Low-Dose Cyclophosphamide Associated With Hyponatremia and Hepatotoxicity.

Cyclophosphamide (CY) is an alkylating agent often used as a chemotherapeutic agent, with increasing use as an immunosuppressant. Cyclophosphamide has many established adverse effects, including hyponatremia and limited reports of hepatotoxicity, particularly in high-dose treatment. A case of simultaneous hyponatremia and acute liver injury associated with the initiation of cyclophosphamide two weeks prior is discussed here. A 73-year-old male with acquired hemophilia A/factor VIII deficiency presented to the emergency department (ED) with four days of hip pain and was found to have jaundice and confusion. Laboratory evaluation demonstrated hyponatremia and an acute liver injury associated with his recent cyclophosphamide use. With the discontinuation of the offending agent and sodium correction, he made a full recovery. Cyclophosphamide-induced hyponatremia is likely secondary to the nephrogenic syndrome of inappropriate antidiuresis (NSIAD) and is most often associated with high-dose regimens. While the mechanism of hepatotoxicity requires further study, it is likely dose-dependent and related to excess levels of 4-hydroxycyclophosphamide (HCY). The management of cyclophosphamide-induced water toxicity and hepatotoxicity is centered around the discontinuation of medication, the correction of electrolyte abnormalities, and supportive treatment.

Association of Preoperative Pulse Pressure and Oxygen Delivery Index During Cardiopulmonary Bypass With Postoperative Acute Kidney Injury.

OBJECTIVE: To investigate if oxygen delivery index during cardiopulmonary bypass (DO2I) was more strongly associated with acute kidney injury (AKI), the higher the patient's preoperative pulse pressure (PP). DESIGN: Retrospective cohort of 1064 patients undergoing cardiac surgery. SETTING: Single academic healthcare center. PARTICIPANTS: Adult patients undergoing coronary artery bypass grafting, valve, aortic, or combined surgery requiring cardiopulmonary bypass. INTERVENTIONS: Hemoglobin, arterial oxygen saturation, and pump flow recorded no fewer than every 30 min were extracted from the patients' perfusion records, and DO2I was calculated. The AKI was assessed from the pre- and postoperative creatinine and urine output values using the Acute Kidney Injury Network criteria. The sample was stratified in 5 categories of progressively higher PP. The patient characteristics and intraoperative variables were evaluated in univariate analysis for a relationship with AKI. The significant risk factors from the univariate analysis then were evaluated in a multivariate analysis and assessed for logistic fit with respect to AKI. PRIMARY OUTCOME: The AKI assessed as a binary outcome. MEASUREMENTS AND MAIN RESULTS: Age, body surface area, DO2I, history of heart failure, and baseline creatinine were associated significantly with AKI, as was an interaction term between the PP category and DO2I (p = 0.0067). The higher the PP category, the stronger the observed association between DO2I and AKI, and the higher the variability in the predicted risk of AKI dependent on DO2I. CONCLUSIONS: A lower DO2I during cardiopulmonary bypass appeared more strongly associated with a higher likelihood of developing AKI, the higher the patient's preoperative pulse pressure.

Association of Patterns of Mild Traumatic Brain Injury with Neurologic Deterioration: Experience at a Level I Trauma Center.

INTRODUCTION: There are about 2.5 million emergency room visits for traumatic brain injury (TBI) every year and 75%-95% of all TBI patients have mild TBI. Previous studies have suggested that a large proportion of mild TBI patients can be treated in a non-aggressive manner, but they have not differentiated mild TBI as per radiological patterns to help in the selection of these patients. Our study aimed to identify different patterns of mild TBI to determine if certain injuries make patients more prone to neurologic worsening than others, and thus require more intensive monitoring. We also studied the factors associated with neurologic deterioration. METHODS: We conducted a retrospective study using an institutional trauma database to identify TBI patients between the years of 2015 and 2016 with admission Glasgow Coma Score (GCS) of 13 to 15, through chart review by the investigators. Radiological and neurological worsening was determined through computed tomography (CT) scan results, GCS scores, and the requirement for neurosurgical intervention. We identified the prevalence of demographic characteristics, radiological patterns, and risk factors. We studied neurologic deterioration (decline in GCS to less than 13 at 48 hours or earlier after admission) and surgical intervention among patients with different radiological patterns of TBI. We further studied the cohort of isolated subdural hematoma (SDH) patients requiring surgery to evaluate the associated risk factors. RESULTS: Out of 374 patients with mild TBI (mean age was 63 years), 59% were male, 77% were Caucasian, the median GCS was 15, majority of patients had isolated SDH (45%), and mixed pattern of hemorrhage (39%); the use of antiplatelet (33%) was the most commonly identified risk factors. Overall 7% of patients were found to have neurologic deterioration (GCS to less than 13) and 9% required surgical intervention at 48 hours or earlier after admission. The most common pattern of TBI requiring surgical intervention was isolated SDH (85%). Among the cohort of patients with isolated SDH, 17% required surgical intervention and 69% of those isolated SDH patients requiring surgery had neurologic deterioration. The most common risk factor in isolated SDH patients requiring surgery was antiplatelet use (34%), anticoagulant use (20%), alcohol abuse (17%), severe renal failure (17%), and thrombocytopenia (7%). Mean size of SDH in patients requiring surgery was 1.6 cm with 0.8 cm of midline shift. CONCLUSION: This study identified the pattern of mild TBI associated with neurological worsening at our Level I Trauma Center. Among patients with mild TBI, SDH patients seem to be at highest risk for deterioration and requirement for surgery. If these results can be externally validated through a multi-center study, these patients could be selectively identified for aggressive monitoring in the intensive care unit (ICU) and repeat CT scans.

Cognitive and behavioral effects of brief seizures in mice.

Comorbidities associated with epilepsy greatly reduce patients' quality of life. Since antiepilepsy drugs show limited success in ameliorating cognitive and behavioral symptoms, there is a need to better understand the mechanisms underlying epilepsy-related cognitive and behavioral impairments. Most prior research addressing this problem has focused on chronic epilepsy, wherein many factors can simultaneously impact cognition and behavior. The purpose of the present study was to develop a testing paradigm using mice that can provide new insight into how short-term biological changes underlying acute seizures impact cognition and behavior. In Experiment 1, naïve C57BL/6J mice were subjected to either three brief, generalized electroconvulsive seizure (ECS) or three sham treatments equally spaced over the course of 30 min. Over the next 2 h, mice were tested in a novel object recognition paradigm. Follow-up studies examined locomotor activity immediately before and after (Experiment 2), immediately after (Experiment 3), and 45 min after (Experiment 4) a set of three ECS or sham treatments. Whereas results demonstrated that there was no statistically significant difference in recognition memory acquisition between ECS and sham-treated mice, measures of anxiety-like behavior were increased and novel object interest was decreased in ECS-treated mice compared with that in sham. Interestingly, ECS also produced a delayed inhibitory effect on locomotion, decreasing open-field activity 45-min posttreatment compared to sham. We conclude that a small cluster of brief seizures can have acute, behaviorally relevant effects in mice, and that greater emphasis should be placed on events that take place before chronic epilepsy is established in order to better understand epilepsy-related cognitive and behavioral impairments. Future research would benefit from using the paradigms defined above to study the effects of individual seizures on mouse cognition and behavior.