ABSTRACT
BACKGROUND: The long-term follow-up of asymptomatic intracranial hemorrhage (aICH) in patients with acute ischemic stroke after endovascular treatment (EVT) remains controversial.ObjectiveTo evaluate the potential effect of aICH in a real-world practice setting using a matched prospective database. METHODS: This observational cohort study enrolled patients between January 2015 and December 2022 in a prospective database. Eligible patients with occlusions in the anterior circulation were given endovascular treatment and achieved successful reperfusion. The primary outcome was functional independence (modified Rankin Scale (mRS) score 0-2). Propensity score (PS)-weighted multivariable logistic regression analyses were adjusted and were repeated in subsequent 1:1 PS-matched cohorts. RESULTS: 732 patients, 516 without any ICH and 216 with aICH, were included. 418 and 348 patients were identified after matching in the aICH substudy and hemorrhagic infarction type aICH substudy, respectively. In the postmatched population, patients with aICH had worse functional outcomes (mRS score 0-2) at 90 days than patients without any ICH (37.8% vs 55.5%: P<0.001). Worse functional outcomes were seen in patients with aICH who were older (OR=5.59 (95% CI 2.91 to 10.74)), had higher baseline National Institutes of Health Stroke Scale score (OR=6.80 (95% CI 3.72 to 12.43)), lower baseline Alberta Stroke Program Early CT Score (OR=2.08 (95% CI 1.23 to 3.51)), and who received general anesthesia (OR=3.37 (95% CI 1.92 to 5.90)). CONCLUSIONS: This matched-control study largely confirmed that asymptomatic ICH after EVT is associated with worse functional outcomes, and the harmful effect is more significant in older patients and those with severe baseline clinical and radiological features.
ABSTRACT
Objective: The prognosis of malignant tumors with peritoneal metastases and cancerous ascites has generally been poor, with limited treatment options. The PRaG regimen, which comprised of hypofractionated radiotherapy, programmed cell death-1 (PD-1) inhibitor, and granulocyte-macrophage colony-stimulating factor (GM-CSF), showed a survival advantage in patients with advanced solid tumors who failed at least the first line of standard systemic treatment. Intraperitoneal infusion of PD-1 inhibitors may be a novel therapeutic strategy for managing malignant ascites. Integrating the PRaG regimen with intraperitoneal perfusion of a PD-1 inhibitor might control malignant ascites and provide further survival benefits in these patients. This proposed study aims to investigate the safety and efficacy of intraperitoneal infusion of serplulimab in combination with the PRaG regimen in patients with simultaneous advanced solid tumors and cancerous ascites who fail at least the first-line treatment. Methods: This proposed study is a prospective, single-arm, open-label, multicenter clinical trial. All eligible patients will receive 2 cycles of intensive treatment, a combination of PRaG regimen with an intraperitoneal infusion of PD-1 inhibitor. The patients who are beneficially treated with intensive treatment will receive consolidation treatment every 2 weeks until ascites disappear, disease progression occurs, intolerable toxicity occurs, or for up to 1 year. Phase I of this study will be conducted using a modified 3 + 3 design. The dose of intraperitoneal infusion of PD-1 inhibitor for phase II will be determined according to dose-limiting toxicity evaluation in the phase I study. Conclusion: This prospective, open-label, multicenter study will potentially lead to intraperitoneal perfusion of a PD-1 inhibitor being a new strategy for malignant ascites patients and provide a meaningful efficacy and safety of the combination of PRaG regimen with an intraperitoneal infusion of PD-1 inhibitor for these patients.
Subject(s)
Ascites , Immune Checkpoint Inhibitors , Infusions, Parenteral , Neoplasms , Humans , Ascites/etiology , Ascites/drug therapy , Ascites/pathology , Female , Male , Middle Aged , Neoplasms/drug therapy , Neoplasms/complications , Neoplasms/pathology , Immune Checkpoint Inhibitors/administration & dosage , Immune Checkpoint Inhibitors/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/adverse effects , Adult , Aged , Peritoneal Neoplasms/drug therapy , Peritoneal Neoplasms/secondary , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Treatment Outcome , Prospective StudiesABSTRACT
Lymphocytes, which are highly sensitive to radiation, play a crucial role in the body's defense against tumors. Radiation-induced lymphopenia has been associated with poorer outcomes in different cancer types. Despite being the largest secondary lymphoid organ, the spleen has not been officially designated as an organ at risk. This study hypothesizes a connection between spleen irradiation and lymphopenia and seeks to establish evidence-based dosage limits for the spleen. We retrospectively analyzed data from 96 patients with locally advanced gastric cancer who received postoperative chemoradiotherapy (CRT) between May 2010 and May 2017. Complete blood counts were collected before, during and after CRT. We established a model for predicting the minimum absolute lymphocyte count (Min ALC) and to investigate potential associations between spleen dosimetric variables and Min ALC. The median follow-up was 60 months. The 5-year overall survival (OS) and disease-free survival (DFS) were 65.2% and 56.8%, respectively. The median values of pre-treatment ALC, Min ALC and post-treatment ALC were 1.40 × 109, 0.23 × 109 and 0.28 × 109/L, respectively. Regression analysis confirmed that the primary tumor location, number of fractions and spleen V5 were significant predictors of Min ALC during radiation therapy. Changes in ALC (ΔALC) were identified as an independent predictor of both OS and DFS. Spleen V5 is an independent predictor for Min ALC, and the maximum dose of the spleen is associated with an increased risk of severe lymphopenia. Therefore, these doses should be restricted in clinical practice. Additionally, ΔALC can serve as a prognostic indicator for adjuvant radiotherapy in gastric cancer.
Subject(s)
Lymphopenia , Spleen , Stomach Neoplasms , Humans , Lymphopenia/etiology , Male , Female , Middle Aged , Spleen/radiation effects , Spleen/pathology , Aged , Stomach Neoplasms/radiotherapy , Stomach Neoplasms/pathology , Adult , Dose-Response Relationship, Radiation , Lymphocyte Count , Disease-Free Survival , Retrospective Studies , Chemoradiotherapy , Radiotherapy Dosage , Aged, 80 and overABSTRACT
Photodegradation via ultraviolet (UV) radiation is an important factor driving plant litter decomposition. Despite increasing attention to the role of UV photodegradation in litter decomposition, the specific impact of UV radiation on the plant litter decomposition stage within biogeochemical cycles remains unclear at regional and global scales. To clarify the variation rules of magnitude of UV effect on plant litter decomposition and their regulatory factors, we conducted a meta-analysis based on 54 published papers. Our results indicated that UV significantly promoted the mass loss of litter by facilitating decay of carbonaceous fractions and release of nitrogen and phosphorus. The promotion effect varied linearly or non-linearly with the time that litter exposed to UV, and with climatic factors. The UV effect on litter decomposition decreased first than increased on precipitation and temperature gradients, reaching its minimum in the area with a precipitation of 400-600 mm, and a temperature of 15-20 °C. This trend might be attributed to a potential equilibrium between the photofacilitation and photo-inhibition effects of UV under this condition. This variation in UV effect on precipitation gradient was in agreement with the fact that UV photodegradation effect was weakest in grassland ecosystems compared to that in forest and desert ecosystems. In addition, initial litter quality significantly influenced the magnitude of UV effect, but had no influence on the correlation between UV effect and climate gradient. Litter with lower initial nitrogen and lignin content shown a greater photodegradation effect, whereas those with higher hemicellulose and cellulose content had a greater photodegradation effect. Our study provides a comprehensive understanding of photodegradation effect on plant litter decomposition, indicates potentially substantial impacts of global enhancements of litter decomposition by UV, and highlights the necessity to quantify the contribution of photochemical minerallization pathway and microbial degradation pathway in litter decomposition.
Subject(s)
Ecosystem , Ultraviolet Rays , Plant Leaves/metabolism , Plants/metabolism , Desert Climate , Nitrogen/metabolismABSTRACT
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a highly fatal disease with limited effective treatment especially after first-line chemotherapy. The human epidermal growth factor receptor 2 (HER-2) immunohistochemistry (IHC) positive is associated with more aggressive clinical behavior and shorter overall survival in PDAC. CASE SUMMARY: We present a case of multiple metastatic PDAC with IHC mismatch repair proficient but HER-2 IHC weakly positive at diagnosis that didn't have tumor regression after first-line nab-paclitaxel plus gemcitabine and PD-1 inhibitor treatment. A novel combination therapy PRaG 3.0 of RC48 (HER2-antibody-drug conjugate), radiotherapy, PD-1 inhibitor, granulocyte-macrophage colony-stimulating factor and interleukin-2 was then applied as second-line therapy and the patient had confirmed good partial response with progress-free-survival of 6.5 months and overall survival of 14.2 month. She had not developed any grade 2 or above treatment-related adverse events at any point. Percentage of peripheral CD8+Temra and CD4+Temra were increased during first two activation cycles of PRaG 3.0 treatment containing radiotherapy but deceased to the baseline during the maintenance cycles containing no radiotherapy. CONCLUSION: PRaG 3.0 might be a novel strategy for HER2-positive metastatic PDAC patients who failed from previous first-line approach and even PD-1 immunotherapy but needs more data in prospective trials.
Subject(s)
Carcinoma, Pancreatic Ductal , Pancreatic Neoplasms , Receptor, ErbB-2 , Humans , Female , Gemcitabine , Deoxycytidine/therapeutic use , Prospective Studies , Immune Checkpoint Inhibitors/therapeutic use , Paclitaxel/therapeutic use , Pancreatic Neoplasms/drug therapy , Carcinoma, Pancreatic Ductal/drug therapy , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Albumins/therapeutic useABSTRACT
It is of great significance to solve the environmental problems caused by the unreasonable treatment of coal gasification slag. This study successfully produced Si-Fe-Al-Ca alloy from low-carbon fine slag with petroleum coke as reducing agent in a plasma furnace with an alternating current magnetic field, which solved the problem of the high reactivity requirement of carbon reductant for plasma smelting. The optimum carbon content of the mixed low-carbon fine slag and petroleum coke is 105% of the theoretical value. As the strength of the alternating current magnetic field increased (from 0% to 100% of the maximum power), the yield of the alloy (from 25.46% to 58.19%) and the recovery ratios of each element (Si, Fe, Al, Ca, Ti) increased. In addition, as the magnetic field strength increased, the pores inside the alloy became smaller, the composition of the alloy became more homogeneous, and a better separation of the alloy from the slag was observed. The main composition of the alloy at the strongest alternating current magnetic field is Si: 51.14 wt%, Fe: 28.41 wt%, Al: 9.14 wt%, Ca: 7.15 wt%, Ti: 2.03 wt%. We attribute the enhanced smelting effect of the alternating current magnetic field to the resistive heat and Lorentz force produced by the induced current. In addition, the skin effect concentrated the induced current on the surface of the oxide particles and carbon particles, which increased the temperature of the reaction interface and promoted the carbothermal reduction reaction.
Subject(s)
Coke , Petroleum , Coal , Alloys , CarbonABSTRACT
INTRODUCTION: The PRaG regimen, which consists of hypofractionated radiotherapy combined with a programmed cell death-1/programmed cell death ligand-1 (PD-1/PD-L1) inhibitor and granulocyte-macrophage colony stimulating factor (GM-CSF), has been demonstrated to have a survival benefit in patients with advanced solid tumours who have failed at least two lines of treatment. Nonetheless, lymphopenia poses an impediment to the enduring efficacy of PD-1/PD-L1 inhibitor therapy. Adequate lymphocyte reserves are essential for the efficacy of immunotherapy. Coupling the PRaG regimen with immunomodulatory agents that augment the number and functionality of lymphocytes may yield further survival benefits in this cohort of patients. OBJECTIVE: The aim of this study is to investigate the effectiveness and safety of a meticulously thymalfasin-controlled PRaG regimen in patients with advanced and chemotherapy-resistant solid tumours. METHODS AND ANALYSIS: The study has a prospective, single-arm, open-label, multicentre design and aims to recruit up to 60 patients with histologically confirmed advanced solid tumours that have relapsed or metastasised. All eligible patients will receive a minimum of two cycles of the PRaG regimen comprising thymalfasin followed by maintenance treatment with a PD-1/PD-L1 inhibitor and thymalfasin for 1 year or until disease progression. Patients will be monitored according to the predetermined protocol for a year or until disease progression after initiation of radiotherapy. ETHICS AND DISSEMINATION: The study protocol was approved by the Ethics Committee of the Second Affiliated Hospital of Soochow University, on 25 November 2022 (JD-LK-2022-151-01) and all other participating hospitals. Findings will be disseminated through national and international conferences. We also plan to publish our findings in high-impact peer-reviewed journal. TRIAL REGISTRATION NUMBER: NCT05790447.
Subject(s)
Immune Checkpoint Inhibitors , Neoplasms , Humans , Thymalfasin/therapeutic use , Prospective Studies , Immune Checkpoint Inhibitors/therapeutic use , Programmed Cell Death 1 Receptor/therapeutic use , Neoplasms/drug therapy , Disease Progression , Antineoplastic Combined Chemotherapy Protocols , Multicenter Studies as TopicABSTRACT
BACKGROUND AND PURPOSE: Whether thrombus burden in acute ischemic stroke modify the effect of intravenous thrombolysis (IVT) before mechanical thrombectomy (MT) remains uncertain. We aim to investigate the treatment effect of stratified clot burden score (CBS) on the efficacy and safety of direct versus bridging MT. MATERIALS AND METHODS: This is an exploratory subgroup analysis of a randomized trial evaluating the effect of CBS on clinical outcome in the DIRECT-MT trial. CBS was divided into 3 groups (0-3, 4-6, and 7-10) based on preoperative CTA, where higher scores indicated a lower clot burden. We report the adjusted common odds ratio for a shift toward better outcomes on the mRS after thrombectomy alone compared with combination treatment by stratified CBS groups. RESULTS: No modification effect of mRS distribution was observed by CBS subgroups (CBS 0-3: adjusted common ratio odds 1.519 [95% CI, 0.928-2.486]; 4-6: 0.924 [0.635-1.345]; 7-10: 1.040 [0.481-2.247]). Patients with CBS 4-6 had a higher rate of early reperfusion (adjusted OR (aOR), 0.3 [95% CI, 0.1-0.9]), final reperfusion (aOR 0.5 [95% CI, 0.3-0.9]), and fewer thrombectomy attempts (aOR 0.4 [95% CI, 0.1-0.7]). Patients with CBS 7-10 had a higher rate of asymptomatic intracranial hemorrhage (14.9% versus 36.8%, P = .0197) for bridging MT. No significant difference was observed in other safety outcomes by trichotomized CBS. CONCLUSIONS: The subgroup analysis of DIRECT-MT suggested that thrombus burden did not alter the treatment effect of IVT before MT on functional outcomes in CBS subgroups.
Subject(s)
Brain Ischemia , Ischemic Stroke , Stroke , Thrombosis , Humans , Tissue Plasminogen Activator/therapeutic use , Stroke/surgery , Thrombolytic Therapy , Brain Ischemia/therapy , Treatment Outcome , Thrombectomy , Thrombosis/drug therapy , Fibrinolytic Agents/therapeutic useABSTRACT
Cancer cells develop multiple strategies to evade T cell-mediated killing. On one hand, cancer cells may preferentially rely on certain amino acids for rapid growth and metastasis. On the other hand, sufficient nutrient availability and uptake are necessary for mounting an effective T cell anti-tumor response in the tumor microenvironment (TME). Here we demonstrate that tumor cells outcompete T cells for cystine uptake due to high Slc7a11 expression. This competition induces T-cell exhaustion and ferroptosis, characterized by diminished memory formation and cytokine secretion, increased PD-1 and TIM-3 expression, as well as intracellular oxidative stress and lipid-peroxide accumulation. Importantly, either Slc7a11 deletion in tumor cells or intratumoral cystine supplementation improves T cell anti-tumor immunity. Mechanistically, cystine deprivation in T cells disrupts glutathione synthesis, but promotes CD36 mediated lipid uptake due to dysregulated cystine/glutamate exchange. Moreover, enforced expression of glutamate-cysteine ligase catalytic subunit (Gclc) promotes glutathione synthesis and prevents CD36 upregulation, thus boosting T cell anti-tumor immunity. Our findings reveal cystine as an intracellular metabolic checkpoint that orchestrates T-cell survival and differentiation, and highlight Gclc as a potential therapeutic target for enhancing T cell anti-tumor function.
Subject(s)
Cystine , Ferroptosis , Cystine/metabolism , CD8-Positive T-Lymphocytes/metabolism , Cell Line, Tumor , Glutathione/metabolism , LipidsABSTRACT
INTRODUCTION: Whether time window affects the intravenous thrombolysis (IVT) effect before endovascular thrombectomy (EVT) is uncertain. We aimed to investigate the effect of different time windows (0-3 h and >3-4.5 h from stroke onset to randomization) on clinical outcomes of EVT with or without IVT in a subgroup analysis of DIRECT-MT. METHODS: The primary outcome was the 90-day modified Rankin Scale (mRS) according to time window. Logistic regression models were used to analyze the effect of different treatments (EVT with or without IVT) on outcomes within 0-3 h or >3-4.5 h. RESULTS: Among 656 patients who were included in the analysis, 282 (43.0%) were randomized within >3-4.5 h after stroke onset (125 without IVT and 157 with IVT), and 374 (57.0%) were randomized within 0-3 h (202 without IVT and 172 with IVT). We noted no significant difference in the thrombectomy-alone effect between the time window subgroups according to 90-day ordinal mRS (adjusted common odds ratio [acOR] in patients within 0-3 h: 1.06 [95% CI: 0.73-1.52], acOR in patients within >3-4.5 h: 1.19 [95% CI: 0.78-1.82]) and 90-day functional independence. Thrombectomy alone resulted in an increased proportion of patients with 90-day mRS 0-3 treated within >3-4.5 h (62.90 vs. 48.72%) but not within 0-3 h (65.84 vs. 63.95%). However, there was no interaction effect regarding all outcomes after the Bonferroni correction. CONCLUSIONS: Our results did not support thrombectomy-alone administration within 3-4.5 h in patients with acute ischemic stroke from large-vessel occlusion in the subgroup analysis of DIRECT-MT.
Subject(s)
Endovascular Procedures , Ischemic Stroke , Thrombectomy , Humans , Endovascular Procedures/methods , Ischemic Stroke/drug therapy , Ischemic Stroke/surgery , Thrombectomy/methods , Thrombolytic Therapy/methods , Treatment Outcome , Time FactorsABSTRACT
BACKGROUND: The DIRECT-MT trial showed that endovascular thrombectomy (EVT) alone was noninferior to EVT preceded by intravenous alteplase. However, the infusion of intravenous alteplase was uncompleted before the initiation of EVT in most cases of this trial. Therefore, the additional benefit and risk of over 2/3-dose intravenous alteplase pretreatment remain to be assessed. METHODS: We assessed patients with acute anterior circulation ischemic stroke who received EVT alone or with over 2/3-dose intravenous alteplase pretreatment from the DIRECT-MT trial. Patients were assigned to the thrombectomy-alone group and the alteplase pretreatment group. The primary outcome was the distribution of modified Rankin Scale (mRS) at 90 days. The interaction of treatment allocation and collateral capacity was assessed. RESULTS: A total of 393 patients (thrombectomy alone: 315; alteplase pretreatment: 78) were identified. The thrombectomy alone was comparable with alteplase pretreatment prior to the thrombectomy on the distribution of mRS at 90 days without significant effect modification by collateral capacity (adjusted common odds ratio (acOR), 1.12; 95% CI, 0.72-1.74; adjusted P for interaction = 0.83). Successful reperfusion before thrombectomy and the number of passes in the thrombectomy alone group differed significantly from the alteplase pretreatment group (2.6% vs. 11.5%; corrected P = 0.02 and 2 vs. 1; corrected P = 0.003). There was no interaction between treatment allocation and collateral capacity on all outcomes. CONCLUSIONS: EVT alone and EVT preceded by over 2/3-dose intravenous alteplase might have equal efficacy and safety for patients with acute anterior circulation large vessel occlusion, except for successful perfusion before thrombectomy and the number of passes.
Subject(s)
Brain Ischemia , Endovascular Procedures , Ischemic Stroke , Stroke , Humans , Tissue Plasminogen Activator/therapeutic use , Fibrinolytic Agents/therapeutic use , Stroke/drug therapy , Stroke/surgery , Brain Ischemia/therapy , Endovascular Procedures/adverse effects , Thrombectomy/adverse effects , Thrombolytic Therapy/adverse effects , Treatment OutcomeABSTRACT
Background and purpose: An aggressive lowering of blood pressure (BP) could lead to neurological worsening, particularly of the area that has not been reperfused in acute stroke patients with large vessel occlusion (LVO). We sought to investigate the association of reperfusion status and BP course following mechanical thrombectomy (MT) with outcomes in LVO. Materials and methods: Consecutive patients with LVO treated with MT between Jan 2020 to Jun 2021 were enrolled in a retrospective cohort study. Hourly systolic BP (SBP) and diastolic BP (DBP) were recorded for 72 h following MT and maximum SBP and DBP levels were identified. The Extended Thrombolysis in Cerebral Infarction (eTICI) scale was used to assess reperfusion extent. LVO patients were stratified in 2 groups based on reperfusion status: complete reperfusion (eTICI 3) and incomplete reperfusion (eTICI 2b/c). Three-month functional independence was defined as a modified Rankin Scale score of 0-2. Results: A total of 263 acute ischemic stroke patients with LVO were retrospectively evaluated. Complete reperfusion was achieved in 210 patients (79.8%). Post-MT maximum SBP over 160 mmHg was significantly related to worse functional outcome (38.1% vs. 55.7%, p = 0.006), higher likelihood of in-hospital mortality and 3-month mortality (19.0% vs. 6.9%, p = 0.004, 27.4% vs. 14.3%, p = 0.012). No statistical correlation was found between reperfusion status and blood pressure level (p > 0.05). In patients with complete reperfusion, patients with an average BP 120-140 mmHg tends to have worse functional outcome compared with 100-120 mmHg (OR = 1.77, 95%CI: 0.97-3.23, p = 0.061). Conclusion: High maximum SBP levels following MT are associated with an increased likelihood of 3-month functional dependence and mortality. An average BP of 100-120 mmHg tends to have better functional independence in completely reperfused patients. The effect of intensive BP control on incomplete reperfusion still warrants further investigations.
ABSTRACT
The diamond wire saw silicon powder (DWSSP) is considered to be a harmful to the environment because of finer particles, the large specific surface area and flammability. Removal of Fe impurity is very essential for recovering Si from DWSSP due to the large amount of Fe introduced during the silicon powder generation process. In the study, the thermodynamics of Fe leaching with HCl was analyzed and determined iron was theoretically present as ions in solution. Furthermore, the effects of different concentrations, temperatures and liquid-solid ratios on Fe leaching from HCl were investigated. The leaching rate of Fe reached 98.37% at the optimal parameters (HCl concentration of 12 wt%, leaching temperature of 333 K, liquid-solid ratio of 15 ml/g) with 100 min. The leaching kinetics of Fe in HCl was analyzed by shrinking core model and homogeneous model, respectively. The study indicated the process of leaching Fe from DWSSP conforms to the secondary reaction model of homogeneous model which coincided with the porous structure of DWSSP due to agglomeration. The apparent activation energy required (49.398 kJ/mol) in the first stage is lower than that (57.817 kJ/mol) in the second stage because of the porous structure. In conclusion, this paper provided a suitable way to purify the diamond wire saw silicon powder. This work provides an important guide for the industrial recovery and preparation of high purity silicon from DWSSP by the most environment-friendly and low-cost approach.
Subject(s)
Iron , Silicon , Powders , Kinetics , DiamondABSTRACT
BACKGROUND: This subgroup analysis of Direct Intraarterial Thrombectomy in Order to Revascularize Acute Ischemic Stroke Patients with Large Vessel Occlusion Efficiently in Chinese Tertiary Hospitals Multicenter Randomized Clinical Trial (DIRECT-MT) aimed to investigate the influence of anesthesia modalities on the outcomes of endovascular treatment. METHODS: Patients were divided into two groups by receiving general anesthesia (GA) or non-general anesthesia (non-GA). The primary outcome was assessed by the between-group difference in the distribution of the modified Rankin Scale (mRS) at 90 days, estimated using the adjusted common odds ratio (acOR) by multivariable ordinal regression. Differences in workflow efficiency, procedural complication, and safety outcomes were analyzed. RESULTS: Totally 636 patients were enrolled (207 for GA and 429 for non-GA groups). There was no significant shift in the mRS distribution at 90 days between the two groups (acOR, 1.093). The median time from randomization to reperfusion was significantly longer in GA group (116 vs. 93 min, P < 0.0001). Patients in non-GA group were associated with a significantly lower NIHSS score at early stages (24 h, 11 vs 15; 5-7 days or discharge, 6.5 vs 10). The rate of severe manipulation-related complication did not differ significantly between GA and non-GA groups (0.97% vs 3.26%; P = 0.08). There are no differences in the rate of mortality and intracranial hemorrhage. CONCLUSIONS: In the subgroup analysis of DIRECT-MT, we found no significant difference in the functional outcome at 90 days between general anesthesia and non-general anesthesia, despite the workflow time being significantly delayed for patients with general anesthesia. Clinical trail registration clinicaltrials.gov Identifier: NCT03469206.
Subject(s)
Anesthesia , Ischemic Stroke , Thrombectomy , Humans , Anesthesia/classification , Ischemic Stroke/surgeryABSTRACT
BACKGROUND: Observational studies suggest an association between blood pressure (BP) and functional outcomes in ischemic stroke patients but whether this is causal or due to confounding is uncertain. We used Mendelian randomization (MR) to assess causality, and also explore whether particular classes of anti-hypertensives were associated with a better outcome after ischemic stroke. METHODS: We selected genetic variants associated with systolic and diastolic BP and BP-lowering variants in genes encoding antihypertensive drugs from genome-wide association studies (GWAS) on 757,601 individuals. The primary outcome was 3-month dependence or death defined as a modified Rankin Scale (mRS) of 3-6. The secondary outcome was disability or death after 90 days defined as mRS 2-6. Cochran's Q statistic in the inverse variance weighted (IVW) model, the weighted median, MR-Egger regression, leave-one-single-nucleotide polymorphism (SNP)-out analysis, MR-Pleiotropy Residual Sum and Outlier methods were adopted as sensitivity analyses. To validate our primary results, we performed independent repeat analyses and Bi-directional MR analyses. RESULTS: Genetic predisposition to higher systolic and diastolic BP was associated with disability or death after ischemic stroke in univariable IVW MR analysis (odds ratio (OR) 1.29, 95% confidence interval (CI): 1.05-1.59, p = 0.014; OR 1.27, 95% CI: 1.07-1.51, p = 0.006, respectively). Pulse pressure was associated with both dependence or death and disability or death after ischemic stroke (OR = 1.05, 95% CI: 1.02-1.08, p = 0.002; OR = 1.04, 95% CI = 1.01-1.07, p = 0.009, respectively). Angiotensin-converting enzyme inhibitor (ACEI) and calcium channel blocker (CCB) were significantly associated with improved functional outcomes (dependence or death, OR 0.76, 95% CI: 0.62-0.94, p = 0.009; OR 0.89, 95% CI: 0.83-0.97, p = 0.005). Proxies for ß-blockers, angiotensin receptor blockers (ARB), and thiazides failed to show associations with functional outcomes (p > 0.05). CONCLUSION: We provide evidence for an association of genetic predisposition to higher BP with a higher risk of 3-month functional dependence after ischemic stroke. Our findings support ACEI and CCB as promising antihypertensive drugs for improving functional outcomes in ischemic stroke.
Subject(s)
Ischemic Stroke , Stroke , Humans , Blood Pressure/genetics , Antihypertensive Agents/therapeutic use , Angiotensin-Converting Enzyme Inhibitors , Angiotensin Receptor Antagonists , Genetic Predisposition to Disease , Genome-Wide Association Study , Mendelian Randomization Analysis , Stroke/drug therapy , Stroke/geneticsABSTRACT
Patients with chemo-refractory metastatic colorectal cancer (mCRC) have poor prognoses. The application of programmed cell death protein 1 (PD-1)/programmed cell death ligand 1 (PD-L1) inhibitors encouragingly improved the survival of mCRC patients with microsatellite instability-high (MSI-H)/mismatch repair-deficient (dMMR). Unfortunately, it was ineffective for mCRC with microsatellite-stable (MSS)/proficient mismatch repair (pMMR), which accounted for 95% of mCRC. Radiotherapy can promote local control by directly killing tumor cells and inducing positive immune activities, which might help synergistically with immunotherapy. We present the report of an advanced MSS/pMMR mCRC patient who had progressive disease (PD) after first-line chemotherapy, palliative surgery and second-line chemotherapy combined with targeted therapy. Then the patient received the therapy of PD-1 inhibitor combined with radiotherapy and granulocyte-macrophage colony-stimulating factor (GM-CSF). According to Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST1.1), the patient showed a complete response (CR) after triple-combined therapy with progression-free survival (PFS) for more than 2 years so far. The patient had no other significant adverse reactions except for fatigue (Grade 1). The triple-combination therapy provided a promising strategy for metastatic chemo-refractory MSS/pMMR mCRC patients.
ABSTRACT
The medical use of molecular hydrogen, including hydrogen-rich water and hydrogen gas, has been extensively explored since 2007. This article aimed to demonstrate the trend in medical research on molecular hydrogen. A total of 1126 publications on hydrogen therapy were retrieved from the PubMed database until July 30, 2021. From 2007 to 2020, the number of publications in this field had been on an upward trend. Medical Gas Research, Scientific Report and Shock have contributed the largest number of publications on this topic. Researchers by the name of Xue-Jun Sun, Ke-Liang Xie and Yong-Hao Yu published the most studies in the field. Analysis of the co-occurrence of key words indicated that the key words "molecular hydrogen," "hydrogen-rich water," "oxidative stress," "hydrogen gas," and "inflammation" occurred most frequently in these articles. "Gut microbiota," "pyroptosis," and "COVID-19" occurred the most recently among the keywords. In summary, the therapeutic application of molecular hydrogen had attracted much attention in these years. The advance in this field could be caught up by subscribing to relevant journals or following experienced scholars. Oxidative stress and inflammation were the most important research directions currently, and gut microbiota, pyroptosis, and coronavirus disease 2019 might become hotspots in the future.
Subject(s)
COVID-19 , Humans , Bibliometrics , Hydrogen/therapeutic use , Oxidative Stress , WaterABSTRACT
Maximizing the use of valuable components in coal gasification slag is of great significance for resource recovery and the environment due to the huge annual emission of coal gasification slag. This study successfully produced Si-Fe-Al-Ca alloy with a composition of 63.83 wt% Si, 19.73 wt% Fe, 7.09 wt% Al, 6.32 wt% Ca, 1.70 wt% Ti, 0.03 wt% P, 0.66 wt% Mn, 0.05 wt% Cr, 0.53 wt% C, and 0.06 wt% others through electric arc furnace smelting from mixed coal gasification fine slag. The alloy composition is close to the standard 65% ferrosilicon, which can be used in the deoxidation of the molten steel industry. Moreover, the alloy yield was increased from 20.53% to 67.78% by using the residual carbon of the coal gasification slag as the reductant directly instead of adding petroleum coke. The transformation of coal gasification fine slag during the smelting process and the formation mechanism of the alloy were studied and the carbothermal reduction mechanism of Al2O3 and CaO can be explained by the reduction and decomposition theory of carbides. The complex liquid phase of the reactant system and product system in the smelting process made the carbothermal reaction of Al2O3 and CaO easier to occur, but it also brought the problem that the reactions were not fully completed.
Subject(s)
Coal , Coke , Alloys , CarbonABSTRACT
A tremendous amount of silicon cutting waste (SCW) is being produced during slicing Si ingots, which leads to a great waste of resources and serious environmental pollution. In this study, a novel method that recycling SCW to produce Si-Fe alloys was proposed, which not only provides a process with low energy consumption, low cost, and short flow for producing high-quality Si-Fe alloys but also achieves a more effective recycling of SCW. The optimal experimental condition is investigated to be a smelting temperature of 1800 °C and a holding time of 10 min. Under this condition, the yield of Si-Fe alloys and the Si recovery ratio of SCW were 88.63% and 87.81%, respectively. Compared with the present industrial recycling method that uses SCW to prepare metallurgy-grade Si ingot by an induction smelting process, this Si-Fe alloying method can achieve a higher Si recovery ratio of SCW at a shorter smelting time. The promoting mechanism of Si recovery by Si-Fe alloying is mainly expressed as follows: (1) facilitating the separation of Si from SiO2-based slag; (2) reducing the oxidization and carbonization loss of Si by accelerating the heating of raw materials and reducing the exposed area of Si.