Remimazolam ameliorates postoperative cognitive dysfunction after deep hypothermic circulatory arrest through HMGB1-TLR4-NF-κB pathway.

BACKGROUND: Postoperative cognitive dysfunction (POCD) is a complication of deep hypothermic circulatory arrest (DHCA). Various amounts of neurologic dysfunctions have been shown after DHCA, which has often been attributed to systemic inflammatory response syndrome and cerebral ischemia/reperfusion injury. Remimazolam is one of the commonly used anesthetic drugs with protective actions against inflammatory diseases, such as sepsis and cerebral ischemia/reperfusion injury. Here, we determined the protective effect and potential mechanism of action of remimazolam against neuronal damage after DHCA. METHODS: A rat model of DHCA was established, and a gradient dosage of remimazolam was administered during cardiopulmonary bypass (CPB). The cognitive function of rats was evaluated by Morris water maze. Hematoxylin and eosin and TUNEL staining were performed to assess hippocampus tissue injury and neuronal apoptosis. Inflammatory cytokines concentration were analyzed by enzyme-linked immunosorbent assay. The protein expression was analyzed using automated electrophoresis western analysis and immunohistochemical analysis. RESULTS: The appropriate dosage of remimazolam reduced histologic injury, neuronal apoptosis, microglia activation, and secondary inflammatory cascades, as well as the downregulation of the expression of the HMGB1-TLR4-NF-κB pathway after DHCA, improved the memory and learning abilities in DHCA rats. Further, administration of a TLR4 antagonist TAK-242 had a similar effect to remimazolam, while the TLR4 agonist LPS attenuated the effect of remimazolam. CONCLUSIONS: Remimazolam could ameliorate POCD after DHCA through the HMGB1-TLR4-NF-κB signaling pathway.

Experiencing anesthesia and surgery early in life impairs cognitive and behavioral development.

Background: The impact of anesthesia and surgery on neurocognitive and behavioral development in infants and children remains inadequately understood. Objective: To investigate the impact of early-life exposure to general anesthesia and surgery on cognitive and behavioral development. Methods and materials: Children aged 0-3 years who underwent general anesthesia and surgical procedures between 2012 and 2015 were included. The cognitive and behavioral development of these children at ages 4-6 years was assessed. Age-, race-, and gender-matched children from the same geographic region, who did not undergo general anesthesia or surgery, served as the control group. The Wechsler Preschool Primary Scale of Intelligence, Fourth Edition (WPPSI-IV) was used to evaluate children's total intelligence quotient (FSIQ) and specific cognitive domains. The Gesell Development Schedules (GSCH) and Child Behavior Checklist (CBCL) were employed to assess behavioral and personality development. Additionally, the study analyzed the effects of various factors including anesthesia drugs, surgery duration, number of surgeries, age, weight, ethnicity, and gender on postoperative neurocognitive and behavioral outcomes. Results: The study included 447 children with anesthesia/surgical exposure (AS) and 459 children in the control group. Analysis of cognitive and behavioral development showed a significant difference in the working memory index (WMI) between the AS and control groups (p < 0.05). Exploratory findings indicated that children administered remifentanil exhibited lower developmental quotient (DQ) values, whereas those given fentanyl showed higher (worse) Child Behavior Checklist (CBCL) total scores. Moreover, increased anesthesia/surgical exposures, younger age and lower body weight at exposure, and longer surgery durations were associated with cognitive and behavioral developmental challenges. Conclusion: This study examined the impact of early-life exposure to surgery and anesthesia on postoperative cognitive and behavioral development. Findings indicate that higher frequency of exposure to surgery and anesthesia, younger age, and lower body weight at exposure could negatively influence cognitive and behavioral development. Furthermore, variations in the effects of different anesthetics on behavior and cognition were observed. Caution is advised regarding the use of opioid analgesics such as remifentanil and fentanyl for more rigorous clinical applications.

Epidemiology and Triggers of Severe Perioperative Anaphylaxis: An 8-Year Single-Center Study.

OBJECTIVE: To determine the features, rescue measures, outcomes, re-allergic reactions, and independent risk factors associated with severe anaphylaxis during surgery. DESIGN: Instances of severe perioperative anaphylaxis were identified through perioperative electronic records, adverse event reporting records, and surveys of anesthesiologists. Confirmed cases were randomly matched 4:1 with control cases on the same operation day. Patient risk factors, surgery type, anesthetic technique, and perioperative medications, fluids, and blood transfusions were given in instances of severe perioperative anaphylaxis were compared with control cases. SETTING: A tertiary hospital in China. PATIENTS: All patients undergoing surgery and anesthesia in the operating room from January 2014 to February 2022. MEASUREMENTS: Incidence and the independent risk factors for severe perioperative anaphylaxis. MAIN RESULTS: Ninety-seven patients experienced severe perioperative allergic responses during the 266,033 surgeries performed, with an incidence rate of 3.6 per 10,000. Three of 97 anaphylaxis patients experienced a severe allergic reaction again during the second surgery. The nested case-control study revealed that the independent triggers during surgery were allergy history (odds ratio 5.23; 95% confidence interval [CI], 2.35-11.68; p < 0.001), cisatracurium use (odds ratio 5.03; 95% CI, 1.22-20.70; p < 0.001), hydroxyethyl starch 130/0.4 use (odds ratio 5.36; 95% CI, 2.99-9.60; p =0.025), and allogeneic plasma (odds ratio 11.02; 95% CI, 3.78-35.95; p < 0.001). CONCLUSIONS: Perioperative severe anaphylaxis is a rare but life-threatening complication. Previous allergic history, cisatracurium, hydroxyethyl starch 130/0.4, and allogeneic plasma may be the independent triggers. Early diagnosis of anaphylaxis and the timely administration of epinephrine are critical to allergic treatment. Avoiding exposure to allergens is effective for preventing severe allergic responses and the efficacy of glucocorticoids and antihistamines is controversial.

Causal effects of socioeconomic traits on frailty: a Mendelian randomization study.

Background: The relationship between socioeconomic status and frailty has been extensively investigated in the literature, but it remains unclear whether a causal relationship exists. Our goal is to evaluate the causal relationship between six socioeconomic traits and the frailty index using summary-level data for single nucleotide polymorphisms from large genome-wide association studies with individuals of European ancestry. Methods: A two-sample MR was performed. We applied the inverse variance weighted (IVW) method for the primary estimate, with sensitivity analyses conducted using alternative MR methods to evaluate the robustness of the findings. A subsequent multivariable MR was undertaken to adjust for the effects of body mass index (BMI). Finally, the MR Steiger directionality test was performed to confirm the causal direction. Results: The IVW MR analysis revealed significant associations between various socioeconomic factors and the frailty index. Specifically, genetically predicated age completed full time education (ß = -0.477, 95% confidence interval [CI]: -0.634 to -0.319) and average total household income before tax (ß = -0.321, 95% CI: -0.410 to -0.232) were negatively associated with the frailty index. On the other hand, genetically predicted job involves heavy manual or physical work (ß = 0.298, 95% CI: 0.113 to 0.484), job involves mainly walking or standing (ß = 0.179, 95% CI: 0.013 to 0.345), Townsend deprivation index at recruitment (ß = 0.535, 95% CI: 0.285 to 0.785), and social isolation/loneliness (ß = 1.344, 95% CI: 0.834 to 1.853) were positively associated with the frailty index. Sensitivity analysis using other MR methods and multivariable MR analysis adjusting for BMI yielded stable results. The MR Steiger directionality test confirmed the causal direction. Conclusion: Our findings highlight the importance of socioeconomic factors in affecting frailty risk. Future research should focus on unraveling the pathways through which these socioeconomic factors exert their effects on frailty, with the ultimate goal of developing targeted strategies to mitigate the risk of frailty.

Comparison of the Effects of Combined Femoral and Sciatic Nerves Block versus General Anesthesia on Hemodynamic Stability and Postoperative Complication in Patients with Diabetic Foot: A Prospective, Double-Blind and Randomized Controlled Trial.

Background: Perioperative anesthetic management of patients with diabetic foot undergoing surgical treatment is challenging due to their poor cardiovascular health status. According to previous literature, general anesthesia and peripheral nerve block have their own advantages and disadvantages for such patients. We reported the effect of these two anesthesia techniques on perioperative hemodynamics and prognosis in these patients. Methods: This study employed a prospective randomized controlled design, where patients meeting the inclusion criteria were assigned to two groups: the general anesthesia group (GA group) and the peripheral nerve block group (PNB group). The primary outcomes were the differences in intraoperative hemodynamic stability and the incidence of postoperative complications between the two groups. The second outcomes were postoperative numerical rating scale scores, analgesic drug remedies, postoperative sleep conditions monitored by sleep bracelets and health status assessed by EQ-5D-5 L scores. Results: One hundred and nine subjects were enrolled in this study, including 54 in the GA group and 55 in the PNB group. The baseline parameters of the two groups were comparable. The GA group exhibited a significantly higher incidence of hypotension, and Colloid intake and total fluid intake were significantly higher in the GA group than in the PNB group. Additionally, a larger proportion of patients in the GA group. The scores of postoperative pain during the 48 hours after surgery were significantly higher, and more patients needed tramadol for postoperative analgesia during the 24 h after surgery in the GA group than in the PNB group. Patients in the PNB group slept better, first feeding time, earlier out-of-bed activity and earlier discharge from the hospital, compared to the GA group. However, there was no obvious difference in postoperative complications between the two groups except pharyngeal pain. Conclusion: Peripheral nerve block is a better option in patients with diabetes undergoing elective below-knee surgery than general anesthesia.

S-ketamine Infusion on Chronic Postoperative Pain Following Breast Cancer Surgery: A Randomized Double-Blind Placebo-Controlled Trial.

BACKGROUND: Chronic postoperative surgical pain (CPSP) is a frequent complication following breast surgery and poses a challenge in terms of treatment. We hypothesized that the incidence of CPSP would be reduced at 3 months post-breast surgery with the administration of S-ketamine compared to a placebo. PATIENTS AND METHODS: Participants were recruited and randomly assigned to either the S-ketamine group (S) or the control group (C). In group S, S-ketamine was administered as a 1.5 mg kg-1 bolus followed by 2 mg kg-1h-1 infusion, while in group C, a placebo of 0.9% saline was administered in the same volume and rate as S-ketamine. The primary outcome was the incidence of CPSP, measured using a 0-10 numeric rating scale (NRS), at 3 months postsurgery. RESULTS: A total of 72 patients scheduled for mastectomy were enrolled (group S, n = 33; group C, n = 32). The incidence of CPSP at 3 months postsurgery was significantly lower in group S compared to group C (18.2% vs. 48.3%, P < .05). There was no statistical difference between the 2 groups in terms of the incidence of moderate to severe pain. NRS scores for postoperative pain at rest and during movement were significantly lower at 4 h and 24 h post-surgery (P < .05, respectively). Patients in Group S had lower Patient Health Questionnaire-9 (PHQ-9) scores at one week and 3 months post-surgery compared to Group C (P < .05, respectively). CONCLUSION: S-ketamine infusion reduces the incidence of CPSP 3 months after breast surgery.

The Influencing Factors of Frailty and Quality of Life in Elderly Patients After Spinal Surgery.

Background: To study the related factors of frailty and quality of life in elderly patients after spinal surgery. Methods: The anxiety, depression, frailty, and quality of life of all patients were assessed by the Anxiety screening scale (GAD-7), Depression screening scale (PHQ-9), Frailty screening scale (FRAIL), and European five-dimensional health scale (EQ-5D-5L) 1 day before surgery (DAY-0). A numeric rating scale (NRS) was used to evaluate patients' pain during activities on the 1st day (POD-1), 3rd day (POD-3), and 30th day (POD-30) after operation. FRAIL scale and EQ-5D-5L were used to evaluate patients' frailty and quality of life on POD-30 and 90th day (POD-90) after the operation. Results: There were significant differences in age, body mass index (BMI), preoperative serum albumin level (ALB), and NRS score on POD-1 between the two groups (P<0.05). Age and PHQ-9 score were positively correlated with EQ-5D-5L score (P<0.05, r Age=0.245, rPHQ-9=0.217), and preoperative ALB level was negatively correlated with EQ-5D-5L score (P<0.05, r ALB=-0.274). Conclusion: The older the age, the larger the BMI and the higher the NRS score on the first day after surgery, the more prone to frailty in elderly patients after spinal surgery; The older age and the lower the preoperative ALB level, the worse the quality of life in elderly patients after spinal surgery.

Association Between Preoperative Sleep Disturbance and Postoperative Delirium in Elderly: A Retrospective Cohort Study.

Purpose: Postoperative sleep disturbance, characterized by diminished postoperative sleep quality, is a risk factor for postoperative delirium (POD); however, the association between pre-existing sleep disturbance and POD remains unclear. This study aimed to evaluate the association between preoperative sleep disturbance and POD in elderly patients after non-cardiac surgery. Patients and methods: This retrospective cohort study was conducted at a single center and enrolled 489 elderly patients who underwent surgery between May 1, 2020, and March 31, 2021. Patients were divided into the sleep disorder (SD) and non-sleep disorder (NSD) groups according to the occurrence of one or more symptoms of insomnia within one month or sleep- Numerical Rating Scale (NRS)≥6 before surgery. The primary outcome was the incidence of POD. Propensity score matching analysis was performed between the two groups. Multiple logistic regression analysis was performed to identify the risk factors for POD. Results: In both the unmatched cohort (16.0% vs 6.7%, P=0.003) and the matched cohort (17.0% vs 6.2%, P=0.023), the incidence of POD was higher in the SD group than in the NSD group. In addition, the postoperative sleep quality and the VAS score at postoperative 24 h were significantly lower in the SD group than in the NSD group. Multivariate logistic regression analysis indicated that age (Odds Ratio, 1.13 [95% CI: 1.04-1.23], P=0.003) and preoperative sleep disturbance (Odds Ratio, 3.03 [95% CI: 1.09-9.52], P=0.034) were independent risk factors for the development of POD. Conclusion: The incidence of POD was higher in patients with pre-existing sleep disturbance than those without it. Whether improving sleep quality for preoperative sleep disturbance may help prevent POD remains to be determined.

The Safety and Efficacy of Remimazolam Compared to Dexmedetomidine for Awake Tracheal Intubation by Flexible Bronchoscopy: A Randomized, Double-Blind, Controlled Trial.

Background: Remimazolam is a novel ultra-short-acting benzodiazepine sedative that has the potential to be an alternative for procedural sedation due to its rapid sedation and recovery, no accumulation effect, stable hemodynamics, minimal respiratory depression, anterograde amnesia effect, and specific antagonist. Here, we aimed to compare the safety and efficacy of remimazolam with dexmedetomidine for awake tracheal intubation by flexible bronchoscopy (ATI-FB). Methods: Ninety patients scheduled for ATI-FB were randomly divided into three groups, each consisting of 30 cases: dexmedetomidine 0.6 µg/kg + sufentanil (group DS), remimazolam 0.073 mg/kg + sufentanil (group R1S), or remimazolam 0.093 mg/kg + sufentanil (group R2S). The primary outcome was the success rate of sedation. Secondary outcomes were MOAA/S scores, hemodynamic and respiratory parameters, intubation conditions, intubation time, tracheal intubation amnesia, and adverse events. Results: The success rates of sedation in groups R2S and DS were higher than that in group R1S (93.3%, 86.7%, respectively, vs 58.6%; P = 0.002), and intubation conditions were better than those in group R1S (P < 0.05). Group R2S had shorter intubation times than groups R1S and DS (P = 0.003), and a higher incidence of tracheal intubation amnesia than group DS (P = 0.006). No patient in the three groups developed hypoxemia or hypotension, and there were no significant differences in oligopnea, PetCO2, or bradycardia (P > 0.05). Conclusion: In conclusion, both DS and R2S had higher success rates of sedation, better intubation conditions, and minor respiratory depression, but R2S, with its shorter intubation time, higher incidence of anterograde amnesia, and ability to be antagonized by specific antagonists, may be a good alternative sedation regimen for patients undergoing ATI-FB.

Remimazolam Attenuates LPS-Derived Cognitive Dysfunction via Subdiaphragmatic Vagus Nerve Target α7nAChR-Mediated Nrf2/HO-1 Signal Pathway.

Sepsis-induced neuroinflammation is significantly associated with sepsis-related brain dysfunction. Remimazolam is a novel ultra-short-acting benzodiazepine anesthetic with multiple organ protective effects. However, it is unknown whether remimazolam can ameliorate LPS-induced brain impairment. In this study, Lipopolysaccharide (5 mg/kg, LPS) severely impaired Sprague-Dawley rats spatial learning ability, memory, and cognitive function. However, remimazolam treatment showed a protective effect on LPS-induced cognitive dysfunction. Remimazolam partly reversed LPS-induced splenomegaly, decreased serum cytokine expression, suppressed hippocampal M1 microglial activation, and mitigated oxidative stress injury and neuroinflammation. Electroacupuncture (EA) or PNU282987 treatment improved LPS-induced cognitive dysfunction and also significantly inhibited neuroinflammation and systemic inflammation. However, MLA, ML385, or subdiaphragmatic vagus nerve (SDV) treatment abolished the protective effects of remimazolam. Further mechanistic studies showed that remimazolam induces protective effects by activating subdiaphragmatic vagus nerve target α7nAChR-mediated Nrf2/HO-1 signaling pathway. These results demonstrate that remimazolam can up-regulate α7nAChR, Cyto-Nrf2, HO-1, and cognitive-related (CREB, BDNF, PSD95) protein expressions, suppress M1 microglia, ameliorate neuroinflammation or systemic inflammation, and reverse cognitive dysfunction. Therefore, this study provides insight into a new therapeutic target for the treatment of sepsis-induced cerebral dysfunction.

Association of peripheral B cells and delirium: combined single-cell sequencing and Mendelian randomization analysis.

Background: Delirium seriously affects the prognosis of patients and greatly reduces the ability to work and live. Peripheral inflammatory events may contribute to the development of delirium, the mechanism of which is still unclear. There is a lack of effective diagnostic and treatments for delirium in clinical practice. The study aims to investigate alterations in peripheral immune cell subsets under inflammatory stress and to explore causal associations with delirium. Methods: Single-cell transcriptional sequencing data of human peripheral blood mononuclear cells (PBMC) before and after lipopolysaccharide (LPS) intervention were processed by the Seurat package in R software. PBMC subsets and cellular markers were defined after downscaling and clustering by the Harmony algorithm to identify characteristic subsets in the context of inflammatory stress. Subsequently, a two-sample Mendelian randomization (MR) study was used to explore the causal associations of these inflammation-related PBMC subsets and their molecular phenotypes with delirium. Based on publicly available genetic data, the study incorporated 70 PBMC-associated immune traits, including 8 types of circulating immune cells, 33 B cell subsets and molecular phenotypes, 13 T cell subsets, and 16 B cell-associated cytokines. The results were also validated for robustness, heterogeneity, and horizontal pleiotropy. Results: Under LPS-induced inflammatory stress, B cells, T cells, monocytes, and dendritic cells in human PBMC showed significant activation and quantitative changes. Of these, only lymphocyte and B cell counts were causally associated with delirium risk. This risk link is also seen in the TNF pathway. Further studies of B cells and their subsets revealed that this association may be related to unswitched memory B cells and CD27 expressed on memory B cells. Annotation of the screened SNPs revealed significant polymorphisms in CD27 and CD40 annotated by rs25680 and rs9883798, respectively. The functions of the key annotated genes may be related to the regulation of immune responses, cell differentiation, proliferation, and intercellular interactions. Conclusion: The present study revealed the potential possibility that B cell, memory B cell subset, and TNF-related molecules may be involved in the development of delirium due to peripheral inflammation, which can provide clues for further investigation of delirium prevention and treatment strategies.

Construction of a predictive model for blood transfusion in patients undergoing total hip arthroplasty and identification of clinical heterogeneity.

A precise forecast of the need for blood transfusions (BT) in patients undergoing total hip arthroplasty (THA) is a crucial step toward the implementation of precision medicine. To achieve this goal, we utilized supervised machine learning (SML) techniques to establish a predictive model for BT requirements in THA patients. Additionally, we employed unsupervised machine learning (UML) approaches to identify clinical heterogeneity among these patients. In this study, we recruited 224 patients undergoing THA. To identify factors predictive of BT during the perioperative period of THA, we employed LASSO regression and the random forest (RF) algorithm as part of supervised machine learning (SML). Using logistic regression, we developed a predictive model for BT in THA patients. Furthermore, we utilized unsupervised machine learning (UML) techniques to cluster THA patients who required BT based on similar clinical features. The resulting clusters were subsequently visualized and validated. We constructed a predictive model for THA patients who required BT based on six predictive factors: Age, Body Mass Index (BMI), Hemoglobin (HGB), Platelet (PLT), Bleeding Volume, and Urine Volume. Before surgery, 1 h after surgery, 1 day after surgery, and 1 week after surgery, significant differences were observed in HGB and PLT levels between patients who received BT and those who did not. The predictive model achieved an AUC of 0.899. Employing UML, we identified two distinct clusters with significantly heterogeneous clinical characteristics. Age, BMI, PLT, HGB, bleeding volume, and urine volume were found to be independent predictors of BT requirement in THA patients. The predictive model incorporating these six predictors demonstrated excellent predictive performance. Furthermore, employing UML enabled us to classify a heterogeneous cohort of THA patients who received BT in a meaningful and interpretable manner.

Transfer of massive mitochondria from astrocytes reduce propofol neurotoxicity.

Studies have shown that propofol-induced neurotoxicity is mediated by disruption of mitochondrial fission and fusion, leading to an imbalance in energy supply for developing neurons. Healthy mitochondria released from astrocytes migrate to compromised neurons to mitigate propofol-induced neurotoxicity, yet the precise mechanisms involved require further clarification. In our investigation, primary neurons were incubated with propofol, which decreased ATP synthesis and mitochondrial membrane potential, increased ROS generation and neuronal apoptosis. Notably, astrocytes did not respond to the deleterious effects of propofol. The culture medium of neurons or astrocytes incubated with propofol was collected. It was found that mitochondrial ratio was decreased and mitochondrial function was impaired. Non-contact co-culture of neuro-astrocytes facilitated transcellular mitochondrial transfer in both physiological and propofol interventions, but failed to reverse propofol-induced neurotoxicity. The more pronounced damage to neuronal mitochondria induced by propofol compared to that in astrocytes alludes to secondary injury. Damaged neurons incubated with large, functional extracellular mitochondria derived from astrocytes demonstrates transfer of mitochondria to neurons, effectively reversing propofol-induced neurotoxicity. This discovery presents a novel mitochondrial transfer of neuro-astrocytes crosstalk that contributes to neuroprotection and neurological recovery in neurotoxicity.

Peripheral inflammation and neurocognitive impairment: correlations, underlying mechanisms, and therapeutic implications.

Cognitive impairments, such as learning and memory deficits, may occur in susceptible populations including the elderly and patients who are chronically ill or have experienced stressful events, including surgery, infection, and trauma. Accumulating lines of evidence suggested that peripheral inflammation featured by the recruitment of peripheral immune cells and the release of pro-inflammatory cytokines may be activated during aging and these conditions, participating in peripheral immune system-brain communication. Lots of progress has been achieved in deciphering the core bridging mechanism connecting peripheral inflammation and cognitive impairments, which may be helpful in developing early diagnosis, prognosis evaluation, and prevention methods based on peripheral blood circulation system sampling and intervention. In this review, we summarized the evolving evidence on the prevalence of peripheral inflammation-associated neurocognitive impairments and discussed the research advances in the underlying mechanisms. We also highlighted the prevention and treatment strategies against peripheral inflammation-associated cognitive dysfunction.

Quantum storage of entangled photons at telecom wavelengths in a crystal.

Quantum storage and distribution of entanglement are the key ingredients for realizing a global quantum internet. Compatible with existing fiber networks, telecom-wavelength entangled photons and corresponding quantum memories are of central interest. Recently, 167Er3+ ions have been identified as a promising candidate for an efficient telecom quantum memory. However, to date, no storage of entangled photons, the crucial step of quantum memory using these promising ions, 167Er3+, has been reported. Here, we demonstrate the storage and retrieval of the entangled state of two telecom photons generated from an integrated photonic chip. Combining the natural narrow linewidth of the entangled photons and long storage time of 167Er3+ ions, we achieve storage time of 1.936 µs, more than 387 times longer than in previous works. Successful storage of entanglement in the crystal is certified using entanglement witness measurements. These results pave the way for realizing quantum networks based on solid-state devices.

Causal association between adiposity and hemorrhoids: a Mendelian randomization study.

Background: Hemorrhoids are a very common anorectal disorder affecting a large number of individuals throughout the world. This study aimed to evaluate the causal effects of four adiposity traits including body mass index (BMI), body fat percentage, waist circumference, and waist-to-hip ratio on hemorrhoids by Mendelian randomization (MR). Methods: We used summary statistics of BMI (N = 461,460), body fat percentage (N = 454,633), waist circumference (N = 462,166), waist-to-hip ratio (N = 212,244), and hemorrhoids (N = 337,199) from large-scale genome wide association studies of European ancestry. Univariable and multivariable MR were carried out to infer causality. The MR Steiger directionality test was used to test the causal direction. Results: The primary MR analysis using the inverse variance weighted (IVW) method showed that there were positive effects of genetically determined BMI [odds ratio (OR) = 1.005, 95% confidence interval (CI): 1.003-1.008, per standard deviation (SD), p = 7.801 × 10-5], body fat percentage (OR = 1.005, 95% CI: 1.001-1.008, per SD, p = 0.008), waist circumference (OR = 1.008, 95% CI: 1.005-1.011, per SD, p = 1.051 × 10-6), and waist-to-hip ratio (OR = 1.010, 95% CI: 1.003-1.017, per SD, p = 0.003) on hemorrhoids. These findings were robust in multivariable MR adjusting for physical activity. The Steiger directionality test showed evidence against reverse causation. Conclusion: Our MR study supports a causal role of adiposity in the development of hemorrhoids. Adiposity prevention may be an important strategy for reducing hemorrhoids risk.

Ultrasonographic Assessment of Gastric Volume in Fasted Patients Undergoing Gastrointestinal Endoscopy Under Sedation.

Purpose: In this prospective observational study, an ultrasonographic measurement of antral cross-sectional area (ACSA) was conducted to evaluate the gastric content and volume as well as to identify high-risk stomach in non-pregnant adult surgical patients adhering to preanesthetic fasting guidelines. Patients and Methods: Fasted patients undergoing gastrointestinal endoscopy under sedation were included. Ultrasonographic measurements of ACSA were conducted in both semi-recumbent and right lateral decubitus positions before endoscopic procedures. Gastroscopy was employed to guide the measurement of suctioned gastric volume (GV). Ultrasonography was performed to assess gastric contents and identify patients with high-risk stomach. The relationship between ACSA and suctioned GV was also evaluated. Results: ACSA was evaluated in 736 out of 782 patients. A significant positive correlation was discovered between ACSA in the right lateral decubitus position and suctioned GV, which was more reliable than in the semi-recumbent position. To analyze high-risk stomach with a GV > 100 mL, the cutoff value of ACSA in the right lateral decubitus was found to be 7.5 cm2, with the AUC, sensitivity and specificity of 0.80 (95% CI, 0.76-0.82; P<0.001), 82.4% and 67.3%, respectively. A novel mathematical model based on ACSA to estimate GV in non-pregnant fasted adults was presented. Conclusion: Ultrasonographic measurement of ACSA can assist anesthesiologists in estimating the risk of pulmonary aspiration of gastric contents during general anesthesia and sedation.

Effects of penehyclidine hydrochloride combined with dexmedetomidine on pulmonary function in patients undergoing heart valve surgery: a double-blind, randomized trial.

AIM: To investigate the effects of penehyclidine hydrochloride combined with dexmedetomidine on pulmonary function in patients undergoing heart valve surgery with cardiopulmonary bypass (CPB). METHODS: A total of 180 patients undergoing elective heart valve surgery with CPB were randomly divided into four groups: 45 in group P (intravenous penehyclidine hydrochloride 0.02 mg/kg 10 min before anesthesia induction and at the beginning of CPB, total 0.04 mg/kg); 43 in group D (dexmedetomidine 0.5 µg/kg/h after induction of anesthesia until the end of anesthesia); 44 in group PD ( penehyclidine hydrochloride 0.04 mg/kg combined with dexmedetomidine 0.5 µg/kg/h intravenously during anesthesia); and 43 in group C (same amount of normal saline 10 min before and after anesthesia induction, to the end of anesthesia, and at the beginning of CPB). The main outcomes were the incidence and severity of postoperative pulmonary complications (PPCs). The secondary outcomes were: (1) extubation time, length of stay in intensive care, and postoperative hospital stay, and adverse events; and (2) pulmonary function evaluation indices (oxygenation index and respiratory index) and plasma inflammatory factor concentrations (tumor necrosis factor-α, interleukin-6, C-reactive protein and procalcitonin) during the perioperative period. RESULTS: The incidence of PPCs in groups P, D and PD after CPB was lower than that in group C (P < 0.05), and the incidence in group PD was significantly lower than that in groups P and D (P < 0.05). The scores for PPCs in groups P, D and PD were lower than those in group C (P < 0.05). CONCLUSION: Combined use of penehyclidine hydrochloride and dexmedetomidine during anesthesia reduced the occurrence of postoperative pulmonary dysfunction, and improved the prognosis of patients undergoing heart valve surgery with CPB. TRIAL REGISTRATION: The trial was registered in the Chinese Clinical Trial Registry on 3/11/2020 (Registration No.: ChiCTR2000039610).

Causal effects of opioids on postpartum depression: a bidirectional, two-sample Mendelian randomization study.

Background: Postpartum depression is the most common psychiatric disorder in pregnant women during the postpartum period and requires early detection and treatment. Previous studies have found that opioids use affects depression and anxiety disorders. Although it has long been suspected that opioids may contribute to the development of postpartum depression, observational studies are susceptible to confounding factors and reverse causality, making it difficult to determine the direction of these associations. Methods: To examine the causal associations between opioids and non-opioid analgesics with postpartum depression, we utilized large-scale genome-wide association study (GWAS) genetic pooled data from two major databases: opioids, salicylate analgesic, non-steroidal anti-inflammatory drugs (NSAIDs), and aniline analgesics GWAS data from the United Kingdom Biobank database. GWAS data for postpartum depression were obtained from the FinnGen database. The causal analysis methods used random-effects inverse variance weighting (IVW), and complementary sensitivity analyses using weighted median, MR-Egger method, and MR-PRESSO test. Results: In the IVW analysis, Mendelian randomization (MR) analysis showed that opioids increased the risk of postpartum depression (OR, 1.169; 95% CI, 1.050-1.303; p = 0.005). Bidirectional analysis showed a significant causal relationship between genetically predicted postpartum depression and increased risk of opioids and non-opioid analgesics use (opioids OR, 1.118; 95% CI, 1.039-1.203; p = 0.002; NSAIDs OR, 1.071; 95% CI, 1.022-1.121; p = 0.004; salicylates OR, 1.085; 95% CI, 1.026-1.146; p = 0.004; and anilides OR, 1.064; 95% CI, 1.018-1.112; p = 0.006). There was no significant heterogeneity or any significant horizontal pleiotropy bias in the sensitivity analysis. Conclusion: Our study suggests a potential causal relationship between opioids use and the risk of postpartum depression. Additionally, postpartum depression is associated with an increased risk of opioids and non-opioid analgesics use. These findings may provide new insights into prevention and intervention strategies for opioids abuse and postpartum depression.