Intrathecal Drug Delivery System in Prepontine Cistern for Patients with Intractable Craniofacial Cancer Pain: A Multicenter Retrospective Study.

BACKGROUND: Patients with craniofacial cancer frequently suffer from severe pain. The traditional intrathecal, oral, or intravenous analgesics could only provide insufficient pain relief with many side effects. Thus, a more effective analgesia approach is required. This study aimed to investigate the safety and efficacy of placing the catheter of an intrathecal morphine pump in the prepontine cistern for the treatment of craniofacial cancer pain. METHODS: We performed a retrospective study of patients with primary or metastatic craniofacial cancer pain who received the catheter placement of an intrathecal morphine pump into the prepontine cistern in eleven medical centers from September 2019 to December 2023. Friedman test and pairwise signed-rank test were used to evaluate the difference in numeric rating scale (NRS) scores, the number of breakthrough pain episodes, dose of intrathecal morphine, and dose of systemic morphine equivalents (oral, patch, intravenous) from preoperative period to postoperative days 1, 7, and 30. P values were corrected for multiple comparisons using Bonferroni test. RESULTS: The study included 33 patients. The median (interquartile range [IQR]) of NRS scores at days 1, 7, and 30 postimplant were 2.0 (1.0-3.5), 2.0 (1.0-2.0), and 1.0 (1.0-2.0), respectively, which was significantly lower than that before surgery (median, 8.0; IQR, 7.0-10.0; all P < .001). Compared to baseline number/d of breakthrough pain episodes (median, 6.0; IQR, 4.5-10.0), there was a progressive decrease in the number/d of breakthrough pain episodes at day 1, day 7, and day 30 postimplant, and the median (IQR) were 1.0 (0.0-3.0), 2.0 (0.0-3.0), and 0.0 (0.0-1.2), respectively (all P < .001). Approximately 78.8% and 96.7% of patients reported pain relief >50% at days 1 and 30 postimplant, respectively. Compared with that at day 1 postimplant, the proportion of patients with a pain relief rate >75% at day 30 postimplant also increased with continued intrathecal treatment. Compared to the dose of baseline systemic morphine equivalents (median, 228 mg.d-1; IQR, 120-408 mg.d-1), the dose of systemic morphine equivalents reduced significantly from 0(0-120) mg.d-1 at day 1 postimplant (P = .001), to 0 (0-0) mg.d-1 at days 7 and 30 postimplant (both P < .001). Few patients reported perioperative adverse events, including nausea, constipation, hypotension, urinary retention, dry mouth, headache, and sedation. No severe adverse events occurred. CONCLUSIONS: Placing the catheter tip of an intrathecal morphine pump into the prepontine cistern could effectively relieve refractory craniofacial cancer pain with an extremely low total morphine dose requirement and few adverse events. This procedure could be considered in patients with severe refractory craniofacial cancer pain.

Technical guideline for intra-prepontine cisternal drug delivery via spinal puncture through subarachnoid catheterization. / ç»è„ŠæŸ±æ¤Žé—´éš™ç©¿åˆºè››ç½‘è†œä¸‹è ”è„‘æ¡¥å‰æ± ç½®ç®¡è¯ç‰©è¾“æ³¨æŠ€æœ¯åº”ç”¨æŒ‡å—.

OBJECTIVES: The distribution characteristics of intrathecal drugs and the limitation of current catheterization techniques make traditional intrathecal analgesic treatment nearly useless for refractory craniofacial pain, such as trigemina neuralgia. This technical guideline aims to promote the widespread and standardize the application of intra-prepontine cisternal drug delivery via spinal puncture and catheterization. METHODS: A modified Delphi approach was used to work for this guideline. On the issues related to the intra-prepontine cisternal targeted drug delivery technique, the working group consulted 10 experts from the field with 3 rounds of email feedback and 3 rounds of conference discussion. RESULTS: For the efficacy and safety of the intra-prepontine cisternal targeted drug delivery technique, a consensus was formed on 7 topics (with an agreement rate of more than 80%), including the principles of the technique, indications and contraindications, patient preparation, surgical specifications for intra-prepontine cisternal catheter placement, analgesic dosage coordination, analgesic management, and prevention and treatment of complications. CONCLUSIONS: Utilizing the intra-prepontine cisternal drug infusion system to manage refractory craniofacial pain could provide advantages in terms of minimally invasive, secure, and effective treatment. This application can not only alleviate the suffering of individuals experiencing the prolonged pain but also support the maintenance of quality of life and dignity in their final moments, justifiing its widespread dissemination and standardized adoption in domestic and international professional fields.

Effect of autologous platelet-rich plasma on patients with acute type A aortic dissection underwent aortic arch replacement: A retrospective cohort study.

BACKGROUND: Coagulopathy and massive bleeding are common complications of patients with Stanford type A acute aortic dissection repair, and patients with these complications require many transfusions. Autologous platelet-rich plasma (PRP) is widely used to reduce the need for blood products. In the present study, we aimed to investigate the effects of PRP on blood conservation and the postoperative conditions of patients who underwent aortic arch replacement. METHODS: Patients with aortic dissection undergoing aortic arch replacement were included initially application In all, 837 patients were divided into the PRP and non-PRP groups according to PRP use, whereupon a propensity score match was performed. The data analyzed included patient basic information, intraoperative information, postoperative biochemical examinations, and CTA reports. RESULTS: In total, 610 patients were finally included (305 patients per group). Groups were well balanced after matching. Compared to the non-PRP group, less cryoprecipitate was transfused in the PRP group (10.0 [7.5, 11.0] vs. 10.0 [10.0, 11.5], P = 0.021), while no differences were found in packed RBC, FFP, and platelets between the two groups. Also, the surgery variables showed no differences. After surgery, patients in the PRP group showed higher postoperative serum albumin (36.43±4.20 vs. 35.39±4.40 g/L, P = 0.004) and total protein levels (59.38±6.25 vs. 58.06±7.19 g/L, P = 0.019) than the non-PRP group, but no significant differences in the levels of ALT, AST, Scr, and BUN. CTA reports showed that the proportion of patients with pleural effusion was lower in the PRP group (76.66% vs. 83.99%, OR = 1.59, 95% CI: 1.04-2.45, P = 0.028), while the proportions of pericardial effusion were not significantly different. CONCLUSIONS: PRP application in aortic arch replacement surgery reduced the transfusion of cryoprecipitate, increased the postoperative serum albumin and total protein levels, and reduced the incidence of pleural effusion. No effect of PRP application was found on other postoperative blood indicators and CTA reports.

Sevoflurane preconditioning alleviates myocardial ischemia reperfusion injury through mitochondrial NAD+-SIRT3 pathway in rats. / 七氟醚预处理通过线粒体NAD+-SIRT3é€šè·¯å‡è½»å¤§é¼ å¿ƒè‚Œç¼ºè¡€å†çŒæ³¨æŸä¼¤.

OBJECTIVES: Myocardial ischemia reperfusion injury (IRI) occurs occasionally in the process of ischemic heart disease. Sevoflurane preconditioning has an effect on attenuating IRI. Preserving the structural and functional integrity of mitochondria is the key to reduce myocardial IRI. Silent information regulator 3 (SIRT3), a class of nicotinamide adenine dinucleotide (NAD+) dependent deacetylases, is an important signal-regulating molecule in mitochondria. This study aims to explore the role of mitochondrial NAD+-SIRT3 pathway in attenuating myocardial IRI in rats by sevoflurane preconditioning. METHODS: A total of 60 male Sprague Dawley (SD) rats were randomly divided into 5 groups (n=12): A sham group (Sham group), an ischemia reperfusion group (IR group), a sevoflurane preconditioning group (Sev group, inhaled 2.5% sevoflurane for 30 min), a sevoflurane preconditioning+SIRT3 inhibitor 3-TYP group (Sev+3-TYP group, inhaled 2.5% sevoflurane for 30 min and received 5 mg/kg 3-TYP), and a 3-TYP group (5 mg/kg 3-TYP). Except for the Sham group, the IR model in the other 4 groups was established by ligating the left anterior descending coronary artery. The size of myocardial infarction was determined by double staining. Serum cardiac troponin I (cTnI) level was measured. The contents of NAD+ and ATP, the activities of mitochondrial complexes I, II, and IV, the content of MDA, the activity of SOD, and the changes of mitochondrial permeability were measured. The protein expression levels of SIRT3, SOD2, catalase (CAT), and voltage dependent anion channel 1 (VDAC1) were detected by Western blotting. The ultrastructure of myocardium was observed under transmission electron microscope. MAP and HR were recorded immediately before ischemia (T0), 30 min after ischemia (T1), 30 min after reperfusion (T2), 60 min after reperfusion (T3), and 120 min after reperfusion (T4). RESULTS: After ischemia reperfusion, the content of NAD+ in cardiac tissues and the expression level of SIRT3 protein were decreased (both P<0.01), and an obvious myocardial injury occurred, including the increase of myocardial infarction size and serum cTnI level (both P<0.01). Correspondingly, the mitochondria also showed obvious damage on energy metabolism, antioxidant function, and structural integrity, which was manifested as: the activities of mitochondrial complexes I, II, and IV, ATP content, protein expression levels of SOD2 and CAT were decreased, while MDA content, VDAC1 protein expression level and mitochondrial permeability were increased (all P<0.01). Compared with the IR group, the content of NAD+ in cardiac tissues and the expression level of SIRT3 protein were increased in the Sev group (both P<0.01); the size of myocardial infarction and the level of serum cTnI were decreased in the Sev group (both P<0.01); the activities of mitochondrial complexes I, II, and IV, ATP content, protein expression levels of SOD2 and CAT were increased, while MDA content, VDAC1 protein expression level, and mitochondrial permeability were decreased in the Sev group (all P<0.01). Compared with the Sev group, the content of NAD+ in cardiac tissues and the expression level of SIRT3 protein were decreased in the Sev+3-TYP group (both P<0.01); the size of myocardial infarction and the level of serum cTnI were increased in the Sev+3-TYP group (both P<0.01); the activities of mitochondrial complexes I, II, and IV, ATP content, protein expression levels of SOD2 and CAT were decreased, while MDA content, VDAC1 protein expression level, and mitochondrial permeability were increased in the Sev+3-TYP group (all P<0.01). CONCLUSIONS: Sevoflurane preconditioning attenuates myocardial IRI through activating the mitochondrial NAD+-SIRT3 pathway to preserve the mitochondrial function.

[Proteomics analysis of myocardium after delayed preconditioning with hydrogen sulfide in rat].

OBJECTIVE: To investigate the changes in protein of myocardium after hydrogen sulfide delayed preconditioning by using proteomics technology. METHODS: Sixteen Sprague-Dawley rats were randomly assigned to control (group S) or hydrogen sulfide group (group H), n = 8 for each group. Myocardial ischemia/reperfusion injury model (ischemia 30 minutes followed by reperfusion 120 minutes) was reproduced at 24 hours after preconditioning either with normal saline or hydrogen sulfide for proteomics analysis in group S or group H, and the myocardial tissue was harvested. The total proteins were extracted and separated by two dimensional gel electrophoresis (2-DE), and the differential protein expression spots were analyzed with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). RESULTS: Analysis of 2-DE showed that 929 ± 14 protein spots were found in group S and 906 ± 10 protein spots in group H, and the expression of 15 protein spots was different between two groups. These protein spots were chosen to undergo MALDI-TOF-MS analysis, and 11 proteins were preliminarily identified, including DNA ligase, cystathionine gamma-lyase, transcription initiation factor, NADH dehydrogenase, guanine nucleotide-releasing factor, fructose-bisphosphate aldolase A, glycogen synthase kinase-3, electron transfer flavoprotein subunit beta, glutathione S-transferase, soluble calcium-activated nucleotidase and S-adenosylmethionine synthetase. CONCLUSIONS: Hydrogen sulfide delayed preconditioning of myocardium resulted in the changes in protein expression profiles in the myocardium. The differential proteins might function as anti-oxidants, to improve the energy metabolism of myocardium, confer cytoprotection and protection of respiratory chain, thus conferring cardioprotection.

[Effect of Gingkgo biloba leaf extract induced delayed preconditioning on cytochrome c oxidase expression during myocardial ischemia-reperfusion in rats].

OBJECTIVE: To determine the effect of Gingkgo biloba leaf extract (EGb761) induced delayed preconditioning on cytochrome c oxidase (CcO) expression during myocardial ischemia-reperfusion in rats. METHODS: Four groups (10 in each) of Sprague-Dawley male rats were studied. In the sham group, the rats received no treatment. Rats in the ischemia-reperfusion (IR) group were treated with NS (1.0 mL/kg intravenously) 24 h before ischemia. Rats in the M group were treated with EGb761 (100 mg/kg intravenously) 24 h before the ischemia. In the D group , EGb761-treated rats that received the 5-hydroxydecanoate (5-HD), an inhibitor of mitochondrial KATP channels 15 min before the ischemia. The IR, M, and D groups were subjected to ischemia by 30 min of coronary artery occlusion before 2 h of reperfusion. At the end of the reperfusion, myocardial infarct size was measured. CcO was measured by Western blot. The myocardial ultrastructure was observed under the electron microscope. RESULTS: The infarct size was significantly smaller in the M group [(23.78 ± 4.82)%] than in the I/R group [(37.87 ± 5.92)%] (P<0.05). The CcO protein expression in the myocardium was significantly higher in the M group than in the I/R group(P<0.05). Microscopic examination showed less myocardial damage in the M group than that in the I/R group. The infarct size, CcO protein expression, and myocardial damage had no significant difference between the D group and the I/R group (P>0.05). CONCLUSION: EGb761 induced delayed preconditioning attenuates myocardial ischemia-reperfusion injury possibly through up-regulating CcO expression in rats.

Pharmacokinetic comparisons of albiflorin and paeoniflorin after oral administration of Shaoyao-Gancao-Tang and single herb Paeony decoction to rats.

Shaoyao-Gancao-Tang (SGT) is a traditional Chinese prescription containing Radix Paeoniae alba and Radix Glycyrrhizae and is commonly used to relieve pains. Albiflorin and paeoniflorin are the main effective compounds of Radix Paeoniae alba, and the pharmacokinetic differences of the two compounds in rats after oral administration of SGT and single herb Paeony decoction were studied. At different time points (5, 10, 15, 20, 30, 45, 60, 90, 120, 180, 240, 360, and 540 min) after administration, plasma concentrations of albiflorin and paeoniflorin were determined using a simple and reliable UPLC method, and main pharmacokinetic parameters were evaluated. It was found that there were significant differences (p < 0.05 or p < 0.01) between the two groups. The results indicated that some components in the other ingredient herb of SGT (Radix Glycyrrhizae) had a pharmacokinetic interaction with albiflorin and paeoniflorin and hence reduced their systematic exposure level.

Delayed preconditioning by sevoflurane elicits changes in the mitochondrial proteome in ischemia-reperfused rat hearts.

BACKGROUND: Delayed myocardial preconditioning by volatile anesthetics involves changes in DNA transcription and translation. Mitochondria play a central role in myocardial ischemia/reperfusion (I/R) injury and in ischemic or pharmacologic preconditioning. In this study, we investigated whether there are alterations in myocardial mitochondrial protein expression after volatile anesthetic preconditioning (APC) to examine the underlying mechanisms of delayed cardioprotection. METHODS: Thirty-six Sprague-Dawley rats were randomly assigned to 1 of 3 groups (n = 12 for each group). Rats in the delayed APC group were exposed to sevoflurane (2.5% for 60 minutes) 24 hours before myocardial ischemia was induced. Myocardial ischemia in the I/R and APC groups was induced by left coronary artery occlusion for 30 minutes, followed by 120 minutes of reperfusion. The control group received no treatment. The mitochondria fractions were prepared by differential centrifugation with density gradient isolation for proteomic analysis. Two-dimensional gel electrophoresis and matrix-assisted laser desorption/ionization with time-of-flight mass spectrometry was used to identify differences in the protein expression from mitochondria of the rat hearts. RESULTS: Fifteen differentially expressed mitochondrial proteins between the APC group and I/R group were identified and the expression patterns of 2 of the proteins were confirmed by Western blot analysis. These proteins were associated with mitochondrial substrate metabolism, respiration, and adenosine triphosphate (ATP)/adenosine diphosphate transport. The modifications of the mitochondrial proteome suggest an enhanced capacity of mitochondria to maintain myocardial ATP levels after I/R injury. CONCLUSION: Delayed sevoflurane myocardial preconditioning induces mitochondrial proteome remodeling, which mainly involves proteins that are related to ATP generation and transport. Therefore, proteomic changes related to bioenergetic balance may be the mechanistic basis of delayed anesthetic myocardial preconditioning.