The ERK phosphorylation levels in the amygdala predict anxiety symptoms in humans and MEK/ERK inhibition dissociates innate and learned defensive behaviors in rats.

We demonstrate that the rate of extracellular signal-related kinase phosphorylation (P-ERK1,2/Total-ERK1,2) in the amygdala is negatively and independently associated with anxiety symptoms in 23 consecutive patients with drug-resistant mesial temporal lobe epilepsy that was surgically treated. In naive Wistar rats, the P-ERK1,2/Total-ERK1,2 ratio in the amygdala correlates negatively with innate anxiety-related behavior on the elevated plus maze (n = 20) but positively with expression of defensive-learned behavior (i.e., freezing) on Pavlovian aversive (fear) conditioning (n = 29). The microinfusion of ERK1/2 inhibitor (FR180204, n = 8-13/group) or MEK inhibitor (U0126, n = 8-9/group) into the basolateral amygdala did not affect anxiety-related behavior but impaired the evocation (anticipation) of conditioned-defensive behavior (n = 9-11/group). In conclusion, the P-ERK1,2/Total-ERK1,2 ratio in the amygdala predicts anxiety in humans and the innate anxiety- and conditioned freezing behaviors in rats. However, the ERK1/2 in the basolateral AMY is only required for the expression of defensive-learned behavior. These results support a dissociate ERK-dependent mechanism in the amygdala between innate anxiety-like responses and the anticipation of learned-defensive behavior. These findings have implications for understanding highly prevalent psychiatric disorders related to the defensive circuit manifested by anxiety and fear. HIGHLIGHTS: The P-ERK1,2/Total-ERK1,2 ratio in the amygdala (AMY) correlates negatively with anxiety symptoms in patients with mesial temporal lobe epilepsy. The P-ERK1,2/Total-ERK1,2 in the amygdala correlates negatively with the anxiety-like behavior and positively with freezing-learned behavior in naive rats. ERK1,2 in the basolateral amygdala is required for learned-defensive but not for the anxiety-like behavior expression in rats.

Amygdala levels of the GluA1 subunit of glutamate receptors and its phosphorylation state at serine 845 in the anterior hippocampus are biomarkers of ictal fear but not anxiety.

Fear is a conscious state caused by exposure to real or imagined threats that trigger stress responses that affect the body and brain, particularly limbic structures. A sub-group of patients with mesial temporal lobe epilepsy related to hippocampus sclerosis (MTLE-HS) have seizures with fear, which is called ictal fear (IF), due to epileptic activity within the brain defensive survival circuit structures. Synaptic transmission efficacy can be bi-directionally modified through potentiation (long-term potentiation (LTP)) or depression (long-term depression (LTD)) as well as the phosphorylation state of Ser831 and Ser845 sites at the GluA1 subunit of the glutamate AMPA receptors, which has been characterized as a critical event for this synaptic plasticity. In this study, GluA1 levels and the phosphorylation at Ser845 and Ser831 in the amygdala (AMY), anterior hippocampus (aHIP) and middle gyrus of temporal neocortex (CX) were determined with western blots and compared between MTLE-HS patients who were showing (n = 06) or not showing (n = 25) IF. Patients with IF had an 11% decrease of AMY levels of the GluA1 subunit (p = 0.05) and a 21.5% decrease of aHIP levels of P-GluA1-Ser845 (p = 0.009) compared to patients not showing IF. The observed associations were not related to imbalances in the distribution of other concomitant types of aura, demographic, clinical or neurosurgical variables. The lower levels of P-GluA1-Ser845 in the aHIP of patients with IF were not related to changes in the levels of the serine/threonine-protein phosphatase PP1-alpha catalytic subunit or protein kinase A activation. Taken together, the GluA1 subunit levels in AMY and P-GluA1-Ser845 levels in the aHIP show an overall accuracy of 89.3% (specificity 95.5% and sensitivity 66.7%) to predict the presence of IF. AMY levels of the GluA1 subunit and aHIP levels of P-GluA1-Ser845 were not associated with the psychiatric diagnosis and symptoms of patients. Taken together with previous findings in MTLE-HS patients with IF who were evaluated by stereotactic implanted depth electrodes, we speculate our findings are consistent with the hypothesis that AMY is not a centre of fear but together with other sub-cortical and cortical structures integrates the defensive circuit that detect and respond to threats. This is the first report to address neuroplasticity features in human limbic structures connected to the defensive survival circuits, which has implications for the comprehension of highly prevalent psychiatric disorders and symptoms.

The prognostic significance of serum aspartate transaminase and gamma-glutamyl transferase in liver deceased donors.

The impact of aspartate transaminases (AST) and gamma-glutamyl transferase (GGT) in serum of deceased donors on outcomes after liver transplantation (LT) is unclear. This study aimed to explore the relationship between donor highest AST value or first donor GGT value and graft survival. All consecutive patients who underwent a primary LT in a single center with available donor AST (N = 1253) and GGT value (N = 1152) were included. There was no significant association between donor AST and 90-day graft survival. We found a moderate association between GGT and 90-day graft survival. We found a significant interaction with a donor history of alcohol abuse (HAA). The risk of graft loss was associated with AST and GGT in donors with an HAA but remains unchanged in donors without HAA. There was no difference in graft survival according to donor AST or GGT with a cutoff ≥95th percentile (475 UI/l for AST and 170 UI/l for GGT). However, graft survival was significantly decreased when donors combined GGT ≥ 170 UI/l and HAA (61% at one year). Hepatic grafts from donors with high AST or high GGT but without alcohol history and no additional risk factors can be transplanted in low-risk recipient.

Quality of life long after temporal lobe epilepsy surgery.

OBJECTIVES: To identify variables independently associated with a meaningful improvement in QOL long after surgical treatment of drug-resistant MTLE-HS patients. MATERIAL & METHODS: We prospectively evaluated 72 consecutive MTLE-HS surgically treated patients and analyzed pre and post-surgical variables independently associated with a meaningful improvement in QOL evaluated by the Quality of Life in Epilepsy-31 (QOLIE-31) overall score, and its domain scores determined at follow-up after 36 to 131 months (mean 93 months) after surgery. RESULTS: The mean overall QOLIE-31 score and its subdomain scores improved significantly after surgery (p < 0.01), and 55 patients (76.4%) had a meaningful QOL improvement. Being seizure-free (Engel IA) after surgery showed a non-significant association (OR 2.63, CI 95% 0.53 to 13.05, p = 0.23) and lower depressive symptoms a significant association (OR 4.15, CI 95% 1.19 to 14.53, p = 0.03) with meaningful improvement of QOL. CONCLUSIONS: Patients with MTLE-HS who underwent epilepsy surgery show a sustained, meaningful improvement in their QOL. Pre-surgical variables do not predict long-term QOL improvement after surgery. Lower levels of depressive symptoms at postoperative evaluation are associated with meaningful QOL improvement.

Anxiety and depressive symptoms long after mesial temporal epilepsy surgery: A prospective study.

BACKGROUND: Anxiety and depressive symptoms are prevalent in patients with refractory mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) before and after anterior temporal lobectomy (ATL). AIMS: (1) To follow the levels of anxiety and depressive symptoms long-term after ATL among patients with refractory MTLE-HS; (2) To identify pre- and postsurgical variables associated with the levels of anxiety and depressive symptoms after surgery. METHODS: We compared the levels of anxiety and depressive symptoms determined by the Hospital Anxiety and Depression Scale (HADS) before and long after ATL (mean 104 months, range 70-130) in 41 consecutive patients refractory MTLE-HS. The last follow-up was between September 2018 and March 2020. We also determined pre- and postsurgical variables independently associated with the HADS scores after surgery. RESULTS: The scores of HADS and its subdomains related to anxiety and depression decreased significantly (p < 0.01) after ATL. After multiple linear regressions, the HADS-Anxiety scores before surgery (B = 0.47, CI 95% 0.20 to 0.75, p = 0.001) and at follow-up after surgery (B = 0.07, CI 0.00 to 0.14, p = 0.05) remain independently and positively associated with HADS-Anxiety scores after surgery. The HADS-Depression scores after surgery were independently positively associated with HADS-Depression scores before surgery (B = 0.39, CI 95% 0.10 to 0.76, p = 0.01) and worse seizure control after surgery (B = 1.55, CI 95% 0.23 to 2.87, p = 0.02). CONCLUSION: Anxiety and depressive symptoms in patients with MTLE-HS significantly improved after ATL. Presurgical levels of anxiety and depressive symptoms, respectively, were positively associated with the postsurgical levels of those symptoms. Length of follow-up is associated with anxiety, and worse seizure control is associated with depressive symptoms after ATL. The results have implications for the surgical management of MTLE-HS patients.

The role of minimally invasive hepatectomy for hilar and intrahepatic cholangiocarcinoma: A systematic review of the literature.

Despite the fact laparoscopic liver resections (LLR) for cholangiocarcinoma is still limited, this systematic review addressed surgical and oncological outcomes of LLR to treat both perihilar cholangiocarcinoma (pCCA) and intrahepatic cholangiocarcinoma (iCCA). Five comparative and 20 noncomparative studies were found. Regarding iCCA, LLR had lower blood loss and less need for Pringle maneuver. However, open liver resections (OLR) were performed more for major hepatectomies, with better lymphadenectomy rates and higher number of harvested lymph nodes. High heterogeneity and selection bias were suggested for iCCA studies.

The quality of life in type I diabetic patients with end-stage kidney disease before and after simultaneous pancreas-kidney transplantation: a single-center prospective study.

Simultaneous pancreas-kidney transplantation (SPKT) aimed at increasing the life expectancy for diabetic patients with end-stage kidney disease (ESKD). However, the risks of surgery complications and immunosuppression therapy make it unclear if the SPKT positively impacts patient's quality of life (QoL). Using the Kidney Disease Quality of Life-Short-Form Health Survey (KDQOL-SF36) and Problems Areas in Diabetes (PAID) measurement tools, we compared the QoL of 57 patients on the pretransplant waiting list with that of 103 patients who had undergone SPKT. Posttransplantation patients were assessed within different time intervals (<1, 1-3, and >3 years). Mean KDQOL-SF36 scores were better among posttransplantation patients in the SF36 and KDQOL domains. It was also observed patients' stress reduction in PAID mean score (P = 0.011) after SPKT. We concluded that patients receiving SPKT had a better perception of QoL than did patients on the waiting list, and this positive perception remained almost entirely comparable over the three different intervals of the posttransplantation time. These positive results showed better outcomes when excluding patients that lost pancreas graft function. Further research is needed to compare diabetic patients with kidney transplant alone using specific measurement tools to evaluate patient's QoL.

Determinants for Meaningful Clinical Improvement of Pain and Health-Related Quality of Life After Spinal Cord Stimulation for Chronic Intractable Pain.

OBJECTIVES: Previous studies demonstrated significant improvement in mean pain scores and quality of life (QOL) scales in patients with chronic pain who underwent spinal cord stimulation (SCS). However, the number of individuals who experience relevant improvements in QOL, termed the meaningful clinical improvement (MCI), is not known. The present study investigated changes in pain measurements based on MCI after SCS. MATERIALS AND METHODS: Thirty-four patients with chronic intractable pain completed scales of pain (visual analogue scale [VAS]), QOL (SF-36), and psychological dimensions during a 22-month follow-up period (mean). Patient-centered MCI of the VAS and SF-36 domain scores were determined based on the MacNab criteria of surgical global effectiveness. Independent presurgical predictors for MCI in the VAS and SF-36 domains were analyzed using multiple binary logistic regression. RESULTS: There was significant improvement of pain and QOL after the SCS (p < 0.00001). Twenty-three patients (67.6%) reached an MCI of pain, and 16 (47.7%)-23 (67.7%) reported an MCI of QOL. Predictors of MCI included ≥80% paresthesia coverage of the painful area, lower levels of anxiety and catastrophizing symptoms, shorter pain duration, female gender and no use of opioids before surgery. MCI of pain and QOL was observed in 50%-70% of patients with chronic pain after SCS. CONCLUSIONS: The identification of determinants for MCI is a challenge to improve the accuracy of prognostic models in SCS for patients with chronic pain. Our results, if confirmed in other populations with a larger sample size, have implications for patients with chronic pain who are candidates for SCS treatment.

Evaluation of high-grade astrocytoma recurrence patterns after radiotherapy in the era of temozolomide: A single institution experience.

AIM: Evaluating the recurrence patterns of high-grade astrocytomas in patients who were treated with radiotherapy (RT) plus temozolomide (TMZ). BACKGROUND: The current literature suggests that reducing the margins added to the CTV does not significantly change the risk of recurrence and overall survival; thus, we decided to analyze our data and to examine the possibility of changing the adopted margins. MATERIALS AND METHODS: From February 2008 till September 2013, 55 patients were treated for high-grade astrocytomas, 20 patients who had been confirmed to have recurrence were selected for the present study. Post-operative MRI was superimposed on the planning CT images in order to correlate the anatomical structures with the treatment targets. Recurrences were defined according to the Response Assessment Criteria for Glioblastoma. The mean margins of the PTVinitial and PTVboost were 1.2 cm and 1.4 cm, respectively. The analysis of the percentage of the recurrence volume (Volrec) within the 100% isodose surface was based on the following criteria: (I) Central: >95% of the Volrec; (II) In-field: 81-95% of the Volrec; (III) Marginal: 20-80% of the Volrec; and (IV) Outside: <20% of the Volrec. RESULTS: Of the 20 patients, 13 presented with central recurrences, 3 with in-field recurrences, 2 with marginal recurrences and 2 with outside recurrences. Therefore, the lower Volrec within 100% of the prescribed dose was considered in the classification. CONCLUSIONS: Of the selected patients, 80% had ≥81-95% of the Volrec within 100% of the prescribed dose and predominantly had central or in-field recurrences. These results are comparable with those from the literature.

Predictors of meaningful improvement in quality of life after temporal lobe epilepsy surgery: A prospective study.

OBJECTIVES: To investigate prospectively the independent predictors of a minimum clinically important change (MCIC) in quality of life (QOL) after anterior temporal lobectomy (ATL) for drug-resistant mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) in Brazilian patients. METHODS: Multiple binary logistic regression analysis was performed to identify the clinical, demographic, radiologic, and electrophysiologic variables independently associated with MCIC in the Quality of Life in Epilepsy-31 Inventory (QOLIE-31) overall score 1 year after ATL in 77 consecutive patients with unilateral MTLE-HS. RESULTS: The overall QOLIE-31 score and all its subscale scores increased significantly (p < 0.0001) 1 year after ATL. In the final logistic regression model, absence of presurgical diagnosis of depression (adjusted odds ratio [OR] 4.4, 95% confidence interval [CI] 1.1-16.1, p = 0.02) and a complete postoperative seizure control (adjusted OR 4.1, 95% CI 1.2-14.5, p = 0.03) were independently associated with improvement equal to or greater than the MCIC in QOL after ATL. The overall model accuracy for MCIC improvement in the QOL was 85.6%, with a 95.2% of sensitivity and 46.7% of specificity. SIGNIFICANCE: These results in Brazilian patients reinforce the external validation of previous findings in Canadian patients showing that presurgical depression and complete seizure control after surgery are independent predictors for meaningful improvement in QOL after ATL, and have implications for the surgical management of MTLE patients.

Decline in word-finding: The objective cognitive finding most relevant to patients after mesial temporal lobe epilepsy surgery.

PURPOSE: The purpose of this study was to investigate the following: i) the objective impairment in neuropsychological tests that were associated with the subjective perception of cognitive function decline in Brazilian patients who underwent mesial temporal lobe epilepsy (MTLE) surgery and ii) the predictive variables for those impaired objective neuropsychological tests. METHODS: Forty-eight adults with MTLE (27 right HS and 23 male) were divided according to their perception of changes (Decline or No-decline) of cognitive function domain of the QOLIE-31 questionnaire applied before and 1year after the ATL. The mean (SD) of changes in the raw score difference of the neuropsychological tests before and after the ATL was compared between Decline and No-decline groups. Receiver Operating Characteristic curves, sensitivity, specificity, and predictive values were used to assess the optimum cutoff points of neuropsychological test score changes to predict patient-reported subjective cognitive decline. KEY FINDINGS: Six (12.5%) patients reported a perception of cognitive function decline after ATL. Among the 25 cognitive tests analyzed, only changes in the Boston Naming Test (BNT) were associated with subjective cognitive decline reported by patients. A reduction of ≥8 points in the raw score of BNT after surgery had 91% of sensitivity and 45% specificity for predicting subjective perception of cognitive function decline by the patient. Left side surgery and age older than 40years were more associated with an important BNT reduction with overall accuracy of 91.7%, 95% predictive ability for no impairment, and 75% for impairment of cognitive function. SIGNIFICANCE: Impairment in word-finding seems to be the objective cognitive finding most relevant to Brazilian patients after mesial temporal lobe epilepsy surgery. Similar to American patients, the side of surgery and age are good predictors for no decline in the BNT, but shows a lower accuracy to predict its decline. If replicated in other populations, the results may have wider implications for the surgical management of patients with drug-resistant MTLE.

Mitochondrial Respiration Chain Enzymatic Activities in the Human Brain: Methodological Implications for Tissue Sampling and Storage.

Mitochondrial respiratory chain complexes enzymatic (MRCCE) activities were successfully evaluated in frozen brain samples. Epilepsy surgery offers an ethical opportunity to study human brain tissue surgically removed to treat drug resistant epilepsies. Epilepsy surgeries are done with hemodynamic and laboratory parameters to maintain physiology, but there are no studies analyzing the association among these parameters and MRCCE activities in the human brain tissue. We determined the intra-operative parameters independently associated with MRCCE activities in middle temporal neocortex (Cx), amygdala (AMY) and head of hippocampus (HIP) samples of patients (n = 23) who underwent temporal lobectomy using multiple linear regressions. MRCCE activities in Cx, AMY and HIP are differentially associated to trans-operative mean arterial blood pressure, O2 saturation, hemoglobin, and anesthesia duration to time of tissue sampling. The time-course between the last seizure occurrence and tissue sampling as well as the sample storage to biochemical assessments were also associated with enzyme activities. Linear regression models including these variables explain 13-17 % of MRCCE activities and show a moderate to strong effect (r = 0.37-0.82). Intraoperative hemodynamic and laboratory parameters as well as the time from last seizure to tissue sampling and storage time are associated with MRCCE activities in human samples from the Cx, AMYG and HIP. Careful control of these parameters is required to minimize confounding biases in studies using human brain samples collected from elective neurosurgery.

Variables associated with physical health-related quality of life in Parkinson's disease patients presenting for deep brain stimulation.

Deep brain stimulation (DBS) benefits Parkinson's disease (PD) patient's quality of life specially in domains as mobility, activities of daily living (ADL) and bodily discomfort (BD), but little is known about the variables associated with these HRQOL domains in patients presenting for DBS. The objective is to evaluate variables associated with of HRQOL in a Brazilian sample of PD patients presenting for DBS treatment, specifically in the domains related with motor symptoms. In a cross-sectional study of 59 PD patients evaluated at outpatient Unit for Movement Disorders, multiple linear regression analysis was performed to identify independent variables associated with mobility, ADL and BD domains of the 39-item Parkinson's disease questionnaire (PDQ-39). UPDRS III "on" scores, duration of the disease, age, presence of comorbidities and anxiety and depressive symptoms quantified by hospital anxiety and depression scale (HADS), were the independent variables. In our results, HADS scores were independently associated to mobility domain: ß coefficient 1.36 (95 % CI 0.55-2.15) and BD domain: ß coefficient 1.57 (95 % CI 0.67-2.48). UPDRS III "on" scores were independently associated to mobility domain: 0.42 (95 % CI 0.03-0.81). The model of each multiple linear regression analysis explains 25 % of the mobility domain variability (p < 0.01) and 24 % of the BD domain variability (p < 0.01). Psychiatric symptoms were at least as relevant to quality of life as motor symptoms in PD patients presenting for DBS treatment. The effect of treating these psychiatric symptoms on patients' HRQOL deserves further investigation.

Risk factors associated with outcome in liver retransplantation: multicentric study.

BACKGROUND/AIMS: To externally validate the predictive mathematical model of survival designed by Linhares et al. (2006). METHODOLOGY: This retrospective study was conducted on 217 individuals submitted to liver retransplantation from January 2000 to December 2008 in four European centers. The following variables were obtained on the recipient: age, creatinine, urgency of retransplantation and time between transplantation and retransplantation. The Kaplan-Meier survival curve and ROC curve were used to validate the mathematical model. RESULTS: The present results showed a similar pattern of survival compared to the study of Linhares et al. (2006) concerning the biological variations, when survival curves were compared for each of the four variables analyzed between both samples. When compared, the areas below the ROC curve (aROC) of derivation (0.733) and validation samples (0.593) presented significant difference (p = 0.005), revealing low relationship of sensitivity and specificity between the two curves. Similarity was observed in Kaplan-Meier survival curves. CONCLUSION: This study allowed external validation by the Kaplan-Meier survival curves of the predictive mathematical model of survival in liver retransplantation proposed by Linhares et al. (2006). However, validation through the ROC curve, the aROC, evidenced weak discrimination ability.

Functional capacity after pediatric liver transplantation: a pilot study.

The prospective cross-sectional study investigated the 6MWT performance in pediatric group of liver transplant recipients (6-17 yr, median post-transplantation time of 22 months) and compared to the normal values obtained in healthy children as well as evaluated the reproducibility of the 6MWT. We analyzed the relationship between walked distance and the 6MWw, distance walked × body weight) with the anthropometric, clinical, and pulmonary functions. In post-transplanted group, the average walked distance was significantly shorter compared with control (687 ± 80 m vs. 511 ± 72 m, p < 0.001). The calculated ICC coefficient confirmed the reproducibility among tests. The Pearson correlation revealed that only walked distance in the 6MWT was moderately correlated with tidal volume. Conversely, the 6MWw was significantly correlated with age, weight, height, BMI, FVC, PEF rate, and volume expiratory. According to multiple regression analysis, age, VE and FVC factors explained 80% of the variance in the 6MWw. In conclusion, the pediatric liver transplant recipients' performance in the 6MWT is significantly lower than the values for healthy children of the same age. Notably, the 6MWw may provide relevant information, constituting an additional parameter in the determination of functional capacity.

Role of hormonal levels on hospital mortality for male patients with severe traumatic brain injury.

INTRODUCTION: Changes in hormone blood levels during the acute phase of traumatic brain injury (TBI) have been described in the literature. The objective was to investigate the association among several hormones plasma levels in the acute phase of severe TBI and the hospital mortality rate of male patients. METHODS: The independent association among plasma levels of TSH, LH, FSH, GH, free T4, cortisol, IGF-1 and total testosterone was measured 10 hours and 30 hours after severe TBI and the hospital mortality of 60 consecutive male patients was evaluated. RESULTS: At least one hormonal level abnormality was demonstrated in 3.6-73.1% of patients. The multiple logistic regressions showed a trend for an independent association among hospital mortality and normal or elevated LH levels measured at 10 hours (OR = 3.7, 95% CI = 0.8-16.3, p = 0.08) and 30 hours (OR = 3.9, 95% CI = 0.9-16.7, p = 0.06). Admission with abnormal pupils and a lower Glasgow Coma Score also were independently associated with hospital mortality. CONCLUSION: The hormonal changes are frequent in the acute phase of severe TBI. The hormones plasma levels, excepting the LH, are not highly consistent with the hospital mortality of male patients.

Molecular profiling and patient selection for the multimodal approaches for patients with resectable colorectal liver metastases.

Colorectal cancer represents the third most common cancer and about 20% are diagnosed with synchronous metastatic disease. From a historical point of view, surgery remains the mainstream treatment for resectable colorectal liver metastases (CRLM). Furthermore, disease outcomes are improving due significant advances in systemic treatments and diagnostic methods. However, the optimal timing for neoadjuvant chemotherapy or upfront surgery for CRLM has not yet been established and remains an open question. Thus, patient selection combining image workouts, time of recurrence, positive lymph nodes, and molecular biomarkers can improve the decision-making process. Nevertheless, molecular profiling is rising as a promising field to be incorporated in the multimodal approach and guide patient selection and sequencing of treatment. Tumor biomakers, genetic profiling, and circulating tumor DNA have been used to offer as much personalized treatment as possible, based on the precision oncology concept of tailored care rather than a guideline-based therapy. This review article discusses the role of molecular pathology and biomarkers as prognostic and predictor factors in the diagnosis and treatment of resectable CRLM.

Interleukin-10 is an independent biomarker of severe traumatic brain injury prognosis.

BACKGROUND: Cytokines have been shown to be involved in traumatic brain injury (TBI). We investigated the independent association between serum levels of IL-10 and TNF-α and hospital mortality of patients with severe TBI. METHODS: Serum IL-10 and TNF-α levels were determined after a median period (interquartile range (IQ) 25-75) of 10 h (IQ 5-18) after severe TBI in 93 consecutive patients and in randomly selected patients with mild (n = 18) and moderate (n = 16) TBI. In patients with severe TBI, additional blood samples were analyzed 30 h (IQ 22-37) and 68 h (IQ 55-78) after TBI. Age, gender, computed tomography findings, Glasgow Coma Scale score (GCS) and pupil reactions at admission, associated trauma and hospital mortality were collected. RESULTS: Elevated serum levels of IL-10, but not TNF-α, correlated significantly with GCS severity (R(2) coefficient, p < 0.0001) and were found to be associated with hospital mortality in patients with severe TBI. Elevated IL-10 remained associated with mortality (p = 0.01) in a subset of patients with isolated severe TBI (n = 74). Multiple logistic regression analysis showed that higher IL-10 levels (>90 pg/ml) at 10 or 30 h after TBI were 6 times (odds ratio (OR) 6.2, 95% confidence interval (CI) 1.2-25.1, p = 0.03) and 5 times (OR 5.4, 95% CI 1.2-25.1, p = 0.03), respectively, more frequently associated with hospital mortality than lower levels (<50 pg/ml), independently of age, GCS as well as pupil reactions at admission and associated trauma. CONCLUSIONS: Serum IL-10 levels may be a useful marker for severe TBI prognosis.

Predictors of quality of life in patients with refractory mesial temporal lobe epilepsy.

PURPOSE: The identification of variables associated with health-related quality of life (HRQoL) in patients with mesial temporal lobe epilepsy related to hippocampal sclerosis (MTLE-HS) would improve surgical decision-making and post-operatory follow-up in this group of patients. METHODS: We analyzed the independent association between the Quality of Life in Epilepsy Inventory-31 (QOLIE-31) of 81 consecutive patients with refractory MTLE-HS. The clinical, demographic, radiological and electrophysiological variables were analyzed by multiple linear regression analysis. KEY FINDINGS: Approximately 36% (adjusted R(2)=0.36; R coefficient=0.66) of the QOLIE-31 overall score variance was explained by the history of initial precipitant injury, family history of epilepsy, disease duration, age of epilepsy onset, seizure frequency and presence of psychiatric axis-II diagnosis. The variance of QOLIE-31 sub-scales was: seizure worry=7%; overall QOL=11%; emotional well-being=32%; energy/fatigue=38%; cognitive function=13%; medication effects=7%; social function=13% (R coefficient between 0.30 and 0.65). SIGNIFICANCE: The pre-surgical variables studied had relatively low prediction capacity for the overall QOLIE-31 score and its sub-scales in this set of Brazilian patients with refractory MTLE-HS.

Evaluation of the clinical and inflammatory responses in exclusively NOTES transvaginal cholecystectomy versus laparoscopic routes: an experimental study in swine.

BACKGROUND: The aim of this study was to evaluate the clinical and inflammatory responses to surgical trauma caused by the natural orifice transluminal endoscopic surgery (NOTES) transvaginal endoscopic procedure compared with those of the laparoscopic route. METHODS: Twenty-one female swine were divided into three groups of seven animals and subjected to cholecystectomy using laparoscopic, laparotomic, and exclusively NOTES transvaginal routes. A group of five animals served as a control. The animals were monitored during surgery to evaluate anesthetic/surgical time and the presence of complications, which were evaluated after surgery with respect to roaming time, feeding, and the presence of clinical occurrence Measurements of TNF-α, IL-1ß, IL-6, CRP, IFN-γ were obtained before and after surgery, on the second and seventh postoperative days, and when the animals were killed and necropsied. RESULTS: All procedures were successfully completed as proposed in each group. Perioperative complications consisted of only gallbladder perforation and hepatic bleeding. The anesthetic/surgical time was longer in the NOTES vaginal group (p < 0.001). The postanesthetic recovery time, roaming, nutrition, and clinical evolution were similar in all groups. IL-1ß and IL-6 were undetectable in all groups. Levels of TNF-α, CRP, and IFN-γ were similar among the groups. However, the evolution of the inflammatory process, measured as the difference between the peak dose and the basal dose of IFN-γ, was lower in the NOTES group than in the laparotomy group. In the necropsy findings, only adhesions were found, with no difference among the groups. CONCLUSIONS: The entirely NOTES transvaginal cholecystectomy was feasible and safe. The surgical time was greater for the NOTES vaginal route. The inflammatory response was similar among the groups based on the levels of CRP and IFN-γ. However, the evolution of the inflammatory process seems to have been shorter in the vaginal NOTES group than in the laparotomy group as demonstrated by the difference between the peak and basal doses of IFN-γ.