Does the diagnostic timing of cancer-associated thromboembolism influence the survival outcome in ovarian cancer patients?

BACKGROUND/PURPOSE: Efforts were made to explore the influence of diagnostic timing for cancer-associated thromboembolic events on survival of ovarian cancer patients. METHODS: We reviewed the medical records of 75 ovarian cancer patients with thromboembolism and evaluated the prognostic factors affecting disease-free survival and overall survival. RESULTS: These 75 patients were classified into two categories by the diagnostic timing of the thromboembolism, during (33 cases) and after (42 cases) initial diagnosis of ovarian cancer groups. The diagnostic timing of thromboembolism was not related to disease-free survival or overall survival of the studied population. Advanced disease stage, clear cell histology, interval debulking surgery, no recurrence/persistence of ovarian cancer, and patients treated with anticoagulant(s) treatment >3 months were associated with the disease-free survival. Advanced disease stage, clear cell histology, body mass index (BMI) ≥24 kg/m2 at the diagnosis of ovarian cancer, and no recurrence/persistence of ovarian cancer influenced the overall survival. In the subgroup analysis, compared to the after initial ovarian cancer diagnosis group, patients with stage I/II disease, BMI <24 kg/m2 at the diagnosis of ovarian cancer, or primary debulking surgery in the during cancer diagnosis group had longer disease-free survival, and overall survival benefit was observed in cases with stage I/II disease, or primary debulking surgery. CONCLUSION: The diagnostic timing of thromboembolism was not related to disease-free or overall survival of ovarian cancer patients, but associated with that of specific patient subgroups.

Next-generation sequencing and bioinformatics to identify genetic causes of malignant hyperthermia.

BACKGROUND/PURPOSE: Malignant hyperthermia (MH) is a life-threatening pharmacogenetic disease with only two known causative genes, RYR1 and CACNA1S. Both are huge genes containing numerous exons, and they reportedly only account for 50-70% of known MH patients. Next-generation sequencing (NGS) technology and bioinformatics could help delineate the genetic diagnosis of MH and several MH-like clinical presentations. METHODS: We established a capture-based targeted NGS sequencing framework to examine the whole genomic regions of RYR1, CACNA1S and the 16.6 Kb mitochondrial genome, as well as 12 other genes related to excitation-contraction coupling and/or skeletal muscle calcium homeostasis. We applied bioinformatics analyses to the variants identified in this study and also to the 48 documented RYR1 pathogenic variants. RESULTS: The causative variants were identified in seven of the eight (87.5%) MH families, but in none of the 10 individuals classified as either normal controls (N = 2) or patients displaying MH-like clinical features later found to be caused by other etiologies (N = 8). We showed that RYR1 c.1565A>G (p.Tyr522Cys)(rs118192162) could be a genetic hot spot in the Taiwanese population. Bioinformatics analyses demonstrated low population frequencies and predicted damaging effects from all known pathogenic RYR1 variants. We estimated that more than one in 1149 individuals worldwide carry MH pathogenic variants at RYR1. CONCLUSION: NGS and bioinformatics are sensitive and specific tools to examine RYR1 and CACNA1S for the genetic diagnosis of MH. Pathogenic variants in RYR1 can be found in the majority of MH patients in Taiwan.

Evaluating soreness symptoms of fibromyalgia: Establishment and validation of the Revised Fibromyalgia Impact Questionnaire with Integration of Soreness Assessment.

BACKGROUND: Fibromyalgia is a chronic disorder characterized by widespread musculoskeletal pain. A common complaint is soreness. However, until now, no assessment tool is available to address soreness and evaluate its impact on disease severity. We aimed to establish a questionnaire for soreness assessment and to evaluate its validity in fibromyalgia patients. METHODS: Patients diagnosed with fibromyalgia per the American College of Rheumatology criteria (2011) were recruited. The Revised Fibromyalgia Impact Questionnaire with an integration of Soreness Assessment (FIQRS) was established by adding five items pertinent to soreness sensation to the existing FIQR. The participants were asked to evaluate their soreness symptoms by filling out the FIQRS twice. The test-retest reliability and internal consistency were assessed. Construct validity was evaluated by correlations with the FIQR and fibromyalgia symptom severity (SS) score. RESULTS: Sixty-two patients with fibromyalgia were recruited, including 57 females (91.9%; mean age: 51.4 years). The intraclass correlation coefficient (ICC) of test-retest reliability was 0.92 for the FIQRS overall score. The Cronbach's α of all the items in the FIQRS was 0.93. The correlation coefficient of the FIQRS total score with the FIQR was 0.97 (p < 0.0001) and that with the fibromyalgia SS scale was 0.52 (p < 0.0001). CONCLUSION: The FIQRS has good reliability and internal consistency for the assessment of disease impact on fibromyalgia patients, thus providing a reliable tool for soreness evaluation. Future studies are warranted for further validation regarding its correlation with other psychometric properties and life quality measurements.

Irradiation Enhances Abscopal Anti-tumor Effects of Antigen-Specific Immunotherapy through Regulating Tumor Microenvironment.

Ionizing radiation therapy is a well-established method of eradicating locally advanced tumors. Here, we examined whether local RT enhanced the potency of an antigen-specific DNA vaccine, and we investigated the possible underlying mechanism. Using the HPV16 E6/E7+ syngeneic TC-1 tumor, we evaluated the combination of CTGF/E7 vaccination with local irradiation with regard to synergistic antigen-specific immunity and anti-tumor effects. Tumor-bearing mice treated with local RT (6 Gy twice weekly) and CTGF/E7 DNA vaccination exhibited dramatically increased numbers of E7-specific CD8+ cytotoxic T cell precursors, higher titers of anti-E7 Abs, and significantly reduced tumor size. The combination of local RT and CTGF/E7 vaccination also elicited abscopal effects on non-irradiated local subcutaneous and distant pulmonary metastatic tumors. Local irradiation induced the expression of high-mobility group box 1 protein (HMGB-1) in apoptotic tumor cells and stimulated dendritic cell (DC) maturation, consequently inducing antigen-specific immune responses. Additionally, local irradiation eventually increased the effector-to-suppressor cell ratio in the tumor microenvironment. Overall, local irradiation enhanced the antigen-specific immunity and anti-tumor effects on local and distant metastatic tumors generated by an antigen-specific DNA vaccine. These findings suggest that the combination of irradiation with antigen-specific immunotherapy is a promising new clinical strategy for cancer therapy.

Stroke 112: A Universal Stroke Awareness Program to Reduce Language and Response Barriers.

BACKGROUND AND PURPOSE: To improve stroke awareness and reduce life-threatening prehospital delays worldwide, a universal stroke educational program is needed. To meet this unmet need, we developed a universal program without language barriers and tested its acceptance in Taiwan, where Chinese is the native language. METHODS: Stroke 112 was developed using the universal emergency phone number, 112. The numbers imply an emergency and correspond to the 3 stroke recognition signs used in FAST (Face, Arm, Speech, and Time): 1 uneven face (crooked mouth); 1 weak arm (arm weakness); 2 incoherent lips (slurred speech). An online survey was used to determine the acceptance of the Stroke 112 program compared with that of FAST in Chinese. The surveys were delivered using SurveyMonkey (http://www.surveymonkey.com) on 2 separate occasions in Taiwan; in August 2017 for an initial estimation of the acceptance of Stroke 112 and in March 2018, 2 weeks after the official release of Stroke 112 in Taiwan, including a special introductory lecture for neurologists hosted by the STARS-Taiwan (Stroke Treatment and Research Society-Taiwan). RESULTS: The initial survey with 465 survey responders, 54.6% thought that Stroke 112 was easier to remember for people in Taiwan compared with FAST (41.2%). After Stroke 112's official release in Taiwan, 610 individuals completed the survey, and the majority (66.4%) thought that Stroke 112 was easier to remember, a significant increase compared with the initial survey (P=0.0001). Among the 130 neurologists who attended the Stroke 112 introductory lecture, 55 completed the online survey. A greater acceptance of Stroke 112 (74.6%) compared with FAST (16.4%) was observed among these 55 neurologists (P=0.0001). CONCLUSIONS: Stroke 112, a universal stroke educational program without language barriers was developed. It could potentially be implemented worldwide, especially where 112 is used as an emergency phone number.

Sensing acidosis: nociception or sngception?

BACKGROUND: Sensing tissue acidosis is an important function of the somatosensory nervous system to response to noxious stimuli. MAIN BODY: In the pain clinic, acid or soreness sensation is a characteristic sensory phenotype of various acute and chronic pain syndromes, such as delayed onset muscle soreness, fibromyalgia, and radicular pain. However, soreness sensation is a sign of successful analgesia for acupuncture and noxipoint therapy. Thus, the nature of acid or soreness sensation is not always nociceptive (or painful) and could be anti-nociceptive. To facilitate the investigation of the molecular and neurobiological mechanisms of soreness sensation, we propose a concept called "sngception (sng- ception)" to describe the response of the somatosensory nervous system to sense tissue acidosis and to distinguish it from nociception. "Sng" is a Taiwanese word that represents the state of soreness while at the same time imitates the natural vocalization of humans feeling sore. CONCLUSION: Here we propose sngception as a specific somatosensory function that transmits the acid sensation from the peripheral to the central nervous system. Sngception could partially overlap with nociception, but it could also transmit antinociception, proprioception, and pruriception.

The role of autonomic dysfunction in predicting 1-year mortality after liver transplantation.

BACKGROUND & AIMS: Model for end-stage liver disease (MELD) score has been extensively used to prioritize patients for liver transplantation and determine their prognosis, but with limited predictive value. Autonomic dysfunction may correlate with increased mortality after liver transplant. In this study, two autonomic biomarkers, complexity and deceleration capacity, were added to the predicting model for 1-year mortality after liver transplantation. METHODS: In all, 30 patients with end-stage liver diseases awaiting liver transplantation were included. Complexity and deceleration capacity were calculated by multi-scale entropy and phase-rectified signal averaging, respectively. Different combinations of autonomic factors and MELD score were used to predict mortality rate of liver transplant after 1-year follow-up. Receiver-operating characteristics curve analysis was performed to determine clinical predictability. Area under the receiver-operating characteristics curve represents the overall accuracy. RESULTS: The 1-year mortality rate was 16.7% (5/30). The overall accuracy of MELD score used for predicting mortality after liver transplantation was 0.752. By adding complexity and deceleration capacity into the predicting model, the accuracy increased to 0.912. Notably, the accuracy of the prediction using complexity and deceleration capacity alone was 0.912. CONCLUSION: Complexity and deceleration capacity, which represent different dynamical properties of a human autonomic system, are critical factors for predicting mortality rate of liver transplantation. We recommend that these pre-operative autonomic factors may be helpful as critical adjuncts to predicting model of mortality rate in prioritizing organ allocation.

Effects of endotoxin absorber hemoperfusion on microcirculation in septic pigs.

BACKGROUND: Endotoxins contribute to systemic inflammatory response and microcirculatory dysfunctions under conditions of sepsis. Polymyxin B hemoperfusion (PMX-HP) is used to remove circulating endotoxins and improve clinical outcomes. This study aims to investigate the effect of PMX-HP on microcirculation in septic pigs. MATERIALS AND METHODS: By using a septic pig model, we tested the hypothesis that PMX-HP can correct intestinal microcirculation, tissue oxygenation saturation, and histopathologic alterations. A total of 18 male pigs were divided into three groups: (1) sham; (2) sepsis (fecal peritonitis); and (3) sepsis + PMX-HP groups. A sidestream dark field video microscope was used to record microcirculation throughout the terminal ileal mucosa, colon mucosa, kidney surface, and sublingual area. A superficial tissue oxygenation monitor employing the light reflectance spectroscopy technique was used to measure the tissue oxygen saturation. Hematoxylin and eosin staining was used for histologic examination. RESULTS: The perfused small vessel density and tissue oxygen saturation of the ileal mucosa at 6 h were higher in the sepsis + PMX-HP group than those in the sepsis group. The fluid amount and norepinephrine infusion rate between the sepsis group and sepsis + PMX-HP groups did not differ significantly. The histologic score for the ileal mucosa was lower in the sepsis + PMX-HP group than that in the sepsis group. Finally, the urine output was higher in the sepsis + PMX-HP group than it was in the sepsis group. CONCLUSIONS: This study demonstrates that PMX-HP attenuates microcirculatory dysfunction, tissue desaturation, and histopathologic alterations in the ileal mucosa in septic pigs.

CXCL12/CXCR4 Signaling Contributes to the Pathogenesis of Opioid Tolerance: A Translational Study.

BACKGROUND: Long-term opioid therapy for chronic pain may lead to analgesic tolerance, especially when administered intrathecally, thus preventing adequate pain relief. Discovering drug targets to treat opioid tolerance using a mechanism-based approach targeting opioid-induced neuroinflammation provides new therapeutic opportunities. In this study, we provide translational evidence that CXCL12/CXCR4 signaling contributes to the pathogenesis of opioid tolerance. METHODS: The CXCL12 levels in the cerebrospinal fluid of opioid-tolerant patients were compared with those of opioid-naive subjects. For further investigation, a rodent translational study was designed using 2 clinically relevant opioid delivery paradigms: daily intraperitoneal morphine injections and continuous intrathecal morphine infusion. We measured rats' tail flick responses and calculated the percentage of maximum possible effects (%MPE) to demonstrate opioid acute antinociception and the development of analgesic tolerance. The effects of exogenous CXCL12, CXCL12 neutralizing antibody, and receptor antagonist AMD3100 were investigated by intrathecal administration. Data were presented as mean ± SEM. RESULTS: CXCL12 was significantly upregulated in the cerebrospinal fluid of opioid-tolerant patients for 892 ± 34 pg/mL (n = 27) versus 755 ± 33 pg/mL (n = 10) in naive control subjects (P = .03). Furthermore, after 2 and 5 days of intrathecal morphine infusion, rat lumbar spinal cord dorsal horn CXCL12 messenger RNA levels were significantly upregulated by 3.2 ± 0.7 (P = .016) and 3.4 ± 0.3 (P = .003) fold, respectively. Results from the daily intraperitoneal morphine injection experiments revealed that administering an intrathecal infusion of CXCL12 for 24 hours before the first morphine injection did not decrease antinociception efficacy on day 1 but accelerated tolerance after day 2 (%MPE 49.5% vs 88.1%, P = .0003). In the intrathecal morphine coinfusion experiments, CXCL12 accelerated tolerance development (%MPE 9.4% vs 43.4% on day 1, P < .0001), whereas coadministration with CXCL12 neutralizing antibody attenuated tolerance (72.5% vs 43.4% on day 1, P < .0001; 47.6% vs 17.5% on day 2, P < .0001). Coadministration of receptor antagonist AMD 3100 can persistently preserve morphine analgesic effects throughout the study period (27.9% ± 4.1% vs 0.9% ± 1.6% on day 5, P = .03). CONCLUSIONS: The CXCL12/CXCR4 pathway contributes to the pathogenesis of opioid tolerance. Our study indicates that intervening with CXCL12/CXCR4 signaling has therapeutic potential for opioid tolerance.

Effects of Dexmedetomidine on Intestinal Microcirculation and Intestinal Epithelial Barrier in Endotoxemic Rats.

BACKGROUND: Dexmedetomidine reduces cytokine production in septic patients and reduces inflammation and mortality in experimental models of endotoxemia and sepsis. This study investigated whether dexmedetomidine attenuates endothelial dysfunction, intestinal microcirculatory dysfunction, and intestinal epithelial barrier disruption in endotoxemic rats. METHODS: Ninety-two male Wistar rats were randomly assigned to the following four groups: (1) Sham; (2) lipopolysaccharide, received IV lipopolysaccharide 15 and 10 mg/kg at 0 and 120 min; (3) dexmedetomidine, received IV dexmedetomidine for 240 min; and (4) lipopolysaccharide + dexmedetomidine, received both lipopolysaccharide and dexmedetomidine. Sidestream dark-field videomicroscope, tissue oxygen monitor, and full-field laser perfusion image were used to investigate the microcirculation of the terminal ileum. Serum endocan level was measured. The Ussing chamber permeability assay, lumen-to-blood gadodiamide passage by magnetic resonance imaging, and bacterial translocation were conducted to determine epithelial barrier function. Mucosal apoptotic levels and tight junctional integrity were also examined. RESULTS: The density of perfused small vessels in mucosa, serosal muscular layer, and Peyer patch in the lipopolysaccharide + dexmedetomidine group was higher than that of the lipopolysaccharide group. Serum endocan level was lower in the lipopolysaccharide + dexmedetomidine group than in the lipopolysaccharide group. Mucosal ratio of cleaved to full-length occludin and spleen bacterial counts were significantly lower in the lipopolysaccharide + dexmedetomidine group than in the lipopolysaccharide group. CONCLUSION: The study finding suggests that dexmedetomidine protects against intestinal epithelial barrier disruption in endotoxemic rats by attenuating intestinal microcirculatory dysfunction and reducing mucosal cell death and tight junctional damage. (Anesthesiology 2016; 125:355-67).

Fast Track ultrasound protocol to detect acute complications after totally implantable venous access device placement.

BACKGROUND: The role of ultrasound examination in detection of postprocedure complications from totally implantable venous access devices (TIVAD) placement is still uncertain. In a cohort of 665 cancer outpatients, we assessed a quick ultrasound examination protocol in early detection of mechanical complications of catheterization. METHODS: Immediately after TIVAD placement, an ultrasound examination and chest radiography were performed to detect hemothorax, pneumothorax, and catheter malposition. The two methods were compared. RESULTS: Of the 668 catheters inserted, 628 were placed into axillary veins and 40 into internal jugular veins. The ultrasound examination took 2.5 ± 1.1 min. No hemothorax was detected, and neither pneumothorax nor catheter malposition was evident among the 40 internal jugular vein cannulations. Ultrasound and chest radiography examinations of the 628 axillary vein cannulations detected five and four instances of pneumothorax, respectively. Ultrasound detected all six catheter malpositions into the internal jugular vein. However, ultrasound failed to detect two out of three malpositions in the contralateral brachiocephalic vein and one kinking inside the superior vena cava. Without revision surgery, the operating time was 34.1 ± 15.6 min. With revision surgery, the operating time was shorter when ultrasound detected catheter malposition than when chest radiography was used (96.8 ± 12.9 vs. 188.8 ± 10.3 min, p < 0.001). CONCLUSIONS: Postprocedure ultrasound examination is a quick and sensitive method to detect TIVAD-related pneumothorax. It also precisely detects catheter malposition to internal jugular vein thus reduces time needed for revision surgery while chest radiography remains necessary to confirm catheter final position.

Laser speckle contrast imaging for assessing microcirculatory changes in multiple splanchnic organs and the gracilis muscle during hemorrhagic shock and fluid resuscitation.

OBJECTIVE: Hemorrhagic shock induces both macrocirculatory and microcirculatory impairment. Persistent microcirculatory dysfunction is associated with the dysfunction of multiple organs, especially in the splanchnic organs. However, few studies have simultaneously investigated microcirculation in multiple organs. In the present study, we used laser speckle contrast imaging to simultaneously investigate microcirculatory changes secondary to hemorrhagic shock and after fluid resuscitation among multiple splanchnic organs and the gracilis muscle. MATERIALS AND METHODS: 72 male Wistar rats were subjected to sham operation, hemorrhagic shock (total blood loss of 30mL/kg) and saline resuscitation. Macrocirculatory parameters, including the mean arterial pressure (MAP) and heart rate, and microcirculatory parameters, including microcirculatory blood flow intensity and tissue oxygen saturation in the liver, kidney, intestine (mucosa, serosal muscular layer, and Peyer's patch), and gracilis muscle were compared in a period of 3h. RESULTS: Hemorrhagic shock induced a significant reduction of microcirculatory blood flow intensity in the kidney and intestine (especially the mucosa). Tissue oxygen saturation reduction secondary to hemorrhagic shock was comparable among the various splanchnic organs but lower than the gracilis muscle. Fluid resuscitation restored the MAP but not the microcirculatory blood flow in the intestine and the tissue oxygen saturation in each splanchnic organ. CONCLUSION: Hemorrhagic shock induced the largest reduction in microcirculatory blood flow intensity in the intestinal mucosa. By comparison, the reduction of tissue oxygen saturation was not significantly different among the various splanchnic organs. Although fluid resuscitation restored the MAP, the intestinal microcirculation remained damaged.

Role of spinal CXCL1 (GROα) in opioid tolerance: a human-to-rodent translational study.

BACKGROUND: The pivotal role of glial activation and up-regulated inflammatory mediators in the opioid tolerance has been confirmed in rodents but not yet in humans. Here, the authors investigated the intraspinal cytokine and chemokine profiles of opioid-tolerant cancer patients; and to determine if up-regulated chemokines could modify opioid tolerance in rats. METHODS: Cerebrospinal fluid samples from opioid-tolerant cancer patients and opioid-naive subjects were compared. The cerebrospinal fluid levels of tumor necrosis factor-alpha, CXCL1, CXCL10, CCL2, and CX3CL1 were assayed. The rat tail flick test was utilized to assess the effects of intrathecal CXCL1 on morphine-induced acute antinociception and analgesic tolerance. RESULTS: CXCL1 level in cerebrospinal fluid was significantly up-regulated in the opioid-tolerant group (n = 30, 18.8 pg/ml vs. 13.2 pg/ml, P = 0.02) and was positively correlated (r = 0.49, P < 0.01) with opioid dosage. In rat experiment, after induction of tolerance by morphine infusion, the spinal cord CXCL1 messenger RNA was up-regulated to 32.5 ± 11.9-fold. Although CXCL1 infusion alone did not affect baseline tail-flick latency, the analgesic efficacy of a single intraperitoneal injection of morphine dropped significantly on day 1 to day 3 after intrathecal infusion of CXCL1. After establishing tolerance by intrathecal continuous infusion of morphine, its development was accelerated by coadministration of CXCL1 and attenuated by coadministration of CXCL1-neutralizing antibody or CXCR2 antagonist. CONCLUSIONS: CXCL1 is up-regulated in both opioid-tolerant patients and rodents. The onset and extent of opioid tolerance was affected by antagonizing intrathecal CXCL1/CXCR2 signaling. Therefore, the CXCL1/CXCR2 signal pathway may be a novel target for the treatment of opioid tolerance.

Hypoxic Preconditioning Suppresses Glial Activation and Neuroinflammation in Neonatal Brain Insults.

Perinatal insults and subsequent neuroinflammation are the major mechanisms of neonatal brain injury, but there have been only scarce reports on the associations between hypoxic preconditioning and glial activation. Here we use neonatal hypoxia-ischemia brain injury model in 7-day-old rats and in vitro hypoxia model with primary mixed glial culture and the BV-2 microglial cell line to assess the effects of hypoxia and hypoxic preconditioning on glial activation. Hypoxia-ischemia brain insult induced significant brain weight reduction, profound cell loss, and reactive gliosis in the damaged hemisphere. Hypoxic preconditioning significantly attenuated glial activation and resulted in robust neuroprotection. As early as 2 h after the hypoxia-ischemia insult, proinflammatory gene upregulation was suppressed in the hypoxic preconditioning group. In vitro experiments showed that exposure to 0.5% oxygen for 4 h induced a glial inflammatory response. Exposure to brief hypoxia (0.5 h) 24 h before the hypoxic insult significantly ameliorated this response. In conclusion, hypoxic preconditioning confers strong neuroprotection, possibly through suppression of glial activation and subsequent inflammatory responses after hypoxia-ischemia insults in neonatal rats. This might therefore be a promising therapeutic approach for rescuing neonatal brain injury.

Ultrasound-Guided Proximal Suprascapular Nerve Block With Radiofrequency Lesioning for Patients With Malignancy-Associated Recalcitrant Shoulder Pain.

The classic suprascapular nerve block has limitations, such as postural requirements and lack of direct nerve visualization. This series investigated the analgesic effect of ultrasound-guided supraclavicular suprascapular nerve blocks in patients with malignancy-associated shoulder pain. Ablative radiofrequency lesioning of the suprascapular nerve in 6 patients provided substantial pain relief. The mean distance from the suprascapular nerve to the brachial plexus was 8.05 mm, and the mean angle of needle entry was 20.6°. This approach appears to be effective in relieving malignancy-associated shoulder pain and is tolerated by patients unable to sit or lie prone.

Evident cognitive impairments in seemingly recovered patients after midazolam-based light sedation during diagnostic endoscopy.

BACKGROUND/PURPOSE: Midazolam is a widely used sedative agent during colonoscopy, with cognitive toxicity. However, the potential cognitive hazard of midazolam-based light sedation has not been sufficiently examined. We aimed to examine the cognitive safety and vulnerability profile under midazolam light sedation, with a particular focus on individual variations. METHODS: We conducted a prospective case-controlled study in an academic hospital. In total, 30 patients undergoing sedative colonoscopy as part of a health check-up were recruited. Neuropsychological testing on the full cognitive spectrum was evaluated at 15 minutes and 120 minutes after low-dose midazolam administration. The modified reliable change index (RCI) was used for intrapersonal comparisons and controlling for practice effects. RESULTS: Midazolam affected psychomotor speed (48%), memory (40%), learning (32%), working memory (17%), and sustained attention (11%), while sparing orientation and the fluency aspect of executive function at the acute stage. Residual memory (10%) and learning (10%) impairments at 2 hours after administration were evidenced in some patients. The three object recall and digit symbol coding tests can serve as useful screening tools. CONCLUSION: Midazolam-based light sedation induced selective cognitive impairments and prolonged cognitive impairments occurred in patients with advanced age. A longer observation time and further screening were recommended for patients due to their at risk state.

Gabapentin reverses central hypersensitivity and suppresses medial prefrontal cortical glucose metabolism in rats with neuropathic pain.

BACKGROUND: Gabapentin (GBP) is known to suppress neuropathic hypersensitivity of primary afferents and the spinal cord dorsal horn. However, its supra-spinal action sites are unclear. We identify the brain regions where GBP changes the brain glucose metabolic rate at the effective dose that alleviates mechanical allodynia using 18 F-fluorodeoxyglucose-positron emission tomography (FDG-PET) scanning. RESULTS: Comparing the PET imaging data before and after the GBP treatment, the spared nerve injury-induced increases of glucose metabolism in the thalamus and cerebellar vermis were reversed, and a significant decrease occurred in glucose metabolism in the medial prefrontal cortex (mPFC), including the anterior cingulate cortex. GBP treatment also reversed post-SNI connectivity increases between limbic cortices and thalamus. CONCLUSIONS: Our results indicate that GBP analgesic effect may be mediated by reversing central hypersensitivity, and suppressing mPFC, a crucial part of the cortical representation of pain, in the brain.