INTRODUCTION: Postoperative urinary retention (POUR) frequently complicates the course of patients following hip and knee arthroplasty. Intrathecal morphine (ITM) was identified as a significant risk factor for POUR. The objective of this study was to investigate the incidence and risk factors for POUR in fast-track total joint arthroplasty (TJA) under spinal anaesthesia (SA) with ITM. METHODS: We conducted a retrospective study of our institutional joint registry of patients who underwent primary TJA under SA with ITM between October 2017 and May 2021. Preoperative (baseline demographics) and perioperative data were collected. The primary outcome was the incidence of POUR after 8 h or earlier, either due to lack of voiding or according to patient's complaints of bladder distension. Univariate and adjusted analyses were performed to identify predictors of POUR. RESULTS: Sixty-nine patients who underwent total knee arthroplasty (TKA) and 36 patients who underwent total hip arthroplasty (THA) under SA with ITM were included in the study. POUR requiring bladder catheterisation was diagnosed in 21% of patients. Independent predictors of POUR were age over 65 years and male gender. CONCLUSIONS SA with ITM for TJA is associated with high rates of POUR in males older than 65 years of age. Other previously identified risk factors such as intraoperative fluid administration or comorbidities may not be as influential.
Humans ; Retrospective Studies ; Male ; Urinary Retention/epidemiology* ; Arthroplasty, Replacement, Knee/adverse effects* ; Anesthesia, Spinal/adverse effects* ; Female ; Arthroplasty, Replacement, Hip/adverse effects* ; Morphine/adverse effects* ; Aged ; Middle Aged ; Risk Factors ; Postoperative Complications/epidemiology* ; Injections, Spinal ; Incidence ; Analgesics, Opioid/adverse effects* ; Aged, 80 and over

BACKGROUND: The incidence of leptomeningeal metastasis (LM) in patients with advanced non-small cell lung cancer (NSCLC) is increasing gradually. However, it poses therapeutic challenges due to limited effective interventions. Intrathecal Pemetrexed (IP) holds broad application prospects in the therapeutic domain of LM. This study aims to evaluate the efficacy, safety, and optimal combination strategies of IP in NSCLC-LM patients with epidermal growth factor receptor (EGFR) mutation-positive status, with the aim of providing real-world data support for exploring more precise personalized treatment strategies for these patients. METHODS: 104 EGFR-mutated NSCLC-LM patients who received IP treatment at Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School from January 2018 to June 2024 were analyzed retrospectively. Clinical parameters, treatment regimens, and survival outcomes were collected. The overall survival (OS), progression-free survival (PFS), clinical response rate and adverse events (AEs) were evaluated. RESULTS: The cohort demonstrated a median PFS of 9.6 months and OS of 13.0 months with 6-month and 1-year OS rates of 80.8% and 56.5%, respectively. Clinical response was observed in 77.9% of patients. The common AEs were myelosuppression (58.7%) and elevation of hepatic aminotransferases (25.0%). Nine (8.7%) patients experienced grade 4 myelosuppression and recovered to normal after receiving symptomatic treatment. Subgroup analyses revealed prolonged OS in patients with Karnofsky performance status (KPS) ≥60 versus <60 (14.4 vs 9.0 months, P=0.0022) and those receiving Bevacizumab therapy versus not (19.2 vs 10.5 months, P=0.0011). CONCLUSIONS IP exhibits promising efficacy and manageable toxicity in EGFR-mutated NSCLC-LM patients. When combined with Bevacizumab, it exerts synergistic antitumor effects with the potential to further improve clinical outcomes.
Humans ; Pemetrexed/therapeutic use* ; Carcinoma, Non-Small-Cell Lung/pathology* ; Male ; Female ; Middle Aged ; Lung Neoplasms/pathology* ; ErbB Receptors/genetics* ; Aged ; Mutation ; Adult ; Retrospective Studies ; Injections, Spinal ; Meningeal Neoplasms/genetics* ; Treatment Outcome ; Aged, 80 and over

OBJECTIVE: The purpose of this study was to determine whether xenon post-conditioning affects mTOR signaling as well as endoplasmic reticulum stress (ERS)-apoptosis pathway in rats with spinal cord ischemia/reperfusion injury. METHODS: Fifty male rats were randomized equally into sham-operated group (Sham group), I/R model group (I/R group), I/R model+ xenon post-conditioning group (Xe group), I/R model+rapamycin (a mTOR signaling pathway inhibitor) treatment group (I/R+ Rapa group), and I/R model + xenon post- conditioning with rapamycin treatment group (Xe + Rapa group).. In the latter 4 groups, SCIRI was induced by clamping the abdominal aorta for 85 min followed by reperfusion for 4 h. Rapamycin (or vehicle) was administered by daily intraperitoneal injection (4 mg/kg) for 3 days before SCIRI, and xenon post-conditioning by inhalation of 1∶1 mixture of xenon and oxygen for 1 h at 1 h after initiation of reperfusion; the rats without xenon post-conditioning were given inhalation of nitrogen and oxygen (1∶ 1). After the reperfusion, motor function and histopathologic changes in the rats were examined. Western blotting and real-time PCR were used to detect the protein and mRNA expressions of GRP78, ATF6, IRE1α, PERK, mTOR, p-mTOR, Bax, Bcl-2 and caspase-3 in the spinal cord. RESULTS: The rats showed significantly lowered hind limb motor function following SCIRI (P < 0.01) with a decreased count of normal neurons, increased mRNA and protein expressions of GRP78, ATF6, IRE1α, PERK, and caspase-3, and elevated p-mTOR/mTOR ratio and Bax/Bcl-2 ratio (P < 0.01). Xenon post-conditioning significantly decreased the mRNA and protein levels of GRP78, ATF6, IRE1α, PERK and caspase-3 (P < 0.05 or 0.01) and reduced p-mTOR/mTOR and Bax/Bcl-2 ratios (P < 0.01) in rats with SCIRI; the mRNA contents and protein levels of GRP78 and ATF6 were significantly decreased in I/R+Rapa group (P < 0.01). Compared with those in Xe group, the rats in I/R+Rapa group and Xe+Rapa had significantly lowered BBB and Tarlov scores of the hind legs (P < 0.01), and caspase-3 protein level and Bax/Bcl-2 ratio were significantly lowered in Xe+Rapa group (P < 0.05 or 0.01). CONCLUSION By inhibiting ERS and neuronal apoptosis, xenon post- conditioning may have protective effects against SCIRI in rats. The mTOR signaling pathway is partially involved in this process.
Animals ; Apoptosis ; Caspase 3/metabolism* ; Endoplasmic Reticulum Stress ; Endoribonucleases/pharmacology* ; Injections, Intraperitoneal ; Male ; Neurons/pathology* ; Nitrogen/metabolism* ; Oxygen/metabolism* ; Protein Serine-Threonine Kinases ; Proto-Oncogene Proteins c-bcl-2/metabolism* ; RNA, Messenger/metabolism* ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reperfusion Injury/metabolism* ; Sirolimus/pharmacology* ; Spinal Cord Ischemia/pathology* ; TOR Serine-Threonine Kinases/metabolism* ; Xenon/therapeutic use* ; bcl-2-Associated X Protein/metabolism*

OBJECTIVES: There are clinical reports of nerve injury caused by ropivacaine. The mechanism for nerve injury induced by ropivacaine has not been fully clarified. This study aims to investigate the changes of pain threshold and L₃ spinal cord genomics at 6 h and 24 h after intrathecal injection of 0.5% and 1.0% ropivacaine, and to explore the underlying mechanisms for nerve injury caused by ropivacaine. METHODS: A total of 30 male Sprague Dawley rats weighing 220-260 g were successfully implanted with microspinal catheter. The rats were randomly divided into 5 groups (each n=6): a control group (given saline), a ropivacaine group 1 and a ropivacaine group 2 (both given 1% ropivacaine), a ropivacaine group 3 and a ropivacaine group 4 (both given 0.5% ropivacaine). The rats received continuous intrathecal injection of corresponding drugs at 8.3 μL/h for 24 h via an implanted intrathecal catheter followed by 24 h-pause of injection for the ropivacaine group 2, the ropivacaine group 4 and the control group, 6 h-pause of injection for the ropivacaine group 1 and the ropivacaine group 3. For each group, the observation of behavioral change and the paw withdrawal mechanical threshold (PWMT) was conducted immediately after the injection and again after the pause of injection. After the PWMT observation, the rats were dissected to acquire L₃ spinal cords. Illumina sequencing was applied to construct gene libraries. Then the statistical methods were used to find out differentially expressed genes between the groups. Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) signaling pathway analysis were conducted for those genes. Real-time RT-PCR was used to determine different expressions of some of those genes. RESULTS: Compared with control group, the PWMT got higher in the ropivacaine group 1-4 and was positively correlated with concentration, negatively correlated with discontinuation duration. Compared with control group, the ropivacaine group 1 had 488 differentially expressed genes, of which 456 were up-regulated and 32 were down-regulated; the ropivacaine group 2 had 1 194 differentially expressed genes, of which 1 092 were up-regulated and 102 were down-regulated; the ropivacaine group 3 had 518 differentially expressed genes, of which 384 were up-regulated and 134 were down-regulated; and the ropivacaine group 4 had 68 differentially expressed genes, of which 46 were up-regulated and 22 were down-regulated. GO enrichment analysis and KEGG signaling pathway analysis showed that most of these differentially expressed genes were related to signaling pathways of inflammatory response. CONCLUSIONS After intrathecal injection of 0.5% ropivacaine and 1.0% ropivacaine for 24 h, the differentially expressed genes in L₃ spinal cord of rats are mainly related to signaling pathways of inflammatory response.
Animals ; Genomics ; Injections, Spinal ; Male ; Rats ; Rats, Sprague-Dawley ; Ropivacaine ; Spinal Cord/metabolism*

Since the coronavirus disease 2019 (COVID-19) affects the cardio-pulmonary function of pregnant women, the anesthetic management and protection of medical staff in the cesarean section is significantly different from that in ordinary surgical operation. This paper reports a case of cesarean section for a woman with COVID-19, which was successfully performed in the First Affiliated Hospital of Zhejiang University School of Medicine on February 8, 2020. Anesthetic management, protection of medical staff and psychological intervention for the pregnant woman during the operation were discussed. Importance has been attached to the preoperative evaluation of pregnant women with COVID-19 and the implementation of anesthesia plan. For moderate patients, intraspinal anesthesia is preferred in cesarean section, and try to reduce its influence in respiration and circulation in both maternal and infant; general anesthesia with endotracheal intubation should be adopted for severe or critically ill patients. Ensure the safety of medical environment, and anesthetists should carry out level-Ⅲ standard protection. Special attention and support should be paid to maternal psychology: fully explanation before operation to reduce anxiety; relieve the discomfort during operation, so as to reduce tension; avoid the bad mood due to pain after operation.
Anesthesia ; Betacoronavirus ; isolation & purification ; Cesarean Section ; methods ; Coronavirus Infections ; complications ; Female ; Humans ; Infant ; Injections, Spinal ; Pandemics ; Pneumonia, Viral ; complications ; Pregnancy

Since the corona virus disease 2019 (COVID-19) affects the cardio-pulmonary function of pregnant women, the anesthetic management in the cesarean section for the patients, as well as the protection for medical staff is significantly different from that in ordinary surgical operation. This paper reports a pregnant woman with COVID-19, for whom a cesarean section was successfully performed in our hospital on February 8, 2020. Anesthetic management, protection of medical staff and psychological intervention for the patients during the operation are discussed. Importance should be attached to the preoperative evaluation of pregnant women with COVID-19 and the implementation of anesthesia plan. For ordinary COVID-19 patients intraspinal anesthesia is preferred in cesarean section, and the influence on respiration and circulation in both maternal and infant should be reduced; while for severe or critically ill patients general anesthesia with endotracheal intubation should be adopted. The safety of medical environment should be ensured, and level-Ⅲ standard protection should be taken for anesthetists. Special attention and support should be given to maternal psychology. It is important to give full explanation before operation to reduce anxiety; to relieve the discomfort during operation to reduce tension; to avoid the bad mood of patients due to pain after operation.
Anesthesia ; Betacoronavirus ; Cesarean Section ; Coronavirus Infections ; complications ; surgery ; Female ; Humans ; Infant ; Injections, Spinal ; Pneumonia, Viral ; complications ; diagnosis ; surgery ; Pregnancy ; Pregnancy Complications, Infectious ; surgery ; Pregnancy Outcome ; Preoperative Care

The approach we suggest was developed for cases in which the fourth and fifth lumbar and first sacral spinal nerves were affected in lumbar degenerative disc disease. Retrodiscal transforaminal epidural injection is known to be very effective for lumbar radiculopathy because of excellent access to primary pathology; however, access below L5 is often restricted by the anatomic characteristics of the L5–S1. In the translateral recess approach (TLR), proper final needle placement (i.e., in the axillary portion between the exiting and traversing nerve roots) can be achieved by setting the direction of the needle laterally and superiorly from the distal tip of the infra-adjacent spinous process toward the medial wall of the pedicle and neural foramen of the given level without neural injury. This approach is possible because of the wide interlaminar space in the L5–S1. Preganglionic epidural injection through TLR is an effective and safe spinal intervention for lumbosacral radiculopathy.
Injections, Epidural ; Needles ; Pathology ; Radiculopathy ; Spinal Nerves

There is accumulating evidence that microRNAs are emerging as pivotal regulators in the development and progression of neuropathic pain. MicroRNA-15a/16 (miR-15a/16) have been reported to play an important role in various diseases and inflammation response processes. However, whether miR-15a/16 participates in the regulation of neuroinflammation and neuropathic pain development remains unknown. In this study, we established a mouse model of neuropathic pain by chronic constriction injury (CCI) of the sciatic nerves. Our results showed that both miR-15a and miR-16 expression was significantly upregulated in the spinal cord of CCI rats. Downregulation of the expression of miR-15a and miR-16 by intrathecal injection of a specific inhibitor significantly attenuated the mechanical allodynia and thermal hyperalgesia of CCI rats. Furthermore, inhibition of miR-15a and miR-16 downregulated the expression of interleukin-1β and tumor-necrosis factor-α in the spinal cord of CCI rats. Bioinformatic analysis predicted that G protein-coupled receptor kinase 2 (GRK2), an important regulator in neuropathic pain and inflammation, was a potential target gene of miR-15a and miR-16. Inhibition of miR-15a and miR-16 markedly increased the expression of GRK2 while downregulating the activation of p38 mitogen-activated protein kinase and NF-κB in CCI rats. Notably, the silencing of GRK2 significantly reversed the inhibitory effects of miR-15a/16 inhibition in neuropathic pain. In conclusion, our results suggest that inhibition of miR-15a/16 expression alleviates neuropathic pain development by targeting GRK2. These findings provide novel insights into the molecular pathogenesis of neuropathic pain and suggest potential therapeutic targets for preventing neuropathic pain development.
Animals ; Computational Biology ; Constriction ; Down-Regulation ; Hyperalgesia ; Inflammation ; Injections, Spinal ; Mice ; MicroRNAs ; Neuralgia ; p38 Mitogen-Activated Protein Kinases ; Phosphotransferases ; Protein Kinases ; Rats ; Sciatic Nerve ; Spinal Cord ; Up-Regulation

STUDY DESIGN: Review article.OBJECTIVES: To assess the evidence for nonoperative treatment of various degenerative spinal degenerative diseases.SUMMARY OF LITERATURE REVIEW: No study has yet evaluated the evidence for preoperative nonoperative treatment of lumbar spinal diseases.METHODS: The evidence regarding nonoperative treatment for each disease was reviewed through NASS guidelines, and the treatment effect compared to surgical treatment was reviewed through the SPORT series. The efficacy of nonoperative treatment according to disease severity and certain special conditions was investigated through corresponding individual articles.RESULTS: No kind of nonoperative treatment could change the fundamental progression of degenerative spinal disease. The natural course of lumbar disc herniation is favorable regardless of treatment. More than 70% of routine cases improve within 6 weeks. However, it does not take a full 6 weeks to decide whether to perform surgery or not. The evidence for transforaminal epidural steroid injections for short-term pain control is grade A. There is grade B evidence for nonoperative treatment with the goal of mid- to long-term pain control. However, we cannot say that those outcomes are better than the natural course of the disease itself. In cases of radicular weakness, the degree of weakness is correlated with the final outcomes, but it is not evident whether the duration of weakness is correlated with surgical outcomes. Early surgery is usually necessary due to intolerable pain, rather than stable motor weakness. The social cost of herniated discs arises from the loss of patients’ productivity, rather than from direct medical expenses. The natural course of spinal stenosis involves provoked pain and the need for palliative care. Unlike disc herniation, rapid deterioration and marked improvement do not occur. The symptoms of mild to moderate lumbar stenosis are unchanged in 70% of cases, improve in 15%, and worsen in 15%. No study has compared nonoperative treatment with the natural course of the disease. There is no evidence for nonoperative treatment of severe stenosis. Epidural spinal injections are effective for controlling short-term pain. Spontaneous recovery of radicular weakness does not occur, and urgent surgery is necessary in such cases. There is no evidence regarding the natural course and nonoperative treatment of degenerative spondylolisthesis. The working group consensus recommends that it should follow the pattern of nonoperative treatment of spinal stenosis when radicular stenosis symptoms are predominant. Overall, 40%–66% of cases of adult bilateral isthmic spondylolysis progress to symptomatic spondylolisthesis. No studies have investigated nonoperative treatment except physical exercise.CONCLUSIONS: Although short-term symptom amelioration can be achieved by nonoperative treatment, the fundamental progression of the disease is not affected. For conditions excluded from most studies, such as prior spine surgery, cauda equina syndrome, progressive neurological deficit, and uncontrollable severe pain associated with instability, deformity, or vertebral fractures, there were not enough studies to reach informed conclusions. Our review found no evidence regarding nonoperative treatment for such conditions. Furthermore, the treatment methods for each disease are not clearly distinguished from each other, and the techniques used for disc herniation have been applied to other diseases without any evidence.
Adult ; Congenital Abnormalities ; Consensus ; Constriction, Pathologic ; Efficiency ; Exercise ; Humans ; Injections, Spinal ; Intervertebral Disc Displacement ; Palliative Care ; Polyradiculopathy ; Spinal Diseases ; Spinal Stenosis ; Spine ; Spondylolisthesis ; Spondylolysis ; Sports

BACKGROUND: Previous studies have shown that sequential intrathecal injection of fentanyl and hyperbaric bupivacaine for cesarean section (CS) anesthesia provides a superior anesthetic effect than use of bupivacaine alone, and prolongs postoperative analgesia. Herein, we investigated whether rapid intrathecal injection of fentanyl followed by slow injection of hyperbaric bupivacaine affects the duration of postoperative analgesia, the effectiveness of anesthesia, and hemodynamic status. METHODS: Fifty-six parturients with American Society of Anesthesiologists physical status I or II, aged 18–40 years, and scheduled to undergo elective CS were randomly assigned to 2 groups of 28 patients each. The normal sequential group received sequential intrathecal injections of fentanyl and hyperbaric bupivacaine at the same rate, each with a 5 ml syringe. The rapid sequential group received a rapid intrathecal injection of fentanyl with an insulin syringe, followed by a slow injection of hyperbaric bupivacaine with a 5 ml syringe. The onset of sensory block, the timing of the first rescue analgesia, the doses of rescue analgesics, the degree of postoperative pain, the onset and duration of motor block, the incidence and duration of hypotension, and spinal anesthesia-related complications were recorded. RESULTS: While both approaches had comparable spinal anesthesia-related complications, incidence and duration of hypotension, and doses of ephedrine, the rapid sequential group exhibited a more rapid onset of sensory block, a higher sensory level, and more prolonged postoperative analgesia. CONCLUSIONS: Rapid sequential injection of fentanyl and hyperbaric bupivacaine produced superior anesthesia and more prolonged postoperative analgesia than sequential injections of both at the same rate.
Analgesia ; Analgesics ; Anesthesia ; Anesthesia, Spinal ; Anesthetics ; Bupivacaine ; Cesarean Section ; Ephedrine ; Female ; Fentanyl ; Hemodynamics ; Humans ; Hypotension ; Incidence ; Injections, Spinal ; Insulin ; Pain, Postoperative ; Pregnancy ; Syringes