospital discharge. However, patients receiving only low-dose corticosteroids without tocilizumab did worse than the other groups. Larger prospective studies are needed to determine the optimal immunosuppression dosing strategy in this patient population.

Successful Treatment of Tenofovir Alafenamide-Induced Lactic Acidosis: A Case Report.

Nucleoside or nucleotide analogues (NAs) have the potential to cause lactic acidosis by inhibiting DNA polymerase-γ of human mitochondria and impairing aerobic metabolism. Patients may be asymptomatic, have mild non-specific symptoms, or present in multisystem organ failure. There is a paucity of data to guide management of life-threatening lactic acidosis due to NA therapy. Here we describe a case of a 60-year old critically ill male with decompensated cirrhosis secondary to hepatitis B virus (HBV) infection who developed severe lactic acidosis (13.8 mmol/L) 2 days after initiation of tenofovir alafenamide (TAF). All other possible etiologies for the elevated lactate were ruled out. Lactic acidosis resolved rapidly with TAF discontinuation and supplementation with cofactors supporting mitochondrial oxidative phosphorylation, including coenzyme Q10, levocarnitine, riboflavin, and thiamine. This case highlights the ability of TAF to cause lactic acidosis early after therapy initiation, especially in susceptible hosts, and reviews the potential role for cofactor supplementation for drug-induced mitochondrial injury.

Longitudinal GFR trends after neoadjuvant chemotherapy prior to nephroureterectomy for upper tract urothelial carcinoma.

PURPOSE: Renal function dictates sequencing and eligibility for definitive therapy in upper tract urothelial carcinoma. We investigated longitudinal glomerular filtration rate (GFR) changes after neoadjuvant chemotherapy (NAC) and nephroureterectomy (RNU). MATERIALS AND METHODS: Patients treated with ≥3 cycles of chemotherapy prior to RNU for UTUC from 2000 to 2019 were included. GFR was calculated by CKD-Epi before chemotherapy, before RNU, 1 to 3 months, and 12 months post-RNU. Pathologic stage and overall survival were compared in those with stable GFR (+/-10% of baseline) to the rest of the cohort. RESULTS: One hundred and fifty-two patients received ≥3 cycles of NAC, with 121 (79%) receiving at least 1 cycle of cisplatin. Renal function dropped by mean of 22.3 ml/min/1.73 m2 from the beginning of chemotherapy to 1-year post-surgery. In patients receiving cisplatin, a mean decline of 26.2 ml/min/1.73 m2 was observed vs. 8.8 ml/min/1.73 m2 without cisplatin-based NAC (P < 0.01). GFR after RNU was unchanged between 3 and 12 months postoperatively. At 1 to 3 months after RNU, 19% of patients had GFR<30 ml/min/1.73m2. Improvement in GFR during NAC was associated with invasive final pathologic stage (P = 0.018) and worse overall survival (P = 0.049). CONCLUSIONS: In patients managed with NAC prior to RNU, renal function stabilizes at 1 to 3 months post-operatively and remains clinically similar for cisplatin or non-cisplatin-based therapy. Improvement in GFR during NAC was associated with higher pathologic stage and poorer survival, especially in those receiving non-cisplatin-based therapy, an observation that requires further investigation.

Real world prescribing practices of apixaban or rivaroxaban lead-in doses for the treatment of venous thromboembolism in hospitalized patients.

The oral factor Xa inhibitors (OFXAi) apixaban and rivaroxaban are increasingly utilized for the treatment of venous thromboembolism (VTE) with recommended initial higher dose 7- and 21-day lead-in regimens, respectively. In patients receiving initial parenteral anticoagulation, it remains unknown if the full recommended higher dose OFXAi lead-in regimens are warranted, or if days can be subtracted. We aimed to describe when clinicians may deviate from recommended lead-in durations and evaluate clinical outcomes in these scenarios. This is a retrospective, observational study of patients 18 years or older who were treated with rivaroxaban or apixaban for acute pulmonary embolism (PE) or symptomatic proximal deep vein thrombosis (DVT) that received parenteral anticoagulation for at least 24 h before transitioning to the OFXAi. Among our cohort of 171 patients with acute VTE who received parenteral anticoagulation for a median of 48 h, 134 (78%) were prescribed a full OFXAi lead-in and 37 (22%) were prescribed a reduced lead-in. Patients in the reduced lead-in group were older with more cardiac comorbidities and antiplatelet use. There were four recurrent thromboembolic events within 3 months, two in the reduced lead-in group and two in the full lead-in group (5% vs. 2%, p = 0.206). Bleeding within 3 months occurred in 9 (5%) patients, with 6 events occurring in the reduced lead-in group and 3 events in the full lead-in group (16% vs. 2%, p = 0.004). Prescribing patterns of OFXAi lead-in therapy duration are variable in patients receiving initial parenteral anticoagulation. Larger cohorts are needed to better define the safety and efficacy of lead-in reduction.

Antithrombotic management for Impella® temporary ventricular assist devices: An analysis of an academic health-system experience.

The use of acute mechanical circulatory support (MCS) has increased over the last decade. For patients with left-ventricular failure, an Impella® (Abiomed, Danvers, MA) may be used to improve cardiac output. The purpose of this study is to describe Impella® anticoagulation patterns and evaluate the safety and effectiveness of our protocol. This is a retrospective review of all adult patients who required at least 24 h of Impella® support and received a heparin-based purge solution. In total, 109 patients were included in the final analysis. The most common indication for Impella® device insertion was cardiogenic shock (76%) with the remaining patients receiving a device for a high-risk procedures; typically coronary artery bypass grafting or percutaneous coronary intervention. A total of 9 thrombotic events occurred among 8 (7%) patients and 50 bleeding events occurred among 43 (39%) patients, with the most common classification being BARC 3a (60%). A univariate analysis revealed that patients were more likely to bleed if they were less than 65 years old, had an indication of cardiogenic shock for Impella®, inserted the device peripherally, were on dual antiplatelet therapy, or had an intra-aortic balloon pump prior to Impella® insertion, the latter of which was confirmed with a multivariate analysis (OR 2.5 [1.072-5.830]; p = 0.034). For those monitored by anti-Xa, the presence of two or more values greater than 0.40 IU/mL was a risk factor for bleeding (p = 0.037). Our study identifies risk factors for bleeding in patients receiving temporary MCS with an Impella®.

High-dose methotrexate dosing strategy in primary central nervous system lymphoma.

The backbone induction therapy for primary central nervous system lymphoma (PCNSL) is high dose methotrexate (HD-MTX) and rituximab, which can be combined with other chemotherapeutic agents. The optimal dose of HD-MTX remains unclear, as doses between 3 and 8 g/m2 have been shown to be effective. In this retrospective study, HD-MTX dosed at 3-5 g/m2 demonstrated an overall response of 81.8%, with 11 (50%) complete responses. The median overall survival was not met at 29 months and median progression free survival was 12.5 months.There were two discontinuations due to nephrotoxicity. The most common adverse event was hepatotoxicity (18.5%), with no treatment-related mortality events observed.Overall, HD-MTX dosed at 3-5 g/m2 demonstrated similar efficacy and lower toxicity compared to higher doses in PCNSL patients. Reducing the initial HD-MTX dose may help ensure tolerability and completion of induction therapy, especially in patients with co-morbidities or older age who have poorer outcomes.

Impact of Streptococcus pneumoniae Urinary Antigen Testing in Patients With Community-Acquired Pneumonia Admitted Within a Large Academic Health System.

BACKGROUND: Limited data support use of pneumococcal urinary antigen testing (PUAT) for patients with community-acquired pneumonia (CAP) as an antimicrobial stewardship tool. At our institution, CAP guidelines and admission order set were standardized to include universal PUAT. METHODS: This was a retrospective study of adults hospitalized in 2019 who had PUAT performed. We compared incidence and timing of de-escalation in PUAT- positive vs -negative groups and described patients' outcomes. RESULTS: We evaluated 910 patients, 121 (13.3%) of whom were PUAT positive. No difference in baseline characteristics, including severity of illness, was observed between groups. Initial de-escalation occurred in 82.9% and 81.2% of PUAT-positive and -negative patients, respectively (P = .749). Median time to de-escalation was shorter in the PUAT-positive group (1 [interquartile range {IQR}, 0-2] day vs 1 [IQR, 1-2] day, P = .01). Within 24 hours of PUAT, more patients in the PUAT-positive group had atypical coverage discontinued (61.3% vs 47.2%, P = .026) without difference in methicillin-resistant Staphylococcus aureus (MRSA) agent discontinuation (or antipseudomonal de-escalation). Among the PUAT-positive group, unadjusted analysis demonstrated shorter median length of stay in patients who were de-escalated compared to those who were not (6 [IQR, 4-10] vs 8 [IQR, 7-12] days, P = .0005), without difference in the incidence of Clostridioides difficile, in-hospital mortality, or 30-day infection-related readmission. CONCLUSIONS: We observed earlier de-escalation in the PUAT-positive group. This seems to be due to discontinuation of atypical rather than anti-MRSA or antipseudomonal coverage. Further antimicrobial stewardship interventions are warranted.