Comparison of Analgesic Effects and Adverse Events of Hydromorphone PCIA Versus Sufentanil PCIA: A Retrospective Analysis.

PURPOSE: The aim of this study was to compare the analgesic effect and adverse events of hydromorphone patient-controlled intravenous analgesia (PCIA) without background dose versus sufentanil PCIA with background dose in patients after surgery. DESIGN: A retrospective analysis. METHODS: From June 2020 to May 2021, 1,594 eligible postoperative patients who received PCIA were included in this study. According to the types of opioids, patients were divided into two groups: the sufentanil group and the hydromorphone group. The Numerical Rating Scale, Functional Activity Scale, and Level of Sedation were used to evaluate the analgesic effects between the two groups. In addition, total patient-controlled analgesia (PCA) use, effective number of PCA compressions, and adverse effects of PCIA were compared between the two groups. FINDINGS: At 24 hours (h) after surgery, the Functional Activity Scale score in the sufentanil group was higher than that in the hydromorphone group (P < .05). Compared with the sufentanil group, total PCA use, total number of PCA compressions and effective number of PCA consumptions were significantly decreased in the hydromorphone group during a 48 hours period (P < .05). There were no statistical differences in Numerical Rating Scale score, Level of Sedation score, and adverse events between two groups at 24 hours and 48 hours after surgery. CONCLUSIONS: Compared with sufentanil PCIA with a background dose, under a similar analgesic effect, hydromorphone PCIA without a background dose provided lower PCA use. Our findings may provide useful evidence for more future studies related to postoperative analgesia.

TBC1D1 is an energy-responsive polarization regulator of macrophages via governing ROS production in obesity.

Energy status is linked to the production of reactive oxygen species (ROS) in macrophages, which is elevated in obesity. However, it is unclear how ROS production is upregulated in macrophages in response to energy overload for mediating the development of obesity. Here, we show that the Rab-GTPase activating protein (RabGAP) TBC1D1, a substrate of the energy sensor AMP-activated protein kinase (AMPK), is a critical regulator of macrophage ROS production and consequent adipose inflammation for obesity development. TBC1D1 deletion decreases, whereas an energy overload-mimetic non-phosphorylatable TBC1D1S231A mutation increases, ROS production and M1-like polarization in macrophages. Mechanistically, TBC1D1 and its downstream target Rab8a form an energy-responsive complex with NOX2 for ROS generation. Transplantation of TBC1D1S231A bone marrow aggravates diet-induced obesity whereas treatment with an ultra-stable TtSOD for removal of ROS selectively in macrophages alleviates both TBC1D1S231A mutation- and diet-induced obesity. Our findings therefore have implications for drug discovery to combat obesity.

Construction and Application of Chain Management Information System for Cancer Pain.

BACKGROUND: With the rapid development of information technology, hospital information systems (HISs) have been deeply applied in the medical field and have shown broad application prospects. There are still some noninteroperable clinical information systems that pose an obstacle to the effective coordination of care, such as cancer pain management. AIM: To construct a chain management information system for cancer pain and explore its clinical application effect. METHODS: A quasiexperimental study was conducted in the inpatient department of Sir Run Run Shaw Hospital, Zhejiang University School of Medicine. A total of 259 patients were nonrandomly divided into two groups: the experimental group (after the system was applied, n = 123) and the control group (before the system was applied, n = 136). The cancer pain management evaluation form score, patient satisfaction with pain control, pain score at admission and discharge, and the worst pain score during hospitalization were compared between the two groups. RESULTS: Compared with the control group, the score of the cancer pain management evaluation form was significantly higher (p < .05). There were no statistically significant differences in worst pain intensity, pain score at admission and discharge, and patients' satisfaction with pain control between the two groups. CONCLUSIONS: The cancer pain chain management information system can enable nurses to evaluate and record pain in a more standardized way, but it has no significant effect on the pain intensity of cancer patients.

Rab8a as a mitochondrial receptor for lipid droplets in skeletal muscle.

Dynamic interaction between lipid droplets (LDs) and mitochondria controls the mobilization of long-chain fatty acids (LCFAs) from LDs for mitochondrial ß-oxidation in skeletal muscle in response to energy stress. However, little is known about the composition and regulation of the tethering complex mediating LD-mitochondrion interaction. Here, we identify Rab8a as a mitochondrial receptor for LDs forming the tethering complex with the LD-associated PLIN5 in skeletal muscle. In rat L6 skeletal muscle cells, the energy sensor AMPK increases the GTP-bound active Rab8a that promotes LD-mitochondrion interaction through binding to PLIN5 upon starvation. The assembly of the Rab8a-PLIN5 tethering complex also recruits the adipose triglyceride lipase (ATGL), which couples LCFA mobilization from LDs with its transfer into mitochondria for ß-oxidation. Rab8a deficiency impairs fatty acid utilization and decreases endurance during exercise in a mouse model. These findings may help to elucidate the regulatory mechanisms underlying the beneficial effects of exercise on lipid homeostasis control.

TRIM24 is an insulin-responsive regulator of P-bodies.

Insulin is a potent inducer of mRNA transcription and translation, contributing to metabolic regulation. Insulin has also been suggested to regulate mRNA stability through the processing body (P-body) molecular machinery. However, whether and how insulin regulates mRNA stability via P-bodies is not clear. Here we show that the E3-ligase TRIM24 is a critical factor linking insulin signalling to P-bodies. Upon insulin stimulation, protein kinase B (PKB, also known as Akt) phosphorylates TRIM24 and stimulates its shuttling from the nucleus into the cytoplasm. TRIM24 interacts with several critical components of P-bodies in the cytoplasm, promoting their polyubiquitylation, which consequently stabilises Pparγ mRNA. Inactivation of TRIM24 E3-ligase activity or prevention of its phosphorylation via knockin mutations in mice promotes hepatic Pparγ degradation via P-bodies. Consequently, both knockin mutations alleviate hepatosteatosis in mice fed on a high-fat diet. Our results demonstrate the critical role of TRIM24 in linking insulin signalling to P-bodies and have therapeutic implications for the treatment of hepatosteatosis.

Spatiotemporal regulation of insulin signaling by liquid-liquid phase separation.

Insulin signals through its receptor to recruit insulin receptor substrates (IRS) and phosphatidylinositol 3-kinase (PI3K) to the plasma membrane for production of phosphatidylinositol-3,4,5-trisphosphate (PIP3) from phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2], which consequently activates protein kinase B (PKB). How insulin signals transduce from the plasma membrane into the cytoplasm is not clearly understood. Here we show that liquid-liquid phase separation (LLPS) plays a critical role in spatiotemporal control of insulin signaling through regulating multiple components including IRS1. Both protein concentration and insulin stimulation can drive the formation of intracellular IRS1 condensates through LLPS. Components including PI(4,5)P2, p85-PI3K and PDK1 are constitutively present in IRS1 condensates whereas production of PIP3 and recruitment of PKB in them are induced by insulin. Thus, IRS1 condensates function as intracellular signal hubs to mediate insulin signaling, whose formation is impaired in insulin resistant cells. Collectively, these data reveal an important function of LLPS in spatiotemporal control of insulin signaling.

Factors affecting sufentanil consumption for intravenous controlled analgesia after hepatectomy: retrospective analysis.

BACKGROUND: Pain control after hepatectomy is usually achieved by opioids. There are significant individual differences in the amount of opioids used after hepatectomy, and the metabolism of opioids is liver-dependent. The purpose of our study was to explore the possible risk factors for opioid consumption during the first 48 h after surgery. METHODS: In a retrospective study design involving 562 patients undergoing open or laparoscopic hepatectomy, all patients were treated with intravenous patient-controlled analgesia (IV-PCA) along with continuous and bolus doses of sufentanil for a duration of 48 h after surgery during the time period of August 2015 and February 2019. The primary endpoint was high sufentanil consumption 48 h after hepatectomy, and patients were divided into two groups: those with or without a high PCA sufentanil dosage depending on the third quartile (Q3). The secondary endpoint was the effect of a high PCA sufentanil dosage on various possible clinical risk factors. The relevant parameters were collected, and correlation and multivariate regression analyses were performed. RESULTS: The median operation time was 185 min (range, 115-250 min), and the median consumption of sufentanil 48 h after the operation was 91 µg (IQR, 64.00, 133.00). Factors related to the consumption of sufentanil at 48 h after hepatectomy included age, operation time, blood loss, intraoperative infusion (red blood cells and fresh-frozen plasma), pain during movement after surgery (day 1 and day 2), preoperative albumin, and postoperative blood urea nitrogen. Age (≤ 60 and > 60 years), extent of resection (minor hepatic resection and major hepatic resection), surgical approach (laparoscope and open) and operation time (min) were independent risk factors for sufentanil consumption at 48 h postoperatively. CONCLUSION: Age younger than 60 years, major hepatic resection, an open approach and a longer operation are factors more likely to cause patients to require higher doses of sufentanil after hepatectomy, and the early identification of such patients can increase the efficacy of perioperative pain management.

Postoperative Analgesic Efficacy of Erector Spinae Plane Block in Patients Undergoing Lumbar Spinal Surgery: A Systematic Review and Meta-Analysis.

Lumbar spine surgery is one of the most widespread types of surgery for treating back and leg pain. However, the postoperative period always presents with severe pain due to the removal of skin, subcutaneous tissues, bones, and ligaments. Patients usually require high doses of opioids to relieve pain during the initial three days after operation, as well as experience drug-related complications and prolonged length of stay in hospital. We found that Erector spinae plane block significantly reduced postoperative opioid consumption and pain scores. The present systematic review revealed that ESPB was effective and safe for postoperative analgesia.

Design of hydroxyapatite bioceramics with micro-/nano-topographies to regulate the osteogenic activities of bone morphogenetic protein-2 and bone marrow stromal cells.

Biomimicking the nanostructure of natural bone apatite to enhance the bioactivity of hydroxyapatite (HA) biomaterials is an eternal topic in the bone regeneration field. In the present study, we designed four kinds of HA bioceramics with micro- to nanosized grains and investigated the effects of bioceramic topographies on the structures of bone morphogenetic protein-2 (BMP-2) and the effects on the responses of bone marrow stromal cells (BMSCs). Compared to the samples with submicron-scale crystalline particles, HA bioceramics with grain sizes of 104.6 ± 27.8 nm exhibited increased roughness, improved hydrophilicity and enhanced mechanical properties. The synergistic effects of these surface characteristics could well maintain the conformation of BMP-2, facilitate cell adhesion and spreading, and activate the osteogenic differentiation of BMSCs. Furthermore, SBF immersion and in vivo canine intramuscular implantation confirmed that the HA bioceramics with nanotopography also processed excellent bone-like apatite forming ability and outstanding osteoinductivity. In summary, these findings suggest that the nanotopography of HA bioceramics is a critical factor to enhance their bioactivity and osteoinductivity.

Nurse-led follow-up to outpatients with cancer pain treated with opioids at home-telephone calls plus WeChat versus telephone calls only: a quasi-experimental study.

Background: Recently, cancer pain management has come increasingly to be provided in outpatient settings, requiring health-care providers and outpatients to take on responsibilities. Pain is among the most distressing symptoms of cancer. Objectives: To compare the effectiveness of nurse-led telephone calls plus WeChat versus telephone calls only for the pain management of outpatients with cancer. Methods: 231 outpatients with cancer pain were classified into two groups (group 1, N=125; group 2, N=106). Group 1 was followed up with weekly telephone calls for eight weeks, and group 2 with weekly telephone calls combined with the booklets through WeChat for eight weeks. Differences between groups in pain level, side effects, medication adherence, and satisfaction with pain management were analyzed, and statistical differences were tested usingan independent-sample t-test and a chi-squared test. Results: Group 2 had a significantly lower rest pain (p<0.01), and lower move pain but there was no statistical difference between the two groups. Among patients in group 2, constipation, nausea and vomiting, and dizziness were less (p<0.01), while medication adherence (p<0.05) and pain management satisfaction were higher (p<0.01) than patients in group 1. Conclusion: Nurse-led follow-up telephone calls combined with WeChat significantly reduced opioid-related health problems, such as pain intensity, side effects and medication adherence.

A Manganese-Superoxide Dismutase From Thermus thermophilus HB27 Suppresses Inflammatory Responses and Alleviates Experimentally Induced Colitis.

BACKGROUND: Superoxide dismutase (SOD) is an attractive therapeutic agent to ameliorate oxidative stress that is critical for the initiation and progression of inflammatory bowel disease (IBD). However, the short life of SOD limits its clinical application. In this study, we aim to examine the therapeutic effects of a hyperthermostable SOD from the Thermus thermophilus HB27 (TtSOD) for treatment of experimentally induced IBD. METHODS: A recombinant TtSOD was expressed and purified from Escherichia coli, and its therapeutic effects were examined in 2 experimental IBD animal models. RESULTS: In IBD induced by 2,4,6-trinitrobenzenesulfonic acid in zebrafish, TtSOD treatment decreased intestinal enlargement and attenuated neutrophil infiltration, resulting in alleviation of enterocolitis. In mice, SOD activity was substantially increased in the intestine after oral gavage of TtSOD, which ameliorated gut inflammation, preserved gut barrier function, and attenuated the severity of dextran sulfate sodium-induced colitis. Furthermore, TtSOD inhibited lipopolysaccharide-induced production of reactive oxygen species and inflammatory responses in mouse bone marrow-derived macrophages. CONCLUSIONS: Our results demonstrate that TtSOD possesses therapeutic activities toward experimentally induced IBD, offering new clinical treatment options for patients with IBD.

Effect of cultural background and healthcare environment on postoperative opioid requirement.

PURPOSE: The objective of this prospective observational study was to investigate the interactions between cultural background, healthcare environment, and postoperative pain experience. METHODS: We enrolled 128 Chinese patients living in rural mainland China and 134 patients in Hong Kong with a higher level of Western cultural influences (defined by educational attainment, place of residence, and ability to understand English). All patients had major abdominal surgery and received patient-controlled analgesia with intravenous morphine for postoperative pain relief. The primary endpoint was total opioid requirement up to 48 hr after surgery. Other measures included pain intensity, opioid-related side effects, and genetic markers for opioid responsiveness. RESULTS: The mean (95% confidence interval) cumulative opioid requirement, expressed as morphine equivalent, during the first 48 hr after surgery was significantly less in patients from mainland China (18.8 [15.7 to 22] mg) compared with patients from Hong Kong (42.0 [38.3 to 45.6] mg, P < 0.0001). In a multivariable analysis, opioid requirement was influenced by ethnicity, duration of surgery, and severity of pain upon admission to the postanesthetic care unit. CONCLUSIONS: These results suggest that postoperative pain behaviours and opioid requirement may be influenced by cultural background and healthcare environment in two populations of Chinese descent. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry (ACTRN12614000601639); registered 6 May, 2014.

RéSUMé: OBJECTIF: L'objectif de cette étude observationnelle prospective était d'étudier les interactions entre le contexte culturel, l'environnement de soins de santé et l'expérience de la douleur postopératoire. MéTHODES: Nous avons recruté 128 patients chinois vivant en zones rurales en Chine continentale et 134 patients vivant à Hong-Kong avec un haut niveau d'influences culturelles occidentales (définies par le niveau d'éducation atteint, le lieu de résidence et la capacité à comprendre l'anglais). Tous les patients avaient subi une chirurgie abdominale majeure et reçu une analgésie contrôlée par le patient par morphine intraveineuse pour le soulagement de la douleur postopératoire. Le critère d'évaluation principal était la demande totale en opioïdes pendant les 48 premières heures suivant la chirurgie. D'autres mesures ont inclus l'intensité de la douleur, les effets indésirables liés aux opioïdes et des marqueurs génétiques de sensibilité aux opioïdes. RéSULTATS: Le besoin cumulé moyen (intervalle de confiance à 95 %) cumulé en opioïdes, exprimé sous forme d'équivalent-morphine, au cours des 48 premières heures suivant la chirurgie était significativement inférieur pour les patients de Chine continentale (18,8 [15,7 à 22] mg) comparativement aux patients de Hong-Kong (42,0 [38,3 à 45,6] mg, P < 0,0001). Une analyse multifactorielle a montré que la demande en opioïdes était influencée par l'origine ethnique, la durée de l'intervention chirurgicale et l'intensité de la douleur au moment de l'arrivée dans l'unité de soins postanesthésiques. CONCLUSIONS: Ces résultats suggèrent que les comportements postopératoires envers la douleur et le besoin d'opioïdes peuvent être influencés par l'arrière-plan culturel et l'environnement des soins de santé dans deux populations différentes d'origine chinoise. ENREGISTREMENT DE L'ESSAI CLINIQUE: Registre des essais cliniques d'Australie et de Nouvelle-Zélande (ACTRN12614000601639); enregistré le 6 mai 2014.

Targeted Epidural Blood Patch Treatment for Refractory Spontaneous Intracranial Hypotension in China.

Objective An epidural blood patch (EBP) is the mainstay of treatment for refractory spontaneous intracranial hypotension (SIH). We evaluated the treatment efficacy of targeted EBP in refractory SIH. Methods All patients underwent brain magnetic resonance imaging (MRI) with contrast and heavily T2-weighted spine MRI. Whole spine computed tomography (CT) myelography with non-ionic contrast was performed in 46 patients, and whole spine MR myelography with intrathecal gadolinium was performed in 119 patients. Targeted EBPs were placed in the prone position one or two vertebral levels below the cerebrospinal fluid (CSF) leaks. Repeat EBPs were offered at 1-week intervals to patients with persistent symptoms, continued CSF leakage, or with multiple leakage sites. Results Brain MRIs showed pachymeningeal enhancement in 127 patients and subdural hematomas in 32 patients. One hundred fifty-two patients had CSF leakages on heavily T2-weighted spine MRIs. CSF leaks were also detected on CT and MR myelography in 43 and 111 patients, respectively. Good recovery was achieved in all patients after targeted EBP. No serious complications occurred in patients treated with targeted EBP during the 1 to 7 years of follow-up. Conclusions Targeted and repeat EBPs are rational choices for treatment of refractory SIH caused by CSF leakage.

Enhanced osteoinductivity of porous biphasic calcium phosphate ceramic beads with high content of strontium-incorporated calcium-deficient hydroxyapatite.

Further biomimicking natural bone and enhancing osteoinductivity to meet the requirements of regenerative medicine is the key development direction of biphasic calcium phosphate (BCP) ceramics. Bone mineral is a kind of Ca-deficient hydroxyapatite (CDHA) with many kinds of trace ions incorporated; however, little is actually known regarding the incorporation of trace ions in CDHA, and trace-ions-incorporated CDHA in BCP ceramics has seldom been studied. The present study introduces an effective approach to fabricate porous BCP ceramic beads with a high content of strontium (Sr)-incorporated CDHA (BCP-Sr), and investigated its biological performance, especially with regard to osteoinductivity. The obtained BCP-Sr possessed a good spherical shape, interconnected pore structure, and a high content of Sr-incorporated CDHA phase. Compared to the commercial BCP ceramic irregular granules (BAM® P2040, BCP-C), BCP-Sr had more micropores, relatively faster degradation, better bone-like apatite formation, higher protein adsorption abilities, and was more likely to promote the related osteogenic genes and protein expressions of BMSCs. Further in vivo canine intramuscular implantation confirmed that BCP-Sr had higher osteoinductivity than BCP-C. Collectively, the enhanced osteoinductivity of porous BCP ceramic beads by introducing a high content of Sr-incorporated CDHA has significant implications for designing highly bioactive BCP ceramics for applying in regenerative medicine.

Enhanced recovery care versus traditional care after laparoscopic liver resections: a randomized controlled trial.

BACKGROUND: Enhanced recovery after surgery (ERAS), with several evidence-based elements, has been shown to shorten length of hospital stay and reduce perioperative hospital costs in many operations. This randomized clinical trial was performed to compare complications and hospital stay of laparoscopic liver resection between ERAS and traditional care. METHODS: A randomized controlled trial was performed for laparoscopic liver resection from August 2015 to August 2016. Patients were randomly divided into ERAS group and traditional care group. The primary outcome was length of hospital stay (LOS) after surgery. Second outcomes included postoperative complications, hospital cost, and 30-day readmissions. Elements used in ERAS group included more perioperative education, nurse navigators, nutrition support for liver diseases, respiratory therapy, oral carbohydrate 2 h before operation, early mobilization and oral intake, goal-directed fluid therapy, less drainages, postoperative nausea and vomiting (PONV) prophylaxis and multimodal analgesia. RESULTS: The study included 58 (two conversion to laparotomy) patients in ERAS group and 61 (three conversion to laparotomy) patients in the traditional care group. Postoperative LOS was significantly shorter in the ERAS group than traditional care group (5 vs. 8 days; p < 0.001). ERAS program significantly reduced the hospital costs (CNY 45413.1 vs. 55794.1; p = 0.006) and complications (36.2 vs. 55.7%; p = 0.033). Duration till first flatus and PONV were significantly reduced in ERAS group. Pain control was better in ERAS (Visual analogue scale (VAS) POD1 (≥ 4) 19.0 vs. 39.3%, p = 0.017; VAS POD1 2.5 vs. 3.1, p = 0.010). There was no difference in the rate of 30-day readmissions (6.9 vs. 8.2%; p = 1.000). CONCLUSION: ERAS protocol is feasible and safe for laparoscopic liver resection. Patients in ERAS group have less pain and complications.

The status of diagnosis and treatment to intracranial hypotension, including SIH.

Intracranial hypotension, especially spontaneous intracranial hypotension (SIH), is a well-recognized entity associated with cerebrospinal fluid (CSF) leaks, and has being recognized better in resent years, while still woefully inadequate. An increasing number of factors including iatrogenic factors are realized to involve in development and progression of intracranial hypotension. The diagnosis remains difficult due to the various clinical manifestations, some of which are nonspecific and easily to be neglected. Multiple imaging tests are optional in CSF leakage identification while clinicians are still confronted with difficulties when making selection resulting from superiorities and disadvantages of different imaging tests. Treatments for intracranial hypotension are multifarious but evidence is anecdotal. Values of autologous epidural blood patching (EBP), the mainstay of first-line interventional treatment currently, is getting more and more regards while there are no systematic review of its efficacy and risks. Hereby, the purpose of this review was to reveal the present strategy of intracranial hypotension diagnosis and treatment by reviewing literatures, coupled with our experience in clinical work.