Enhanced hemolysis in pediatric patients requiring extracorporeal membrane oxygenation and continuous renal replacement therapy

PURPOSE: Hemolysis during extracorporeal membrane oxygenation (ECMO) may be associated with the development of hemoglobinuria (Hb) nephropathy and acute renal failure. For patients requiring ECMO, continuous renal replacement therapy (CRRT) can be simultaneously performed by attaching a hemofilter to the ECMO circuit, thereby shunting part of the ECMO blood flow through the hemofilter. However, the possibility that CRRT may further enhance hemolysis (and the risk of Hb nephropathy) in patients on ECMO has not been previously investigated. METHODS: Medical records of 42 children (1 day-12 years old) who required ECMO (ECMO group, n=25) or ECMO and CRRT (ECMO+CRRT group, n=17) after cardiac surgery were reviewed. RESULTS: Forty-one out of 42 patients had elevated plasma-free hemoglobin (FHb) on the first day of ECMO. For all subjects, peak change (mean+/-SD) in FHb (Peak%C-FHb, 83.6+/-183%) correlated with serum lactic dehydrogenase (150+/-324%, r=0.49, p<0.05) and marginally with ECMO blood flow rate (BFR) (Peak%C-BFR, 36.8+/-51.0%, r=0.29, p=0.06). Compared with the ECMO group, the ECMO+CRRT group had a higher Peak%C-FHb (160+/-259%, p<0.05) and Peak%C-BFR (62+/-64%, p<0.05). Also, there was a significant increase in FHb one day after the initiation of CRRT compared with the level prior to CRRT (73.3+/-49.2 vs. 50.0+/-30.3 mg/dL, respectively, p=0.012). Serum creatinine (but not blood urea nitrogen) was significantly higher in the ECMO+CRRT group compared with the ECMO group. The percent change in serum creatinine during ECMO did not correlate with Peak%C-FHb in the ECMO group. CONCLUSION: Our findings suggest that there is enhanced hemolysis during combined ECMO and CRRT compared with ECMO alone. However, the clinical impact of increased hemolysis on renal function in patients receiving ECMO with or without CRRT remains to be determined.     

Differential etiology of posttraumatic stress disorder with conduct disorder and major depression in male veterans.

BACKGROUND: Epidemiologic studies reveal that posttraumatic stress disorder (PTSD) is highly comorbid with both conduct disorder and major depression in men. The genetic and environmental etiology of this comorbidity has not been examined. METHODS: Data were analyzed from 6744 middle-aged male-male monozygotic and dizygotic twins from the Vietnam Era Twin Registry. Conduct disorder, major depression, and PTSD were assessed via telephone interview using the Diagnostic Interview Schedule for the DSM-III-R in 1992. Structural equation modeling was used to estimate additive genetic, shared environmental, and individual-specific environmental effects common and specific to conduct disorder, major depression, and PTSD. RESULTS: The association between conduct disorder and PTSD was explained primarily by common shared environmental influences; these explained 10% (95% confidence interval: 6%-17%) of the variance in PTSD. The association between major depression and PTSD was largely explained by common genetic influences; these explained 19% (95% confidence interval: 11%-26%) of the variance in PTSD. CONCLUSIONS: Our findings suggest that different etiologic mechanisms explain the association of conduct disorder and major depression with PTSD in male veterans. If replicated in other populations, results suggest research aimed at identifying specific genetic and environmental factors that influence PTSD may benefit from starting with those that have been more consistently and strongly associated with major depression and conduct disorder.     

Pyruvate-modified perfadex improves lung function after long-term hypothermic storage.

BACKGROUND: Lungs harvested for transplantation are stored while inflated with oxygen, which can serve to support oxidative metabolism. However, strategies aimed at increasing graft metabolism during storage have received little attention. In this study, we added pyruvate to the preservation solution Perfadex and measured the effects on oxidative metabolism and reperfusion lung function. METHODS: Rat lungs were stored for 6 and 24 hours in low-potassium dextran solution at 10 degrees C containing either 5 mmol/liter uniformly carbon-13 (U-(13)C) labeled glucose (Perfadex), 32 mmol/liter 3-(13)C pyruvate (pyruvate), or both (combined). Oxidation of exogenous substrates was measured as the incorporation of (13)C into tricarboxylic acid cycle intermediates by magnetic resonance spectroscopy. Additional groups of lungs with each substrate modification were preserved for 6 or 24 hours and then reperfused. RESULTS: Enrichment of tricarboxylic acid cycle intermediates was low in the Perfadex group (9% at 6 hours and 32% at 24 hours of storage, respectively). In contrast, enrichment was significantly increased in both the pyruvate group (50% and 59%, respectively) and combined group (39% and 54%, respectively) compared with the Perfadex group (p<0.01). Graft function was excellent after 6-hour storage in all groups. All lungs stored for 24 hours exhibited inferior lung function, but oxygenation, pulmonary artery pressures, and airway pressures in the combined group were significantly improved compared with the Perfadex group (p<0.05). CONCLUSIONS: Preservation solution substrate composition influences graft metabolism during storage. The addition of pyruvate to Perfadex increases metabolism during storage and improves reperfusion lung function.     

Parallel imaging reconstruction for arbitrary trajectories using k-space sparse matrices (kSPA).

Although the concept of receiving MR signal using multiple coils simultaneously has been known for over two decades, the technique has only recently become clinically available as a result of the development of several effective parallel imaging reconstruction algorithms. Despite the success of these algorithms, it remains a challenge in many applications to rapidly and reliably reconstruct an image from partially-acquired general non-Cartesian k-space data. Such applications include, for example, three-dimensional (3D) imaging, functional MRI (fMRI), perfusion-weighted imaging, and diffusion tensor imaging (DTI), in which a large number of images have to be reconstructed. In this work, a systematic k-space-based reconstruction algorithm based on k-space sparse matrices (kSPA) is introduced. This algorithm formulates the image reconstruction problem as a system of sparse linear equations in k-space. The inversion of this system of equations is achieved by computing a sparse approximate inverse matrix. The algorithm is demonstrated using both simulated and in vivo data, and the resulting image quality is comparable to that of the iterative sensitivity encoding (SENSE) algorithm. The kSPA algorithm is noniterative and the computed sparse approximate inverse can be applied repetitively to reconstruct all subsequent images. This algorithm, therefore, is particularly suitable for the aforementioned applications.     

Comorbid alcohol and substance abuse dependence in depression: impact on the outcome of antidepressant treatment.

Major depressive disorder often co-occurs with substance use disorders, especially alcohol use disorders, and the course of each of these problems seems be complicated by the other. Diagnosing and treating these patients is challenging. A significant difficulty for clinicians is deciding whether to treat a mood episode in a patient who has current substance use or a substance use disorder, and what is the optimal treatment for that patient. This article discusses the prevalence of depressive and substance use disorder, the course of illness of comorbid depression and substance use disorders, and treatment response.     

Revascularization of the Posterior Circulation

The primary objective of revascularization procedures in the posterior circulation is the prevention of vertebrobasilar ischemic stroke. Specific anatomical and neurophysiologic characteristics such as posterior communicating artery size affect the susceptibility to ischemia. Current indications for revascularization include symptomatic vertebrobasilar ischemia refractory to medical therapy and ischemia caused by parent vessel occlusion as treatment for complex aneurysms. Treatment options include endovascular angioplasty and stenting, surgical endarterectomy, arterial reimplantation, extracranial-to-intracranial anastomosis, and indirect bypasses. Pretreatment studies including cerebral blood flow measurements with assessment of hemodynamic reserve can affect treatment decisions. Careful blood pressure regulation, neurophysiologic monitoring, and neuroprotective measures such as mild brain hypothermia can help minimize the risks of intervention. Microscope, microinstruments and intraoperative Doppler are routinely used. The superficial temporal artery, occipital artery, and external carotid artery can be used to augment blood flow to the superior cerebellar artery, posterior cerebral artery, posterior inferior cerebellar artery, or anterior inferior cerebellar artery. Interposition venous or arterial grafts can be used to increase length. Several published series report improvement or relief of symptoms in 60 to 100% of patients with a reduction of risk of future stroke and low complication rates.