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Background The combination therapy of hydrocortisone, vitamin C, and thiamine has been proposed as a potential treatment in patients with sepsis and septic shock. However, subsequent trials have reported conflicting results in relation to survival outcomes. Hence, we performed this randomized controlled trial (RCT) to evaluate the efficacy and safety of early combination therapy among adult patients with septic shock. Methods This single-center, double-blind RCT enrolled adult patients with diagnosis of septic shock within 12 h from Northern Jiangsu People's Hospital between February 2019 and June 2021. Recruited patients were randomized 1:1 to receive intervention (hydrocortisone 200 mg daily, vitamin C 2 g every 6 h, and thiamine 200 mg every 12 h) or placebo (0.9% saline) for 5 days or until ICU discharge. The primary endpoint was 90-day mortality. The secondary endpoints included mortality at day 28, ICU discharge, and hospital discharge; shock reversal; 72-h Delta SOFA score; ICU-free days, vasopressor-free days, and ventilator support -free days up to day 28; ICU length of stay (LOS) and hospital LOS. Results Among 426 patients randomized, a total of 408 patients with septic shock were included in the per-protocol (PP) analysis, of which 203 were assigned to the intervention group and 205 to the placebo group. In the PP population, the primary outcome of 90-day mortality was 39.9% (81/203) and 39.0% (80/205) in the intervention and the placebo groups, respectively, and was not significantly different ( P  = 0.86). There was no significant difference between two groups in 28-day mortality (36.5% vs. 36.1%, P  = 0.94) or the ICU mortality (31.5% vs. 28.8%, P  = 0.55) and hospital mortality (34.5% vs. 33.2%, P  = 0.78). No other secondary outcomes showed significant differences between two groups, including shock reversal, vasopressor-free days, and ICU LOS. Intention-to-treat analysis included all the 426 patients and confirmed these results (all P  > 0.05). Conclusion Among adult patients with septic shock, early use of hydrocortisone, vitamin C, and thiamine combination therapy compared with placebo did not confer survival benefits. Trial registration ClinicalTrials.gov: NCT03872011 , registration date: March 12, 2019. Graphic Abstract

Background Small trials suggest that levosimendan is associated with a favorable outcome in patients undergoing cardiac surgery. However, recently published larger-scale trials did not provide evidence for a similar benefit from levosimendan. We performed a meta-analysis to assess the survival benefits of levosimendan in patients undergoing cardiac surgery and to investigate its effects in subgroups of patients with preoperative low-ejection fraction (EF). Methods We identified randomized clinical trials through 20 April 2017 that investigated levosimendan therapy versus control in patients undergoing cardiac surgery. Individual patient data from each study were compiled. Meta-analyses were performed for primary outcomes, secondary outcomes and serious adverse events, and subgroup analyses according to the preoperative EF of enrolled patients were also conducted. The risk of bias was assessed using the Cochrane risk-of-bias tool. Results Seventeen studies involving a total of 2756 patients were included. Levosimendan therapy was associated with a significant reduction in 30-day mortality (RR 0.67; 95% CI, 0.49 to 0.93; p  = 0.02) and reduced the risk of death in single-center trials (RR 0.49; 95% CI, 0.30 to 0.79; p  = 0.004) and in subgroup trials of inferior quality (RR 0.39; 95% CI, 0.17 to 0.92; p  = 0.02); however, in multicenter and in high-quality subgroup-analysis trials, no significant difference in mortality was observed between patients who received levosimendan therapy and controls ( p  > 0.05). However, in high-quality subgroup trials, levosimendan therapy was associated with reduced mortality in patients in a preoperative low-EF subgroup (RR 0.58; 95% CI, 0.38 to 0.88; p = 0.01). Similarly, only patients in the preoperative low-EF subgroup benefited in terms of reduced risk of renal replacement therapy (RR 0.54; 95% CI, 0.34 to 0.85; p  = 0.007). Furthermore, levosimendan therapy was associated with a significant reduction in intensive care unit (ICU) length of stay (MDR −17.19; 95% CI, −34.43 to −2.94; p  = 0.02). Conclusions In patients undergoing cardiac surgery, the benefit of levosimendan in terms of survival was not shown in multicenter or in high-quality trials; however, levosimendan therapy was associated with reduced mortality in patients with preoperative ventricular systolic dysfunction.

Physiologic dose hydrocortisone is part of the suggested adjuvant therapies for patients with septic shock. However, the association between the corticosteroid therapy and mortality in patients with septic shock is still not clear. Some authors considered that the mortality is related to the time frame between development of septic shock and start of low dose hydrocortisone. Thus we designed a placebo-controlled, randomized clinical trial to assess the importance of early initiation of low dose hydrocortisone for the final outcome. A total of 118 patients with septic shock were recruited in the study. All eligible patients were randomized to receive hydrocortisone (n=58) or normal saline (n=60). The study medication (hydrocortisone and normal saline) was initiated simultaneously with vasopressors. The primary end-point was 28-day mortality. The secondary end-points were the reversal of shock, in-hospital mortality and the duration of ICU and hospital stay. The proportion of patients with reversal of shock was similar in the two groups (P=0.602); There were no significant differences in 28-day or hospital all-cause mortality; length of stay in the ICU or hospital between patients treated with hydrocortisone or normal saline. The early initiation of low-dose of hydrocortisone did not decrease the risk of mortality, and the length of stay in the ICU or hospital in adults with septic shock. Trial registration: www.clinicaltrials.govNCT02580240.

Surgery for pancreatic cancer with liver metastases (PCL) is not recommended in the international guidelines, and investigation of its clinical significance in patients with PCL is very limited. This study explored whether surgery, especially synchronous resection of the primary tumor and liver metastases (SPL), could improve survival in PCL. Data of 14,248 patients with PCL from Surveillance, Epidemiology, and End Results database was analyzed. Patients were divided into following groups: SPL, synchronous primary site, and other resection (SPO), single resection of the primary site (SPS), and no resection (NR). In this study, only 93 (0.7%) underwent SPL, 88 (0.6%) for SPO, and 232 (1.6%) for SPS. Multivariate Cox analysis showed surgical procedures of both the primary site and other sites were independent protective prognostic factors for pancreatic cancer cause-specific survival (PCSS) (all < 0.001). Patients in the SPL group showed the most survival benefit, with a significant and gradually increased difference as compared with the SPO, SPS, and NR groups (median survival: 54, 34, 15, and 3 months, respectively, all < 0.001). Compared with the NR group, mortalities were significant and gradually declining in the SPS, SPO, and SPL groups, with hazard ratio 0.329 (95% confidence interval [CI], 0.281 to 0.386), 0.220 (95% CI, 0.164 to 0.294), and 0.162 (95% CI, 0.118 to 0.222), respectively (all < 0.001). Surgical procedures for both primary site and other sites improved survival. SPL, particularly, showed a considerable survival benefit in well-selected patients with PCL.

Background The optimal red blood cell transfusion (RBCT) strategy for traumatic brain injury (TBI) patients remains a topic of debate. This systematic review and meta-analysis aimed to compare the outcomes of a liberal transfusion strategy versus a restrictive strategy in critically ill patients with TBI. Methods PubMed, Web of Science, Embase, and Cochrane Library were searched from inception to November 17, 2024. We included randomized controlled trials (RCTs) of critically ill adult patients with TBI, reporting data on RBCT strategies. The outcomes included intensive care unit (ICU) mortality, long-term mortality, unfavorable functional outcomes, and the incidence of adverse events, such as transfused acute respiratory distress syndrome (TARDS) and venous thromboembolism. We also performed subgroup analyses comparing the association between disease severity and long-term mortality. This review was submitted to PROSPERO (Registration number: CRD42024558797). Results In the results, our analysis revealed that compared to a restrictive transfusion strategy, a liberal strategy did not significantly reduce the risk of ICU mortality (RR: 0.74; 95% CI 0.28–1.91; P  = 0.53) and long-term mortality (RR: 1.02; 95% CI 0.83–1.25; P = 0.87), but it was able to reduce the risk of unfavorable functional outcomes (RR: 0.90; 95% CI 0.82–0.98; P  = 0.01), although there may be a false positive error. In addition, the liberal transfusion strategy was associated with a higher incidence of Transfused Acute Respiratory Distress Syndrome (TARDS) (RR: 1.78; 95% CI 1.06–2.98; P  = 0.03). Conclusions In critically ill patients with TBI, a liberal RBCT strategy appears to improve functional outcomes but carries the risk of false positive errors. In addition, this strategy does not seem to improve survival and may increase the risk of TARDS. Despite this, there remains insufficient evidence to recommend either strategy in this population.

Sepsis bundles can decrease mortality in patients with severe sepsis or septic shock. However, current methods of measuring pressure, such as central venous pressure, are inadequate. This study investigated the effect of improved sepsis bundles informed by pulse-indicated continuous cardiac output. We compared the outcome of treatment with sepsis bundles informed by either conventional pressure measurements or pulse-indicated continuous cardiac output. Patients in 2 groups received fluid resuscitation, standard antibiotics, and oxygen therapy. A total of 105 patients with septic shock were randomly divided into 2 groups: the conventional sepsis bundle group (n = 52) or the improved sepsis bundle group (ISBG, n =53). The ISBG significantly reduced the mean Acute Physiology and Chronic Health Evaluation II and Sepsis-related Organ Failure Assessment scores. Significantly fewer ISBG-treated patients received vasoactive drugs compared to conventional sepsis bundle group–treated patients. In addition, patients in the ISBG exhibited a significantly increased arterial blood lactate clearance rate and required less total fluid resuscitation and a shorter duration of mechanical ventilation and stay in the intensive care unit. Pulse-indicated continuous cardiac output–directed sepsis bundles can reduce the severity of septic shock, provide more accurate fluid resuscitation, and reduce the duration of mechanical ventilation and stay in the intensive care unit.

By means of self-organizing clustering, a new color-based image retrieval method is proposed in the paper. According to the colors’ distributing information in the image, every pixel is assigned a weighing value and thus the initial number of clustering can be confirmed. Therefore, those weighed pixels are clustered and the dominant colors’ statistical features are acquired. Based on the dominant colors spread in the image, the colors’ moment features are extracted to present their spatial features simultaneously. Therefore, the whole image’s content can be expressed from general statistic to partial distributing by the two kinds of features. The experiments verify the method mentioned above more efficiently than those ways based on color histogram

Electroacupuncture at Dazhui(GV14) and Mingmen(GV4) on the Governor Vessel has been shown to exhibit curative effects on spinal cord injury; however, the underlying mechanism remains poorly understood. In this study, we established rat models of spinal cord injury using a modified Allen’s weight-drop method. Ninety-nine male Sprague-Dawley rats were randomly divided into three equal groups: sham(only laminectomy), SCI(induction of spinal cord injury at T10), and EA(induction of spinal cord injury at T10 and electroacupuncture intervention at GV14 and GV4 for 20 minutes once a day). Rats in the SCI and EA groups were further randomly divided into the following subgroups: 1-day(n = 11), 7-day(n = 11), and 14-day(n = 11). At 1, 7, and 14 days after electroacupuncture treatment, the Basso, Beattie and Bresnahan locomotor rating scale showed obvious improvement in rat hind limb locomotor function, hematoxylin-eosin staining showed that the histological change of injured spinal cord tissue was obviously alleviated, and immunohistochemistry and western blot analysis showed that Wnt1, Wnt3 a, β-catenin immunoreactivity and protein expression in the injured spinal cord tissue were greatly increased compared with the sham and SCI groups. These findings suggest that electroacupuncture at GV14 and GV4 upregulates Wnt1, Wnt3 a, and β-catenin expression in the Wnt/β-catenin signaling pathway, exhibiting neuroprotective effects against spinal cord injury.

Electroacupuncture at Dazhui（GV14） and Mingmen（GV4） on the Governor Vessel has been shown to exhibit curative effects on spinal cord injury; however, the underlying mechanism remains poorly understood. In this study, we established rat models of spinal cord injury using a modified Allen＇s weight-drop method. Ninety-nine male Sprague-Dawley rats were randomly divided into three equal groups： sham（only laminectomy）, SCI（induction of spinal cord injury at T10）, and EA（induction of spinal cord injury at T10 and electroacupuncture intervention at GV14 and GV4 for 20 minutes once a day）. Rats in the SCI and EA groups were further randomly divided into the following subgroups： 1-day（n = 11）, 7-day（n = 11）, and 14-day（n = 11）. At 1, 7, and 14 days after electroacupuncture treatment, the Basso, Beattie and Bresnahan locomotor rating scale showed obvious improvement in rat hind limb locomotor function, hematoxylin-eosin staining showed that the histological change of injured spinal cord tissue was obviously alleviated, and immunohistochemistry and western blot analysis showed that Wnt1, Wnt3 a, β-catenin immunoreactivity and protein expression in the injured spinal cord tissue were greatly increased compared with the sham and SCI groups. These findings suggest that electroacupuncture at GV14 and GV4 upregulates Wnt1, Wnt3 a, and β-catenin expression in the Wnt/β-catenin signaling pathway, exhibiting neuroprotective effects against spinal cord injury.

The optical characteristics of three types of black holes (BHs) surrounded by a thin accretion disk are discussed, namely the Schwarzschild BH, Bardeen BH, and Hayward BH. We calculate the deflection angle of light as it traverses the vicinity of each BH using numerical integration and semi-analytical methods, revealing that both approaches can effectively elucidate the deflection of light around the BH. We investigate the optical appearance of the accretion disk and its corresponding observational images at various viewing angles, discovering that the luminosity in the region near the BH on the inner side of the accretion disk is higher than that on the outer side owing to higher material density in closer proximity to the BH. We observe a significant accumulation of brightness on the left side of the accretion disk, attributed to the motion of matter and geometric effects. Our findings emphasize the significant influence of the observation inclination angle on the observed outcomes. An increase in the observation inclination angle results in the separation of higher-order images. With the improvement in EHT observation accuracy, we believe that the feature of a minimal distance between the innermost region of the direct image of the Hayward BH and the outermost region of the secondary image can be used as an indicator for identifying Hayward BHs.