Different origin-derived exosomes and their clinical advantages in cancer therapy.

Exosomes, as a class of small extracellular vesicles closely related to the biological behavior of various types of tumors, are currently attracting research attention in cancer diagnosis and treatment. Regarding cancer diagnosis, the stability of their membrane structure and their wide distribution in body fluids render exosomes promising biomarkers. It is expected that exosome-based liquid biopsy will become an important tool for tumor diagnosis in the future. For cancer treatment, exosomes, as the "golden communicators" between cells, can be designed to deliver different drugs, aiming to achieve low-toxicity and low-immunogenicity targeted delivery. Signaling pathways related to exosome contents can also be used for safer and more effective immunotherapy against tumors. Exosomes are derived from a wide range of sources, and exhibit different biological characteristics as well as clinical application advantages in different cancer therapies. In this review, we analyzed the main sources of exosomes that have great potential and broad prospects in cancer diagnosis and therapy. Moreover, we compared their therapeutic advantages, providing new ideas for the clinical application of exosomes.

The prognostic and immune significance of PLBD1 in pan-cancer and its roles in proliferation and invasion of glioma.

Cancer is a destructive disease and is currently the leading cause of major threats to human health. PLBD1 is a transcription factor that regulates phospholipid metabolism, but its role in tumors is unknown. We assessed pan-cancer expression, methylation, and mutation data of PLBD1 by multiple databases to investigate its clinical prognostic value. In addition, we examined the pan-cancer immunological signature of PLBD1, particularly in gliomas. Furthermore, we assessed the impact of PLBD1 knockdown on the proliferation and invasive capacity of glioma cells by in vitro experiments. Our results suggest that PLBD1 is highly expressed in multiple types of cancers, and it can serve as an independent prognostic factor for gliomas. In addition, we found that the epigenetic alterations of PLBD1 were highly heterogeneous in a variety of cancers, including gliomas, and that its high methylation was associated with poor prognosis in a broad range of cancers. Immunological profiling demonstrated that PLBD1 was significantly associated with immune cell infiltration and multiple immune checkpoints in gliomas and is a potential biomarker for gliomas. Furthermore, cellular experiments showed that knockdown of PLBD1 significantly inhibited the proliferation and invasive ability of glioma cells. In conclusion, PLBD1 is a potential tumor prognostic biomarker and immunotherapeutic target that plays a crucial role in glioma cell proliferation, invasion and immunotherapy.

Frontiers and future of immunotherapy for pancreatic cancer: from molecular mechanisms to clinical application.

Pancreatic cancer is a highly aggressive malignant tumor, that is becoming increasingly common in recent years. Despite advances in intensive treatment modalities including surgery, radiotherapy, biological therapy, and targeted therapy, the overall survival rate has not significantly improved in patients with pancreatic cancer. This may be attributed to the insidious onset, unknown pathophysiology, and poor prognosis of the disease. It is therefore essential to identify and develop more effective and safer treatments for pancreatic cancer. Tumor immunotherapy is the new and fourth pillar of anti-tumor therapy after surgery, radiotherapy, and chemotherapy. Significant progress has made in the use of immunotherapy for a wide variety of malignant tumors in recent years; a breakthrough has also been made in the treatment of pancreatic cancer. This review describes the advances in immune checkpoint inhibitors, cancer vaccines, adoptive cell therapy, oncolytic virus, and matrix-depletion therapies for the treatment of pancreatic cancer. At the same time, some new potential biomarkers and potential immunotherapy combinations for pancreatic cancer are discussed. The molecular mechanisms of various immunotherapies have also been elucidated, and their clinical applications have been highlighted. The current challenges associated with immunotherapy and proposed strategies that hold promise in overcoming these limitations have also been discussed, with the aim of offering new insights into immunotherapy for pancreatic cancer.

Design and discovery of novel pyrazole-pyrrolopyrimidine derivatives as anti-glioma agents via promoting apoptosis, inhibiting cell cycle and EGFR-TK.

Glioma is an aggressive type of brain malignancy responsible for significant morbidity and mortality. In the current scenario, epidermal growth factor receptor (EGFR) kinases targeted therapy showed significant benefits in glioma patients. Therefore, in the present study, we intend to investigate the anti-glioma potential of a novel class of pyrazole-pyrrolopyrimidine derivatives and their mechanism of action. The compounds will be synthesized in a straight-forward synthetic route in excellent yields and subsequently tested for EGFR kinase inhibition. The compounds showed a diverse range of inhibitory activity against EGFR (IC50 = 3.4-873.2 nM). With an IC50 of 1.5 nM, compound 4i was determined to be the most effective EGFR inhibitor, even superior to the standard erlotinib (IC50 2.3 nM). Among them, the three most potent compounds (4i, 4j, and 4k) were further subjected to the anticancer activity against the panel of various cancer cell lines MCF-7 (breast cancer), A549 (lung cancer), U87 (glioblastoma cell)-EGFR-Wild Type, U87 (mutant glioblastoma cells) EGFR-mutant cell, MCF-12A (normal cells). The compound 4i showed the most potent activity against glioblastoma cells as compared to other cancer cells. The effect of compound 4i was also studied on the apoptosis of U87 cells, where it showed induction of apoptosis in a concentration-dependent manner. It also showed inhibition of the G2/M cell cycle phase of U87 cells. Our study demonstrated the development of novel pyrazole-pyrrolopyrimidine derivatives as a novel class of anti-glioma agents.

Cell-based and cell-free immunotherapies for glioblastoma: current status and future directions.

Glioblastoma (GBM) is among the most fatal and recurring malignant solid tumors. It arises from the GBM stem cell population. Conventional neurosurgical resection, temozolomide (TMZ)-dependent chemotherapy and radiotherapy have rendered the prognosis of patients unsatisfactory. Radiotherapy and chemotherapy can frequently induce non-specific damage to healthy brain and other tissues, which can be extremely hazardous. There is therefore a pressing need for a more effective treatment strategy for GBM to complement or replace existing treatment options. Cell-based and cell-free immunotherapies are currently being investigated to develop new treatment modalities against cancer. These treatments have the potential to be both selective and successful in minimizing off-target collateral harm in the normal brain. In this review, several aspects of cell-based and cell-free immunotherapies related to GBM will be discussed.

Inhibition of STAT3 signaling as critical molecular event in HUC-MSCs suppressed Glioblastoma Cells.

Objective: We investigated the effect of human umbilical cord mesenchymal stem cells (HUC-MSCs) supernatants on proliferation, migration, invasion, and apoptosis in glioblastoma (GBM) cell lines RG-2, U251, U87-MG, and LN-428, as well as their apoptosis and autophagy-mediated through IL-6/JAK2/STAT3 signaling pathway to explore the molecular mechanisms. Methods: In this study, RG-2, U251, U87-MG, and LN-428 cells were treated with 9 mg/ml HUC-MSCs supernatants. Their responses to HUC-MSCs supernatants treatment and the status of STAT3 signaling were analyzed by multiple experimental approaches to elucidate the importance of HUC-MSCs supernatants for GBM. Results: The results demonstrated that after treatment with HUC-MSCs supernatants, in vitro proliferation of RG-2, U251, U87-MG, and LN-428 cells were inhibited, and their sustained growth was also blocked. RG-2, U251, and U87-MG cells showed significant S phase accumulation, while LN-428 cells were blocked in G0/G1 phase. Their migratory invasive capacities were inhibited, and their apoptosis and autophagy ratios were increased. These effects were mediated through the IL-6/JAK2/STAT3 and its downstream signaling pathway. Conclusion: Our data showed that HUC-MSCs supernatants had anti-tumor effects on GBM cells. It inhibited the proliferation, migration, and invasion of GBM cells and promoted their apoptosis. Negative regulation of the IL-6/JAK2/STAT3 signaling pathway enhanced apoptosis and autophagy in tumor cells, thereby improving the therapeutic effect on GBM.

Noninvasive evaluation of intracranial pressure in patients with traumatic brain injury by transcranial Doppler ultrasound.

INTRODUCTION: The purpose of this study was to investigate the relationship between pulsatility index (PI) or optic nerve sheath diameter (ONSD) and intracranial pressure (ICP) in patients with traumatic brain injury (TBI), and the ability of ONSD and ICP to predict intracranial hypertension. METHODS: A total of 68 patients with TBI were included in this retrospective study. After receiving surgery treatment, they underwent transcranial Doppler ultrasound (TCD). The statistical correlation between PI or ONSD and ICP 1 week after surgery was analyzed. Furthermore, the areas under the curve (AUCs) of ONSD or PI or a combination of them were calculated to predict intracranial hypertension. RESULTS: There was a correlation between ONSD and ICP. This correlation still remained at ONSD ≥ 5 mm. Furthermore, there was a strong correlation between PI and ICP. There was a moderate correlation between ICP and PI on days 3, 4, and 5 after surgery (r = 0.508, p < .001), and a strong correlation on days 6 and 7 after surgery (r = 0.645, p < .001). Moreover, for predicting intracranial hypertension with PI ≥ 1.2 mm or ONSD ≥ 5 mm or a combination of them, the AUC was 0.729, 0.900, and 0.943, respectively (p < .001). CONCLUSIONS: The correlation between ONSD or PI and invasive ICP was different with different levels of ICP in different periods in patients with TBI after surgery. When ONSD ≥ 5 mm and PI ≥ 1.2, it could predict elevated ICP more accurately.

Risk Factors and Neurologic Outcomes in Patients with Traumatic Brain Injury and Coagulopathy Within 72 h After Surgery.

OBJECTIVE: The purpose of this study was to explore the effect of coagulopathy in patients with traumatic brain injury (TBI) during the early postoperative period. METHODS: The baseline characteristics, intraoperative management, and follow-up data of 462 patients with TBI between January 2015 and June 2019 were collected and retrospectively analyzed by multivariate logistic regression. Coagulopathy was defined as activated partial thromboplastin time > 40 s, international normalized ratio > 1.4, or platelet counts < 100×109/L. RESULTS: Multivariate logistic regression analysis revealed that the Glasgow Coma Scale (GCS) on admission, Injury Severity Score (ISS) on admission, pupil mydriasis, duration of surgery, intraoperative blood loss, and intraoperative crystalloid resuscitation were independent risk factors for patients who developed coagulopathy after surgery. There were statistical differences in mortality (p = 0.049), the Glasgow Outcome Scale-Extended (GCS-E; p = 0.024), and the modified Rankin Scale (p = 0.043) between the patients with and without coagulopathy 1 week after surgery. Coagulopathy within 72 h after surgery revealed the higher mortality at 1 week (66.7%), 3 months (71.4%), and 6 months (76.2%). Coagulopathy within 72 h after surgery in patients with a TBI predicted worse disease progression and unfavorable neurologic outcomes. CONCLUSION: Taking practical and reasonable measures to manage these risk factors may protect patients with TBI from postoperative coagulopathy.

Temozolomide chemotherapy combined with radiotherapy versus radiotherapy alone after surgery in patients with high-risk low-grade gliomas.

PURPOSE: The purpose of this study was to compare the clinical efficacy and safety of temozolomide (TMZ) combined with three-dimensional conformal radiotherapy (3D-CRT) and radiotherapy alone after surgery in patients with high-risk low-grade gliomas (LGGs). METHODS: Patients (N=110) with LGGs were enrolled. Patients receiving TMZ chemotherapy combined with radiotherapy were considered as combination group (n=55), while those treated with radiotherapy alone were regarded as control group (n=55). The patients were followed up, and the overall survival (OS) and progression-free survival (PFS) were recorded. Finally, factors possibly affecting prognosis were analyzed. RESULTS: The follow-up results exhibited median OS [(67.4±8.8) months vs. (63.9±8.6) months] and median PFS [(51.1±7.6) months vs. (46.8±6.9) months] as well as three-year OS rate and three-year PFS rate in combination group and control group. Log-rank test indicated that the difference in OS was not statistically significant between the two groups of patients, and PFS in combination group was significantly superior to that in control group. The results of univariate and multivariate analysis displayed that age <40 years old and complete tumor resection were independent factors affecting the three-year OS of patients with high-risk LGGs. Besides, age <40 years old, complete tumor resection and TMZ chemotherapy combined with radiotherapy after surgery were independent factors affecting the three-year PFS of patients with high-risk LGGs. CONCLUSION: TMZ chemotherapy combined with radiotherapy after surgery in patients with high-risk LGGs can prominently improve clinical efficacy, prolong PFS, and facilitate tolerance to adverse reactions, but not prolong the OS of patients. The OS is notably prolonged in patients aged <40 years old and receiving complete tumor resection.

Management of Postoperative Pain after Elective Craniotomy: A Prospective Randomized Controlled Trial of a Neurosurgical Enhanced Recovery after Surgery (ERAS) Program.

Objective: To prospectively evaluate the efficacy of a neurosurgical enhanced recovery after surgery (ERAS) protocol on the management of postoperative pain after elective craniotomies. Methods: This randomized controlled trial was conducted in the neurosurgical center of Tangdu Hospital (Fourth Military Medical University, Xi'an, China). A total of 129 patients undergoing craniotomies between October 2016 and July 2017 were enrolled in a randomized clinical trial comparing an ERAS protocol to a conventional postoperative care regimen. The primary outcome was the postoperative pain score assessed by a verbal numerical rating scale (NRS). Results: Patients in the ERAS group had a significant reduction in their postoperative pain scores on POD 1 compared to patients in the control group (p < 0.05). More patients (n = 44, 68.8%) in the ERAS group experienced mild pain (NRS: 1 to 3) on POD1 compared with patients (n = 23, 35.4%) in the control group (p < 0.05). A further reduction in pain scores was also observed on POD 2 and maintained on POD 3 in the ERAS group compared with that in the control group. In addition, the median postoperative length of hospital stay was significantly decreased with the incorporation of the ERAS protocol compared to controls (ERAS: 4 days, control: 7 days, P<0.001). Conclusion: The implementation of a neurosurgical ERAS protocol for elective craniotomy patients has significant benefits in alleviating postoperative pain and enhancing recovery leading to early discharge after surgery compared to conventional care. Further evaluation of this protocol in larger, multi-center studies is warranted.

Impact of neurosurgical enhanced recovery after surgery (ERAS) program on health-related quality of life in glioma patients: a secondary analysis of a randomized controlled trial.

INTRODUCTION: A novel neurosurgical enhanced recovery after surgery (ERAS) program shortens postoperative hospital stay and accelerates functional recovery in elective craniotomy patients. There is a need to evaluate the impact of ERAS program on patients' health-related quality of life (HRQOL). METHODS: In a single-center randomized controlled trial, patients were randomized 1:1 to receive perioperative ERAS or conventional care. As a secondary outcome, HRQOL was measured with the EORTC QLQ-C30/BN20 prior to randomization (baseline), at discharge, and at 3- and 6-month follow-up. RESULTS: A total of 65 patients (ERAS: n = 36, conventional care: n = 29) with pathologically confirmed glioma (WHO grade 2-4) were included in the analysis. Progression-free survival at 6 months and HRQOL at baseline were similar between the two groups. Changes of scores did not vary significantly over time, but differed significantly between intervention groups. A clinically relevant better QoL (at 3-month follow-up), physical functioning (at 6-month follow-up) and role functioning (at discharge) was observed in patients in the ERAS group. Symptom scores of constipation (at discharge), motor dysfunction (at discharge, 3- and 6-month follow-up), drowsiness (at 3- and 6-month follow-up), weakness of legs (at 3-month follow-up), and nausea/vomiting (at discharge and 6-month follow-up) were significantly lower in the ERAS group. CONCLUSIONS: The neurosurgical ERAS program seems to improve functioning and symptoms scores in glioma patients within 6-month follow-up compared with conventional care. The intervention has a significant main effect HRQOL changes without significant interaction with time. Future well-powered multicenter studies are warranted to confirm this result and address long-term benefits. This study has been registered in the Chinese Clinical Trial Registry ( http://www.chictr.org.cn/showproj.aspx?proj=16480 ) with registration number ChiCTR-INR-16009662.

Ambulatory Surgery Protocol for Endoscopic Endonasal Resection of Pituitary Adenomas: A Prospective Single-arm Trial with Initial Implementation Experience.

Endoscopic endonasal transsphenoidal resection has been accepted as a routine therapy for pituitary adenoma, but the postoperative hospital stay is typically several days long. With the advantages of reduced cost and improved patient satisfaction, the application of ambulatory surgery (AS) has developed rapidly. However, AS was still rarely adopted in neurosurgery. Here we designed an AS treatment protocol for pituitary adenoma with the endoscopic endonasal approach (EEA), and reported our initial experiences regarding the safety and efficacy of the AS protocol. 63 patients who presented with pituitary adenoma were screened at the Department of Neurosurgery, Tangdu Hospital from July to September, 2017. A total of 20 pituitary adenoma patients who met the inclusion criteria underwent EEA surgery using this evidence-based AS protocol, which emphasized adequate assessment for eligibility, full preparation to minimize invasiveness, enhanced recovery, and active perioperative patient education. Of the 20 patients enrolled, 18 were discharged on the afternoon of the operation day with a median total length of stay (LOS) of 31 hours (range, 29-32) hours. The median LOS after surgery was 6.5 (range, 5-8) hours. Two patients were transferred from the AS protocol to conventional care due to intraoperative cerebrospinal fluid leakage (one case) and an unsatisfying post-anesthetic discharge score (one case). Complications included transient and reversible mild postoperative nausea and vomiting [visual analog scale (VAS) score <3], headache (VAS score <3) after the operation or early after discharge. No patient was readmitted. Our results supported the safety and efficacy of the AS protocol for pituitary adenoma patients undergoing EEA resection among eligible patients, and further evaluation of this protocol in controlled studies with a larger sample size is warranted.

Successful implementation of an enhanced recovery after surgery (ERAS) protocol reduces nausea and vomiting after infratentorial craniotomy for tumour resection: a randomized controlled trial.

BACKGROUND: Infratentorial craniotomy patients have a high incidence of postoperative nausea and vomiting (PONV). Enhanced Recovery After Surgery (ERAS) protocols have been shown in multiple surgical disciplines to improve outcomes, including reduced PONV. However, very few studies have described the application of ERAS to infratentorial craniotomy. The aim of this study was to examine whether our ERAS protocol for infratentorial craniotomy could improve PONV. METHODS: We implemented an evidence-based, multimodal ERAS protocol for patients undergoing infratentorial craniotomy. A total of 105 patients who underwent infratentorial craniotomy were randomized into either the ERAS group (n = 50) or the control group (n = 55). Primary outcomes were the incidence of vomiting, nausea score, and use of rescue antiemetic during the first 72 h after surgery. Secondary outcomes included postoperative anxiety level, sleep quality, and complications. RESULTS: Over the entire 72 h post-craniotomy observation period, the cumulative incidence of vomiting was significantly lower in the ERAS group than in the control group. Meanwhile, the incidence of vomiting was significantly lower in the ERAS group on postoperative days (PODs) 2 and 3. Notably, the proportion of patients with mild nausea (VAS 0-4) was higher in the ERAS group as compared to the control group on PODs 2 or 3. Additionally, the postoperative anxiety level and quality of sleep were significantly better in the ERAS group. CONCLUSION: Successful implementation of our ERAS protocol in infratentorial craniotomy patients could attenuate postoperative anxiety, improve sleep quality, and reduce the incidence of PONV, without increasing the rate of postoperative complications. TRIAL REGISTRATION: ChiCTR-INR-16009662, 27 Oct 2016, Clinical study on the development and efficacy evaluation of Enhanced Recovery After Surgery (ERAS) in Neurosurgery.

Enhanced Recovery After Intraspinal Tumor Surgery: A Single-Institutional Randomized Controlled Study.

OBJECTIVE: To evaluate the safety and efficacy of an enhanced recovery after surgery (ERAS) program for intraspinal tumors in a single-institutional prospective randomized controlled trial. METHODS: A multimodal and multidisciplinary ERAS protocol for intraspinal tumor surgery was developed. A total of 94 enrolled patients were randomized into 2 groups: 48 were managed following the ERAS protocol (ERAS group), and 46 received conventional perioperative care (control group). The primary end point was postoperative length of stay (LOS). The secondary outcomes included postoperative pain score and pain medication use, urinary catheterization, ambulation, mortality, reoperation/readmission rates, complication rates, patient satisfaction, and overall cost. RESULTS: A significant reduction in LOS was achieved in patients undergoing ERAS protocol compared with the controls (5 vs. 8 days; P < 0.0001). Moreover, patients in the ERAS group had better postoperative pain scores (1.0 ± 1.3 vs. 1.9 ± 1.3; P = 0.007), decreased use of patient-controlled analgesia (4.2% vs. 19.6%; P = 0.020) and oral opioid (37.5% vs. 58.7%; P = 0.040), early urinary catheter removal (58.3% vs. 6.5%; P < 0.0001), greater ambulation (68.8% vs. 17.4%; P < 0.0001), and higher satisfaction scores (91.8 ± 4.4 vs. 88.2 ± 6.8; P = 0.022) than did the control group. There were no deaths or 30-day readmission/reoperation in both groups, nor did the postoperative complication rates differ between groups. CONCLUSIONS: The ERAS protocol for intraspinal tumor surgery seems to be feasible, effective, and safe in shortening postoperative LOS, improving postoperative pain control with reduced opioid use, and accelerating functional recovery without increasing rates of complications or reoperation/readmission. Adoption of spine ERAS programs could be encouraged in practice, although validation with larger-scale multicenter trials is warranted.

Neurosurgical enhanced recovery after surgery (ERAS) programme for elective craniotomies: are patients satisfied with their experiences? A quantitative and qualitative analysis.

OBJECTIVE: To evaluate patient satisfaction and associated predictors at discharge, as well as patient experience at 30-day follow-up, in a neurosurgical enhanced recovery after surgery (ERAS) programme. DESIGN: A single-centre, prospective, randomised controlled study. SETTING: A tertiary hospital in China. PARTICIPANTS: A total of 140 neurosurgical patients aged 18-65 years old who had a single intracranial lesion and were admitted for elective craniotomy between October 2016 and July 2017 were included. INTERVENTIONS: Patients were randomised into two groups: 70 patients received care according to a novel neurosurgical ERAS protocol (ERAS group) and 70 patients received conventional perioperative care (control group). OUTCOME MEASURES: Patient satisfaction at discharge was evaluated using a multimodal questionnaire. A secondary analysis of patient experience regarding participation in the ERAS programme was conducted using a semistructured qualitative interview via telephone at 30-day follow-up. RESULTS: The mean patient satisfaction was significantly higher in the ERAS group than in the control group at discharge (92.2±4.3 vs 86.8±7.4, p=0.0001). The most important predictors of patient satisfaction included age (OR=6.934), postoperative nausea and vomiting (PONV) Visual Analogue Scale (VAS) score (OR=0.184), absorbable skin suture (OR=0.007) and postoperative length of stay (LOS) (OR=0.765). Analysis on patient experience revealed five themes: information transfer, professional support, shared responsibility and active participation, readiness for discharge, and follow-up, all of which are closely related and represent positive and negative aspects. CONCLUSIONS: Measures that include decreasing PONV VAS score, incorporating absorbable skin suture and shortening LOS seem to increase patient satisfaction in a neurosurgical ERAS programme. Analysis of data on patient experience highlights several aspects to achieve patient-centred and high-quality care. Further studies are warranted to standardise the assessment of patient satisfaction and experience in planning, employing and appraising the ERAS programme. TRIAL REGISTRATION NUMBER: ChiCTR-INR-16009662.

A randomized controlled study of preoperative oral carbohydrate loading versus fasting in patients undergoing elective craniotomy.

OBJECT: The aim of this study was to evaluate the effect of preoperative oral carbohydrate loading versus fasting on the outcomes of patients undergoing elective craniotomy. METHODS: In a single-center randomized controlled study, 120 neurosurgical patients who were admitted for elective craniotomy were included and randomized into 2 groups: 58 patients received 400 mL of oral carbohydrate loading 2 h before surgery (intervention group), and 62 patients were fasting for 8 h prior to surgery as routine management (control group). The primary end point was glucose homeostasis. Secondary outcomes included handgrip strength, pulmonary function and postoperative complications. RESULTS: Better glucose homeostasis (5.6 ± 1.0 mmol/L vs. 6.3 ± 1.2 mmol/L, P = 0.001) was achieved in patients who received preoperative oral carbohydrate loading compared to fasting. Furthermore, patients in the intervention group had better handgrip strength (25.3 ± 7.1 kg vs. 19.9 ± 7.5 kg, P < 0.0001) and pulmonary function (in terms of peak expiratory flow rate) (315.8 ± 91.5 L/min vs. 270.0 ± 102.7 L/min, P = 0.036) compared to the controls postoperatively. The rates of postoperative surgical and non-surgical complications did not differ between the groups. Both postoperative and total hospital length of stay (LOS) reduced significantly in the intervention group (-3d, P < 0.0001 and P = 0.004). CONCLUSIONS: Oral carbohydrate loading given 2 h before surgery in patients undergoing elective craniotomy seems to improve glucose homeostasis, handgrip strength and pulmonary function as well as decrease LOS without increasing the risk of postoperative complications. Routine use of preoperative oral carbohydrate loading could be suggested in clinical settings, though further evaluation of its safety and efficacy is warranted.

Safety and efficacy of a novel neurosurgical enhanced recovery after surgery protocol for elective craniotomy: a prospective randomized controlled trial.

OBJECTIVEAlthough enhanced recovery after surgery (ERAS) programs have gained acceptance in various surgical specialties, no established neurosurgical ERAS protocol for patients undergoing elective craniotomy has been reported in the literature. Here, the authors describe the design, implementation, safety, and efficacy of a novel neurosurgical ERAS protocol for elective craniotomy in a tertiary care medical center located in China.METHODSA multidisciplinary neurosurgical ERAS protocol for elective craniotomy was developed based on the best available evidence. A total of 140 patients undergoing elective craniotomy between October 2016 and May 2017 were enrolled in a randomized clinical trial comparing this novel protocol to conventional neurosurgical perioperative management. The primary endpoint of this study was the postoperative hospital length of stay (LOS). Postoperative morbidity, perioperative complications, postoperative pain scores, postoperative nausea and vomiting, duration of urinary catheterization, time to first solid meal, and patient satisfaction were secondary endpoints.RESULTSThe median postoperative hospital LOS (4 days) was significantly shorter with the incorporation of the ERAS protocol than that with conventional perioperative management (7 days, p < 0.0001). No 30-day readmission or reoperation occurred in either group. More patients in the ERAS group reported mild pain (visual analog scale score 1-3) on postoperative day 1 than those in the control group (79% vs. 33%, OR 7.49, 95% CI 3.51-15.99, p < 0.0001). Similarly, more patients in the ERAS group had a shortened duration of pain (1-2 days; 53% vs. 17%, OR 0.64, 95% CI 0.29-1.37, p = 0.0001). The urinary catheter was removed within 6 hours after surgery in 74% patients in the ERAS group (OR 400.1, 95% CI 23.56-6796, p < 0.0001). The time to first oral liquid intake was a median of 8 hours in the ERAS group compared to 11 hours in the control group (p < 0.0001), and solid food intake occurred at a median of 24 hours in the ERAS group compared to 72 hours in the control group (p < 0.0001).CONCLUSIONSThis multidisciplinary, evidence-based, neurosurgical ERAS protocol for elective craniotomy appears to have significant benefits over conventional perioperative management. Implementation of ERAS is associated with a significant reduction in the postoperative hospital stay and an acceleration in recovery, without increasing complication rates related to elective craniotomy. Further evaluation of this protocol in large multicenter studies is warranted.Clinical trial registration no.: ChiCTR-INR-16009662 (chictr.org.cn).

Comparison of Treatment of Acute Unstable Distal Clavicle Fractures Using Anatomical Locking Plates with Versus without Additional Suture Anchor Fixation.

BACKGROUND Surgical managements were recommended for unstable distal clavicle fracture owing to the high incidence of nonunion. The present study compared the efficacy of anatomical locking plate with versus without additional suture anchor fixation for the treatment of unstable Neer type II distal clavicle fractures. MATERIAL AND METHODS Between January 2013 to January 2015, 28 consecutive patients with unstable Neer type II  fractures were treated by using anatomical locking plate with or without additional suture anchor fixation. The patients were divided into anatomical locking plate group (group A) and anatomical locking plate combined with suture anchor group (group B) according to the surgical method. The operative-related parameters such as operation time, blood loss, length of hospitalization, union time, functional outcomes (Constant score, UCLA score and DASH score) and CC distance were compared. RESULTS The mean follow-up period of the 28 patients was 19.60 months (21.80 versus 18.39 months, respectively). No statistical differences in general and peri-operative parameters were found between 2 groups. The group B had significant higher Constant score than group A (P=0.004, 91.67 versus 83.10). While no statistical differences were reached in the UCLA score and DASH score between 2 groups (P=0.112 and 0.163, respectively). The group A had longer CC distance than group B (11.67 versus 8.94 mm), while no statistic difference was found (P=0.067). CONCLUSIONS For the treatment of acute unstable Neer type II distal clavicle fractures, both surgical methods could offer satisfactory outcome. However, anatomical locking plate combined with additional suture anchor fixation had a better functional and radiographic outcome than that without additional suture anchor fixation.

Critical roles of chemokine receptor CCR5 in regulating glioblastoma proliferation and invasion.

Glioblastoma (GBM) is the most prevalent malignant primary brain tumor in adults and exhibits a spectrum of aberrantly aggressive phenotype. Tumor cell proliferation and invasion are critically regulated by chemokines and their receptors. Recent studies have shown that the chemokine CCL5 and its receptor CCR5 play important roles in tumor invasion and metastasis. Nonetheless, the roles of the CCR5 in GBM still remain unclear. The present study provides the evidence that the chemokine receptor CCR5 is highly expressed and associated with poor prognosis in human GBM. Mechanistically, CCL5-CCR5 mediates activation of Akt, and subsequently induces proliferation and invasive responses in U87 and U251 cells. Moreover, down-regulation of CCR5 significantly inhibited the growth of glioma in U87 tumor xenograft mouse model. Finally, high CCR5 expression in GBM is correlated with increased p-Akt expression in patient samples. Together, these findings suggest that the CCR5 is a critical molecular event associated with gliomagenesis.