Regional Cerebral Oxygen Saturation Changes After Decompressive Craniectomy for Malignant Cerebral Venous Thrombosis: A Prospective Cohort Study

Background: Decompressive craniectomy (DC) is a life-saving intervention for malignant cerebral venous thrombosis (CVT). Earlier studies have shown increase in cerebral oxygenation after DC in traumatic brain injury but similar studies are lacking in CVT. We hypothesized that regional cerebral (tissue) oxygen saturation (rSO2) on the side of CVT is lower than the contralateral side and improves after DC. Materials and Methods: In this prospective cohort study, rSO2 was monitored using near-infrared spectroscopy technique, before and after DC on both cerebral hemispheres. Data regarding factors likely to affect rSO2 such as systolic blood pressure, partial pressure of oxygen and carbon dioxide in blood (PaO2 and PaCO2), and hemoglobin were simultaneously collected. The primary outcome measure was pre-post change in rSO2 on the ipsilateral cerebral hemisphere. The secondary outcomes were in-hospital mortality and duration of postoperative hospital stay. Results: Seventeen patients underwent DC during the 6-month study period. Their mean age was 39.2±12.4 years. The pre-post DC change in rSO2 on the hemisphere with CVT was significant (mean difference=3.6%; 95% confidence interval, 1.5-5.7; P=0.002). One patient died in the hospital. There was no difference in the duration of postoperative hospital stay (10 d [range, 6 to 21 d] vs. 14 d [range, 1 to 30 d], P=0.92) between patients with preoperative ipsilateral rSO2 60%. There was no correlation between PaO2, PaCO2, systolic blood pressure, and hemoglobin with rSO2. Conclusions: Patients with malignant CVT had a lower rSO2 on ipsilateral side of the lesion, which improved significantly after DC. Preoperative rSO2 was not correlated with the duration of hospital stay. The authors have no funding or conflicts of interest to disclose. Address correspondence to: Kamath Sriganesh, DM, Department of Neuroanaesthesia and Neurocritical Care, 3rd Floor, Neurosciences Faculty Block, NIMHANS, Hosur Road, Bengaluru 560029, India (e-mail: drsri23@gmail.com). Received November 7, 2017 Accepted January 25, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved

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Stretching the limits: from homeostasis to stem cell plasticity in wound healing and cancer

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Gene expression: Developmental enhancers in action

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Integrative omics for health and disease

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Brainstem catecholaminergic neurones and breathing control during postnatal development in male and female rats

Abstract

The respiratory network undergoes significant development during the postnatal phase, including the maturation of the catecholaminergic (CA) system. However, postnatal development of this network and its effect on the control of pulmonary ventilation (V̇_E), is not fully understood. We investigated the involvement of brainstem CA neurones in respiratory control during postnatal (P) development (P7-8, P14-15 and P20-21), in male and female rats, through chemical injury with conjugated saporin anti-dopamine beta-hydroxylase (DβH-SAP). Thus, DβH-SAP (420 ng μL⁻¹), saporin (SAP) or phosphate buffered solution (PBS) was injected into the 4th ventricle of neonatal Wistar rats of both sexes. V̇_E and oxygen consumption were recorded one week after the injections in unanaesthetized neonatal and juvenile rats during room air and hypercapnia. The resting ventilation was higher in both male and female P7-8 lesioned rats by 33%, and a decrease in respiratory variability was observed in males. The hypercapnic ventilatory response (HCVR) was altered in male and female lesioned rats at all postnatal ages. At P7-8, the HCVR for males and females was increased by 37% and 30%, respectively. For both sexes at P14-15 rats, the increase in V̇_E during hypercapnia was 37% higher for lesioned rats. A sex-specific difference in HCRV was observed at P20-21, with lesioned males showing a 33% decrease, and lesioned females showing an increase of 33%. We conclude that brainstem CA neurones exert a tonic inhibitory effect on V̇_E in the early postnatal days of a rat's life, increase variability in P7-8 males and modulate HCRV during the postnatal phase.

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Post-mortem analysis of suicide victims shows ABCB1 haplotype 1236T–2677T–3435T as a candidate predisposing factor behind adverse drug reactions in females

Background Genetic variation in efflux transporter, permeability glycoprotein (P-gp), has recently been associated with completed violent suicides and also violent suicide attempts. As depression is known to be a risk factor for suicide and many antidepressants are P-gp substrates, it has been speculated that inadequate antidepressant treatment response or adverse side effects could be involved. Objectives The aim of this study was to investigate whether there is an association between the P-gp coding ABCB1 gene and completed suicides in citalopram users. Also, the effect of sex and suicide method used (violent vs. non-violent) was evaluated. Materials and methods All cases included in the study population, 349 completed suicide victims and 284 controls, were shown to be positive for antidepressant citalopram in a post-mortem toxicological drug screen. ABCB1 1236C>T, 2677G/A>T, and 3435C>T polymorphisms were determined by TaqMan genotyping assays. Haplotypes were constructed from genotype data using the PHASE software. The association between the manner of death and the ABCB1 haplotype was tested with logistic regression analysis. Results No statistically significant differences were observed in the ABCB1 allele or genotype frequencies between the suicide and control groups. However, the ABCB1 1236T–2677T–3435T haplotype was associated with completed suicides of female citalopram users (odds ratio: 2.23; 95% confidence interval: 1.22–4.07; P=0.009). After stratification by the method used for suicide, the association emerged in fatal intoxications (odds ratio: 2.51; 95% confidence interval: 1.29–4.87; P=0.007). In other groups, no statistically significant associations were observed. Conclusion Our results suggest that female citalopram users with ABCB1 1236T–2677T–3435T are more vulnerable to adverse effects of the drugs as this haplotype was enriched in non-violent suicides of female citalopram users. Even though the biological mechanism behind this observation is unknown, the results provide another example of the importance of sex-based segregation in pharmacogenetics studies. Correspondence to Anna-Liina Rahikainen, MSc, Department of Forensic Medicine, PO Box 40 (Kytösuontie 11) University of Helsinki, Helsinki FI-00014, Finland Tel: +358 504 151 573; e-mail: anna-liina.rahikainen@helsinki.fi Received November 10, 2017 Accepted January 27, 2018 Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.

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Spinal Cord Stimulation 50 Years Later: Clinical Outcomes of Spinal Cord Stimulation Based on Randomized Clinical Trials—A Systematic Review

To assess the efficacy of spinal cord stimulation (SCS) for each indication, one must critically assess each specific clinical outcome to identify outcomes that benefit from SCS therapy. To date, a comprehensive review of clinically relevant outcome-specific evidence regarding SCS has not been published. We aimed to assess all randomized controlled trials from the world literature for the purpose of evaluating the clinical outcome-specific efficacy of SCS for the following outcomes: perceived pain relief or change pain score, quality of life, functional status, psychological impact, analgesic medication utilization, patient satisfaction, and health care cost and utilization. Interventions were SCS, without limitation to the type of controls or the type of SCS in the active arms. For each study analyzed, a quality assessment was performed using a validated scale that assesses reporting, external validity, bias, confounding, and power. Each outcome was assessed specific to its indication, and the primary measure of each abovementioned outcome was a summary of the level of evidence. Twenty-one randomized controlled trials were analyzed (7 for trunk and limb pain, inclusive of failed back surgery syndrome; 8 for refractory angina pectoris; 1 for cardiac X syndrome; 3 for critical limb ischemia; 2 for complex regional pain syndrome; and 2 for painful diabetic neuropathy). Evidence assessments for each outcome for each indication were depicted in tabular format. Outcome-specific evidence scores were established for each of the abovementioned indications, providing both physicians and patients with a summary of evidence to assist in choosing the optimal evidence-based intervention. The evidence presented herein has broad applicability as it encompasses a breadth of patient populations, variations of SCS therapy, and comparable controls that, together, reflect comprehensive clinical decision making. Accepted for publication October 22, 2017. Address correspondence to: Nagy Mekhail, MD, PhD, Cleveland Clinic, C25, 9500 Euclid Ave, Cleveland, OH 44195 (e-mail: mekhain@ccf.org). The authors declare no conflict of interest. Copyright © 2018 by American Society of Regional Anesthesia and Pain Medicine.

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