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Beyond the Pain: A Systematic Narrative Review of the Latest Advancements in Fibromyalgia Treatment.Cureus Oct 2023Fibromyalgia is a complex chronic pain disorder that significantly impacts the quality of life of affected individuals. The etiology of fibromyalgia remains elusive,... (Review)
Review
Fibromyalgia is a complex chronic pain disorder that significantly impacts the quality of life of affected individuals. The etiology of fibromyalgia remains elusive, necessitating effective treatment options. This review aims to provide an overview of current treatment options for fibromyalgia and highlight recent updates in managing the condition. The methodology employed in this systematic review comprised the following key steps. We conducted a comprehensive search across various databases to identify pertinent studies published between 2000 and 2023. Inclusion criteria were defined to specifically target studies involving adult individuals diagnosed with fibromyalgia, with a focus on both pharmacological and non-pharmacological interventions for managing the condition. The review encompassed a range of study types, including randomized controlled trials, observational studies, and systematic reviews. To ensure the quality of the selected studies, we employed appropriate assessment tools, and data extraction and synthesis adhered to established guidelines. This rigorous approach allowed for a robust analysis of the literature on fibromyalgia management. In the course of our review, it became evident that a spectrum of treatment approaches holds significant promise in the management of fibromyalgia. Specifically, pharmacological interventions, including selective serotonin-norepinephrine reuptake inhibitors, anticonvulsants, cannabinoids, tropisetron, and sodium oxybate, have exhibited substantial potential in alleviating fibromyalgia symptoms. Concurrently, non-pharmacological strategies, such as cognitive-behavioral therapy, exercise regimens, and complementary and alternative therapies, have yielded positive outcomes in improving the condition's management. Recent developments in the field have introduced innovative pharmacological agents like milnacipran and pregabalin, in addition to non-pharmacological interventions like mindfulness-based stress reduction and aquatic exercise, expanding the array of options available to enhance fibromyalgia care and alleviating patient symptoms. Fibromyalgia necessitates a multidisciplinary approach to treatment, encompassing both pharmacological and non-pharmacological interventions. Recent updates in fibromyalgia management offer additional options to alleviate symptoms and improve the quality of life for individuals with fibromyalgia. Healthcare professionals should remain informed about these advancements to provide evidence-based care, addressing the complex symptoms associated with fibromyalgia and enhancing patient outcomes.
PubMed: 38034135
DOI: 10.7759/cureus.48032 -
Scientific Reports Nov 2023Obsessive-compulsive disorder (OCD) is the fourth most common mental disorder, and selective serotonin reuptake inhibitors (SSRIs) are the cornerstone of its... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of 5-hydroxytryptamine-3 (5-HT3) receptor antagonists in augmentation with selective serotonin reuptake inhibitors (SSRIs) in the treatment of moderate to severe obsessive-compulsive disorder: a systematic review and meta-analysis of randomized clinical trials.
Obsessive-compulsive disorder (OCD) is the fourth most common mental disorder, and selective serotonin reuptake inhibitors (SSRIs) are the cornerstone of its pharmacological treatment. About 40-60% of the cases are treatment-refractory, and this makes searching for second-line treatment necessary. 5-Hydroxytryptamine-3 (5-HT3) antagonists are among the many medications that have been used in augmentation with SSRIs. In this systematic review and meta-analysis, we assessed the efficacy and safety of 5-HT3 receptor antagonists in augmentation with SSRIs in treating moderate to severe OCD. We searched PubMed, Web of Science, Scopus, Cochrane library, and Google Scholar for relevant trials published up to December 2022. The effect size was the mean difference in Yale-Brown obsessive compulsive scale (Y-BOCS) scores before and after receiving 5-HT3 receptor antagonist drugs in augmentation with SSRIs in moderate to severe OCD patients. We included 6 randomized-controlled trails (RCTs) with 334 patients assessing the effect of the augmentation of SSRIs with ondansetron, granisetron, and tropisetron on treating moderate to severe OCD. Our results were in favor of the experimental group in total (Z = 8.37, P < 0.00001), in the compulsion subgroup (Z = 5.22, P < 0.00001), and in the obsession subgroup (Z = 8.33, P < 0.00001). They are well-tolerated, and have mild side effects and do not result in withdrawal. Augmentation of 5-HT3 antagonists with SSRIs can be beneficial in treating moderate to severe OCD. Further multi-center trials under adequate conditions in longer periods are needed to help come up with a comprehensive action plan.
Topics: Humans; Selective Serotonin Reuptake Inhibitors; Serotonin; Receptors, Serotonin, 5-HT3; Treatment Outcome; Randomized Controlled Trials as Topic; Obsessive-Compulsive Disorder; Drug Therapy, Combination
PubMed: 38012263
DOI: 10.1038/s41598-023-47931-x -
Drug Design, Development and Therapy 2023Perioperative multimodal analgesia can prevent chronic pain after breast cancer surgery. This study aimed to investigate the efficacy of combined perioperative oral... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Perioperative multimodal analgesia can prevent chronic pain after breast cancer surgery. This study aimed to investigate the efficacy of combined perioperative oral pregabalin and postoperative esketamine in preventing chronic pain after breast cancer surgery.
METHODS
Ninety patients undergoing elective breast cancer surgery were randomized into the combined pregabalin and esketamine group (EP group) and the general anesthesia alone group (Control group). The EP group received 150 mg of oral pregabalin 1 h before surgery and twice daily for seven days postoperatively, and a patient-controlled analgesia pump after surgery that delivered 100 μg sufentanil + 1.25 mg/kg esketamine + 4 mg tropisetron in 100 mL saline solution intravenously. The Control group received placebo capsules before and after the surgery and routine postoperative analgesia (100 μg sufentanil + 4 mg tropisetron in 100 mL saline solution). The primary outcome was the incidence of chronic pain three and six months after surgery. Secondary outcomes included acute postoperative pain, postoperative opioid consumption, and incidence of adverse events.
RESULTS
The incidence of chronic pain in the EP group was significantly lower than in the Control group three (14.3% vs 46.3%, = 0.005) and six (7.1% vs 31.7%, = 0.009) months postoperatively. The rest numerical rating scale (NRS) pain scores 1-3 days postoperatively and coughing NRS pain scores 1-7 days postoperatively in the EP group were significantly lower than in the Control group (all ˂ 0.05). The cumulative sufentanil consumption in the EP group during postoperative 0-12, 12-24, and 24-48, 0-24, and 0-48 hours were significantly lower than in the Control group (all ˂ 0.05).
CONCLUSION
Combined perioperative oral pregabalin and postoperative esketamine effectively prevented chronic pain after breast cancer surgery, improved acute postoperative pain, and reduced postoperative opioid consumption.
Topics: Humans; Female; Breast Neoplasms; Pregabalin; Analgesics, Opioid; Chronic Pain; Saline Solution; Sufentanil; Tropisetron; Pain, Postoperative
PubMed: 37313456
DOI: 10.2147/DDDT.S413273 -
EClinicalMedicine Mar 2024Antipsychotics are the gold standard treatment for schizophrenia, but many patients who receive treatment experience persistent symptoms. The aim of this network...
BACKGROUND
Antipsychotics are the gold standard treatment for schizophrenia, but many patients who receive treatment experience persistent symptoms. The aim of this network meta-analysis was to determine the efficacy of augmentation drugs for the treatment of schizophrenia.
METHODS
In accordance with the PRISMA statement, the PubMed, Web of Science, Google Scholar, CENTRAL, clinical trial and EUDRACT databases were searched from inception to May 15th, 2023. To ensure the robustness of the results, only double-blind randomised controlled trials with a low risk of bias (measured by the Risk Of Bias v2 (ROB2) tool) were included. The studies were categorised according to the background regimen: participants were treated with risperidone, mixed antipsychotics or clozapine. A Bayesian network meta-analysis was conducted using a random effects model. PROSPERO register: CRD42023420964.
FINDINGS
A total of 44 trials (comprising 45 augmentation drugs and 3358 participants) were included in the analysis. One-third of the drugs (16 drugs) demonstrated significant efficacy vs. placebo for at least one outcome. The most notable effect sizes (ESs) were observed for the use of tropisetron (standard mean difference: -0.83 [95% interval confidence -1.12 to -0.55]), memantine (-0.50 [-0.66 to -0.32]) and minocycline (-0.56 [-0.72 to -0.39]) to treat negative symptoms among patients treated with risperidone (moderate-to-high ESs). Studies involving mixed antipsychotics yielded lower ESs (small-to-moderate). Sodium benzoate (-0.41 [-0.60 to -0.21]) and memantine (-0.23 [-0.36 to -0.11]) were found have significant effects on positive symptoms, while memantine demonstrated efficacy for negative symptoms (-0.32 [-0.45 to -0.19]) and general psychopathology (-0.32 [-0.44 to -0.20]). Studies focusing exclusively on patients treated with clozapine revealed that duloxetine produced the best results (negative symptoms: -1.12 [-1.35 to -0.91]). Sodium benzoate was the only augmentation drug that demonstrated efficacy in relieving persistent positive symptoms (-0.32 [-0.59 to -0.08]) among patients treated with clozapine. Treatment with clozapine in combination with antipsychotics yielded small-to-moderate ESs.
INTERPRETATION
The GRADE framework indicated that the quality of the evidence among the included studies was moderate, primarily due to the limited number of randomised controlled trials with a low risk of bias. Important drugs did not appear in these results due to insufficient low-risk-of-bias data for these medications. These results highlight new pathways for treating schizophrenia that should be incorporated into future guidelines after further validation.
FUNDING
No funding.
PubMed: 38356727
DOI: 10.1016/j.eclinm.2024.102473 -
The Journal of Spinal Cord Medicine Mar 2024Tropisetron is an alpha 7 nicotinic acetylcholine receptor (α7nAChR) agonist and is a commonly used antiemetic clinically. α7nAChRs activation modulating nociception...
OBJECTIVES
Tropisetron is an alpha 7 nicotinic acetylcholine receptor (α7nAChR) agonist and is a commonly used antiemetic clinically. α7nAChRs activation modulating nociception transmissions and cholinergic anti-inflammation may decrease neuropathic pain. This study was set to investigate the effects of tropisetron on neuropathic pain and neuroinflammation as well as the underlying mechanisms in rats.
METHODS
Neuropathic pain behavior was assessed in rats using the paw mechanical withdrawal threshold and paw thermal withdrawal latency before and after the establishment of a spared nerve injury (SNI) pain model in rats treated with tropisetron treatment in the presence or absence of the α7nAChR antagonist methyllycaconitine (MLA) through intrathecal injection. Their spinal cords were then harvested for inflammatory cytokines, the α7nAChR, p38 mitogen-activated protein kinase (p-p38MAPK) and cAMP-response element binding protein (CREB) measurement.
RESULTS
Tropisetron effectively alleviated mechanical allodynia and thermal hyperalgesia; decreased IL-6, IL-1ß and TNF-a; and down-regulated the phosphorylation of p38MAPK and CREB. Pre-treatment with MLA abolished these effects of tropisetron.
CONCLUSION
Our data indicate that tropisetron alleviates neuropathic pain may through inhibition of the p38MAPK-CREB pathway via α7nAChR activation. Thus, tropisetron may be a potential new therapeutic strategy for chronic neuropathic pain.
Topics: Rats; Animals; Tropisetron; alpha7 Nicotinic Acetylcholine Receptor; Rats, Sprague-Dawley; Neuroinflammatory Diseases; Spinal Cord Injuries; Neuralgia; Hyperalgesia
PubMed: 35353023
DOI: 10.1080/10790268.2022.2046923 -
EClinicalMedicine Sep 2023Convincing clinical evidence regarding completely opioid-free postoperative pain management using erector spinae plane block (ESPB) in patients undergoing open major...
Analgesic efficacy of an opioid-free postoperative pain management strategy versus a conventional opioid-based strategy following open major hepatectomy: an open-label, randomised, controlled, non-inferiority trial.
BACKGROUND
Convincing clinical evidence regarding completely opioid-free postoperative pain management using erector spinae plane block (ESPB) in patients undergoing open major hepatectomy (OMH) is lacking. Herein, we aimed to compare the postoperative analgesic efficacy of the visualised continuous opioid-free ESPB (VC-ESPB) and conventional intravenous opioid-based postoperative pain management in hepatocellular carcinoma (HCC) patients undergoing OMH.
METHODS
This open-label, randomised, controlled, non-inferiority trial enrolled patients with HCC undergone open major hepatectomy in Fujian Provincial Hospital and compared the postoperative analgesic efficacy of VC-ESPB (VC-ESPB group) and conventional intravenous opioid-based pain management regimen (conventional group). Patients were randomly assigned (1:1) to VC-ESPB group and conventional group. Patients were not masked to treatment allocation. The VC-ESPB group was treated with intermittent injections of 0.25% ropivacaine (bilateral, 30 mL each side) given every 12 h through catheters placed in the space of erector spinae and an opioid-free intravenous pump (10-mg tropisetron diluted to 100 mL with 0.9% normal saline [NS]) for postoperative pain management. The conventional group did not receive ESPB and was treated with a conventional intravenous opioid-based pump (2.5-μg/kg sufentanil and 10-mg tropisetron diluted to 100 mL with 0.9% NS). Patients in the VC-ESPB group underwent magnetic resonance imaging (MRI) to identify local anaesthetic diffusion after ESPB was performed under ultrasound guidance. The primary outcome was postoperative analgesic efficacy, which was indicated by the cumulative area under the curve (AUC) of the pain visual analogue scale scores (range, 0-10; a higher score indicates more pain) obtained at rest and at movement until 48 h postoperatively after leaving the post-anaesthesia care unit (PACU). Herein, an AUC of 26.5 was set as the noninferiority margin, which needed to be satisfied for both cumulative AUC at rest and cumulative AUC at movement. Per protocol participants were included in primary and safety analyses. This trial was registered with ChiCTR.org.cn (ChiCTR1900026583).
FINDINGS
Between October 30, 2019, and May 1, 2023, 106 patients were enrolled and randomly assigned to the VC-ESPB group (n = 53) and the conventional group (n = 53). After the dropout (n = 5), a total of 101 patients (VC-ESPB group, n = 50; conventional group, n = 51) were analysed. Both the level of cumulative AUC (at rest: 160.08 ± 38.00 164.94 ± 31.00; difference [90% CI], -4.861 [-16.308, 6.585]) and cumulative AUC (at movement: 209.64 ± 28.98 212.59 ± 33.11; difference [90% CI], -2.948 [-13.236, 7.339]) were similar between the VC-ESPB and control groups within the first postoperative 48 h. The upper limit of the 90% CIs for the difference in cumulative ACUP at rest and at movement did not reach the upper inferiority margin (26.5). During the first postoperative 48 h, the rate of nonsteroidal anti-inflammatory drug rescue analgesia was similar between the VC-ESPB group and conventional group (n = 16, 32.0% n = 11, 21.6%; = 0.236). Treatment-related death was not observed in the VC-ESPB group (n = 0, 0%) and conventional group (n = 0, 0%). In VC-ESPB group, local site paralysis (n = 1, 2.0%) was observed in one patient and rash (n = 1, 2.0%) was observed in another patient. One patient in the conventional group was observed with rash preoperatively (n = 1, 2.0%). The VC-ESPB group had significantly lower rates of postoperative nausea (n = 2, 4.0%, n = 9, 17.6%, = 0.028), vomiting (n = 1, 2.0% n = 8, 15.7%, = 0.031) and lower incidence of major complications (n = 4, 8.0% n = 6, 11.8%; = 0.033).
INTERPRETATION
This study demonstrates the noninferiority of VC-ESPB when compared with the conventional opioid-based approach for postoperative pain management after OMH, suggesting that it is feasible to achieve opioid-free postoperative pain management for OMH.
FUNDING
The Joint Funds for the Innovation of Science and Technology, Fujian Province, China; the Youth Scientific Research Project of Fujian Provincial Health Commission; the Fujian Research and Training Grants for Young and Middle-aged Leaders in Healthcare; and the Key Clinical Specialty Discipline Construction Program of Fujian, China.
PubMed: 37692074
DOI: 10.1016/j.eclinm.2023.102188 -
Iranian Journal of Basic Medical... 2024The kidney ages faster than other organs due to changes in energy metabolism, mitochondrial dysfunction, and oxidative stress. This study looked into the anti-aging...
OBJECTIVES
The kidney ages faster than other organs due to changes in energy metabolism, mitochondrial dysfunction, and oxidative stress. This study looked into the anti-aging effect of tropisetron.
MATERIALS AND METHODS
D-galactose was administrated subcutaneously in a mouse model for eight weeks in order to induce renal aging. Three separate intraperitoneal doses of tropisetron (1, 3, and 5 mg/kg body weight) were given at the same time. We assessed markers of mitochondrial dysfunction, oxidative stress, and inflammation. Via Real-Time PCR, the expressions of genes linked to aging (SIRT1) and apoptosis (Bax and Bcl-2) were ascertained. In addition, an assessment of histopathological changes, blood urea nitrogen, and creatinine concentrations was done.
RESULTS
In kidney tissue, tropisetron reduces mitochondrial dysfunction and oxidative stress, which are caused by D-galactose-induced overproduction of inflammatory mediators. Additionally, tropisetron demonstrated antiapoptotic activity in renal tissue and augmented the decrease in SIRT1 gene expression associated with D-galactose administration. Besides, tropisetron significantly improved the histological alterations in the renal tissues of aged mice and effectively decreased the elevated levels of creatinine and also blood urea nitrogen.
CONCLUSION
The results provided additional insight into the effect of tropisetron on renal aging and the underlying mechanisms, particularly through its ability to modulate SIRT1 signaling.
PubMed: 38629089
DOI: 10.22038/IJBMS.2024.74025.16098 -
Naunyn-Schmiedeberg's Archives of... Dec 2023Ergometrine (6aR,9R)-N-((S)-1-hydroxypropan-2-yl)-7-methyl-4,6,6a,7,8,9-hexa-hydro-indolo-[4,3-fg]chinolin-9-carboxamide or lysergide acid β-ethanolamide or ergonovine)...
Ergometrine (6aR,9R)-N-((S)-1-hydroxypropan-2-yl)-7-methyl-4,6,6a,7,8,9-hexa-hydro-indolo-[4,3-fg]chinolin-9-carboxamide or lysergide acid β-ethanolamide or ergonovine) activates several types of serotonin and histamine receptors in the animal heart. We thus examined whether ergometrine can activate human serotonin 5-HT receptors (h5-HTR) and/or human histamine H receptors (hHR) in the heart of transgenic mice and/or in the human isolated atrium. Force of contraction or beating rates were studied in electrically stimulated left atrial or spontaneously beating right atrial preparations or spontaneously beating isolated retrogradely perfused hearts (Langendorff setup) of mice with cardiac specific overexpression of the h5-HTR (5-HT-TG) or of mice with cardiac specific overexpression of the hHR (H-TG) or in electrically stimulated human right atrial preparations obtained during cardiac surgery. Western blots to assess phospholamban (PLB) phosphorylation on serine 16 were performed. Ergometrine exerted concentration- and time-dependent positive inotropic effects and positive chronotropic effects in atrial preparations starting at 0.3 µM and reaching a plateau at 10 µM in H-TGs (n = 7). This was accompanied by an increase in PLB phosphorylation at serine 16. Ergometrine up 10 µM failed to increase force of contraction in left atrial preparations from 5-HT-TGs (n = 5). Ten micrometer ergometrine increased the force of contraction in isolated retrogradely perfused spontaneously beating heart preparations (Langendorff setup) from H-TG but not 5-HT-TG. In the presence of the phosphodiesterase inhibitor cilostamide (1 µM), ergometrine at 10 µM exerted positive inotropic effects in isolated electrically stimulated human right atrial preparations, obtained during cardiac surgery, and these effects were eliminated by 10 µM of the HR antagonist cimetidine but not by 10 µM of the 5-HTR antagonist tropisetron. Furthermore, ergometrine showed binding to human histamine H receptors (at 100 µM and 1 mM) using HEK cells in a recombinant expression system (pK < 4.5, n = 3). In conclusion, we suggest that ergometrine is an agonist at cardiac human HRs.
Topics: Humans; Mice; Animals; Serotonin; Histamine; Atrial Fibrillation; Myocardial Contraction; Heart Atria; Mice, Transgenic; Serine; Receptors, Histamine H2
PubMed: 37354215
DOI: 10.1007/s00210-023-02573-8 -
Pain Reports Jun 2024Postoperative rebound pain after peripheral nerve block increases patient suffering and delays recovery after surgery.
INTRODUCTION
Postoperative rebound pain after peripheral nerve block increases patient suffering and delays recovery after surgery.
OBJECTIVES
We tested whether the 5HT-3 receptor antagonist and α7nAChR agonist tropisetron could prevent postoperative rebound pain.
METHODS
A total of 115 patients were randomized to receive 5-mg/5-mL tropisetron or the same volume of normal saline. Pain intensity was measured with the numerical rating scale of pain (NRS). Rebound pain was defined as a change from mild pain (NRS ≤ 3) measured in the postanesthesia care unit to severe pain (NRS ≥ 7) within 24 hours after peripheral nerve blockade. Logistic regression was used to identify relevant factors associated with postoperative rebound pain.
RESULTS
Tropisetron did not affect the NRS score or the incidence of rebound pain after peripheral nerve block. Logistic regression revealed that preoperative pain, bone surgery, and length of incision were risk factors for postoperative rebound pain, and patient-controlled analgesia was protective against postoperative rebound pain.
CONCLUSION
Tropisetron does not affect the incidence of rebound pain after peripheral nerve block. Patients at high risk of postoperative rebound pain should be identified for appropriate management. Registration site: www.chictr.org.cn (ChiCTR2300069994).
PubMed: 38756786
DOI: 10.1097/PR9.0000000000001163 -
World Journal of Surgical Oncology Feb 2024In patients undergoing laparoscopic radical gastrectomy, the use of subcostal transversus abdominis plane block (STAPB) for completely opioid-free postoperative pain... (Randomized Controlled Trial)
Randomized Controlled Trial
Analgesic efficacy of an opioid-free postoperative pain management strategy versus a conventional opioid-based strategy following laparoscopic radical gastrectomy: an open-label, randomized, controlled, non-inferiority trial.
OBJECTIVE
In patients undergoing laparoscopic radical gastrectomy, the use of subcostal transversus abdominis plane block (STAPB) for completely opioid-free postoperative pain management lacks convincing clinical evidence.
METHODS
This study included 112 patients who underwent laparoscopic radical gastrectomy at the 900TH Hospital of the Joint Logistics Support Force from October 2020 to March 2022. Patients were randomly divided into (1:1) continuous opioid-free STAPB (C-STAPB) group and conventional group. In the C-STAPB group, 0.2% ropivacaine (bilateral, 20 ml per side) was injected intermittently every 12 h through a catheter placed on the transverse abdominis plane for postoperative pain management. The conventional group was treated with a conventional intravenous opioid pump (2.5 μg/kg sufentanil and 10 mg tropisetron, diluted to 100 ml with 0.9% NS). The primary outcomes were the accumulative area under the curve of the numeric rating scale (NRS) score at 24 and 48 h postoperatively at rest and during movement. The secondary outcomes were postoperative recovery outcomes, postoperative daily food intake, and postoperative complications.
RESULTS
After exclusion (n = 16), a total of 96 patients (C-STAPB group, n = 46; conventional group, n = 49) were included. We found there were no significant differences in the cumulative AUC of NRS score PACU-24 h and PACU-48 h between the C-STAPB group and conventional group at rest [(mean difference, 1.38; 95% CI, - 2.21 to 4.98, P = 0.447), (mean difference, 1.22; 95% CI, - 6.20 to 8.65, P = 0.744)] and at movement [(mean difference, 2.90; 95% CI, - 3.65 to 9.46; P = 0.382), (mean difference, 4.32; 95% CI, - 4.46 to 13.1; P = 0.331)]. The 95% CI upper bound of the difference between rest and movement in the C-STAPB group was less than the inferior margin value (9.5 and 14 points), indicating the non-inferiority of the analgesic effect of C-STPAB. The C-STAPB group had faster postoperative recovery profiles including earlier bowel movement, defecation, more volume of food intake postoperative, and lower postoperative nausea and vomiting compared to conventional groups (P < 0.001).
CONCLUSIONS
After laparoscopic radical gastrectomy, the analgesic effect of C-STAPBP is not inferior to the traditional opioid-based pain management model.
TRIAL REGISTRATION
ChiCTR2100051784.
Topics: Humans; Analgesics; Analgesics, Opioid; Anesthetics, Local; Gastrectomy; Laparoscopy; Pain, Postoperative; Ultrasonography, Interventional
PubMed: 38360661
DOI: 10.1186/s12957-023-03298-x