Spatial enrichment of the type 1 interferon signature in the brain of a neuropsychiatric lupus murine model.

Among systemic lupus erythematosus (SLE) patients, neuropsychiatric symptoms are highly prevalent, being observed in up to 80% of adult and 95% of pediatric patients. Type 1 interferons, particularly interferon alpha (IFNα), have been implicated in the pathogenesis of SLE and its associated neuropsychiatric symptoms (NPSLE). However, it remains unclear how type 1 interferon signaling in the central nervous system (CNS) might result in neuropsychiatric sequelae. In this study, we validate an NPSLE mouse model and find an elevated peripheral type 1 interferon signature alongside clinically relevant NPSLE symptoms such as anxiety and fatigue. Unbiased single-nucleus sequencing of the hindbrain and hippocampus revealed that interferon-stimulated genes (ISGs) were among the most highly upregulated genes in both regions and that gene pathways involved in cellular interaction and neuronal development were generally repressed among astrocytes, oligodendrocytes, and neurons. Using image-based spatial transcriptomics, we found that the type 1 interferon signature is enriched as spatially distinct patches within the brain parenchyma of these mice. Our results suggest that type 1 interferon in the CNS may play an important mechanistic role in mediating NPSLE behavioral phenotypes by repressing general cellular communication pathways, and that type 1 interferon signaling modulators are a potential therapeutic option for NPSLE.

Perioperative Supplemental Oxygen and Postoperative Nausea and Vomiting: Subanalysis of a Trial, Systematic Review, and Meta-analysis.

BACKGROUND: Intraoperative supplemental oxygen may reduce postoperative nausea and vomiting by mitigating hypoxic stress on the gastrointestinal tract. The authors therefore tested the hypothesis that supplemental oxygen reduces nausea and vomiting in adults recovering from colorectal surgery at the Cleveland Clinic between January 28, 2013, and March 11, 2016. METHODS: Initially, the authors conducted an unplanned subanalysis of a previous trial that evaluated the effect of 80% versus 30% intraoperative inspired oxygen on surgical site infection. Specifically, they assessed the effect of 80% versus 30% oxygen concentration on the incidence of postoperative nausea and/or vomiting. Thereafter, the authors conducted a systematic review and meta-analysis of the effect of supplemental oxygen on postoperative nausea and vomiting. RESULTS: The authors' underlying analysis included 5,057 colorectal surgeries on 4,001 patients. For 2,554 surgeries, assignment was to 80% oxygen, and in 2,503 surgeries, to 30%. Postoperative nausea and vomiting was 852 of 2,554 (33%) in 80% oxygen and 814 of 2,503 (33%) in 30% oxygen. The estimated relative risk (95% CI) of 80% versus 30% oxygen on postoperative nausea and vomiting was 1.04 (0.96 to 1.12) in a generalized estimating equation model adjusting for within-patient correlation for patients with multiple surgeries, P = 0.355. Furthermore, supplemental oxygen did not reduce antiemetic use (P = 0.911) or the severity of nausea and vomiting (P = 0.924). The authors' meta-analysis included 10 qualifying trials (6,749 patients) and did not find a difference in postoperative nausea and vomiting: relative risk, 0.97 [95% CI, 0.86 to 1.08], P = 0.55, I2 = 52%. CONCLUSIONS: The incidence of postoperative nausea and vomiting did not differ in patients assigned to 80% or 30% inspired oxygen. A meta-analysis of available trials similarly indicated that supplemental intraoperative oxygen does not reduce postoperative nausea and vomiting. Therefore, supplemental oxygen should not be given in the expectation that it will reduce nausea and vomiting.

Serratus anterior and pectoralis plane blocks for robotically assisted mitral valve repair: a randomised clinical trial.

BACKGROUND: Minimally invasive cardiac surgery provokes substantial pain and therefore analgesic consumption. The effect of fascial plane blocks on analgesic efficacy and overall patient satisfaction remains unclear. We therefore tested the primary hypothesis that fascial plane blocks improve overall benefit analgesia score (OBAS) during the initial 3 days after robotically assisted mitral valve repair. Secondarily, we tested the hypotheses that blocks reduce opioid consumption and improve respiratory mechanics. METHODS: Adults scheduled for robotically assisted mitral valve repairs were randomised to combined pectoralis II and serratus anterior plane blocks or to routine analgesia. The blocks were ultrasound-guided and used a mixture of plain and liposomal bupivacaine. OBAS was measured daily on postoperative Days 1-3 and were analysed with linear mixed effects modelling. Opioid consumption was assessed with a simple linear regression model and respiratory mechanics with a linear mixed model. RESULTS: As planned, we enrolled 194 patients, with 98 assigned to blocks and 96 to routine analgesic management. There was neither time-by-treatment interaction (P=0.67) nor treatment effect on total OBAS over postoperative Days 1-3 with a median difference of 0.08 (95% confidence interval [CI]: -0.50 to 0.67; P=0.69) and an estimated ratio of geometric means of 0.98 (95% CI: 0.85-1.13; P=0.75). There was no evidence of a treatment effect on cumulative opioid consumption or respiratory mechanics. Average pain scores on each postoperative day were similarly low in both groups. CONCLUSIONS: Serratus anterior and pectoralis plane blocks did not improve postoperative analgesia, cumulative opioid consumption, or respiratory mechanics during the initial 3 days after robotically assisted mitral valve repair. CLINICAL TRIAL REGISTRATION: NCT03743194.

Association between postoperative hypotension and acute kidney injury after noncardiac surgery: a historical cohort analysis.

PURPOSE: The extent to which postoperative hypotension contributes to renal injury remains unclear, much less what the harm thresholds might be. We therefore tested the primary hypothesis that there is an absolute hypotensive arterial pressure threshold for acute kidney injury during the initial seven days after noncardiac surgery. METHODS: We conducted a single-centre historical cohort analysis of adults who had noncardiac surgery and had creatinine recorded preoperatively and postoperatively. Our exposure was the lowest postoperative mean arterial pressure, defined as the average of the three lowest postoperative pressure measurements. Our primary analysis was the association between the lowest mean arterial pressure and acute kidney injury, defined according to Kidney Disease: Improving Global Outcomes initiative criteria. Our analysis was adjusted for potentially relevant confounding factors including intraoperative hypotension. RESULTS: Among 64,349 patients analyzed, 2,812 (4.4%) patients had postoperative acute kidney injury. Each 5-mm Hg decrease in the lowest mean arterial pressure was associated with a 28% (97.5% confidence interval [CI], 23 to 32; P < 0.001) increase in the odds of acute kidney injury for lowest mean arterial pressures < 80 mm Hg. Higher lowest pressures were not associated with acute kidney injury (odds ratio, 1.08; 97.5% CI, 0.99 to 1.17; P = 0.04) for each 5-mm Hg decrease in the lowest mean arterial pressure. CONCLUSION: Postoperative hypotension, defined as the lowest postoperative mean arterial pressure < 80 mm Hg, was associated with acute kidney injury after noncardiac surgery. A prospective trial will be required to determine whether the observed association is causal and thus amenable to modification.

RéSUMé: OBJECTIF: Nous ne savons pas dans quelle mesure l'hypotension postopératoire contribue aux lésions rénales, et nous connaissons encore moins les seuils de lésion. Nous avons donc testé l'hypothèse primaire selon laquelle il existerait un seuil absolu de tension artérielle hypotensive pour l'insuffisance rénale aiguë au cours des sept premiers jours suivant une chirurgie non cardiaque. MéTHODE: Nous avons mené une analyse de cohorte historique monocentrique auprès d'adultes ayant bénéficié d'une chirurgie non cardiaque et pour lesquel·les les taux de créatinine avant et après l'opération avaient été enregistrés. Notre exposition était la tension artérielle moyenne postopératoire la plus basse, définie comme la moyenne des trois mesures de tension postopératoire les plus basses. Notre analyse principale a porté sur l'association entre la tension artérielle moyenne la plus basse et l'insuffisance rénale aiguë, définies selon les critères de l'initiative KDIGO (Kidney Disease: Improving Global Outcomes). Notre analyse a été ajustée pour tenir compte des facteurs de confusion potentiellement pertinents, notamment de l'hypotension peropératoire. RéSULTATS: Parmi les 64 349 patient·es analysé·es, 2812 (4,4 %) ont présenté une insuffisance rénale aiguë postopératoire. Chaque diminution de 5 mm Hg de la tension artérielle moyenne la plus faible était associée à une augmentation de 28 % (intervalle de confiance [IC] de 97,5 %, 23 à 32; P < 0,001) des risques d'insuffisance rénale aiguë pour les tensions artérielles moyennes les plus faibles < 80 mm Hg. Des tensions les plus faibles plus hautes n'ont pas été associées à une insuffisance rénale aiguë (rapport de cotes, 1,08; IC 97,5 %, 0,99 à 1,17; P = 0,04) pour chaque diminution de 5 mm Hg de la tension artérielle moyenne la plus faible. CONCLUSION: L'hypotension postopératoire, définie comme la tension artérielle moyenne postopératoire < 80 mm Hg la plus basse, a été associée à une insuffisance rénale aiguë après une chirurgie non cardiaque. Une étude prospective sera nécessaire pour déterminer si l'association observée est causale et donc susceptible d'être modifiée.

Relative contributions of anaemia and hypotension to myocardial infarction and renal injury: Post hoc analysis of the POISE-2 trial.

BACKGROUND: Hypotension and postoperative anaemia are associated with myocardial and renal injury after noncardiac surgery, but the interaction between them remains unknown. OBJECTIVES: To test the hypothesis that a double-hit of postoperative anaemia and hypotension synergistically worsens a 30-day composite of myocardial infarction (MI) and mortality and acute kidney injury (AKI). Characterising the interaction when hypotension and anaemia occur at same time on myocardial infarction and acute kidney injury. DESIGN: Post hoc analysis of the POISE-2 trial. SETTING: Patients were enrolled between July 2010 and December 2013 at 135 hospitals in 23 countries. PATIENTS: Adults at least 45 years old with known or suspected cardiovascular disease. We excluded patients without available postoperative haemoglobin measurements or hypotension duration records. Exposures were the lowest haemoglobin concentration and the average daily duration of SBP less than 90 mmHg within the first four postoperative days. MAIN OUTCOME MEASURES: The primary outcome was a collapsed composite of nonfatal MI and all-cause mortality during the initial 30 postoperative days; our secondary outcome was AKI. RESULTS: We included 7940 patients. The mean ±â€ŠSD lowest postoperative haemoglobin was 10 ±â€Š2 g dl -1 , and 24% of the patients had SBP less than 90 mmHg with daily duration ranging from 0 to 15 h. Four hundred and nine (5.2%) patients had an infarction or died within 30 postoperative days, and 417 (6.4%) patients developed AKI. Lowest haemoglobin concentrations less than 11 g dl -1 , and duration of SBP less than 90 mmHg was associated with greater hazard of composite outcome of nonfatal MI and all-cause mortality, as well as with AKI. However, we did not find significant multiplicative interactions between haemoglobin splines and hypotension duration on the primary composite or on AKI. CONCLUSION: Postoperative anaemia and hypotension were meaningfully associated with both our primary composite and AKI. However, lack of significant interaction suggests that the effects of hypotension and anaemia are additive rather than multiplicative. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01082874.

An Ultrahigh-Affinity Complement C4b-Specific Nanobody Inhibits In Vivo Assembly of the Classical Pathway Proconvertase.

The classical and lectin pathways of the complement system are important for the elimination of pathogens and apoptotic cells and stimulation of the adaptive immune system. Upon activation of these pathways, complement component C4 is proteolytically cleaved, and the major product C4b is deposited on the activator, enabling assembly of a C3 convertase and downstream alternative pathway amplification. Although excessive activation of the lectin and classical pathways contributes to multiple autoimmune and inflammatory diseases and overexpression of a C4 isoform has recently been linked to schizophrenia, a C4 inhibitor and structural characterization of the convertase formed by C4b is lacking. In this study, we present the nanobody hC4Nb8 that binds with picomolar affinity to human C4b and potently inhibits in vitro complement C3 deposition through the classical and lectin pathways in human serum and in mouse serum. The crystal structure of the C4b:hC4Nb8 complex and a three-dimensional reconstruction of the C4bC2 proconvertase obtained by electron microscopy together rationalize how hC4Nb8 prevents proconvertase assembly through recognition of a neoepitope exposed in C4b and reveals a unique C2 conformation compared with the alternative pathway proconvertase. On human induced pluripotent stem cell-derived neurons, the nanobody prevents C3 deposition through the classical pathway. Furthermore, hC4Nb8 inhibits the classical pathway-mediated immune complex delivery to follicular dendritic cells in vivo. The hC4Nb8 represents a novel ultrahigh-affinity inhibitor of the classical and lectin pathways of the complement cascade under both in vitro and in vivo conditions.

Emerging drugs for the treatment of postsurgical pain.

INTRODUCTION: Postoperative pain is a distressful experience and remains to be a significant concern after surgery. Current agents either fail to prevent or minimize postoperative pain or cause a series of adverse effects, addiction, or abuse. Opioids have been the gold standard in the treatment of postoperative pain despite their well-described adverse effects. Many new agents with different mechanisms of action have been recently introduced to address this issue. AREAS COVERED: This current review summarizes the list of new and emerging drugs investigated for their efficacy in controlling the postoperative pain and decreasing the need for rescue opioid use, adverse effect profile, abuse, and addiction potential. EXPERT OPINION: Opioids have unrivaled analgesic efficacy. However adverse effects of opioids led to the search for better options. In mild pain most of the emerging drugs have been shown to control postoperative pain and decrease the use of rescue opioid, however fail to control pain after major surgeries causing severe pain. Specific agents such as Oliceridine, new local anesthetics, etc., are effective in controlling severe pain and hold a promise to replace opioids in the near future.

Evidence that melatonin downregulates Nedd4-1 E3 ligase and its role in cellular survival.

Indolamine melatonin structurally resembles non-covalent proteasome inhibitors; however, the role of ubiquitin proteasome system (UPS) in neuronal survival and how melatonin carries out UPS inhibition remain largely unknown. With the use of melatonin treated cells, we evaluated the expression of Nedd4-1, an E3 ligase, how melatonin regulates its activity and its relationship with neuronal survival. Nedd4-1 was upregulated in the hypoxic condition in both control and Nedd4-1 overexpressed cells and melatonin treatment reversed its expression in both normoxic and hypoxic conditions, which was associated with increased cellular survival. Melatonin had no effect on the expression of Nedd4-1 at mRNA level. However, when melatonin was administered along with protein synthesis inhibitor cycloheximide, protein level of Nedd4-1 was further reduced, indicating that melatonin possibly downregulates Nedd4-1 after its synthesis. Notably, co-immunoprecipitation analyses followed by Liquid chromatography-Mass Spectrometry (LC-MS/MS) revealed that melatonin may dissociate ribosomal proteins, such as RS19, RL23A, and nucleophosmin from Nedd4-1, while 40S ribosomal protein S7 and 60S ribosomal protein L35 came into contact with Nedd4-1 upon melatonin treatment. By using IPA analyses, we obtained further data indicated novel target molecules of melatonin in hypoxic conditions, including OTOF, SF3B2, IPO5, ST13, FGFR3, Mx1/Mx2, playing roles in RNA splicing and trafficking, growth factor and interferon signaling. Here, we described a new insight into the role of melatonin in UPS functioning by proposing a molecular mechanism through which melatonin regulates Nedd4-1.

Blood bupivacaine concentrations after pecto-serratus and serratus anterior plane injections of plain and liposomal bupivacaine in robotically-assisted mitral valve surgery: Sub-study of a randomized trial.

STUDY OBJECTIVE: To investigate the timing of peak blood concentrations and potential toxicity when using a combination of plain and liposomal bupivacaine for thoracic fascial plane blocks. DESIGN: Pharmacokinetic analysis. SETTING: Operating room. PATIENTS: Eighteen adult patients undergoing robotically-assisted mitral valve surgery. INTERVENTIONS: Ultrasound-guided pecto-serratus and serratus anterior plane blocks using a mixture of 0.5% bupivacaine HCl up to 2.5 mg/kg and liposomal bupivacaine up to 266 mg. MEASUREMENTS: Arterial plasma bupivacaine concentration. MAIN RESULTS: Samples from 13 participants were analyzed. There was substantial inter-patient variability in plasma concentrations. A geometric mean maximum bupivacaine concentration was 1492 ng/ml (range 660 to 4650 ng/ml) at median time of 30 min after injection. In 4/13 (31%) patients, plasma bupivacaine concentrations exceeded our predefined 2000 ng/ml toxic threshold. A second much smaller peak was observed about 32 h after the injection. No obvious signs of local anesthetic toxicity were observed. CONCLUSIONS: Combined injection of plain and liposomal bupivacaine for pecto-serratus/serratus anterior plane blocks produced a biphasic pattern, with the highest arterial plasma concentrations observed within 30 min. Maximum concentrations exceeded the potential toxic threshold in nearly a third of patients, but without clinical evidence of toxicity. Clinicians should not assume that routine combinations of plain and liposomal bupivacaine for thoracic fascial plane blocks are inherently safe.

Processing speed test and 30-day readmission in elderly non-cardiac surgery patients- A retrospective study.

Background and Aims: Preoperative cognitive function screening can help identify high-risk patients, but resource-intensive testing limits its widespread use. A novel self-administered tablet computer-based Processing Speed Test (PST) was used to assess cognitive "executive" function in non-cardiac surgery patients, but the relationship between preoperative test scores and postoperative outcomes is unclear. The primary outcome was a composite of 30-day readmission/death. The secondary outcome was a collapsed composite of discharge to a long-term care facility/death. Exploratory outcomes were 1) time to discharge alive, 2) 1-year mortality and 3) a collapsed composite of postoperative complications. Methods: This retrospective study, after approval, was conducted in elective non-cardiac surgery patients ≥65 years old. We assessed the relationship between processing speed test scores and primary/secondary outcomes using multivariable logistic regression, adjusting for potential confounding variables. Results: Overall 1568 patients completed the PST, and the mean ± standard deviation test score was 33 ± 10. The higher PST score is associated with better executive function. A 10-unit increase in the test score was associated with an estimated 19% lower 30-day readmission/death odds, with an odds ratio (OR) and 95% confidence interval (CI) of 0.81 (0.68, 0.96) (P = 0.015). Similarly, 10-unit increase in test score was associated with an estimated 26% lower odds of long-term care need/death, with OR (95% CI) of 0.74 (0.61, 0.91) (P = 0.004). We also found statistically significant associations between the test scores and time to discharge alive and to 1-year mortality, however, not with a composite of postoperative complications. Conclusion: Elderly non-cardiac surgery patients with better PST scores were less likely to be readmitted, need long-term care after discharge or die within 30 days. Preoperative assessment of cognitive function using a simple self-administered test is feasible and may guide perioperative care.

Hypoventilation in the PACU is associated with hypoventilation in the surgical ward: Post-hoc analysis of a randomized clinical trial.

OBJECTIVE: To evaluate the association between early postoperative hypoventilation in the last hour of the post-anesthesia care unit (PACU) stay and hypoventilation during the rest of the first 48 postoperative hours in the surgical ward. DESIGN: Sub-analysis of a clinical trial. SETTING: PACU and surgical wards of a single medical center. PATIENTS: Adults having abdominal surgery under general anesthesia. INTERVENTIONS: Monitoring with a respiratory volume monitor from admission to PACU until the earlier of 48 h after surgery or discharge. MEASUREMENTS: The exposure was having at least one low minute-ventilation (MV) event during the last hour of PACU stay, defined as MV lower than 40% the predicted value lasting at least 1 min. The primary outcome was low MV events lasting at least 2 min during the rest of the first 48 postoperative hours, while in the surgical ward. The secondary outcome was the rate of low MV events per monitored hour. MAIN RESULTS: Data of 292 patients were analyzed, of which 20 (6.8%) patients had a low MV event in PACU. Low MV events in the surgical ward were found in 81 (28%) patients. All patients who had low MV events in PACU had events again in the ward, while 61/272 (22%) had an event in the ward but not in PACU. The incidence rate of low MV events per hour was 24 (95% CI: 13, 46) among patients having an event in the PACU, and 2 (1, 4) among those who did not. CONCLUSIONS: In adults recovering from abdominal surgery, events of hypoventilation during the first postoperative hour are associated with similar events during the rest of the first 48 postoperative hours, with positive predictive value approaching 100%. Sixty-one patients had ward hypoventilation that was not preceded by hypoventilation in PACU.

[WITHDRAWN] Spatial enrichment of the type 1 interferon signature in the brain of a neuropsychiatric lupus murine model.

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Correlation of low back pain caused by lumbar spinal stenosis and depression in women: a clinical study.

OBJECTIVE: Low back pain (LBP) due to spinal stenosis may be one of the most debilitating symptoms to decrease the quality of life. The cause and effect association of LBP and depression is vague. Pain may also be a somatization symptom of depression. This is more frequent in the female population. This clinical study was designed to evaluate the correlation between the level of back pain caused by lumbar spinal stenosis and depression in the female population. METHOD: The study included 50 consecutive female patients with spinal stenosis. The stenosis diagnosis is made by neurological examination and neuro-imaging. The study group was psychiatrically evaluated and grouped as those with and without depression. Visual analog scale (VAS), Oswestry disability index (ODI) and Hamilton Depression Scale (HDS) were utilized in initial evaluation of the group. RESULTS: Twenty-one patients with lumbar spinal stenosis had depression (DLS Group) and 29 did not (LSS Group). Mean HDS scores were 8.97 and 32.48 for Group LSS and Group DLS, respectively. There was a statistically significant difference between the VAS scores of the groups (the mean VAS scores were 5.6 and 7.6, for groups LSS and DLS, respectively). The mean ODI values for LSS (65.24 ± 4.58) and DLS (75.1 ± 6.7) groups were also significantly different. In Group DLS, there were positive correlations between ODI and VAS with HDS (p < 0.001). CONCLUSION: Our findings indicated a relationship between lumbar spinal stenosis associated pain levels and depression. However, the cause and result relationship still needs to be established yet.

Immunological response of polysaccharide nanogel-incorporating PEG hydrogels in an in vivo diabetic model.

Cell-based therapies hold significant advantages in comparison with the traditional drug-based or injection-based treatments. However, for long-term functional cellular implants, immune acceptance must be established. To accomplish the acceptance of the implanted cells, various biomaterial systems have been studied. Nanogels have shown great potential for modulation of cellular microenvironments, acting as a physical barrier between the immune system and the implant. However, internalization of nano-scale materials by implanted cells is not desirable and is yet to be overcome. In this study, we incorporated acrylate modified cholesterol-bearing pullulan (CHPOA) nanogels into poly (ethylene glycol) diacrylate (PEGDA) hydrogels through covalent crosslinking, where we used visible light-induced photopolymerization. We characterized morphology and swelling properties of CHPOA incorporated PEG composite hydrogels using FE-SEM and gravimetric analysis. Also, we investigated the biocompatibility properties of composite hydrogels in vivo, where we used both healthy and diabetic mice. We induced diabetes in mice using a low dose streptozotocin (STZ) injections and implanted composite hydrogels in both diabetic and healthy mice through subcutaneous route. Immune cell infiltration of the retrieved tissue was examined through histological analysis, where we observed minimum immune response levels of 0-2 rareness, according to ISO standard of biological evaluation of medical devices. Our observation suggests that the composite hydrogel developed here can be used to introduce nanostructured domains into bulk hydrogels and that this system has potential to be used as immunologically acceptable composite material in cellular therapy without internalization of nanoparticles.

Relations Between L2 Proficiency and L1 Lexical Property Evaluations.

The present study investigates the relations between L2-English proficiency and L1-Turkish lexical property evaluations. We asked whether L2 proficiency affects lexical properties, including imageability and concreteness ratings of 600 Turkish words selected from the Word Frequency Dictionary of Written Turkish. Seventy-two participants (L1-Turkish - L2-English) provided ratings of concreteness and imageability for 600 words on a 7-point scale. In order to assess their L2 proficiency, we administered Peabody Picture Vocabulary Test-IV (PPVT-IV). We divided categories into two subcategories as high and low for the frequency, concreteness, imageability, and age of acquisition (AoA). The relationship between these subcategories and imageability-concreteness was examined by mixed effects linear regression analyses. We found that L2 proficiency and imageability ratings were positively correlated and specifically, this positive association was evident for low-frequency words and later acquired words. Results are in line with the interaction of bilingual representation under the dual-coding theory which suggests that bilinguals develop an interconnected imaginal representation for two languages as opposed to separate verbal representations. As L2 proficiency increased, the imageability also increased. These findings have implications for literature investigating the relationship between L2 proficiency and linguistic outcomes. Additionally, findings point to the importance of considering the L2 proficiency of participants when lexical tasks that involve cue words or word lists are used.

Effect of intraoperative subhypnotic infusion of propofol on postoperative nausea and vomiting: A retrospective analysis.

STUDY OBJECTIVE: To measure the possible association between subhypnotic propofol infusion during general balanced anesthesia and the incidence of PONV. DESIGN: Retrospective Cohort Analysis Using Propensity Score Matching. SETTING: Postanesthesia care unit and inpatient unit. PATIENTS: Patients with American Society of Anesthesiologists (ASA) physical status I-IV, undergoing non-cardiac surgery lasting >2 h were included. Patients were excluded if transferred to the intensive care unit after surgery or received ketamine. Initially 70,976 patients were screened, and a cohort of 51,707 eligible adult patients undergoing non-cardiac surgery under general balanced anesthesia between 2015 and 2019 were included. Using a propensity score matching, 3185 patients who received subhypnotic propofol during general balanced anesthesia were matched with 5826 patients who did not receive subhypnotic propofol in a 1:2 ratio. INTERVENTIONS: None. MEASUREMENTS: The primary outcome was the incidence of PONV during PACU stay. The secondary outcome was the incidence of PONV within the first 24 h after surgery. Exploratory outcomes were time-to-extubation and length of hospital stay. MAIN RESULTS: A total of 9011 patients were included (3185 patients who received propofol infusion, and 5826 patients who did not receive propofol infusion) after propensity score matching. The adjusted odds ratio for PONV incidence was 1.03 (95% CI: 0.90, 1.18; p = 0.635) in PACU, and 1.05 (95% CI: 0.90, 1.23; P = 0.50) within 24 h after surgery. The length of hospital stay was 6 h shorter (ratio of means (95% CI) of 0.92, 0.89, 0.94), p < 0.001) and time-to-extubation was 2 min longer (ratio of means 1.24 (1.20, 1.28), p < 0.001) in patients receiving subhypnotic propofol infusion. CONCLUSIONS: Our study suggests that subhypnotic propofol infusion during general balanced anesthesia is not associated with a reduction in the incidence of PONV during PACU stay and within the first 24 h after surgery. However, it is associated with decreased LOS and increased time-to-extubation, but differences in neither outcome were clinically important.

Diurnal blood pressure variation in adults after abdominal surgery-An observational cohort study.

OBJECTIVE: To describe the prevalence of various circadian blood pressure patterns in adults recovering from abdominal surgery, and to evaluate the association between loss of normal circadian variation in blood pressure and hypotension during the initial 2 postoperative days. DESIGN: A post-hoc analysis of data obtained from two randomized trials. SETTING: Operating rooms of the Cleveland Clinic. PATIENTS: Adults having abdominal surgery from 2015 to 2019 with at least one overnight stay. Participants were continuously monitored by wearable vital signs monitors starting in the post-anesthesia care unit and for the first 48 postoperative hours. INTERVENTIONS: None. The exposure of interest was the degree of nocturnal decrease in blood pressure - normal nocturnal decrease in blood pressure ("normal dipping", more than 10% decrease compared to day-time), no nocturnal decrease ("non-dipping", less than 10% nocturnal decrease), or nocturnal increase in blood pressure ("rising"). MEASUREMENTS: Postoperative hypotension, defined by the time weighted average (TWA) area under a mean arterial pressure (MAP) threshold of 70 mmHg. RESULTS: In total, 590 patients were eligible for analysis (mean(SD) age 50(15) years, 56% females, median [IQR] surgery duration 4.0 [2.7, 5.8] hours). Median TWA area under a MAP threshold of 70 mmHg was 0.96 (95%CI 0.59, 1.33) mmHg*minute per monitoring hour lower in patients with either no nocturnal blood pressure decrease (N = 317, 54%), or an increase in nocturnal blood pressure (N = 211, 36%), than in the reference group of patients with normal nocturnal decrease (N = 62, 11%), P < 0.001 for both. CONCLUSIONS: Abnormal diurnal blood pressure patterns are common in adults during the initial 2 days after abdominal surgery. Lack of normal night-time decrease in blood pressure is associated with less postoperative hypotension. Future studies should evaluate whether abnormal postoperative diurnal blood pressure patterns are associated with worse outcomes.

Chest pain in patients recovering from noncardiac surgery: A retrospective analysis.

STUDY OBJECTIVE: Chest pain is relatively common postoperatively. Myocardial infarction (MI) is one cause of chest pain after surgery, but chest pain also results from less severe conditions. Because of its potential severity, chest pain usually prompts the activation of Rapid Response Systems (RRS). While chest pain is a cardinal symptom of myocardial ischemia in the non-surgical setting, the significance and relevance of chest pain after noncardiac surgery remains unclear. DESIGN: We conducted a retrospective analysis of noncardiac surgical inpatients for whom postoperative chest pain triggered our multidisciplinary RRS. SETTING: Surgical wards at Cleveland Clinic, Cleveland, OH. PATIENTS: Postsurgical patients after noncardiac surgery in whom the RSS system was activated for chest pain. INTERVENTIONS: RRS specified interventions like ECG readings, troponin measurements, transfer to ICU. MEASUREMENTS: Our primary outcome was MI. Secondary outcomes included the proportion of patients who had an ECG performed, troponin measurements, echocardiography, cardiac catheterization, and were admitted to the Intensive Care Unit (ICU). MAIN RESULTS: 5850 surgical patients experienced postoperative chest pain and triggered an RRS activation between 2009 and 2019. A total of 3110 patients had troponin T measured within 6 h after RRS activation, and 538 of them (17%) had elevated troponin, meeting the Fourth Universal Definition criteria for MI. Additionally, 2 patients had ST-segment elevation infarction (STEMI) without troponin measurement. Among the 540 patients with MI, only 19 (3.5%) were diagnosed with a STEMI by ECG, 388 (72%) had echocardiography, 43 patients (8%) had cardiac catheterization, 8 patients (1.5%) required emergent cardiac surgery, and 424 (79%) were admitted to an ICU. CONCLUSION: Chest pain is a serious clinical sign, often indicating a postoperative myocardial infarction, and therefore should be taken seriously. Troponin screening should be routinely considered in postsurgical patients who report chest pain.