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PURPOSE: Anxiety and pain commonly occur during nerve block, we aimed to investigate the sedation efficacy of different doses of remimazolam with sufentanil in young and elderly patients. METHODS: In this randomized trial, patients aged 18-85 years who underwent nerve block was enrolled. All patients received sufentanil 0.08 µg/kg for analgesia. Young patients (age < 65 years) were randomized into the control group (Group C, 0.9% saline), medium-dose remimazolam (Group M, 0.06 mg/kg) and high-dose remimazolam group (Group H, 0.08 mg/kg). Elderly patients (age ≥ 65 years) were randomized into the Group C, low-dose remimazolam group (Group L, 0.04 mg/kg) and Group M. Primary outcome was the success rate of procedure sedation. Respiratory depression and hypoxia were the interested safety outcomes. RESULTS: Ninety young and 114 elderly patients were enrolled, respectively. In comparison with Groups C and M, young patients in Group H had the highest success rate of procedure sedation (80.0 vs. 73.3 vs. 43.3%, P = 0.006). Elderly patients in Groups M and L had similar success rates of procedure sedation, which were significantly higher than that in Group C (78.9 vs. 78.9 vs. 50.0%, P = 0.007). In elderly patients, the incidence of respiratory depression and hypoxia tended to be higher in Group M than those in Groups L and C (both P < 0.001). CONCLUSION: Remimazolam 0.08 mg/kg provided the best sedation efficacy in young patients while remimazolam 0.04 mg/kg with the trend of less respiratory adverse events was more optimal for elderly patients. TRIAL REGISTRATION: http://www.chictr.org.cn/showproj.aspx?proj=122016 .
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Bloqueio Nervoso , Insuficiência Respiratória , Idoso , Humanos , Sufentanil/efeitos adversos , Hipnóticos e Sedativos/efeitos adversos , Método Duplo-Cego , Benzodiazepinas/efeitos adversos , Dor/induzido quimicamenteRESUMO
BACKGROUND: Postoperative pulmonary complications are common. Aging and respiratory disease provoke airway hyperresponsiveness, high-risk surgery induces diaphragmatic dysfunction, and general anesthesia contributes to atelectasis and peripheral airway injury. This study therefore tested the hypothesis that inhalation of penehyclidine, a long-acting muscarinic antagonist, reduces the incidence of pulmonary complications in high-risk patients over the initial 30 postoperative days. METHODS: This single-center double-blind trial enrolled 864 patients age over 50 yr who were scheduled for major upper-abdominal or noncardiac thoracic surgery lasting 2 h or more and who had an Assess Respiratory Risk in Surgical Patients in Catalonia score of 45 or higher. The patients were randomly assigned to placebo or prophylactic penehyclidine inhalation from the night before surgery through postoperative day 2 at 12-h intervals. The primary outcome was the incidence of a composite of pulmonary complications within 30 postoperative days, including respiratory infection, respiratory failure, pleural effusion, atelectasis, pneumothorax, bronchospasm, and aspiration pneumonitis. RESULTS: A total of 826 patients (mean age, 64 yr; 63% male) were included in the intention-to-treat analysis. A composite of pulmonary complications was less common in patients assigned to penehyclidine (18.9% [79 of 417]) than those receiving the placebo (26.4% [108 of 409]; relative risk, 0.72; 95% CI, 0.56 to 0.93; P = 0.010; number needed to treat, 13). Bronchospasm was less common in penehyclidine than placebo patients: 1.4% (6 of 417) versus 4.4% (18 of 409; relative risk, 0.327; 95% CI, 0.131 to 0.82; P = 0.011). None of the other individual pulmonary complications differed significantly. Peak airway pressures greater than 40 cm H2O were also less common in patients given penehyclidine: 1.9% (8 of 432) versus 4.9% (21 of 432; relative risk, 0.381; 95% CI, 0.171 to 0.85; P = 0.014). The incidence of other adverse events, including dry mouth and delirium, that were potentially related to penehyclidine inhalation did not differ between the groups. CONCLUSIONS: In high-risk patients having major upper-abdominal or noncardiac thoracic surgery, prophylactic penehyclidine inhalation reduced the incidence of pulmonary complications without provoking complications.
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Espasmo Brônquico , Atelectasia Pulmonar , Espasmo Brônquico/induzido quimicamente , Espasmo Brônquico/complicações , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Atelectasia Pulmonar/complicações , Quinuclidinas/efeitos adversos , Quinuclidinas/uso terapêuticoRESUMO
Background: Obstructive sleep apnea (OSA) is common in surgical patients and associated with worse perioperative outcomes. Objectives: To investigate the effect of mini-dose dexmedetomidine supplemented analgesia on postoperative sleep quality pattern in patients at high risk of OSA. Design: A pilot randomized, double-blind, placebo-controlled trial. Setting: A tertiary university hospital in Beijing, China. Patients: One hundred and fifty-two adult patients who had a STOP-Bang score ≥3 and a serum bicarbonate level ≥28 mmol/L and were scheduled for major noncardiac surgery between 29 January 2021 and 20 September 2022. Intervention: After surgery, patients were provided with high-flow nasal cannula and randomized in a 1:1 ratio to receive self-controlled opioid analgesia supplemented with either mini-dose dexmedetomidine (median 0.02 µg/kg/h) or placebo. We monitored polysomnogram from 9:00 pm to 6:00 am during the first night. Main outcome measures: Our primary outcome was the percentage of stage 2 non-rapid eye movement (N2) sleep. Secondary and exploratory outcomes included other postoperative sleep structure parameters, sleep-respiratory parameters, and subjective sleep quality (Richards-Campbell Sleep Questionnaire; 0-100 score range, higher score better). Results: All 152 patients were included in intention-to-treat analysis; 123 patients were included in sleep structure analysis. Mini-dose dexmedetomidine supplemented analgesia increased the percentage of stage N2 sleep (median difference, 10%; 95% CI, 1 to 21%; p = 0.029); it also decreased the percentage of stage N1 sleep (median difference, -10%; 95% CI, -20% to -1%; p = 0.042). Other sleep structure and sleep-respiratory parameters did not differ significantly between the two groups. Subjective sleep quality was slightly improved with dexmedetomidine on the night of surgery, but not statistically significant (median difference, 6; 95% CI, 0 to 13; p = 0.060). Adverse events were similar between groups. Conclusion: Among patients at high risk of OSA who underwent noncardiac surgery, mini-dose dexmedetomidine supplemented analgesia may improve sleep quality without increasing adverse events. Clinical trial registration: Clinicaltrials.gov, identifier NCT04608331.
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PR-SET7 (also named SET8 or KMT5a) is a sole lysine methyltransferase that catalyzes monomethylation of histone H4 lysine 20 (H4K20me1) in higher eukaryotes. The abundance of PR-SET7 is dynamically mediated by the distinct E3 ubiquitin ligases in different cell cycle phases. PR-SET7 is closely related to the regulation of cell proliferation, and the H4K20me1 catalyzed by PR-SET7 has been implicated in regulating the diverse biological processes, including DNA replication, chromosome condensation and the activation of DNA replication checkpoints. Loss of PR-SET7 results in mas-sive DNA damage, cell cycle arrest and induction of apoptosis. In addition, PR-SET7 involves in regulating the transcrip-tion of several genes, such as ERa, Wnt and p53. PR-SET7 is also essential for individual development and participates in the formation of genomic imprinting. Moreover, PR-SET7 has been reported to promote tumorigenesis and metastasis, sug-gesting that PR-SET7 may be a potential target for cancer treatment. In this review, we focus on analyzing the structure of PR-SET7 and factors influencing histone modification on regulation of PR-SET7, and discuss the mechanisms by which PR-SET7 modulates cell-cycle progression, gene transcription, individual development and tumorigenesis.
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Histona-Lisina N-Metiltransferase/metabolismo , Animais , Ciclo Celular/fisiologia , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Cromatina/metabolismo , Regulação da Expressão Gênica , Histona-Lisina N-Metiltransferase/química , Histona-Lisina N-Metiltransferase/genética , Histonas/metabolismo , Humanos , Transcrição GênicaRESUMO
Pregnancy-related acute myocardial infarction (PAMI) is rare but life-threatening. The incidence of PAMI is growing over time for multiple reasons, and the management of parturients with acute myocardial infarction is challenging in terms of diagnosis and treatment. To date, there are still no clear guidelines on the best practice for PAMI. We present a case of a 41-year-old woman with PAMI at 31 weeks of pregnancy. Through multidisciplinary collaboration, successful outcomes were achieved for both the mother and fetus.
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BACKGROUND: Preoperative carbohydrate drink is used to improve patients' comfort and recovery, but evidence remains limited in diabetic patients. Herein we investigated the effects of preoperative carbohydrate loading with individualized supplemental insulin regimen in diabetic patients undergoing gastrointestinal surgery. METHODS: A total of 63 adult patients with type 2 diabetes mellitus undergoing major gastrointestinal surgery were randomized to receive either carbohydrate loading with individualized supplemental insulin (Carbohydrate group) or routine management (Control group). The primary outcome was time to first flatus after surgery. Among secondary outcomes, subjective feelings of thirsty, hunger and fatigue were assessed with the Visual Analogue Scale (scores range from 0 to 100, where 0 indicate no discomfort and 100 the most severe discomfort) before and after surgery. Adverse events were monitored until 24 h after surgery. RESULTS: All patients were included in the intention-to-treat analysis. Time to first flatus did not differ between groups (median 41 h [IQR 18-69] in the Control group vs. 43 h [27-54] in the Carbohydrate group; hazard ratio 1.24 [95% CI 0.74-2.07]; P = 0.411). The VAS score of preoperative subject feeling of thirsty (median difference -33 [95% CI -50 to -15], P < 0.001), hunger (-25 [-40 to -10], P < 0.001), and fatigue (-5 [-30 to 0], P = 0.004), as well as postoperative subject feeling of thirsty (-50 [-60 to -30], P < 0.001), hunger (-20 [-40 to 0], P = 0.003), and fatigue (0 [-20 to 0], P = 0.020) were all significantly lower in the Carbohydrate group than in the Control group. Intraoperative hypotension (40.6% [13/32] vs. 16.1% [5/31], P = 0.031) and postoperative nausea and vomiting within 24 h (31.3% [10/32] vs. 9.7% [3/31], P = 0.034) occurred less in patients given carbohydrate drink. CONCLUSION: In diabetic patients undergoing gastrointestinal surgery, preoperative carbohydrate loading with individualized supplemental insulin did not promote gastrointestinal recovery but improved perioperative well-being.
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Diabetes Mellitus Tipo 2 , Procedimentos Cirúrgicos do Sistema Digestório , Adulto , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Dieta da Carga de Carboidratos , Humanos , Insulina , Complicações Pós-Operatórias , Cuidados Pré-OperatóriosRESUMO
BACKGROUND: Postoperative pulmonary complications (PPCs) are major causes of morbidity, mortality, and prolonged hospital stay in patients after surgery. Using effective strategies to prevent its occurrence is essential to improve outcome. However, despite various efforts, the incidence of PPCs remains elevated in high-risk patients. Anticholinergic inhalation is used to reduce high airway resistance and improve pulmonary function; it may be helpful to decrease the risk of PPCs. Penehyclidine is a long-acting anticholinergic agent which selectively blocks M1 and M3 receptors. We hypothesize that, in high-risk patients, prophylactic penehyclidine inhalation may decrease the incidence of PPCs. METHODS: This is a randomized, double-blind, placebo-controlled trial with two parallel arms. A total of 864 patients at high risk of PPCs will be enrolled and randomized to receive prophylactic inhalation of either penehyclidine or placebo (water for injection). Study drug inhalation will be administered from the night (7 pm) before surgery until the second day after surgery, in an interval of every 12 hours. The primary outcome is the incidence of PPCs within 30 days after surgery. Secondary outcomes include the time to onset of PPCs (from end of surgery to first diagnosis of PPCs), the number of PPCs (indicates the number of diagnosed individual PPCs), the incidence of postoperative extrapulmonary complications, the length of stay in hospital after surgery, and the 30-day all-cause mortality. DISCUSSION: Results of the present study will provide evidence to guide clinical practice in using prophylactic inhalation of an anticholinergic to prevent PPCs in high-risk patients. TRIAL REGISTRATION: The study was registered prospectively in Chinese Clinical Trial Registry ( www.chictr.org.cn , ChiCTR-IPC-15006603 ) on 14 May 2015 and retrospectively in ClinicalTrials.gov ( NCT02644876 ) on 30 December 2015.