Association of type 2 Diabetes Mellitus and bone mineral density: a two-sample Mendelian randomization study.

BACKGROUND: Observational studies have suggested that type 2 Diabetes Mellitus (DM2) is a potentially modifiable risk factor for lower BMD, but the causal relationship is unclear. This study aimed to examine whether the association of DM2 with lower BMD levels was causal by using Mendelian randomization (MR) analyses. METHODS: We collected genome-wide association study data for DM2 and BMD of total body and different skeletal sites from the IEU database. Subsequently, we performed a two-sample Mendelian randomization analysis using the Two Sample MR package. RESULTS: We identified a positive association between DM2 risk (61,714 DM2 cases and 596,424 controls) and total BMD, and other skeletal sites BMD, such as femoral neck BMD, ultra-distal forearm BMD and heel BMD. However, non-significant trends were observed for the effects of DM2 on lumbar-spine BMD. CONCLUSION: In two-sample MR analyses, there was positive causal relationship between DM2 and BMD in both overall samples. In summary, while observational analyses consistently indicate a strong association between DM2 and low BMD, our MR analysis introduces a nuanced perspective. Contrary to the robust association observed in observational studies, our MR analysis suggests a significant link between DM2 and elevated BMD.

Does vertebral osteoporosis delay or accelerate lumbar disc degeneration? A systematic review.

The effect of vertebral osteoporosis on disc degeneration is still debated. The purpose of this study was to provide a systematic review of studies in this area to further reveal the relationship between the two. Relevant studies were searched in electronic databases, and studies were screened according to inclusion and exclusion criteria, and finally, basic information of the included studies was extracted and summarized. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. A total of 34 publications spanning 24 years were included in our study. There were 19 clinical studies, including 12 prospective studies and 7 retrospective studies. Of these, 7 considered vertebral osteoporosis to be positively correlated with disc degeneration, 8 considered them to be negatively correlated, and 4 considered them to be uncorrelated. Two cadaveric studies were included, one considered the two to be negatively correlated and one considered them not to be correlated. Seven animal studies were included, of which five considered a positive correlation between vertebral osteoporosis and disc degeneration and two considered a negative correlation between the two. There were also 6 studies that used anti-osteoporosis drugs for intervention, all of them were animal studies. Five of them concluded that vertebral osteoporosis was positively associated with disc degeneration, and the remaining one concluded that there was no correlation between the two. Our systematic review shows that the majority of studies currently consider an association between vertebral osteoporosis and disc degeneration, but there is still a huge disagreement whether this association is positive or negative. Differences in observation time and follow-up time may be one of the reasons for the disagreement. A large number of clinical and basic studies are still needed in the future to further explore the relationship between the two.

Continuous renal replacement therapy with the adsorptive oXiris filter may be associated with the lower 28-day mortality in sepsis: a systematic review and meta-analysis.

BACKGROUND: The oXiris is a novel filter for continuous renal replacement therapy (CRRT) featuring an adsorption coating to adsorb endotoxins and remove inflammatory mediators. Given that no consensus has been reached on its potential benefits in treating sepsis, a meta-analysis was conducted to assess its impact on the clinical outcomes of this patient population. METHODS: Eleven databases were retrieved to find relevant observational studies and randomized controlled trials. The Newcastle-Ottawa Scale and the Cochrane Risk of Bias Tool were used to assess the quality of the included studies. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) process was employed to assess the certainty of evidence. The 28-day mortality was the primary outcome. Secondary outcomes were 7-, 14-, and 90-day mortality, length of intensive care unit (ICU) and hospital stay, ICU and hospital mortality, norepinephrine (NE) dose, interleukin-6 (IL-6) and lactate levels, and Sequential Organ Failure Assessment (SOFA) score. RESULTS: The meta-analysis, pooling data from 14 studies, involving 695 patients, showed significant reductions in 28-day mortality [odds ratio (OR) 0.53; 95% confidence interval (CI) 0.36-0.77, p = 0.001] and length of ICU stay [weighted mean difference (WMD) - 1.91; 95% CI - 2.56 to - 1.26, p < 0.001)] in patients with sepsis using the oXiris filter compared to other filters. Besides, the SOFA score, NE dose, IL-6 and lactate levels, and 7- and 14-day mortalities were lower in the oXiris group. However, the 90-day mortality, ICU and hospital mortality, and length of hospital stay were comparable. The quality assessment of the ten observational studies indicated intermediate to high quality (average Newcastle-Ottawa score: 7.8). However, all four randomized controlled trials (RCTs) had an unclear risk of bias. The evidence for all outcomes had a low or very low level of certainty because the original study design was mainly observational studies and the RCTs included had an unclear risk of bias and a small sample size. CONCLUSION: The treatment with the oXiris filter during CRRT in sepsis patients may be associated with lower 28-, 7-, and 14-day mortalities, lactate levels, SOFA score, NE dose, and shorter length of ICU stay. However, due to the low or very low quality of evidence, the effectiveness of oXiris filters was still uncertain. Besides, no significant difference was observed for the 90-day mortality, ICU and hospital mortality, and length of hospital stay.

Biomechanical and clinical research of Isobar semi-rigid stabilization devices for lumbar degenerative diseases: a systematic review.

While lumbar spinal fusion using rigid rods is a prevalent surgical technique, it can lead to complications such as adjacent segment disease (ASDis). Dynamic stabilization devices serve to maintain physiological spinal motion and alleviate painful stress, yet they are accompanied by a substantial incidence of construct failure and subsequent reoperation. Compared to traditional rigid devices, Isobar TTL semi-rigid stabilization devices demonstrate equivalent stiffness and effective stabilization capabilities. Furthermore, when contrasted with dynamic stabilization techniques, semi-rigid stabilization offers improved load distribution, a broader range of motion within the fixed segment, and reduced mechanical failure rates. This paper will review and evaluate the clinical and biomechanical performance of Isobar TTL semi-rigid stabilization devices. A literature search using the PubMed, EMBASE, CNKI, Wanfang, VIP, and Cochrane Library databases identified studies that met the eligibility criteria. Twenty-eight clinical studies and nine biomechanical studies were included in this systematic review. The VAS, the ODI, and Japanese Orthopedic Association scoring improved significantly in most studies. UCLA grading scale, Pfirrmann grading, and modified Pfirrmann grading of the upper adjacent segments improved significantly in most studies. The occurrence rate of ASD was low. In biomechanical studies, Isobar TTL demonstrated a superior load sharing distribution, a larger fixed segment range of motion, and reduced stress at the rod-screw/screw-bone interfaces compared with titanium rods. While findings from mechanical studies provided promising results, the clinical studies exhibited low methodological quality. As a result, the available evidence does not possess sufficient strength to substantiate superior outcomes with Isobar semi-rigid system in comparison to titanium rods. To establish more conclusive conclusions, further investigations incorporating improved protocols, larger sample sizes, and extended follow-up durations are warranted.

Isobar hybrid dynamic stabilization with posterolateral fusion in mild and moderate lumbar degenerative disease.

OBJECTIVE: The aim of this study was to investigate the feasibility of using the Isobar TTL system and posterolateral fusion in a two-segment hybrid fixation approach, combined with spinal decompression, for treating mild and moderate lumbar degenerative disease. Specifically, we sought to evaluate the effectiveness of this approach for managing two-segment mild and moderate lumbar degenerative disease, and to determine whether it could provide a safe and reliable alternative to traditional surgical methods. METHODS: This retrospective study included 45 consecutive patients with two-level lumbar disc herniation or spinal stenosis, 24 of whom underwent the TTL system and posterolateral fusion combined (TTL group), and 21 of whom underwent posterolateral fusion alone (Rigid group). The surgical segment, admission diagnosis, operation time, and intraoperative bleeding were recorded separately for the two groups of patients. Imaging studies included pre- and postoperative radiography, magnetic resonance imaging, and computed tomography. The clinical outcomes were measured by Oswestry Disability Index (ODI) scores, and a visual analogue scale (VAS) for back and leg pain. RESULTS: All patients completed the surgery successfully with a mean follow-up of 56.09 months. The operative time and intraoperative bleeding were lower in the TTL group than in the Rigid group (p < 0.05). All patients showed significant improvements in clinical outcomes, including VAS for back and leg pain, and ODI scores (p < 0.05). ODI scores, the TTL group was better than the Rigid group at 1 year after surgery and at the final follow-up (p < 0.05). Postoperative surgical segment range of motion (ROM) decreased in both groups (p < 0.05). The postoperative ROM of the upper adjacent segment increased in both groups and was significantly higher in both groups at the last follow-up compared with the preoperative period (p < 0.05), and the superior adjacent segment rom of the TTL group was lower than the Rigid group (p < 0.05). The modified Pfrrmann classification of the superior adjacent segment was significantly increased in both groups at the last follow-up (p < 0.05). And in the TTL group, ROM, DH, and modified Pfrrmann grading of dynamic segment outperformed fusion segments. According to the UCLA classification, the incidence of adjacent segment degeneration (ASD) was 4.2% in the TTL group and 23.8% in the Rigid group, and the incidence of ASD was lower in the TTL group than in the Rigid group (P < 0.05). CONCLUSION: The Isobar TTL System was utilized in two-level lumbar hybrid surgery, resulting in no evident indications of lumbar instability being detected on X-rays captured at a minimum of 4 years after the operation, while retaining partial range of motion of the surgical segment. The general clinical efficacy is equivalent to titanium rod fusion surgery, presenting an alternative treatment for individuals with mild and moderate lumbar degenerative disease.

Correlation between surgical segment mobility and paravertebral muscle fatty infiltration of upper adjacent segment in single-segment LDD patients: retrospective study at a minimum 2 years' follow-up.

OBJECTIVE: The purpose of this study was to investigate the relationship between surgical segment mobility and fatty infiltration of the adjacent segment paravertebral muscles in patients with single-segment lumbar degenerative disease (LDD) who underwent decompression with fusion or dynamic stabilization. METHODS: Retrospective analysis of patients who underwent lumbar decompression combined with titanium rod fixation intertransverse fusion (PITF group), Isobar TTL dynamic stabilization (TTL group) or Isobar EVO dynamic stabilization (EVO group) for single-segment lumbar degenerative disease, from March 2012 to July 2018. The preoperative and final follow-up clinical indexes C-LDSI and the measured imaging indexes (range of motion of the surgical segment and the upper adjacent segment, and Goutallier grade of the upper adjacent segment) were counted, and the differences between the preoperative and final follow-up indexes were compared. RESULTS: According to the inclusion and exclusion criteria, 68 patients were included in this study, 21 in the PITF group, 24 in the TTL group, and 23 in the EVO group. At the final follow-up, the C-LSDI score had significantly higher in the PITF group than the TTL and EVO groups, and the C-LSDI score was a very strongly negatively correlated with ROM of surgical segment (r=-0.7968, p < 0.001). There was a strong negative correlation between surgical segment and upper adjacent segment mobility (r = -0.6959, p < 0.001). And there was a very strong negative correlation between ROM of surgical segment and upper adjacent segment paravertebral muscle Goutallier classification (r = -0.8092, p < 0.001), whereas the ROM of the upper adjacent segment was strong positive correlated with the Goutallier classification (r = 0.6703, P < 0.001). CONCLUSION: Compared with decompression combined with rigid fusion, decompression combined with dynamic fixation for single-segment lumbar degenerative disease can significantly reduce postoperative low back stiffness. And a certain range of increased mobility of the dynamic stabilization device can effectively reduce the compensatory mobility of the upper adjacent segment and slow down the fatty infiltration of the paravertebral muscle in the adjacent segment.

Comparison between single-segment Isobar EVO dynamic stabilization and Isobar TTL dynamic stabilization in the treatment of lumbar degenerative diseases: a single center retrospective study over 4 years.

OBJECTIVE: Posterior instrumented fusion is the most widely accepted surgical treatment for spinal stenosis and disc herniation. However, fusion can affect daily activities due to lumbar stiffness. In recent years, dynamic stabilization has been introduced to overcome the drawbacks of fusion, however, it is inconclusive whether dynamic stabilization requires the maintenance of a level of activity that is closer to the physiological state of activity for better clinical efficacy. The purpose of this study was to compare the effectiveness of dynamic stabilization with different levels of activity (Isobar EVO and TTL) in the treatment of spinal stenosis and disc herniation. METHODS: This study retrospectively reviewed 80 consecutive patients with lumbar degenerative diseases who were undergoing surgical treatment between March 2014 and July 2018. 41 patients (EVO group) and 39 patients (TTL group) underwent fenestrated decompression with Isobar EVO stabilization and Isobar TTL stabilization, respectively. Clinical outcomes, radiographic data, and postoperative complications were compared between the two groups. RESULTS: At an average follow-up of 52.23 ± 2.97 months, there were no significant differences in the oswestry disability index (ODI) (P > 0.05). The visual analog scale for back pain (VASback) and visual analog scale for the leg pain (VASleg) of the EVO group were lower compared with the TTL group (P < 0.05). The range of motion (ROM) of operated segments were significantly higher in the EVO group as compared to the TTL group (P < 0.05). The intervertebral space height (ISH) of upper adjacent segments were significantly higher in the EVO group as compared to the TTL group (P < 0.05). The overall complications were less in the EVO group, but the difference was not statistically significant (P > 0.05). CONCLUSION: Both Isobar EVO dynamic stabilization and TTL dynamic stabilization can improve clinical outcomes of patients with spinal stenosis and disc herniation. Isobar EVO has advantages over Isobar TTL in terms of improving low back and leg pain, maintaining mobility of the operated segment, and preventing further degeneration of the upper adjacent segment.

Emerging insights into the role of IL-1 inhibitors and colchicine for inflammation control in type 2 diabetes.

Type 2 diabetes mellitus (T2DM), a prevalent chronic metabolic disorder, is closely linked to persistent low-grade inflammation, significantly contributing to its development and progression. This review provides a comprehensive examination of the inflammatory mechanisms underlying T2DM, focusing on the role of the NLRP3 inflammasome and interleukin-1ß (IL-1ß) in mediating inflammatory responses. We discuss the therapeutic potential of IL-1 inhibitors and colchicine, highlighting their mechanisms in inhibiting the NLRP3 inflammasome and reducing IL-1ß production. Recent studies indicate that these agents could effectively mitigate inflammation, offering promising avenues for the prevention and management of T2DM. By exploring the intricate connections between metabolic disturbances and chronic inflammation, this review underscores the need for novel anti-inflammatory strategies to address T2DM and its complications.

MAGNESIUM SULFATE AMELIORATES HISTONE-INDUCED COAGULATION DYSFUNCTION AND LUNG DAMAGE IN MICE.

ABSTRACT: Introduction: Extracellular histones have been determined as significant mediators of sepsis, which can induce endothelial cell injury and promote coagulation activation, and ultimately contribute to multiorgan failure. Evidence suggests that magnesium sulfate (MgSO 4 ) exerts a potential coagulation-modulating activity; however, whether MgSO 4 ameliorates histone-induced coagulation dysfunction and organ damage remains unclear. Methods: To measure circulating histone levels, blood specimens were collected from septic patients and mice, and the relationship between circulating histone levels, coagulation parameters, and Mg 2+ levels in sepsis was investigated. Furthermore, to explore the possible protective effects of MgSO 4 , we established a histone-induced coagulation model in mice by intravenous histone injection. The survival rate of mice was assessed, and the histopathological damage of the lungs (including endothelial cell injury and coagulation status) was evaluated using various methods, including hematoxylin and eosin staining, immunohistochemistry, immunofluorescence, electron microscopy, and quantitative polymerase chain reaction. Results: The circulating histone levels in septic patients and mice were significantly associated with several coagulation parameters. In septic patients, histone levels correlated negatively with platelet counts and positively with prothrombin time and D-dimer levels. Similarly, in cecal ligation and puncture mice, histones correlated negatively with platelet counts and positively with D-dimer levels. Interestingly, we also observed a positive link between histones and Mg 2+ levels, suggesting that Mg 2+ with anticoagulant activity is involved in histone-mediated coagulation alterations in sepsis. Further animal experiments confirmed that MgSO 4 administration significantly improved survival and attenuated histone-mediated endothelial cell injury, coagulation dysfunction, and lung damage in mice. Conclusion: These results suggest that therapeutic targeting of histone-mediated endothelial cell injury, coagulation dysfunction, and lung damage, for example, with MgSO 4 , may be protective in septic individuals with elevated circulating histone levels.

Magnesium alleviates extracellular histone-induced apoptosis and defective bacterial phagocytosis in macrophages by regulating intracellular calcium signal.

Extracellular histones have been determined as important mediators of sepsis, which induce excessive inflammatory responses in macrophages and impair innate immunity. Magnesium (Mg2+), one of the essential nutrients of the human body, contributes to the proper regulation of immune function. However, no reports indicate whether extracellular histones affect survival and bacterial phagocytosis in macrophages and whether Mg2+ is protective against histone-induced macrophage damage. Our clinical data revealed a negative correlation between circulating histone and monocyte levels in septic patients, and in vitro experiments confirmed that histones induced mitochondria-associated apoptosis and defective bacterial phagocytosis in macrophages. Interestingly, our clinical data also indicated an association between lower serum Mg2+ levels and reduced monocyte levels in septic patients. Moreover, in vitro experiments demonstrated that Mg2+ attenuated histone-induced apoptosis and defective bacterial phagocytosis in macrophages through the PLC/IP3R/STIM-mediated calcium signaling pathway. Importantly, further animal experiments proved that Mg2+ significantly improved survival and attenuated histone-mediated lung injury and macrophage damage in histone-stimulated mice. Additionally, in a cecal ligation and puncture (CLP) + histone-induced injury mouse model, Mg2+ inhibited histone-mediated apoptosis and defective phagocytosis in macrophages and further reduced bacterial load. Overall, these results suggest that Mg2+ supplementation may be a promising treatment for extracellular histone-mediated macrophage damage in sepsis.

Polyetheretherketone (PEEK) rods versus titanium rods for posterior lumbar fusion surgery: a systematic review and meta-analysis.

BACKGROUND: Rigid fixation, represented by titanium rods, is a widely used fixation technique for lumbar fusion. However, this technique carries the risk of degeneration of adjacent segments. In recent years, the semi-rigid fixation technique represented by PEEK rods has gradually matured, and its effectiveness has been verified by numerous studies. The aim of this study was to systematically evaluate the effectiveness of these two fixation modalities in posterior lumbar fusion surgery. METHODS: Studies meeting the inclusion criteria were searched in PubMed, Cochrane Library, ScienceDirect, Embase, CNKI, and Wanfang databases. After data extraction and quality assessment of included studies, meta-analysis was performed using STATA 15.1 software. The protocol for this systematic review was registered on INPLASY (2021110049) and is available in full on the inplasy.com ( https://inplasy.com/inplasy-2021-11-0049/ ). RESULTS: Fifteen relevant studies were finally included, including eight prospective studies and seven retrospective studies. The results of meta-analysis showed that in ODI (P = 0.000), JOA score (P = 0.017), VAS score for lower limb pain (P = 0.027), fusion rate of bone graft at week 12 (P = 0.001), fusion rate of bone graft at last follow-up (P = 0.028), there was a statistical difference between the two groups. The PEEK rod group was superior to the titanium rod group in the above aspects. While in VAS score for LBP (P = 0.396), there was no statistical difference between the two groups. CONCLUSION: Both PEEK rods and titanium rods are effective fixation materials in lumbar fusion surgery. PEEK rods may be superior to titanium rods in improving postoperative function and improving bone graft fusion rates. However, given the limitations of this study, whether these conclusions are applicable needs further research.

Potential benefits of vitamin D for sepsis prophylaxis in critical ill patients.

Background: Vitamin D deficiency is common in critically ill patients with suspected infection and is strongly associated with the predisposition of sepsis and a poor prognosis. The effectiveness of vitamin D supplementation for preventing sepsis remains unclear. This retrospective cohort study investigated the effect of vitamin D supplementation on sepsis prophylaxis in critically ill patients with suspected infection. Methods: This retrospective cohort study included 19,816 adult patients with suspected infection in intensive care units (ICU) from 2008 to 2019 at the Beth Israel Deaconess Medical Center, Boston, USA. The included patients were divided into the vitamin D cohort or non-vitamin D cohort according to vitamin D administration status. The primary outcomes were the incidence of sepsis in ICU. The secondary outcomes included 28-day all-cause mortality, length of ICU and hospital stay and the requirements of vasopressors or mechanical ventilation. A propensity score matching cohort was used to test the differences in primary and secondary outcomes between groups. Results: The results showed that vitamin D supplementation demonstrated a lower risk of sepsis (odd ratio 0.46; 95% CI 0.35-0.60; P < 0.001) and a lower risk of new mechanical ventilation requirement (odd ratio 0.70; 95% CI 0.53-0.92; P = 0.01), but no significant difference in the risk of 28-day mortality was observed (hazard ratio 1.02; 95% CI 0.77-1.35; P = 0.89). In the sensitive analysis, among the patients who suspected infection within 24 h before or after ICU admission, a lower risk of sepsis and a lower percentage of new mechanical ventilation also were detected in the vitamin D cohort. Conclusion: Vitamin D supplementation may have a positively prophylactic effect on sepsis in critically ill patients with suspected infection.

Evaluation of the Efficacy of Stem Cell Therapy in Animal Models of Intervertebral Disc Degeneration Based on Imaging Indicators: A Systematic Review and Meta-Analysis.

Objective: The purpose of this study is to make a systematic review of the therapeutic effect of stem cells in animal models of disc degeneration from an imaging point of view. Methods: Data were extracted by searching electronic databases for RCTs that met the inclusion criteria. Data analysis was performed using RevMan 5.3 and STATA 15.1 software. This meta-analysis was registered with INPLASY, registration number INPLASY202240148. Results: A total of 34 studies were included, covering four species of animals, rabbits, sheep, rats, and mice, with a total of 1163 intervertebral discs. In terms of DHI, the efficacy of stem cell group in rabbits (P < 0.001), mice (P < 0.001), sheep (P < 0.001), and rats (P = 0.001) was better than that in control group. In terms of disc height, the efficacy of stem cell group in rats (P < 0.001) was better than that in control group, while in sheep (P = 0.355), there was no statistical difference between two groups. In terms of MRI index, the efficacy of stem cell group in rats (P < 0.001), mice (P < 0.001), and rabbits (P = 0.016) was better than that in control group. In terms of MRI signal score, the efficacy of stem cell group in rabbits (P < 0.001) was better than that of control group. In terms of T2 signal intensity, stem cell group was more effective than control group in rabbits (P < 0.001), mice (P < 0.001), and rats (P = 0.003). Conclusion: Stem cell therapy can improve intervertebral disc-related imaging parameters in animal models of disc degeneration, indicating that stem cell therapy has a repairing effect on intervertebral discs. However, given the heterogeneity and limitations of this study, this conclusion still needs to be tested by a large number of studies.

Effects of posterior lumbar nonfusion surgery with isobar devices versus posterior lumbar interbody fusion surgery on clinical and radiological features in patients with lumbar degenerative diseases: a meta-analysis.

PURPOSE: The aim of this study was to systematically evaluate the efficacy of posterior lumbar isobar nonfusion with isobar devices versus posterior lumbar interbody fusion (PLIF) in the treatment of patients with lumbar degenerative diseases (LDDs). MATERIALS AND METHOD: We performed a literature review and meta-analysis in accordance with the Cochrane methodology. The analysis included a Group Reading Assessment and Diagnostic Evaluation assessments, Jadad Quality Score evaluations, and Risk of Bias in Randomized Studies of Interventions assessments. The PubMed, Ovid, EMBASE, Web of Science, MEDLINE, CNKI, VIP and WanFang databases were searched to collect and compare relevant randomized controlled trials and cohort studies of isobar nonfusion and PLIF in the treatment of lumbar degenerative diseases. The retrieval time was from database inception to June 2021. Two evaluators independently screened the literature, extracted data, and evaluated the quality of the included studies. Outcome measures of interest included low back pain, disability, and radiological features. The protocol for this systematic review was registered on INPLASY (2021110059) and is available in full on inplasy.com ( https://inplasy.com/inplasy-2021-11-0059/ ). RESULTS: Of the 7 RCTs, 394 patients met the inclusion criteria. The meta-analysis results showed that isobar nonfusion surgery shortened the surgical duration (P = 0.03), reducing intraoperative bleeding (P = 0.001), retained the ROM of surgical segment (P < 0.00001) and the ROM of the lumbar spine (P < 0.00001), and reduced the incidence of ASD (P = 0.0001). However, no significant difference in the postoperative ODI index (P = 0.81), VAS score of LBP (P = 0.59, VAS score of lower limb pain (P = 0.05, and JOA score (P = 0.27) was noted. CONCLUSIONS: Posterior lumbar nonfusion surgery with isobar devices is superior to PLIF in shortening the surgical duration, reducing intraoperative bleeding, retaining the ROM of surgical segments and the lumbar spine to a certain extent, and preventing ASD. Given the possible publication bias, we recommend further large-scale studies.

Adjunctive granisetron therapy in patients with sepsis or septic shock (GRANTISS): A single-center, single-blinded, randomized, controlled clinical trial.

Background: In preclinical experiments, we demonstrated that the 5-HT3 receptor antagonist granisetron results in reduced inflammation and improved survival in septic mice. This randomized controlled trial was designed to assess the efficacy and safety of granisetron in patients with sepsis. Methods: Adult patients with sepsis and procalcitonin ≥ 2 ng/ml were randomized in a 1:1 ratio to receive intravenous granisetron (3 mg every 8 h) or normal saline at the same volume and frequency for 4 days or until intensive care unit discharge. The primary outcome was 28-day all-cause mortality. Secondary outcomes included the duration of supportive therapies for organ function, changes in sequential organ failure assessment scores over 96 h, procalcitonin reduction rate over 96 h, the incidence of new organ dysfunction, and changes in laboratory variable over 96 h. Adverse events were monitored as the safety outcome. Results: The modified intention-to-treat analysis included 150 septic patients. The 28-day all-cause mortalities in the granisetron and placebo groups were 34.7% and 35.6%, respectively (odds ratio, 0.96; 95% CI, 0.49-1.89). No differences were observed in secondary outcomes. In the subgroup analysis of patients without abdominal or digestive tract infections, the 28-day mortality in the granisetron group was 10.9% lower than mortality in the placebo group. Adverse events were not statistically different between the groups. Conclusion: Granisetron did not improve 28-day mortality in patients with sepsis. However, a further clinical trial targeted to septic patients without abdominal/digestive tract infections perhaps is worthy of consideration.

Combined Treatment With Hydrocortisone, Vitamin C, and Thiamine for Sepsis and Septic Shock: A Randomized Controlled Trial.

BACKGROUND: Whether hydrocortisone, vitamin C, and thiamine treatment can reduce the mortality of patients with sepsis is controversial. RESEARCH QUESTION: To evaluate the efficacy and safety of hydrocortisone, vitamin C, and thiamine combination treatment for patients with sepsis or septic shock (HYVCTTSSS). STUDY DESIGN AND METHODS: This single-blind, randomized controlled trial evaluated treatment with hydrocortisone (50 mg every 6 h for 7 days), vitamin C (1.5 g every 6 h for 4 days), and thiamine (200 mg every 12 h for 4 days) vs placebo (normal saline) in patients with sepsis. The intention-to-treat analysis was used. Primary outcome was 28-day all-cause mortality, and secondary outcomes were organ protection, procalcitonin reduction, and adverse events related to hydrocortisone, vitamin C, and thiamine. RESULTS: Eighty patients were randomized to receive combination treatment (n = 40) or normal saline (n = 40). No difference in 28-day all-cause mortality was observed (27.5% vs 35%, respectively; P = .47); however, treatment was associated with a significant improvement of 72-h change in Sequential Organ Failure Assessment score (P = .02). In adverse events analysis, the treatment group exhibited more incidents of hypernatremia (P = .005). In prespecified subgroup analysis, patients of the treatment subgroup diagnosed with sepsis within 48 h showed lower mortality than those in the control subgroup (P = .02). The study was terminated after the midterm analysis. INTERPRETATION: Among patients with sepsis or septic shock, the combination of hydrocortisone, vitamin C, and thiamine did not reduce mortality compared with placebo. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT03258684; URL: www.clinicaltrials.gov.

Adjunctive granisetron therapy in patients with sepsis or septic shock (GRANTISS): Study protocol for a randomized controlled trial.

INTRODUCTION: The incidence, mortality, and treatment costs of sepsis are high and, thus, present a major challenge for critical care medicine. Our previous studies suggest that intestinal metabolite granisetron has a potential therapeutic effect on sepsis. Granisetron is a clinically widely used antiemetic, which is safe, inexpensive, and reliable. However, its value in the treatment of sepsis remains unclear. This study aims to explore the efficacy and safety of granisetron in the treatment of sepsis. METHODS AND ANALYSIS: A single-center, single-blind, randomized, controlled clinical trial will be conducted on 154 patients with sepsis. Patients who meet sepsis 3.0 diagnostic criteria, aged ≥18 and ≤80 years, with PCT ≥ 2 ng/mL will be recruited. Patients will be randomized to receive intravenous granisetron 3 mg every 8 hours (n = 77) or an equal volume of normal saline (n = 77) for a treatment period of 4 days or to ICU discharge. The primary outcome is 28-day all-cause mortality. Secondary outcome measures include requirements for organ function support, changes of organ function, changes in infection biomarkers, changes in inflammatory and immune biomarkers, and the proportion of new organ failure. Adverse events and serious adverse events also will be observed closely. ETHICS AND DISSEMINATION: The study was approved by the Clinical Ethics Committee of Zhujiang Hospital of Southern Medical University (2018-ZZJHZX-009). The trial results will be disseminated at national and international conferences and through peer-reviewed journal. TRIAL REGISTRATION: NCT03924518.URL: www.clinicaltrials.gov. PROTOCOL DATE: 1 May 2019. version 2.1.