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Biomolecules Jun 2024The relationship between type 2 diabetes mellitus (T2DM) and colorectal cancer (CRC) has long been extensively recognized, but their crosstalk mechanisms based on gene...
The relationship between type 2 diabetes mellitus (T2DM) and colorectal cancer (CRC) has long been extensively recognized, but their crosstalk mechanisms based on gene regulation remain elusive. In our study, for the first time, bulk RNA-seq and single-cell RNA-seq data were used to explore the shared molecular mechanisms between T2DM and CRC. Moreover, Connectivity Map and molecular docking were employed to determine potential drugs targeting the candidate targets. Eight genes (, , , , , , , ) were identified as characteristic comorbidity genes for T2DM and CRC, with and further identified as core comorbidity genes. Our results demonstrated that upregulation of EVPL and downregulation of ENTPD3 were intrinsic molecular features throughout T2DM and CRC and were significantly associated with immune responses, immune processes, and abnormal immune landscapes in both diseases. Single-cell analysis highlighted a cancer-associated fibroblast (CAF) subset that specifically expressed ENTPD3 in CRC, which exhibited high heterogeneity and unique tumor-suppressive features that were completely different from classical cancer-promoting CAFs. Furthermore, ENTPD3 CAFs could notably predict immunotherapy response in CRC, holding promise to be an immunotherapy biomarker at the single-cell level. Finally, we identified that droperidol may be a novel drug simultaneously targeting EVPL and ENTPD3. In conclusion, previous studies have often focused solely on metabolic alterations common to T2DM and CRC. Our study establishes EVPL and ENTPD3 as characteristic molecules and immune biomarkers of comorbidity in T2DM and CRC patients, and emphasizes the importance of considering immunological mechanisms in the co-development of T2DM and CRC.
Topics: Humans; Colorectal Neoplasms; Diabetes Mellitus, Type 2; Single-Cell Analysis; Comorbidity; Gene Expression Regulation, Neoplastic; Molecular Docking Simulation; Male
PubMed: 38927096
DOI: 10.3390/biom14060693 -
Journal of Neurosurgical Anesthesiology Oct 2022Low-dose droperidol has been reported to suppress the amplitude of transcranial electrical motor-evoked potentials (TCE-MEPs), but no randomized controlled trials have... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Low-dose droperidol has been reported to suppress the amplitude of transcranial electrical motor-evoked potentials (TCE-MEPs), but no randomized controlled trials have been conducted to assess this. This randomized, double-blinded, placebo-controlled trial aimed to test the hypothesis that low-dose droperidol reduced TCE-MEP amplitudes.
METHODS
Twenty female patients with adolescent idiopathic scoliosis, aged between 12 and 20 years, and scheduled to undergo corrective surgery were randomly allocated to receive droperidol (20 µg/kg) or 0.9% saline. After recording baseline TCE-MEPs, the test drug was administered, following which TCE-MEP recordings were carried out every 2 minutes for up to 10 minutes. The primary outcome was the minimum relative TCE-MEP amplitude (peak-to-peak amplitude, percentage of baseline value) recorded in the left tibialis anterior muscle. Secondary outcomes included minimum relative MEP amplitudes recorded from all other muscle groups monitored in the study. Data are expressed as medians (interquartile range).
RESULTS
The TCE-MEP amplitude of the left tibialis anterior muscle was significantly reduced following droperidol administration compared with saline (37% [30% to 55%] vs. 76% [58% to 93%], respectively, P <0.01). In the other muscles, the amplitudes were reduced in the droperidol group, except for the bilateral abductor pollicis brevis and the left quadriceps femoris muscles. The relative amplitude of the bilateral F waves recorded from the gastrocnemius was decreased in the droperidol group.
CONCLUSIONS
Low-dose droperidol (20 µg/kg) reduced TCE-MEP amplitudes. Anesthesiologists should pay attention to the timing of droperidol administration during intraoperative TCE-MEP recordings, even if used in a low dose.
Topics: Adolescent; Adult; Child; Droperidol; Evoked Potentials, Motor; Female; Humans; Monitoring, Intraoperative; Muscle, Skeletal; Young Adult
PubMed: 34411060
DOI: 10.1097/ANA.0000000000000784 -
Expert Opinion on Drug Metabolism &... Jun 2024Dopamine (D)-receptor antagonists (RAs) were the first antiemetics used in the prophylaxis of chemotherapy-induced nausea and vomiting (CINV). (Review)
Review
INTRODUCTION
Dopamine (D)-receptor antagonists (RAs) were the first antiemetics used in the prophylaxis of chemotherapy-induced nausea and vomiting (CINV).
AREAS COVERED
Eight D-RAs, amisulpride, domperidone, droperidol, haloperidol, metoclopramide, metopimazine, olanzapine and prochlorperazine are reviewed focusing on pharmacokinetics, pharmacodynamics, antiemetic effect and side effects.
EXPERT OPINION
Since the introduction of D-RAs, antiemetics such as corticosteroids, 5-hydroxytryptamine (5-HT)-RAs and neurokinin (NK)-RAs have been developed. The classical D-RAs are recommended in the prophylaxis of CINV from low emetic risk chemotherapy, but not as a fixed component of an antiemetic regimen for moderately or highly (HEC) emetic risk chemotherapy. D-RAs are also used in patients with breakthrough nausea and vomiting. It should be emphasized, that most of these drugs are not selective for dopamine receptors.The multi-receptor targeting agent, olanzapine, is recommended in the prophylaxis of HEC-induced CINV as part of a four-drug antiemetic regimen, including a 5-HT-RA, dexamethasone and a NK-RA. Olanzapine is the most effective agent to prevent chemotherapy-induced nausea.Side effects differ among various D-RAs. Metopimazine and domperidone possess a low risk of extrapyramidal side effects. Domperidone and metoclopramide are prokinetics, whereas metopimazine delays gastric emptying and haloperidol does not influence gastric motility. Many D-RAs increase the risk of prolonged QTc interval; other side effects include sedation and orthostatic hypotension.
Topics: Humans; Nausea; Vomiting; Antiemetics; Antineoplastic Agents; Dopamine Antagonists; Animals; Dopamine D2 Receptor Antagonists; Receptors, Dopamine D3
PubMed: 38878283
DOI: 10.1080/17425255.2024.2367593 -
Brazilian Journal of Anesthesiology... 2022Procedures for Postoperative Nausea and Vomiting (PONV) prevention are mostly based on identification of the risk factors before administering antiemetic drugs. The...
BACKGROUNDS
Procedures for Postoperative Nausea and Vomiting (PONV) prevention are mostly based on identification of the risk factors before administering antiemetic drugs. The purpose of this study was to evaluate the impact of the extended use of antiemetic on the PONV in the Postanesthetic Care Unit (PACU).
METHODS
Two separate 4-year periods (2007...2010, P1, and (2015...2018, P2) were evaluated. During P1, the protocol consisted of dexamethasone and droperidol for patients with a locally adapted high PONV score, followed by ondansetron for rescue in the PACU. For Period 2, dexamethasone (8 mg) and ondansetron (4 mg) were administered in patients under general or regional anesthesia, or sedation longer than 30 minutes, while droperidol (1.25 mg) in rescue was injected in cases of PONV in the PACU. An Anesthesia Information Management System was used to evaluate the intensity score of PONV (1 to 5), putative compliance, sedation, and perioperative opioid consumption upon arrival in the PACU.
RESULTS
A total of 27,602 patients were assessed in P1 and 36,100 in P2. The administration of dexamethasone and ondansetron increased several fold (p < 0.0001). The high PONV scores were more improved in P2 than in P1, with scores (3+4+5) for P1 vs. P2, p < 0.0001. Overall, 99.7% of the patients in P2 were asymptomatic at discharge. Morphine consumption decreased from 6.9..1.5 mg in P1 to 3.5 .. 1.5 mg in P2 (p < 0.0001).
DISCUSSION
The extension of pharmacological prevention of PONV was associated with a decrease in the intensity of severe PONV. However, uncertainty regarding confounding factors should not be ignored. IRB: n.. 92012/33465.
Topics: Humans; Postoperative Nausea and Vomiting; Ondansetron; Droperidol; Retrospective Studies; Antiemetics; Neoplasms; Dexamethasone; Double-Blind Method
PubMed: 34216701
DOI: 10.1016/j.bjane.2021.06.007 -
Cureus Dec 2023Background A preoperative sciatic nerve block (SNB) before total knee arthroplasty (TKA) frequently causes postoperative drop foot; however, this can also occur as an...
Background A preoperative sciatic nerve block (SNB) before total knee arthroplasty (TKA) frequently causes postoperative drop foot; however, this can also occur as an unintended result of surgical invasion. This study assessed the benefits of a postoperative SNB at the subgluteal space for patients who underwent TKA. Methodology This was a single-center, retrospective cohort study. Patients who underwent TKA under general anesthesia between May 2018 and June 2019 at the Teikyo University School of Medicine were screened for inclusion. They received either a preoperative femoral nerve block alone (control group; n = 87) or a preoperative femoral nerve block and postoperative SNB at the subgluteal space (post-SNB group; n = 40). The primary outcome was the pain-related Numerical Rating Scale (NRS) scores. The secondary outcomes were postoperative nausea and vomiting (PONV), intravenous patient-controlled analgesia (iv-PCA) suspension, and postoperative complications. Results No significant differences were observed in the characteristics, NRS scores, time to first drug use for pain, and iv-PCA suspension between groups. However, the incidence of PONV was significantly lower in the post-SNB group (p = 0.03). Logistic regression analysis revealed that droperidol doses of iv-PCA and the presence of postoperative SNB were independently associated with PONV occurrence [A1] {(p = 0.008, 95% confidence intervals (CI) [0.46, 0.89] and (p = 0.02, 95% CI [0.25, 0.88])}. Conclusions A postoperative SNB at the subgluteal space following TKA does not improve postoperative pain control; however, it may have contributed to reduced PONV.
PubMed: 38249241
DOI: 10.7759/cureus.50882 -
International Journal of Obstetric... Nov 2019This study aimed to compare the postoperative analgesic effects of ultrasound-guided posterior quadratus lumborum block with spinal morphine, after cesarean section,... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
This study aimed to compare the postoperative analgesic effects of ultrasound-guided posterior quadratus lumborum block with spinal morphine, after cesarean section, using the visual analogue scale pain score.
METHODS
One-hundred-and-seventy-six pregnant women scheduled for elective cesarean section with spinal anesthesia were randomly allocated into four groups to receive spinal morphine 0.1 mg (group M); spinal saline (M); posterior quadratus lumborum block using either 0.3% ropivacaine (0.45 mL/kg each side, maximum 150 mg) group pQ); or saline (pQ). All patients received 11-13 mg hyperbaric bupivacaine 0.5% and 10 μg fentanyl. Intravenous droperidol, fentanyl and acetaminophen were administered during surgery. Bilateral posterior quadratus lumborum block was performed immediately after surgery. Postoperative pain was assessed at 0.5, 1, 2, 4, 6, 18 and 24 h after surgery, and the pain score 6 h after surgery was the primary endpoint.
RESULTS
One-hundred-and-forty-six patients were included in the final analysis. Pain scores 6 h after surgery, both at rest and when moving, were significantly different when comparing the MpQ group with the MpQ or MpQ groups, and when comparing the MpQ group with the M pQ or M pQ groups (all P <0.05). There was no significant difference between the MpQ and MpQ groups, or between the MpQ and MpQ groups.
CONCLUSION
Spinal morphine improved postoperative analgesia but the combination of posterior quadratus lumborum block with spinal morphine did not lead to further improvement.
Topics: Adult; Analgesia, Obstetrical; Analgesics, Opioid; Anesthesia, Spinal; Cesarean Section; Double-Blind Method; Female; Humans; Morphine; Nerve Block; Pain, Postoperative; Pregnancy; Prospective Studies; Treatment Outcome
PubMed: 31353177
DOI: 10.1016/j.ijoa.2019.06.008 -
Journal of Paediatrics and Child Health Jan 2022Studies reporting factors associated with paediatric/adolescent acute behavioural disturbance (ABD) in the Emergency Department (ED) are lacking. The aim of this study...
AIM
Studies reporting factors associated with paediatric/adolescent acute behavioural disturbance (ABD) in the Emergency Department (ED) are lacking. The aim of this study is to describe paediatric/adolescent ED presentations involving ABD events.
METHODS
A retrospective chart review of presentations involving ABD events, identified via hospital security log, to a tertiary referral paediatric ED during the 2017 calendar year. Data reported included: cause of presentation, use of sedation/physical restraint, ED/inpatient length of stay (LOS) and time requiring security staff presence.
RESULTS
From 280 reported ABD episodes 26 were excluded leaving 254 events involving 150 patients across 233 presentations of whom 38 (25.3%) presented on multiple occasions. Median age was 14 years (interquartile range (IQR): 13-16), 132/233 (56.7%) were female, 167/233 (71.7%) primary mental health complaints, 30/233 (12.9%) deliberate self-harm, 18/233 (7.7%) deliberate self-poisoning, 11/233 (4.7%) acute intoxication and 7/233 (3.0%) other. Transport to hospital involved police and ambulance in 124/233 (53.2%), ambulance only 71/233 (30.5%), police only 16/233 (6.9%), relative or carer 20/233 (8.6%), with self-presentation in 2/233 (0.9%). Sedation or physical restraint was used in 81/233 (34.8%), both 38/233 (16.3%), restraint only 26/233 (11.2%) and sedation only 17/234 (7.3%). Intra-muscular droperidol accounted for 57/96 (59.4%) sedations, IM/IV benzodiazepines 15/96 (15.6%), IM/IV ketamine 5/96 (5.2%) and 19/96 (19.8%) other. Discharge from ED occurred in 171/233 (73.1%) with median ED LOS 5.1 h (IQR: 3.5-7.7) and median hospital LOS 92.4 h (IQR: 47.5-273.4) for those admitted. The Mental Health Act was utilised in 183/233 (78.5%) presentations. Median security staff time requirement per presentation was 2.4 h (IQR: 1.0-3.9).
CONCLUSIONS
Paediatric/adolescent ED presentations involving ABD are primarily due to mental health complaints. Less than half require the use of sedation/physical restraint. Time requiring security staff involvement is a significant resource consumption.
Topics: Adolescent; Child; Emergency Service, Hospital; Female; Humans; Length of Stay; Patient Discharge; Police; Retrospective Studies
PubMed: 34375471
DOI: 10.1111/jpc.15668 -
BMC Chemistry Jan 2024A green, efficient, sensitive and accurate detection method by HPLC-DAD and LC-MS/MS was developed and validated for the quantification of morphine, hydromorphone,...
A green, efficient, sensitive and accurate detection method by HPLC-DAD and LC-MS/MS was developed and validated for the quantification of morphine, hydromorphone, oxycodone, ketamine tramadol, dezocine, ropivacaine, remifentanil, butorphanol, bupivacaine, droperidol, fentanyl, lornoxicam and sufentanil. The 14 mixtures were chromatographed via HPLC-DAD method which employed 0.05 mol/L potassium dihydrogen phosphate solution-acetonitrile as the mobile phase, the analytes were gradient elution on a SinoChrom ODS-BP C column with a total separation time of 35 min, and 14 mixtures showed a good linear relationship in the linear range. The Limit of Quantitation (LOQ) ranged from 0.10 to 20.0 µg/mL, the inter-day and intra-day precision of each analyte is within 1.1-2.0% and 0.4-1.3%, and the average absolute recovery of all compounds was above 98%. The LC-MS/MS method was used to successfully separate the 14 mixtures within 10 min which employed 0.1% formic acid-acetonitrile as the mobile phase, the analytes were gradient elution on a ACQUITY UPLC-BEH C column with a total separation time of 13 min, and 14 mixtures showed a good linear relationship in the linear range. The LOQ ranged from 0.005 to 0.2 ng/mL, the inter-day and intra-day precision of each analyte is within 1.2-4.1% and 0.6-3.3%, and the average absolute recovery of all compounds was above 93%. The proposed method has been successfully applied in the clinic and provides a strong technical basis for the quantitative detection of these 14 mixtures for detecting drug abuse, and for studying the stability and compatibility of analgesic solutions. The proposed methods were validated against ICH guidelines.
PubMed: 38200560
DOI: 10.1186/s13065-024-01113-6 -
The Medical Letter on Drugs and... Dec 2020
Topics: Administration, Intravesical; Amisulpride; Antiemetics; Double-Blind Method; Humans; Postoperative Nausea and Vomiting; Randomized Controlled Trials as Topic
PubMed: 33451177
DOI: No ID Found -
Emergency Medicine Australasia : EMA Aug 2021Rapidly and safely managing severe acute behavioural disturbance (ABD) in the prehospital setting is important for the welfare of both patient and prehospital clinician... (Observational Study)
Observational Study
OBJECTIVE
Rapidly and safely managing severe acute behavioural disturbance (ABD) in the prehospital setting is important for the welfare of both patient and prehospital clinician alike. We investigated the safety and effectiveness of ketamine as rescue sedation in patients with severe ABD.
METHODS
This prospective observational study investigated ketamine use by a state ambulance service as rescue sedation for patients with severe ABD who remained agitated following droperidol administration. The primary outcome was the proportion of adverse events (vomiting, hypersalivation, emergence, over-sedation, airway obstruction, laryngospasm, hypoxia, bradypnoea and intubation). Secondary outcomes included time to sedation, requirement for additional sedation and rate of successful sedation.
RESULTS
There were 105 presentations (males 69/102 [69%]; median age 31 years (16-83 years). The commonest causes of ABD were illicit drug (39%) and alcohol (33%) intoxication. The median total dose of intramuscular ketamine was 200 mg (interquartile range [IQR] 150-200 mg). There were 64 adverse events in 40 (38%) patients. Four had vomiting, two had hypersalivation, two had emergence, 15 were oversedated, four had hypoxia, three had bradypnoea and 16 were intubated. Sedation was achieved in 103 (98%) patients at a median time post-ketamine of 8 min (IQR 5-13 min). Additional sedation was administered to 41 patients (nine prehospital and 37 within 1 h of arriving to hospital). In 44 (42%) patients, ketamine successfully sedated the patient with no adverse effects and no ongoing sedation requirement.
CONCLUSION
The use of ketamine as rescue sedation in prehospital patients with severe ABD is effective. Adverse events are common but can be managed supportively.
Topics: Adult; Conscious Sedation; Droperidol; Emergency Service, Hospital; Humans; Ketamine; Male; Prospective Studies
PubMed: 33202484
DOI: 10.1111/1742-6723.13682