Cognitive and Cerebrospinal Fluid Alzheimer's Disease-related Biomarker Trajectories in Older Surgical Patients and Matched Nonsurgical Controls.

BACKGROUND: Anesthesia and/or surgery accelerate Alzheimer's disease pathology and cause memory deficits in animal models, yet there is a lack of prospective data comparing cerebrospinal fluid (CSF) Alzheimer's disease-related biomarker and cognitive trajectories in older adults who underwent surgery versus those who have not. Thus, the objective here was to better understand whether anesthesia and/or surgery contribute to cognitive decline or an acceleration of Alzheimer's disease-related pathology in older adults. METHODS: The authors enrolled 140 patients 60 yr or older undergoing major nonneurologic surgery and 51 nonsurgical controls via strata-based matching on age, sex, and years of education. CSF amyloid ß (Aß) 42, tau, and p-tau-181p levels and cognitive function were measured before and after surgery, and at the same time intervals in controls. RESULTS: The groups were well matched on 25 of 31 baseline characteristics. There was no effect of group or interaction of group by time for baseline to 24-hr or 6-week postoperative changes in CSF Aß, tau, or p-tau levels, or tau/Aß or p-tau/Aß ratios (Bonferroni P > 0.05 for all) and no difference between groups in these CSF markers at 1 yr (P > 0.05 for all). Nonsurgical controls did not differ from surgical patients in baseline cognition (mean difference, 0.19 [95% CI, -0.06 to 0.43]; P = 0.132), yet had greater cognitive decline than the surgical patients 1 yr later (ß, -0.31 [95% CI, -0.45 to -0.17]; P < 0.001) even when controlling for baseline differences between groups. However, there was no difference between nonsurgical and surgical groups in 1-yr postoperative cognitive change in models that used imputation or inverse probability weighting for cognitive data to account for loss to follow up. CONCLUSIONS: During a 1-yr time period, as compared to matched nonsurgical controls, the study found no evidence that older patients who underwent anesthesia and noncardiac, nonneurologic surgery had accelerated CSF Alzheimer's disease-related biomarker (tau, p-tau, and Aß) changes or greater cognitive decline.

Use of a Superficial Abdominal Wall Vein in a Gravida Patient for Emergency Vascular Access.

Obtaining vascular access through a superficial vein of the abdominal wall of a gravida patient is an option in an emergency Cesarean surgery when other means fail. Such superficial veins may be mistaken for striae gravidarum on physical exam. A small intravenous (IV) cannula is not ideal but could save valuable time and avoid delaying induction of general anesthesia. Once the airway is secured, a larger bore IV can then be inserted while surgical exposure is undergoing. Analysis of the risks and benefits of inducing general anesthesia with a small gauge IV for a gravida patient should take into consideration risk factors for massive peripartum hemorrhage such as placental disorders (accreta, increta, precreta, abruption, or previa), presence of uterine fibroids, preeclampsia, hemolysis, elevated liver enzymes, low platelet count (HELP syndrome), severe polyhydramnios, history of grand multiparty, and bleeding disorders such as Von Willibrands and hemophilia.

Responding to Cultural Limitations on Patient Autonomy: A Clinical Ethics Case Study.

This paper is a clinical ethics case study which sheds light on several important dilemmas which arise in providing care to patients from cultures with non-individualistic conceptions of autonomy. Medical professionals face a difficult challenge in determining how to respond when families of patients ask that patients not be informed of bad medical news. These requests are often made for cultural reasons, by families seeking to protect patients. In these cases, the right that patients have to their own medical information in order to make autonomous decisions is in tension with the possibility that patients could hold values that require limiting their autonomy with regard to medical information disclosure, often based on the idea that family should take on difficult decision-making as an act of care. We describe one such case, of an 83-year old Russian woman whose husband requested she not be informed of a new cancer diagnosis. The appropriate response to this request was to ask the patient about her values separately, without disclosing any medical information until her values were clear. This patient indicated she wanted the care team to uphold her husband's request. This response makes the importance of determining a patient's values before moving forward with disclosure clear: she would not have wanted to be informed of her cancer. We describe our conversation strategy, which allowed value exploration without disclosure and highlighted that the obligation to respect a patient's autonomy sometimes includes an obligation to allow a patient to choose to limit their own autonomy. This case also highlights that this kind of conversation prioritizes the patient's values rather than the family's or care team's, centering patients in the way that is ethically appropriate.

Electroencephalogram-Based Complexity Measures as Predictors of Post-operative Neurocognitive Dysfunction.

Physiologic signals such as the electroencephalogram (EEG) demonstrate irregular behaviors due to the interaction of multiple control processes operating over different time scales. The complexity of this behavior can be quantified using multi-scale entropy (MSE). High physiologic complexity denotes health, and a loss of complexity can predict adverse outcomes. Since postoperative delirium is particularly hard to predict, we investigated whether the complexity of preoperative and intraoperative frontal EEG signals could predict postoperative delirium and its endophenotype, inattention. To calculate MSE, the sample entropy of EEG recordings was computed at different time scales, then plotted against scale; complexity is the total area under the curve. MSE of frontal EEG recordings was computed in 50 patients ≥ age 60 before and during surgery. Average MSE was higher intra-operatively than pre-operatively (p = 0.0003). However, intraoperative EEG MSE was lower than preoperative MSE at smaller scales, but higher at larger scales (interaction p < 0.001), creating a crossover point where, by definition, preoperative, and intraoperative MSE curves met. Overall, EEG complexity was not associated with delirium or attention. In 42/50 patients with single crossover points, the scale at which the intraoperative and preoperative entropy curves crossed showed an inverse relationship with delirium-severity score change (Spearman ρ = -0.31, p = 0.054). Thus, average EEG complexity increases intra-operatively in older adults, but is scale dependent. The scale at which preoperative and intraoperative complexity is equal (i.e., the crossover point) may predict delirium. Future studies should assess whether the crossover point represents changes in neural control mechanisms that predispose patients to postoperative delirium.

A template for physical resilience research in older adults: Methods of the PRIME-KNEE study.

BACKGROUND: Older adults with similar health conditions often experience widely divergent outcomes following health stressors. Variable recovery after a health stressor may be due in part to differences in biological mechanisms at the molecular, cellular, or system level, that are elicited in response to stressors. We describe the PRIME-KNEE study as an example of ongoing research to validate provocative clinical tests and biomarkers that predict resilience to specific health stressors. METHODS: PRIME-KNEE is an ongoing, prospective cohort study that will enroll 250 adults ≥60 years undergoing total knee arthroplasty. Data are collected at baseline (pre-surgery), during surgery, daily for 7 days after surgery, and at 1, 2, 4, and 6 months post-surgery. Provocative tests include a cognition-motor dual-task walking test, cerebrovascular reactivity assessed by functional near-infrared spectroscopy, peripheral blood mononuclear cell reactivity ex vivo to lipopolysaccharide toxin and influenza vaccine, and heart rate variability during surgery. Cognitive, psychological, and physical performance batteries are collected at baseline to estimate prestressor reserve. Demographics, medications, comorbidities, and stressor characteristics are abstracted from the electronic medical record and via participant interview. Blood-based biomarkers are collected at baseline and postoperative day 1. Repeated measures after surgery include items from a delirium assessment tool and pain scales administered daily by telephone for 7 days and cognitive change index (participant and informant), lower extremity activities of daily living, pain scales, and step counts assessed by Garmin actigraphy at 1, 2, 4, and 6 months after surgery. Statistical models use these measures to characterize resilience phenotypes and evaluate prestressor clinical indicators associated with poststressor resilience. CONCLUSION: If PRIME-KNEE validates feasible clinical tests and biomarkers that predict recovery trajectories in older surgical patients, these tools may inform surgical decision-making, guide pre-habilitation efforts, and elucidate mechanisms underlying resilience. This study design could motivate future geriatric research on resilience.

Chronic Pain Secondary to a Cervical Intramedullary Ependymoma: A Case Report.

Intramedullary spinal cord tumors (IMSCT) are a rare subset of neoplasms classified based on anatomical location. The most common presenting symptom is pain; however, the high prevalence of back pain in the general public secondary to common causes including degenerative disc disease or osteoarthritis, makes diagnosing spinal cord tumors a challenge. We present a case of a 43-year-old male with a cervical intramedullary ependymoma to discuss the clinical presentation, diagnosis, and treatment of these spinal tumors.

Migrating Pericardial Cyst Mimicking a Pleural Pseudotumor.

We discuss an atypical presentation of a pericardial cyst appearing as a mobile lesion extending into and out of the right pulmonary major fissure. With the patient in the supine position, the cyst mimicked a pleural pseudotumor along the right oblique fissure. In the left lateral decubitus position, the cyst migrated to the right cardiophrenic angle and assumed an appearance more characteristic of a pericardial cyst. At surgery, a stalk was discovered attaching the cyst to the pericardium explaining its migrating nature. We conclude that computed tomography scanning in the decubitus position is useful for differentiating a mobile pericardial cyst from a pleural pseudotumor.

Lifestyle interventions for patients with and at risk for type 2 diabetes: a systematic review and meta-analysis.

BACKGROUND: The effect of multifaceted lifestyle interventions on clinically oriented outcomes across a spectrum of metabolic risk factors and abnormal glucose is unclear. PURPOSE: To systematically review the effectiveness of lifestyle interventions on minimizing progression to diabetes in high-risk patients or progression to clinical outcomes (such as cardiovascular disease and death) in patients with type 2 diabetes. DATA SOURCES: 5 electronic databases (1980 to June 2013), reference lists, and gray literature. STUDY SELECTION: Two reviewers independently identified randomized, controlled trials of lifestyle interventions (≥3 months' duration) that included exercise, diet, and at least 1 other component; the comparator was standard care. DATA EXTRACTION: One reviewer extracted and a second verified data. Two reviewers independently assessed methodological quality. DATA SYNTHESIS: Nine randomized, controlled trials with patients who were at risk for diabetes and 11 with patients who had diabetes were included. Seven studies reported that lifestyle interventions decreased the risk for diabetes from the end of intervention up to 10 years after it. In patients with diabetes, 2 randomized, controlled trials (which included pharmacotherapy) reported no improvement in all-cause mortality (risk ratio, 0.75 [95% CI, 0.53 to 1.06]). Composite outcomes for cardiovascular disease were too heterogeneous to pool. One trial reported improvement in microvascular outcomes at 13-year follow-up. LIMITATION: Most trials focused on surrogate measures (such as weight change, blood pressure, and lipids) for which clinical relevance was unclear. CONCLUSION: Comprehensive lifestyle interventions effectively decrease the incidence of type 2 diabetes in high-risk patients. In patients who already have type 2 diabetes, there is no evidence of reduced all-cause mortality and insufficient evidence to suggest benefit on cardiovascular and microvascular outcomes. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality.

RAB-5- and RAB-11-dependent vesicle-trafficking pathways are required for plasma membrane repair after attack by bacterial pore-forming toxin.

Pore-forming toxins (PFTs) secreted by pathogenic bacteria are the most common bacterial protein toxins and are important virulence factors for infection. PFTs punch holes in host cell plasma membranes, and although cells can counteract the resulting membrane damage, the underlying mechanisms at play remain unclear. Using Caenorhabditis elegans as a model, we demonstrate in vivo and in an intact epithelium that intestinal cells respond to PFTs by increasing levels of endocytosis, dependent upon RAB-5 and RAB-11, which are master regulators of endocytic and exocytic events. Furthermore, we find that RAB-5 and RAB-11 are required for protection against PFT and to restore integrity to the plasma membrane. One physical mechanism involved is the RAB-11-dependent expulsion of microvilli from the apical side of the intestinal epithelial cells. Specific vesicle-trafficking pathways thus protect cells against an attack by PFTs on plasma membrane integrity, via altered plasma membrane dynamics.