Reelin Plasma Levels Identify Cognitive Decline in Alcohol Use Disorder Patients During Early Abstinence: The Influence of APOE4 Expression.

BACKGROUND: Apolipoprotein E (APOE)-4 isoform, reelin, and clusterin share very-low-density liporeceptor and apolipoprotein E receptor 2 receptors and are related to cognition in neuropsychiatric disorders. These proteins are expressed in plasma and brain, but studies involving plasma expression and cognition are scarce. METHODS: We studied the peripheral expression (plasma and peripheral blood mononuclear cells) of these proteins in 24 middle-aged patients with alcohol use disorder (AUD) diagnosed at 4 to 12 weeks of abstinence (t = 0) and 34 controls. Cognition was assessed using the Test of Detection of Cognitive Impairment in Alcoholism. In a follow-up study (t = 1), we measured reelin levels and evaluated cognitive improvement at 6 months of abstinence. RESULTS: APOE4 isoform was present in 37.5% and 58.8% of patients and controls, respectively, reaching similar plasma levels in ε4 carriers regardless of whether they were patients with AUD or controls. Plasma reelin and clusterin were higher in the AUD group, and reelin levels peaked in patients expressing APOE4 (P < .05, η2 = 0.09), who showed reduced very-low-density liporeceptor and apolipoprotein E receptor 2 expression in peripheral blood mononuclear cells. APOE4 had a negative effect on memory/learning mainly in the AUD group (P < .01, η2 = 0.15). Multivariate logistic regression analyses identified plasma reelin as a good indicator of AUD cognitive impairment at t = 0. At t = 1, patients with AUD showed lower reelin levels vs controls along with some cognitive improvement. CONCLUSIONS: Reelin plasma levels are elevated during early abstinence in patients with AUD who express the APOE4 isoform, identifying cognitive deterioration to a great extent, and it may participate as a homeostatic signal for cognitive recovery in the long term.

Outcomes of cervical arthroplasty versus anterior cervical arthrodesis: a systematic review and meta-analysis of randomized clinical trials with a minimum follow-up of 7-year.

PURPOSE: Compare the outcomes of randomized clinical trials of cervical disc arthroplasty (CDA) versus anterior cervical discectomy with fusion (ACDF), with a minimum follow-up of 7 years. METHODS: Nine randomized clinical trials were selected. The clinical, radiological, and surgical outcomes were analyzed, including functional and pain scores, range of motion, adjacent segment degeneration, adverse events, and need for reoperation. RESULTS: 2664 patients were included in the study. Pooled results indicated that the CDA group had a significantly higher overall success rate (p < 0.001), a higher improvement in the neck disability index (NDI) (p = 0.002), less VAS arm pain (p = 0.01), and better health questionnaire SF-36 physical component (p = 0.01) than ACDF group. Likewise, the pooled results indicated a significantly higher motion rate (p < 0.001), less adjacent syndrome (p < 0.05), and a lower percentage of reoperation (p < 0.001) in the CDA group. There were no significant differences between the CDA and ACDF groups in the neck pain scale (p = 0.11), the health questionnaire SF-36 mental component (p = 0.10), and in adverse events (p = 0.42). CONCLUSION: In long-term follow-up, CDA showed a better overall success rate, better improvement in NDI, less VAS arm pain, better health questionnaire SF-36 physical component, a higher motion rate, less adjacent syndrome, and less reoperation rate than ACDF. No significant differences were found in the neck pain scale, SF-36 mental component, and in adverse events.

Upregulation of TLR4/MyD88 pathway in alcohol-induced Wernicke's encephalopathy: Findings in preclinical models and in a postmortem human case.

Wernicke's encephalopathy (WE) is a neurologic disease caused by vitamin B1 or thiamine deficiency (TD), being the alcohol use disorder its main risk factor. WE patients present limiting motor, cognitive, and emotional alterations related to a selective cerebral vulnerability. Neuroinflammation has been proposed to be one of the phenomena that contribute to brain damage. Our previous studies provide evidence for the involvement of the innate immune receptor Toll-like (TLR)4 in the inflammatory response induced in the frontal cortex and cerebellum in TD animal models (animals fed with TD diet [TDD] and receiving pyrithiamine). Nevertheless, the effects of the combination of chronic alcohol consumption and TD on TLR4 and their specific contribution to the pathogenesis of WE are currently unknown. In addition, no studies on TLR4 have been conducted on WE patients since brains from these patients are difficult to achieve. Here, we used rat models of chronic alcohol (CA; 9 months of forced consumption of 20% (w/v) alcohol), TD hit (TDD + daily 0.25 mg/kg i.p. pyrithiamine during 12 days), or combined treatment (CA + TDD) to check the activation of the proinflammatory TLR4/MyD88 pathway and related markers in the frontal cortex and the cerebellum. In addition, we characterized for the first time the TLR4 and its coreceptor MyD88 signature, along with other markers of this proinflammatory signaling such as phospo-NFκB p65 and IκBα, in the postmortem human frontal cortex and cerebellum (gray and white matter) of an alcohol-induced WE patient, comparing it with negative (no disease) and positive (aged brain with Alzheimer's disease) control subjects for neuroinflammation. We found an increase in the cortical TLR4 and its adaptor molecule MyD88, together with an upregulation of the proinflammatory signaling molecules p-NF-ĸB and IĸBα in the CA + TDD animal model. In the patient diagnosed with alcohol-induced WE, we observed cortical and cerebellar upregulation of the TLR4/MyD88 pathway. Hence, our findings provide evidence, both in the animal model and the human postmortem brain, of the upregulation of the TLR4/MyD88 proinflammatory pathway in alcohol consumption-related WE.

Is routine blood typing and screening necessary for degenerative cervical spine surgery patients in specialty surgical hospitals?

BACKGROUND: Blood loss warranting transfusion is a relatively rare requirement for degenerative cervical spine surgery. Despite this rarity, pretransfusion testing (blood typing, screening, and cross-matching) has become routine in most parts of the world. We sought to determine if such routine testing is necessary for patients who undergo degenerative cervical spine surgery patients in specialty surgical hospitals by (1) measuring the current rate of intraoperative transfusions in degenerative cervical spine surgery and (2) identifying risk factors for transfusions. STUDY METHODS: Retrospective review was performed on patients who underwent degenerative cervical spine surgery in two institutions. Demographic and baseline clinical and laboratory data were collected and analyzed to identify predictors of transfusion. Bivariate and multivariate logistic regression analysis was performed to identify perioperative transfusion risk factors. RESULTS: Overall transfusion rate was 1.9% (7/372), with no emergent transfusions. Decreases between preoperative and postoperative hemoglobin and hematocrit were 1.4 (SD 1.1) g/dL and 7.2 (SD 4.1) %, respectively. Multivariate logistic regression identified preoperative Hgb lower than 12 gr/dl (OR 27.62; 95% CI 4.31-176.96; p < 0.001) as significant independent transfusion risk factor. The receiver operating characteristic (ROC) curve for the model showed a very good discriminatory power with an area under the curve of 0.91. DISCUSSION: Our study suggests that pretransfusion testing for all patients undergoing degenerative cervical spine surgery is unnecessary. We recommend that only patients with preoperative Hgb lower than 12 gr/dl would routinely need pretransfusion testing.

Subcutaneous Radiographic Measurement: A Marker to Evaluate Surgical Site Infection Risk in Elderly Hip Fracture Patients.

Objectives: Obesity is a documented comorbidity that is prevalent in the elderly population and a known predictor for surgical site infection (SSI). Body mass index is a convenient method to classify obesity, but it fails to account for fat distribution. The objective of our study was to evaluate the association between surgical site infection and a subcutaneous radiographic measurement (SRM) in elderly hip fracture patients. Materials and Methods: A retrospective case-control study was conducted to compare SRMs at the hip in patients diagnosed with surgical site infection after hip fracture surgery with patients that were not diagnosed with surgical site infection. Each case was matched to two controls. An SRM was defined as the distance from the tip of the greater trochanter to the skin following a perpendicular line to the femoral diaphysis in anteroposterior hip radiographs. Clinical diagnosis of acute surgical site infection was based on Tsukayama criteria. Results: Patients with an SRM greater than 6.27cm had a 7-fold increase in the odds of surgical site infection (OR=7.42, 95% Confidence Interval (CI)=3.01-18.28, p<0.001) compared to those with smaller measurements. The odds ratio (OR) for infection of patients with an ASA score of 3 was 15.82(95% CI=5.11-48.9, p-value<0.001) A statistically significant difference between cases and controls was also found when SRM at the hip was analyzed as a continuous variable. Patients with an infection had a 2.24cm (95% CI=1.59 - 2.90; p<0.001) greater mean SRM. Conclusion: Results of our study suggest an association between the SRM at the hip and the risk of SSI in elderly patients with surgically treated hip fractures. SRM may be a helpful tool for evaluating the risk of SSI in elderly hip fracture patients.