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Objective: To determine the relationship between affective measures and cognition before and after non-cardiac surgery in older adults., Methods: Observational prospective cohort study in 103 surgical patients age ≥ 60 years old . All participants underwent cognitive testing, Center for Epidemiologic Studies-Depression, and State Anxiety Inventory screening before and 6 weeks after surgery. Cognitive test scores were combined by factor analysis into 4 cognitive domains, whose mean was defined as the continuous cognitive index (CCI). Postoperative global cognitive change was defined by CCI change from before to after surgery, with negative CCI change indicating worsened postoperative global cognition and vice versa., Results: Lower global cognition before surgery was associated with greater baseline depression severity (Spearman's r = -0.30, p = 0.002) and baseline anxiety severity (Spearman's r = -0.25, p = 0.010), and these associations were similar following surgery (r = -0.36, p < 0.001; r = -0.26, p = 0.008, respectively). Neither baseline depression or anxiety severity, nor postoperative changes in depression or anxiety severity, were associated with pre- to postoperative global cognitive change., Conclusions: Greater depression and anxiety severity were each associated with poorer cognitive performance both before and after surgery in older adults. Yet, neither baseline depression or anxiety symptoms, nor postoperative change in these symptoms, were associated with postoperative cognitive change.

Arachidonic acid (AA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) derived lipids play key roles in initiating and resolving inflammation. Neuro-inflammation is thought to play a causal role in perioperative neurocognitive disorders, yet the role of these lipids in the human central nervous system in such disorders is unclear. Here we used liquid chromatography-mass spectrometry to quantify AA, DHA, and EPA derived lipid levels in non-centrifuged cerebrospinal fluid (CSF), centrifuged CSF pellets, and centrifuged CSF supernatants of older adults obtained before, 24 h and 6 weeks after surgery. GAGE analysis was used to determine AA, DHA and EPA metabolite pathway changes over time. Lipid mediators derived from AA, DHA and EPA were detected in all sample types. Postoperative lipid mediator changes were not significant in non-centrifuged CSF (p > 0.05 for all three pathways). The AA metabolite pathway showed significant changes in centrifuged CSF pellets and supernatants from before to 24 h after surgery (p = 0.0000247, p = 0.0155 respectively), from before to 6 weeks after surgery (p = 0.0000497, p = 0.0155, respectively), and from 24 h to 6 weeks after surgery (p = 0.0000499, p = 0.00363, respectively). These findings indicate that AA, DHA, and EPA derived lipids are detectable in human CSF, and the AA metabolite pathway shows postoperative changes in centrifuged CSF pellets and supernatants.

Background and Objectives: Heparin-induced thrombocytopenia (HIT) is an antibody-mediated condition that leads to thrombocytopenia and possible thrombosis. Patients with HIT who require cardiac surgery pose a challenge as high doses of heparin or heparin alternatives are required to permit cardiopulmonary bypass (CPB). Intraoperative therapeutic plasma exchange (TPE) is a valuable adjunct in the management of antibody-mediated syndromes including HIT. The clinical impact of TPE on thromboembolic events, bleeding and mortality after heparin re-exposure is not well established. We hypothesized that TPE with heparin re-exposure will not lead to HIT-related thromboembolic events, bleeding or increased mortality after cardiac surgery with CPB., Materials and Methods: We reviewed 330 patients who received perioperative TPE between September 2012 and September 2017., Results: Twenty four patients received TPE for HIT before anticipated heparin use for CPB. Most patients were males (79%) scheduled for advanced heart failure therapies. Three patients (12·5%) died within 30 days after surgery but none of the deaths were considered HIT-related. Thromboembolic events (TE) occurred in 3 patients within 7 days of surgery; of those, two were possibly HIT-related., Conclusion: Therapeutic plasma exchange with heparin re-exposure was not strongly associated with HIT-related thrombosis/death after cardiac surgery with CPB., (© 2020 International Society of Blood Transfusion.)

Background: Postoperative cognitive dysfunction (POCD), a syndrome of cognitive deficits occurring 1-12 months after surgery primarily in older patients, is associated with poor postoperative outcomes. POCD is hypothesized to result from neuroinflammation; however, the pathways involved remain unclear. Unbiased proteomic analyses have been used to identify neuroinflammatory pathways in multiple neurologic diseases and syndromes but have not yet been applied to POCD., Objective: To utilize unbiased mass spectrometry-based proteomics to identify potential neuroinflammatory pathways underlying POCD., Methods: Unbiased LC-MS/MS proteomics was performed on immunodepleted cerebrospinal fluid (CSF) samples obtained before, 24 hours after, and 6 weeks after major non-cardiac surgery in older adults who did (n = 8) or did not develop POCD (n = 6). Linear mixed models were used to select peptides and proteins with intensity differences for pathway analysis., Results: Mass spectrometry quantified 8,258 peptides from 1,222 proteins in > 50%of patient samples at all three time points. Twelve peptides from 11 proteins showed differences in expression over time between patients with versus withoutPOCD (q < 0.05), including proteins previously implicated in neurodegenerative disease pathophysiology. Additionally, 283 peptides from 182 proteins were identified with trend-level differences (q < 0.25) in expression over time between these groups. Among these, pathway analysis revealed that 50 were from 17 proteins mapping to complement and coagulation pathways (q = 2.44*10-13)., Conclusion: These data demonstrate the feasibility of performing unbiased mass spectrometry on perioperative CSF samples to identify pathways associated with POCD. Additionally, they provide hypothesis-generating evidence for CSF complement and coagulation pathway changes in patients with POCD.

Background: APOE4 has been hypothesized to increase Alzheimer's disease risk by increasing neuroinflammation, though the specific neuroinflammatory pathways involved are unclear., Objective: Characterize cerebrospinal fluid (CSF) proteomic changes related to APOE4 copy number., Methods: We analyzed targeted proteomic data from ADNI CSF samples using a linear regression model adjusting for age, sex, and APOE4 copy number, and additional linear models also adjusting for AD clinical status or for CSF Aβ, tau, or p-tau levels. False discovery rate was used to correct for multiple comparisons correction., Results: Increasing APOE4 copy number was associated with a significant decrease in a CRP peptide level across all five models (q < 0.05 for each), and with significant increases in ALDOA, CH3L1 (YKL-40), and FABPH peptide levels (q < 0.05 for each) except when controlling for AD clinical status or neurodegeneration biomarkers (i.e., CSF tau or p-tau). In all models except the one controlling for CSF Aβ levels, though not statistically significant, there was a consistent inverse direction of association between APOE4 copy number and the levels of all 24 peptides from all 8 different complement proteins measured. The odds of this happening by chance for 24 unrelated peptides would be less than 1 in 16 million., Conclusion: Increasing APOE4 copy number was associated with decreased CSF CRP levels across all models, and increased CSF ALDOA, CH3L1, and FABH levels when controlling for CSF Aβ levels. Increased APOE4 copy number may also be associated with decreased CSF complement pathway protein levels, a hypothesis for investigation in future studies.

Reported incidence of postoperative opioid-induced respiratory depression (OIRD) ranges from 0.5-41% and is not reliably predicted by traditional risk factors. This study tests a new methodology to investigate ventilatory chemosensitivity as a new potential risk factor and explore OIRD distribution across sleep and wakefulness. Preoperative patient ventilatory chemosensitivity was quantified by hypercapnic ventilatory responses with (HCVR REMI , effect site concentration 0.7 or 2.0 ng/mL) and without (HCVR BL ) remifentanil during hyperoxia and hypoxia. Postoperative opioid consumption was recorded during hospital stays. OIRD frequency was the primary outcome of the study, detected as incidences of respiratory rate < 60% of baseline, minute ventilation < 60% of predicted value, pulse oximetry [Formula: see text] < 90% (breathing room air) or 92% (supplemental O 2 ), transcutaneous Pco 2 > 50 mmHg, and central and obstructive apnea/hypopnea. Sleep stages were recorded until the first postoperative morning to determine the OIRD sleep distribution as the secondary outcome. The methodology was feasible in implementation and posed no obstacles to standard care. In the nine patients studied (2 females, mean age 65 ± 7.5 yr), remifentanil depressed HCVR to a highly variable degree. High OIRD frequency was generally observed with lower HCVR REMI . OIRD predominantly occurred during light sleep. This study supports ventilatory chemosensitivity as an important predictor of OIRD, lending a new perspective to classify risk for OIRD and detailing a methodology in which to pursue this investigation for future studies. NEW & NOTEWORTHY Our new and noteworthy methodology allows for exploration of preoperative ventilatory chemosensitivity, measured as the hypercapnic ventilatory response (HCVR), as a risk factor for postoperative opioid-induced respiratory depression (OIRD). This feasible and reliable methodology produced preliminary data that showed highly variable depression of HCVR by remifentanil, predominance of OIRD during light sleep, and potentially negative correlation between OIRD frequency generally and HCVR measurements when measured in the presence of remifentanil. Although the results are preliminary in nature, this novel methodology may guide future studies that can one day lead to effective clinical screening tools.

Acute kidney injury (AKI) and primary graft dysfunction (PGD) are serious complications after heart transplantation (HT). The relationship between AKI and PGD is poorly understood. We sought to examine the incidence of AKI and identify risk factors associated with AKI. We hypothesized that PGD is one of the risk factors independently associated with post-HT AKI. We gathered data for all adult patients who underwent HT between 2009 and 2014. AKI was defined by the KDIGO criteria. PGD was categorized using ISHLT criteria. We assessed univariable and multivariable logistic regression to identify risk factors independently associated with post-HT AKI. Out of 316 patients, postoperative AKI occurred in 273 (86%) patients: 188 (68%) stage I, 44 (16%) stage II, and 41 (15%) stage III. Stage II/III AKI was associated with increased risk of mortality at 1 year. There was significant association between severe PGD and stage II/III AKI (P = 0.001, OR 3.63, 95% CI: 1.69-7.94). Other clinical factors significantly associated with stage II/III AKI included longer donor brain death duration and lower recipient baseline creatinine. We found that stage II/III AKI is common and independently associated with severe PGD. Another potentially modifiable risk factor is donor brain death duration., (© 2020 Steunstichting ESOT. Published by John Wiley & Sons Ltd.)

Objective: Lumbar punctures (LPs) are important for obtaining CSF in neurology studies but are associated with adverse events and feared by many patients. We determined adverse event rates and pain scores in patients prospectively enrolled in two cohort studies who underwent LPs using a standardized protocol and 25 g needle., Methods: Eight hundred and nine LPs performed in 262 patients age ≥ 60 years in the MADCO-PC and INTUIT studies were analyzed. Medical records were monitored for LP-related adverse events, and patients were queried about subjective complaints. We analyzed adverse event rates, including headaches and pain scores., Results: There were 22 adverse events among 809 LPs performed, a rate of 2.72% (95% CI 1.71-4.09%). Patient hospital stay did not increase due to adverse events. Four patients (0.49%) developed a post-lumbar puncture headache (PLPH). Twelve patients (1.48%) developed nausea, vasovagal responses, or headaches that did not meet PLPH criteria. Six patients (0.74%) reported lower back pain at the LP site not associated with muscular weakness or paresthesia. The median pain score was 1 [0, 3]; the mode was 0 out of 10., Conclusions: The LP protocol described herein may reduce adverse event rates and improve patient comfort in future studies.

Chronic pain after lung transplantation is a significant concern, in particular given the heterogeneity of the patient population and the challenges of achieving adequate pain control amid concerns related to complex immunosuppressant regimens and the possibility of respiratory depression. We undertook a patient-reported outcomes (PRO) survey administered via our electronic health care portal to examine the postoperative incisional pain prevalence in a cohort of lung transplant recipients at a single, high-volume center where bilateral thoracosternotomy is the preferred surgical approach. The Patient Reported Outcomes Measurement Information System (PROMIS) Global Health and Pain Intensity short forms were sent to a total of 173 lung transplant recipients who were more than 2 months postsurgery at the time of the study. A total of 64 patients responded to both PROMIS surveys (response rate 38%). In the cohort of survey respondents, we observed a chronic pain incidence of 58% after lung transplantation (median pain score 1/10) and an overall good quality of life score (median score 4/5); however, only 9.4% reported moderate-severe pain (pain score ≥5/10). Survey nonrespondents had higher rates of pretransplant opioid and psychiatric medication use compared with respondents. In this study, we demonstrated the feasibility of using an electronic PRO survey for assessing postoperative pain outcomes after lung transplantation. However, measuring pain outcomes using this type of tool highlights issues of response rate and potential selection bias. Larger studies are needed to adequately assess the risk and predictors of chronic pain after lung transplantation and its impact on quality of life.

Background: Perioperative neurocognitive disorders (PND) are common complications in older adults associated with increased 1-year mortality and long-term cognitive decline. One risk factor for worsened long-term postoperative cognitive trajectory is the Alzheimer's disease (AD) genetic risk factor APOE4. APOE4 is thought to elevate AD risk partly by increasing neuroinflammation, which is also a theorized mechanism for PND. Yet, it is unclear whether modulating apoE4 protein signaling in older surgical patients would reduce PND risk or severity., Objective: MARBLE is a randomized, blinded, placebo-controlled phase II sequential dose escalation trial designed to evaluate perioperative administration of an apoE mimetic peptide drug, CN-105, in older adults (age≥60 years). The primary aim is evaluating the safety of CN-105 administration, as measured by adverse event rates in CN-105 versus placebo-treated patients. Secondary aims include assessing perioperative CN-105 administration feasibility and its efficacy for reducing postoperative neuroinflammation and PND severity., Methods: 201 patients undergoing non-cardiac, non-neurological surgery will be randomized to control or CN-105 treatment groups and receive placebo or drug before and every six hours after surgery, for up to three days after surgery. Chart reviews, pre- and postoperative cognitive testing, delirium screening, and blood and CSF analyses will be performed to examine effects of CN-105 on perioperative adverse event rates, cognition, and neuroinflammation. Trial results will be disseminated by presentations at conferences and peer-reviewed publications., Conclusion: MARBLE is a transdisciplinary study designed to measure CN-105 safety and efficacy for preventing PND in older adults and to provide insight into the pathogenesis of these geriatric syndromes.

Animal models suggest postoperative cognitive dysfunction may be caused by brain monocyte influx. To study this in humans, we developed a flow cytometry panel to profile cerebrospinal fluid (CSF) samples collected before and after major noncardiac surgery in 5 patients ≥60 years of age who developed postoperative cognitive dysfunction and 5 matched controls who did not. We detected 12,654 ± 4895 cells/10 mL of CSF sample (mean ± SD). Patients who developed postoperative cognitive dysfunction showed an increased CSF monocyte/lymphocyte ratio and monocyte chemoattractant protein 1 receptor downregulation on CSF monocytes 24 hours after surgery. These pilot data demonstrate that CSF flow cytometry can be used to study mechanisms of postoperative neurocognitive dysfunction.

Objective: To determine if the perioperative administration of valproic acid reduces the incidence of chronic pain three months after amputation or revision surgery., Design: Multicenter, randomized, double-blind, placebo-controlled trial., Setting: Academic, military, and veteran medical centers., Subjects: One hundred twenty-eight patients undergoing amputation or amputation revision surgery at Duke University Hospital, Walter Reed National Military Medical Center, or the Durham Veterans Affairs Medical Center for either medical disease or trauma., Methods: Patients were randomized to placebo or valproic acid for the duration of hospitalization and treated with multimodal analgesic care, including regional anesthetic blockade. Primary outcome was the proportion of patients with chronic pain at three months (average numeric pain score intensity of 3/10 or greater). Secondary outcomes included functional trajectories (assessed with the Brief Pain Inventory short form and the Defense and Veterans Pain Rating Scale)., Results: The overall rate of chronic pain was 68.2% in the 107 patients who completed the end point assessment. There was no significant effect of perioperative valproic acid administration, with a rate of 65.45% (N = 36) in the treatment group and a rate of 71.15% (N = 37) in the placebo group. Overall, pain scores decreased from baseline to follow-up (median = -2 on the numeric pain scale). Patients additionally experienced improvements in self-perceived function., Conclusions: The rate of chronic pain after amputation surgery is not significantly improved with the perioperative administration of valproic acid. In this cohort treated with multimodal perioperative analgesia and regional anesthetic blockade, we observed improvements in both pain severity and function., (© 2019 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Minimum alveolar concentration (MAC) and MAC-awake decrease with age. We hypothesised that, in clinical practice, (i) end-tidal MAC fraction in older patients would decline by less than the predicted age-dependent MAC decrease (i.e. older patients would receive relatively excessive anaesthetic concentrations), and (ii) bispectral index (BIS) values would therefore be lower in older patients., Methods: We examined the relationship between end-tidal MAC fraction, BIS values, and age in 4699 patients > 30 yr in age at a single centre using unadjusted local regression (locally estimated scatterplot smoothing), Spearman's correlation, stratification, and robust univariable and multivariable linear regression., Results: The end-tidal MAC fraction in older patients declined by 3.01% per decade (95% confidence interval [CI]: 2.56-3.45; P<0.001), less than the 6.47% MAC decrease per decade that we found in a meta-regression analysis of published studies of age-dependent changes in MAC (P<0.001), and less than the age-dependent decrease in MAC-awake. The BIS values correlated positively with age (ρ=0.15; 95% CI: 0.12-0.17; P<0.001), and inversely with the age-adjusted end-tidal MAC (aaMAC) fraction (ρ= -0.13; 95% CI: -0.16, -0.11; P<0.001)., Conclusions: The age-dependent decline in end-tidal MAC fraction delivered in clinical practice at our institution was less than the age-dependent percentage decrease in MAC and MAC-awake determined from published studies. Despite receiving higher aaMAC fractions, older patients paradoxically showed higher BIS values. This most likely suggests that the BIS algorithm is inaccurate in older adults., (Copyright © 2019 British Journal of Anaesthesia. Published by Elsevier Ltd. All rights reserved.)

Background: Cognitive decline after cardiac surgery occurs frequently and persists in a significant proportion of patients. Preclinical studies and human trials suggest that intravenous lidocaine may confer protection in the setting of neurologic injury. It was hypothesized that lidocaine administration would reduce cognitive decline after cardiac surgery compared to placebo., Methods: After institutional review board approval, 478 patients undergoing cardiac surgery were enrolled into this multicenter, prospective, randomized, double-blinded, placebo-controlled, parallel group trial. Subjects were randomized to lidocaine 1 mg/kg bolus after the induction of anesthesia followed by a continuous infusion (48 μg · kg · min for the first hour, 24 μg · kg · min for the second hour, and 10 μg · kg · min for the next 46 h) or saline with identical volume and rate changes to preserve blinding. Cognitive function was assessed preoperatively and at 6 weeks and 1 yr postoperatively using a standard neurocognitive test battery. The primary outcome was change in cognitive function between baseline and 6 weeks postoperatively, adjusting for age, years of education, baseline cognition, race, and procedure type., Results: Among the 420 allocated subjects who returned for 6-week follow-up (lidocaine: N = 211; placebo: N = 209), there was no difference in the continuous cognitive score change (adjusted mean difference [95% CI], 0.02 (-0.05, 0.08); P = 0.626). Cognitive deficit (greater than 1 SD decline in at least one cognitive domain) at 6 weeks occurred in 41% (87 of 211) in the lidocaine group versus 40% (83 of 209) in the placebo group (adjusted odds ratio [95% CI], 0.94 [0.63, 1.41]; P = 0.766). There were no differences in any quality of life outcomes between treatment groups. At the 1-yr follow-up, there continued to be no difference in cognitive score change, cognitive deficit, or quality of life., Conclusions: Intravenous lidocaine administered during and after cardiac surgery did not reduce postoperative cognitive decline at 6 weeks.

Background/objectives: Every year, up to 40% of the more than 16 million older Americans who undergo anesthesia/surgery develop postoperative cognitive dysfunction (POCD) or delirium. Each of these distinct syndromes is associated with decreased quality of life, increased mortality, and a possible increased risk of Alzheimer's disease. One pathologic process hypothesized to underlie both delirium and POCD is neuroinflammation. The INTUIT study described here will determine the extent to which postoperative increases in cerebrospinal fluid (CSF) monocyte chemoattractant protein 1 (MCP-1) levels and monocyte numbers are associated with delirium and/or POCD and their underlying brain connectivity changes., Design: Observational prospective cohort., Setting: Duke University Medical Center, Duke Regional Hospital, and Duke Raleigh Hospital., Participants: Patients 60 years of age or older (N = 200) undergoing noncardiac/nonneurologic surgery., Measurements: Participants will undergo cognitive testing before, 6 weeks, and 1 year after surgery. Delirium screening will be performed on postoperative days 1 to 5. Blood and CSF samples are obtained before surgery, and 24 hours, 6 weeks, and 1 year after surgery. CSF MCP-1 levels are measured by enzyme-linked immunosorbent assay, and CSF monocytes are assessed by flow cytometry. Half the patients will also undergo pre- and postoperative functional magnetic resonance imaging scans. 32-channel intraoperative electroencephalogram (EEG) recordings will be performed to identify intraoperative EEG correlates of neuroinflammation and/or postoperative cognitive resilience. Eighty patients will also undergo home sleep apnea testing to determine the relationships between sleep apnea severity, neuroinflammation, and impaired postoperative cognition. Additional assessments will help evaluate relationships between delirium, POCD, and other geriatric syndromes., Conclusion: INTUIT will use a transdisciplinary approach to study the role of neuroinflammation in postoperative delirium and cognitive dysfunction and their associated functional brain connectivity changes, and it may identify novel targets for treating and/or preventing delirium and POCD and their sequelae. J Am Geriatr Soc 67:794-798, 2019., (© 2019 The American Geriatrics Society.)

Objectives: Acute kidney injury (AKI) is a common complication of cardiac surgery, and early detection is difficult. This study was performed to determine the sensitivity, specificity, positive predictive value, negative predictive value, and statistical performance of renal angina (RA) as an early predictor of AKI in an adult cardiac surgical patient population., Design: Retrospective, nonrandomized, observational study., Setting: A single, university-affiliated, quaternary medical center., Participants: The study comprised 324 consecutive patients undergoing coronary artery bypass grafting or cardiac valvular surgery from February 1 through July 30, 2014., Interventions: None., Measurements and Main Results: One hundred-seven patients at moderate or high risk of developing postoperative renal injury were identified, 82 of whom met criteria for RA. The occurrence of RA was found to have an 80.9% sensitivity and 30.8% specificity for the prediction of AKI using Acute Kidney Injury Network criteria and 89.3% sensitivity and 27.8% specificity when paired with the Risk, Injury, Failure, Loss, End Stage Renal Disease criteria. A receiver operating characteristic area under the curve analysis revealed a nonsignificant predictive ability of 55.8% (95% confidence interval 0.47-0.65) when RA was paired with Acute Kidney Injury Network criteria; however, the receiver operating characteristic area under the curve was significant when paired with Risk, Injury, Failure, Loss, End Stage Renal Disease criteria, with a predictive ability of 0.586 (0.509-0.662)., Conclusions: RA is a sensitive, but nonspecific, predictor of postcardiac surgery AKI, with clinical utility most suited as a screening tool., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Background: Postoperative atrial fibrillation (POAF) frequently complicates cardiac surgery and is associated with worse outcomes. The cardiac autonomic nervous system is implicated in the pathogenesis of POAF., Objective: The purpose of this study was to determine the efficacy and safety of selective cardiac autonomic modulation in preventing POAF., Methods: In this randomized, double-blind, placebo-controlled trial, adults undergoing cardiac surgery were randomized 1:1 to intraoperative injection of 250 units onabotulinumtoxinA (botulinum toxin type A [BoNTA]) or placebo into epicardial fat pads. The study was powered to detect a 40% reduction in relative risk of POAF. Time to first episode of in-hospital POAF was the primary outcome, evaluated in patients receiving injection. Additionally, incidence of POAF, length of stay (LOS), and adverse events were examined., Results: The trial assigned 145 patients to injection, 15 of whom were dropped before treatment, leaving 130 patients for analysis. Overall, 36.5% (23/63) of BoNTA-treated patients developed POAF compared with 47.8% (32/67) of placebo-treated patients. The time-to-event analysis revealed a hazard ratio of 0.69 (95% confidence interval 0.41-1.19; P = .18) for the BoNTA vs placebo arm. There were no significant differences in postoperative hospital LOS (median [interquartile range] 6.0 [3.4] vs 6.2 [3.7] days; P = .51) or adverse events prolonging LOS (27/63 [42.9%] vs 30/67 [44.8%]; P = .83) in patients receiving BoNTA vs placebo., Conclusion: Epicardial injection of onabotulinumtoxinA was without discernible adverse effects, but we failed to detect a significant difference in risk of POAF. Future large-scale studies of epicardial onabotulinumtoxinA injection as a potential POAF prevention strategy should be designed to study smaller, but clinically meaningful, treatment effects., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: There are few prospective studies providing comprehensive assessment of risk factors for acute and persistent pain after breast surgery. This prospective observational study assessed patient-related, perioperative, and genetic risk factors for severe acute pain and persistent pain following breast cancer surgery., Methods: Women presenting for elective breast cancer surgery completed State Trait Anxiety Inventory, Beck Depression Inventory, and Pain Catastrophizing Scale questionnaires preoperatively. Diffuse noxious inhibitory control and mechanical temporal summation were assessed. A blood sample was obtained for genetic analysis. Analgesic consumption and pain scores were collected in the post-anesthesia care unit, and at 24 and 72 hours. Patients were contacted at 1, 3, 6, and 12 months to assess persistent pain. Primary outcome was maximum acute pain score in first 72 hours and secondary outcome was persistent pain., Results: One hundred twenty-four patients were included in analysis. Increased duration of surgery, surgeon, and higher pain catastrophizing scores were associated with increased severity of acute pain, while preoperative radiotherapy was associated with reduced severity. Persistent pain was reported by 57.3% of patients. Postdischarge chemotherapy (OR 2.52, 95% CI 1.13 to 5.82), postdischarge radiation (OR 3.39, 95% CI 1.24 to 10.41), severe acute pain (OR 5.39, 95% CI 2.03 to 15.54), and moderate acute pain (OR 5.31, 95% CI 1.99 to 15.30) were associated with increased likelihood of persistent pain., Conclusions: Increased duration of surgery, higher pain catastrophizing score, and surgeon were associated with increased severity of acute pain. Preoperative radiation was associated with lower acute pain scores. Postsurgery radiation, chemotherapy, and severity of acute pain were associated with increased likelihood of persistent pain., Trial Registration: NCT03307525., (© American Society of Regional Anesthesia & Pain Medicine 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Patients with chronic overlapping pain conditions have decreased levels of catechol-O-methyltransferase (COMT), an enzyme that metabolizes catecholamines. Consistent with clinical syndromes, we previously demonstrated that COMT inhibition in rodents produces persistent pain and heightened immune responses. Here, we sought to determine the efficacy of manual acupuncture in resolving persistent pain and neuroinflammation in the classic inbred C57BL/6 strain and the rapid-wound healing MRL/MpJ strain. Mice received subcutaneous osmotic minipumps to deliver the COMT inhibitor OR486 or vehicle for 13 days. On day 7 after pump implantation, acupuncture was performed at the Zusanli (ST36) point or a non-acupoint for 6 consecutive days. Behavioral responses to mechanical stimuli were measured throughout the experiment. Immunohistochemical analysis of spinal phosphorylated p38 mitogen-activated protein kinase, a marker of inflammation, and glial fibrillary acidic protein, a marker of astrogliosis, was performed on day 13. Results demonstrated that ST36, but not sham, acupuncture resolved mechanical hypersensitivity and reduced OR486-dependent increases in phosphorylated p38 and glial fibrillary acidic protein in both strains. The magnitude of the analgesic response was greater in MRL/MpJ mice. These findings indicate acupuncture as an effective treatment for persistent pain linked to abnormalities in catecholamine signaling and, furthermore, that analgesic efficacy may be influenced by genetic differences. PERSPECTIVE: Chronic overlapping pain conditions remain ineffectively managed by conventional pharmacotherapies. Here, we demonstrate that acupuncture alleviates persistent pain and neuroinflammation linked to heightened catecholaminergic tone. Mice with superior healing capacity exhibit greater analgesic efficacy. Findings indicate acupuncture as an effective treatment for chronic overlapping pain conditions and provide insight into treatment response variability., (Copyright © 2018 the American Pain Society. Published by Elsevier Inc. All rights reserved.)

Background: Obesity is prevalent among pregnant women in the United States; obstructive sleep apnea is highly comorbid with obesity and is associated with adverse pregnancy outcomes. Screening for obstructive sleep apnea in pregnant women has remained a challenge because of a lack of validated screening tools., Objective: The purpose of this study was to evaluate established obstructive sleep apnea screening tools, a sleepiness scale, and individual component items in a cohort of pregnant women with extreme obesity in mid pregnancy with the use of objective testing to determine obstructive sleep apnea status and to describe the prevalence of obstructive sleep apnea among women with extreme obesity., Study Design: Adult pregnant subjects, between 24 and 35 weeks gestation, with a body mass index ≥40 kg/m 2 at the time of enrollment completed obstructive sleep apnea screening tools (Berlin Questionnaire, American Society of Anesthesiologists checklist, and STOP-BANG questionnaire) and the Epworth Sleepiness Scale; they also underwent physical examination of the neck, mouth, and airway. The published obstructive sleep apnea in pregnancy prediction score was calculated for each subject. Obstructive sleep apnea status for each subject was determined by the results of an overnight, unattended type III home sleep apnea test., Results: Twenty-four percent of pregnant women with extreme obesity had obstructive sleep apnea on home sleep apnea testing in mid pregnancy (Apnea-Hypopnea Index, ≥5 events per hour]. Established obstructive sleep apnea screening tools performed very poorly to screen for obstructive sleep apnea in this cohort. Age, body mass index, neck circumference, frequently witnessed apneas, and highly likely to fall asleep while driving were associated most strongly with obstructive sleep apnea status in this cohort., Conclusion: We found that 24% of pregnant women with body mass index ≥40 kg/m 2 between 24 and 35 weeks gestation have obstructive sleep apnea, defined as Apnea-Hypopnea Index ≥5 events per hour on an overnight type III home sleep apnea test. We found the Berlin Questionnaire, American Society of Anesthesiologists checklist, STOP-BANG, obstructive sleep apnea in pregnancy score by Facco et al, and the Epworth Sleepiness Scale were not useful screening tools for obstructive sleep apnea in a cohort of obese pregnant women. However, age, body mass index, neck circumference, frequently witnessed apneas, and likely to fall asleep while driving were associated with obstructive sleep apnea in this cohort. Further studies are needed to adjust the criteria and thresholds within the available screening tools to better predict obstructive sleep apnea in pregnant women with obesity., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Purpose: The Multicenter Study of Perioperative Ischemia (McSPI) AFRisk index predicts postoperative atrial fibrillation (POAF) after cardiac surgery, but requires pre-, intra-, and postoperative data. Other more abbreviated risk indices exist, but there is no consensus on which risk index is optimal. We compared the discriminatory capacity of the McSPI AFRisk index with three indices containing only preoperative data (the CHA 2 DS 2 Vasc score, POAF score, and Kolek clinical risk prediction model), hypothesizing that the McSPI AFRisk index would have superior predictive capacity., Methods: We retrospectively evaluated 783 patients undergoing cardiac surgery using cardiopulmonary bypass. The predictive capacity of each index was assessed by comparing receiver-operating characteristic (ROC) curves, scaled Brier scores, net reclassification indices, and the integrated discrimination indices., Results: The incidence of POAF was 32.6%. The area under the curve (AUC) of the ROC curve were 0.77, 0.58, 0.66, and 0.66 for the McSPI AFRisk index, CHA 2 DS 2 Vasc score, POAF score, and Kolek clinical risk prediction model, respectively. The McSPI AFRIsk index had the highest AUC (P < 0.0001). The scaled Brier scores for the McSPI AFRisk index, CHA 2 DS 2 Vasc score, POAF score, and Kolek clinical risk prediction model were 0.23, 0.02, 0.08, and 0.07, respectively. Both net reclassification indices and integrated discrimination indices showed that the McSPI AFRisk index more appropriately identified patients at high risk of POAF., Conclusions: The McSPI AFRisk index showed superior ability to predict POAF after cardiac surgery compared with three other indices. When clinicians and investigators wish to measure the risk of POAF after cardiac surgery, they should consider using the McSPI AFRisk index.