Effect of Oxycodone-Based Multimodal Analgesia on Visceral Pain After Major Laparoscopic Gastrointestinal Surgery: A Randomised, Double-Blind, Controlled Trial.

Purpose: Oxycodone is a potent µ- and κ-opioid receptor agonist that can relieve both somatic and visceral pain. We assessed oxycodone- vs sufentanil-based multimodal analgesia on postoperative pain following major laparoscopic gastrointestinal surgery. Methods: In this randomised double-blind controlled trial, 40 adult patients were randomised (1:1, stratified by type of surgery) to receive oxycodone- or sufentanil-based multimodal analgesia, comprising bilateral transverse abdominis plane blocks, intraoperative dexmedetomidine infusion, flurbiprofen axetil, and oxycodone- or sufentanil-based patient-controlled analgesia. The co-primary outcomes were time-weighted average (TWA) of visceral pain (defined as intra-abdominal deep and dull pain) at rest and on coughing during 0-24 h postoperatively, assessed using the numerical rating scale (0-10) with a minimal clinically important difference of 1. Results: All patients completed the study (median age, 64 years; 65% male) and had adequate postoperative pain control. The mean (SD) 24-h TWA of visceral pain at rest was 1.40 (0.77) in the oxycodone group vs 2.00 (0.98) in the sufentanil group (mean difference=-0.60, 95% CI, -1.16 to -0.03; P=0.039). Patients in the oxycodone group had a significantly lower 24-h TWA of visceral pain on coughing (2.00 [0.83] vs 2.98 [1.26]; mean difference=-0.98, 95% CI, -1.66 to -0.30; P=0.006). In the subgroup analyses, the treatment effect of oxycodone vs sufentanil on the co-primary outcomes did not differ in terms of age (18-65 years or >65 years), sex (female or male), or type of surgery (colorectal or gastric). Secondary outcomes (24-h TWA of incisional and shoulder pain, postoperative analgesic usage, rescue analgesia, adverse events, and patient satisfaction) were comparable between groups. Conclusion: For patients undergoing major laparoscopic gastrointestinal surgery, oxycodone-based multimodal analgesia reduced postoperative visceral pain in a statistically significant but not clinically important manner. Trial Registration: Chinese Clinical Trial Registry (ChiCTR2100052085).

Clinical manifestations and spermatogenesis outcomes in Chinese patients with congenital hypogonadotropic hypogonadism caused by inherited or de novo FGFR1 mutations.

ABSTRACT: Fibroblast growth factor receptor 1 (FGFR1) mutations are associated with congenital hypogonadotropic hypogonadism (CHH) through inheritance or spontaneous occurrence. We detected FGFR1 mutations in a Chinese cohort of 210 CHH patients at Peking Union Medical College Hospital (Beijing, China) using next-generation and Sanger sequencing. We assessed missense variant pathogenicity using six bioinformatics tools and compared clinical features and treatment outcomes between inherited and de novo mutation groups. Among 19 patients with FGFR1 mutations, three were recurrent, and 16 were novel variants. Sixteen of the novel mutations were likely pathogenic according to the American College of Medical Genetics and Genomics (ACMG) guidelines, with the prevalent P366L variant. The majority of FGFR1 mutations was inherited (57.9%), with frameshift mutations exclusive to the de novo mutation group. The inherited mutation group had a lower incidence of cryptorchidism, short stature, and skeletal deformities. In the inherited mutation group, luteinizing hormone (LH) levels were 0.5 IU l-1, follicle-stimulating hormone (FSH) levels were 1.0 IU l-1, and testosterone levels were 1.3 nmol l-1. In contrast, the de novo group had LH levels of 0.2 IU l-1, FSH levels of 0.5 IU l-1, and testosterone levels of 0.9 nmol l-1, indicating milder hypothalamus-pituitary-gonadal axis (HPGA) functional deficiency in the inherited group. The inherited mutation group showed a tendency toward higher spermatogenesis rates. In conclusion, this study underscores the predominance of inherited FGFR1 mutations and their association with milder HPGA dysfunction compared to de novo mutations, contributing to our understanding of the genetic and clinical aspects of FGFR1 mutations.

Effect of rScO2-Guided Blood Pressure Management on Postoperative Complications in Elderly Patients After Major Noncardiac Surgery: Protocol for a Randomized Controlled Trial.

Background: Postoperative complications are common after major surgical procedures, leading to increased morbidity and mortality. Regional cerebral oxygen saturation (rScO2) reflects cerebral and global perfusion, and thus it can be used to guide hemodynamic management. We aim to explore the effect of rScO2-guided blood pressure management strategy on postoperative major complications in older adults who undergo major noncardiac surgery. Methods: This randomized controlled clinical trial includes a total of 400 elderly patients receiving major noncardiac surgery and general anesthesia. Patients will be randomized (1:1) to one of two blood pressure management groups: a standard care group (targeting mean arterial pressure >65 mmHg or within 20% of baseline value), and a rScO2-guided group (absolute value of rScO2 >60% or decrease in rScO2 <10% of baseline). The primary outcome is the composite outcome of major complications (including infectious, respiratory, neurologic, cardiovascular, renal, thromboembolic gastrointestinal, and surgical complications) and deaths within the first 7 days after surgery. Secondary outcomes include the individual components of the primary outcome by day 7 after surgery and 30-day mortality. Data will be analyzed in the modified intention-to-treat population. Discussion: This study will provide evidence for improving postoperative outcomes using the rScO2-guided blood pressure management among older adults who undergo major noncardiac surgery. Trial Registration: Chinese Clinical Trial Registry (Identifier: ChiCTR2200060816).

This is a protocol for a prospective, randomized, controlled clinical trial to evaluate the use of intraoperative individualized regional cerebral oxygen saturation (rScO₂) optimization for blood pressure management in older adults undergoing major noncardiac surgery. The primary focus of this trial is the composite outcome of major complications (including infectious, respiratory, neurologic, cardiovascular, renal, thromboembolic gastrointestinal, and surgical complications) and deaths within the first 7 days after surgery. The secondary outcomes are the individual components of the primary outcome by day 7 after surgery and 30-day mortality. The findings of this trial will provide clinical evidence for the rScO₂-guided blood pressure management to improve postoperative outcomes in older patients who are scheduled for major noncardiac surgery.

Preoperative Prevalence and Risk Factors For Calf Muscular Vein Thrombosis in Elderly Patients with Hip Fracture.

OBJECTIVE: Increasing evidence has shown that calf muscular vein thrombosis (CMVT) can develop into proximal deep vein thrombosis, even causing pulmonary embolism. However, opinions about the prevalence and risk factors are still controversial. This study aimed to investigate the prevalence and risk factors for CMVT in elderly patients with hip fractures to facilitate their preoperative management. METHODS: We included 419 elderly patients with hip fracture who were treated in the orthopaedic department of our hospital from June 2017 to December 2020. The patients were divided into CMVT and non-CMVT groups based on color Doppler ultrasound screening of the venous system in the lower extremities. Clinical data, such as age, sex, body mass index, time from injury to admission, and laboratory data were collected. Univariate and multivariate logistic regression analyses were performed to determine independent risk factors for CMVT. A receiver operating characteristic curve was used to analyze the predictive effectiveness of the model. Finally, the clinical utility of the model was analyzed using decision curve analysis and clinical impact curves. RESULTS: The prevalence of preoperative CMVT was 30.5% (128/419). Independent predictors of preoperative CMVT identified by univariate and multivariate logistic regression analyses were sex, time from injury to admission, American Society of Anesthesiologists (ASA) classification, C-reactive protein (CRP) level, and D-dimer level (p < 0.05). The area under curve (AUC) was 0.750 (95% CI: 0.699-0.800, p < 0.001) and the sensitivity and specificity were 0.698 and 0.711, respectively, which meant the prediction model has a good efficacy in the prediction of CMVT risk. In addition, the fitting degree of the prediction model was also good (Hosmer-Lemeshow χ2 = 8.447, p > 0.05). The clinical utility of the model was verified using decision curve analysis and clinical impact curves. CONCLUSION: Sex, time from injury to admission, ASA classification, CRP level, and D-dimer levels are independent preoperative predictors of CMVT in elderly patients with hip fractures. Measures should be taken for patients with these risk factors to prevent the occurrence and deterioration of CMVT.

Intraindividual variance of lower limb rotation in patients with bilateral knee osteoarthritis.

Purpose: To determine the side-to-side difference in intraindividual rotation alignment of patients with bilateral varus-type knee osteoarthritis (OA) and compare it with control subjects. Methods: This retrospective study enrolled 60 patients with bilateral varus-type knee OA and 50 control subjects. All cases underwent bilateral lower limb CT angiography. Bilateral femoral and tibial rotation alignment were measured, and the overall lower limb rotation was calculated by two different methods. Method 1 was calculated by subtracting angle of the femoral torsion from the tibial torsion and method 2 was determined by relative rotation of the femoral neck angle to bimalleolar angle. The intraindividual variance and differences between the two groups were analyzed. Results: Both OA and control samples showed significant differences between right and left for all measurements. Femoral torsion for control group was 10.4 ± 5.5°, tibial torsion was -22.1 ± 6.1°, and overall leg rotation by method 1 was -15.6 ± 7.2° and method 2 was -11.7 ± 8.2°. Femoral torsion, tibial torsion, method 1, and method 2 in the patients with OA were 8.2 ± 6.3°, -18.6 ± 4.1°, -14.9 ± 7.9°, and -10.4 ± 7.6°, respectively. Patients with OA showed a more pronounced retroversion in the femur (p = 0.008) and more internal rotation in the tibia (p < 0.001). No statistical significance of both methods was found between the two groups. Patients with OA had a greater median side-to-side absolute difference in all measurements, though the differences of both two methods of overall lower limb rotation were not statistically significant. Conclusions: The discrepancy of side-to-side differences of bilateral lower limb rotation ought to be noticed with caution in diagnosing and treating rotational deformities of the lower limb, especially for patients with bilateral knee OA.

Highly fluorescent N doped C-dots as sensor for selective detection of Hg2+ in beverages.

In this work, nitrogen doped carbon dots (NCDs) were synthesized through one step hydrothermal reaction using citric acid and ethylenediamine as precursors. The prepared NCDs exhibit high quantum yield of 67.4%, good stability, excellent selectivity and sensitivity. It was found that the NCDs have potential as a fluorescence sensor for the detection of Hg2+. Under optimal conditions, good linearity between the change in NCDs fluorescence intensity and Hg2+ concentration was obtained in the range of 0.3 to 2.0 µM with a detection limit at 0.24 µM. The possible detection mechanism was static quenching of NCDs by Hg2+. The established method was successfully applied to the determination of Hg2+ in beverage samples. The results indicated that the NCDs-based sensor has potential for detection of Hg2+ in real beverage sample.

Withholding vs. Continuing Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Blockers Before Non-cardiac Surgery in Older Patients: Study Protocol for a Multicenter Randomized Controlled Trial.

Background: Older hypertensive adults are at increased risk for postoperative morbidity and mortality. As first line antihypertensive drug therapy, angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) have many beneficial effects. However, the use of ACEIs/ARBs in the perioperative period remains controversial. This study aims to determine the effects of withholding vs. continuing ACEIs/ARBs before non-cardiac surgery on perioperative hypotension and postoperative outcomes in older patients. Methods: In this multicenter, randomized, double-blind, placebo-controlled trial, a total of 2036 patients aged 60-80 years undergoing non-cardiac surgical procedures will be randomly assigned, in a 1:1 ratio, to receive oral ACEIs/ARBs (the ACEIs/ARBs continued group) or inactive placebos (the ACEIs/ARBs withheld group) on the morning of surgery. For both groups, the ACEIs/ARBs will be continued from the first postoperative day. The primary outcome measure is the incidence of perioperative hypotensive events, defined as mean blood pressure (MBP) < 65 mmHg or ≥30% reduction in MBP from baseline during surgery and in a post-anesthesia care unit. The secondary outcomes include duration of perioperative hypotension, intraoperative use of fluids and vasopressors, hypotensive events within postoperative 3 days, and perioperative neurocognitive disorders, major adverse cardiocerebral events (a composite outcome of stroke, coma, myocardial infarction, heart block, and cardiac arrest), and mortality within 30 days after surgery. Discussion: The results of this trial will offer an evidence-based perioperative ACEIs/ARBs therapy for older hypertensive adults undergoing non-cardiac surgery. Study Registration: This study is approved by the Medical Ethics Committee of The First Affiliated Hospital of Soochow University (Approval No. 2020-077-1) and by the institutional ethics review board of each participating center. This protocol is registered at the Chinese Clinical Trials Registry (ChiCTR2000039376).

Dexmedetomidine Attenuates Ischemia/Reperfusion-Induced Myocardial Inflammation and Apoptosis Through Inhibiting Endoplasmic Reticulum Stress Signaling.

BACKGROUND: Endoplasmic reticulum stress (ERS)-mediated myocardial inflammation and apoptosis plays an important role in myocardial ischemia/reperfusion (I/R) injury. Dexmedetomidine has been used clinically with sedative, analgesic, and anti-inflammatory properties. This study aimed to determine the effects of dexmedetomidine pretreatment on inflammation, apoptosis, and the expression of ERS signaling during myocardial I/R injury. METHODS: Rats underwent myocardial ischemia for 30 min and reperfusion for 6 h, and H9c2 cardiomyocytes were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) injury (OGD for 12 h and reoxygenation for 3 h). Dexmedetomidine was administered prior to myocardial ischemia in rats or ODG in cardiomyocytes. In addition, the α2-adrenergic receptor antagonist (yohimbine) or the PERK activator (CCT020312) was given prior to dexmedetomidine treatment. RESULTS: Dexmedetomidine pretreatment decreased serum levels of cardiac troponin I, reduced myocardial infarct size, alleviated histological structure damage, and improved left ventricular function following myocardial I/R injury in rats. In addition, dexmedetomidine pretreatment increased cell viability and reduced cytotoxicity following OGD/R injury in cardiomyocytes. Mechanistically, the cardioprotection offered by dexmedetomidine was mediated via the inhibition of inflammation and apoptosis through downregulating the expression of the ERS signaling pathway, including glucose-regulated protein 78 (GRP78), protein kinase R-like endoplasmic reticulum kinase (PERK), C/EBP homologous protein (CHOP), inositol-requiring protein 1 (IRE1), and activating transcription factor 6 (ATF6). Conversely, the protective effects of dexmedetomidine were diminished by blocking the α2 adrenergic receptors with yohimbine or promoting PERK phosphorylation with CCT020312. CONCLUSION: Dexmedetomidine pretreatment protects the hearts against I/R injury via inhibiting inflammation and apoptosis through downregulation of the ERS signaling pathway. Future clinical studies are needed to confirm the cardioprotective effects of dexmedetomidine in patients at risk of myocardial I/R injury.

Research on Standard Compliance Test Algorithm Based on Electronic Medical Records of Traditional Chinese Medicine Outpatients.

Objectives: To effectively evaluate the compliance degree between the electronic medical records of Traditional Chinese Medicine (TCM) hospitals, as well as the information platform, and the related information standards of electronic medical records, a standard compliance testing scheme based on electronic medical records of TCM outpatients is proposed. Methods: This research selected the data of clinical outpatients accumulated in 10 years by the Digital Medicine Institute of Chengdu University of TCM and processed the data through security check and desensitization process. And then 28348 cases of processed electronic medical records of TCM outpatients were inputted into the standard compliance testing platform for assessment. The result was then outputted. Results: There are 924 cases among the 28348 that can be rated as five-star medical records, 84 cases four-star, 132 cases three-star, 12460 cases two-star, 13488 one-star, and 1260 cases zero-star through the integrity and standardization test. Conclusion: By the way of assessing the integrity and standardization of data, the standard compliance test algorithm scheme for electronic medical records of TCM outpatients introduced in this paper can solve the problems such as data unavailability caused by ununified codes and incomplete data in the data-sharing process and provides technical support for the construction of data standardization testing in electronic medical records of TCM outpatients.

Metabolic Effects of Testosterone Replacement Therapy in Patients with Type 2 Diabetes Mellitus or Metabolic Syndrome: A Meta-Analysis.

BACKGROUND: Testosterone replacement therapy (TRT) is commonly used for the treatment of hypogonadism in men, which is often associated with type 2 diabetes mellitus (T2DM) and metabolic syndrome (Mets). Recent compiling evidence shows that TRT has beneficial metabolic effects on these patients. OBJECTIVE: A meta-analysis has been conducted to evaluate the effects of TRT on cardiovascular metabolic factors. METHODS: We conducted a systemic search on PubMed, Embase, Cochrane Library, Wanfang, and CNKI and selected randomized controlled trials (RCTs) to include. The efficacy of TRT on glycemia, insulin sensitivity, lipid profile, and body weight was meta-analyzed by Review Manager. RESULTS: A total of 18 RCTs, containing 1415 patients (767 in TRT and 648 in control), were enrolled for the meta-analysis. The results showed that TRT could reduce HbA1c (MD = -0.67, 95% CI -1.35, -0.19, and P=0.006) and improve HOMA-IR (homeostatic model assessment of insulin resistance) (SMD = -1.94, 95% CI -2.65, -1.23, and P < 0.0001). TRT could also decrease low-density lipoprotein (SMD = -0.50, 95% CI -0.82, -0.90, and P=0.002) and triglycerides (MD = -0.64, 95% CI -0.91, -0.36, and P < 0.0001). In addition, TRT could reduce body weight by 3.91 kg (MD = -3.91, 95% CI -4.14, -3.69, and P < 0.00001) and waist circumference by 2.8 cm (MD -2.80, 95% CI -4.38, -1.21 and P=0.0005). Erectile dysfunction (measured by IIEF-5) did not improve, while aging-related symptoms (measured by AMS scores) significantly improved. CONCLUSIONS: TRT improves glycemic control, insulin sensitivity, and lipid parameters in hypogonadism patients with T2DM and MetS, partially through reducing central obesity.

Dexmedetomidine preconditioning for myocardial protection in ischaemia-reperfusion injury in rats by downregulation of the high mobility group box 1-toll-like receptor 4-nuclear factor κB signalling pathway.

Pharmacological preconditioning reduces myocardial infarct size in ischaemia-reperfusion (I-R) injury. Dexmedetomidine, a selective α2 -adrenoceptor agonist, has a proven cardioprotective effect when administered prior to I-R, although the underlying mechanisms for this effect are not fully understood. We evaluated whether dexmedetomidine preconditioning could induce a myocardio-protective effect against I-R injury by inhibiting associated inflammatory processes through downregulation of the high mobility group box 1 (HMGB1)-toll-like receptor 4 (TLR4)-nuclear factor κB (NF-κB) signalling pathway. Seventy rats were randomly assigned to seven groups: a control and six test groups, involving I-R for 30 and 120 minutes, respectively, in isolated rat hearts and different pretreatment protocols with dexmedetomidine (10 nmol/L) as well as yohimbine (1 µmol/L) and recombinant HMGB1 peptide (rHMGB1; 20 µg/L), alone or in combination with dexmedetomidine. Cardiac function was recorded; myocardial HMGB1, TLR4, and NF-κB activities and levels of tumour necrosis factor-α (TNF-α) and interleukin-6 (IL-6) were measured as were lactate dehydrogenase (LDH) and creatine kinase (CK) in coronary outflow. Dexmedetomidine preconditioning significantly improved cardiac function (P<.05), downregulated the expression of HMGB1-TLR4-NF-κB, reduced levels of TNF-α and IL-6 in isolated ventricles during I-R injury, and significantly reduced CK and LDH levels in coronary outflow (P<.05). All of these effects were partially reversed by yohimbine (P<.05) or rHMGB1 (P<.05). Dexmedetomidine preconditioning alleviated myocardial I-R injury in rats through inhibition of inflammatory processes associated with downregulation of the HMGB1-TLR4-NF-κB signalling pathway via activation at α2 -adrenergic receptors.

Elevated glycated hemoglobin levels may increase the risk of atrial fibrillation in patients with diabetes mellitus.

BACKGROUND: As the most common cardiac arrhythmia, atrial fibrillation (AF) is always accompanied with various complications if without detection and treatment timely. Blood-based pleiotropic molecule biomarkers have now been popularly applied in clinical detection. We hence performed this meta-analysis to evaluate the correlation of serum glycated hemoglobin (HbA1c) levels with the risk of AF in patients with diabetes mellitus (DM). METHODS: Covering myriads of computerized databases, we identified potential relevant studies for statistical analysis. We used a standard reporting form to extract data from each included study. Newcastle-Ottawa Scale (NOS) criteria was used for methodological quality assessment. Statistical analyses were conducted with the STATA statistical software. RESULTS: Six cohort studies in full text fulfilled our inclusion criteria, and following overestimation indicated that serum levels of HbA1c in DM patients with AF was higher than that in DM patients without AF (SMD = 0.67, 95% CI: 0.39-0.94, P < 0.001). Subgroup analyses by sample size and detection method implicated that elevated serum HbA1c levels exhibited significant correlations with an increased risk of AF in DM patients in the large-size subgroup (n ≥ 200), the small-size subgroup (n < 200), the high performance liquid chromatography (HPLC) subgroup and the non-HPLC subgroup (Large-size: SMD = 0.70, 95% CI: 0.38-1.03, P < 0.001; Small-size: SMD = 0.64, 95% CI: 0.09-1.19, P = 0.023; HPLC: SMD = 0.81, 95% CI: 0.49-1.12, P < 0.001; Non-HPLC: SMD = 0.36, 95% CI: 0.04-0.68, P = 0.029; respectively). CONCLUSION: Elevated serum HbA1c levels may be associated with an increased risk of AF in DM patients, possibly reflecting that serum HbA1c level might be a potential biomarker in the prediction of AF in DM patients.

Pharmacokinetic- pharmacodynamic analysis of the role of CYP2C19 genotypes in short-term rabeprazole-based triple therapy against Helicobacter pylori.

AIMS: The aim was to explore the role of CYP2C19 polymorphism in short-term rabeprazole-based triple therapy against Helicobacter pylori infection. METHODS: Patients with H. pylori infection were tested for CYP2C19 genotype as poor metabolizers (PMs) or extensive metabolizers (EMs, homozygous EM or heterozygous EM) and given rabeprazole for 7 days. Antibiotics (clarithromycin and amoxicillin) were given on days 1-4, days 4-7, or days 1-7. A direct link model with an effect compartment was used in the population pharmacokinetic-pharmacodynamic analysis. The status of H. pylori infection was evaluated. RESULTS: Rabeprazole clearance was lower in CYP2C19 PMs than in EMs (with average values of 10.7 vs. 16.8 l h(-1) in PMs and EMs, respectively), resulting in higher plasma levels in the former group. The values of EC(50) and k(eo) of gastrin response increased with multiple doses of rabeprazole. The k(eo) values were lower in CYP2C19 PMs than in EMs on day 1 (0.012 vs. 0.017 x 10(-4) l min(-1)), and higher than in EMs on day 4 (0.804 vs. 0.169 x 10(-4) l min(-1)) of rabeprazole treatment. The predicted gastrin-time profile showed a higher response in CYP2C19 PMs than in EMs on days 4 and 7. Helicobacter pylori was eradicated in all CYP2C19 PMs except in one patient infected by a resistant strain. In contrast, in CYP2C19 EMs the eradication rates ranged from 58 to 85%. CONCLUSIONS: CYP2C19 genotypes play a role in H. pylori eradication therapy. Rabeprazole-based short-term triple therapy may be applicable in CYP2C19 PMs for H. pylori eradication.