Therapeutic efficacy of tranexamic acid on traumatic brain injury: a systematic review and meta-analysis.

OBJECTIVE: Tranexamic acid (TXA) demonstrates therapeutic efficacy in the management of traumatic brain injury (TBI). The objective of this systematic review and meta-analysis was to evaluate the safety and effectiveness of TXA in patients with TBI. METHODS: The databases, namely PubMed, Embase, Web of Science, and Cochrane Library databases, were systematically searched to retrieve randomized controlled trials (RCTs) investigating the efficacy of TXA for TBI from January 2000 to November 2023. RESULTS: The present meta-analysis incorporates ten RCTs. Compared to the placebo group, administration of TXA in patients with TBI resulted in a significant reduction in mortality (P = 0.05), hemorrhage growth (P = 0.03), and volume of hemorrhage growth (P = 0.003). However, no significant impact was observed on neurosurgery outcomes (P = 0.25), seizure occurrence (P = 0.78), or pulmonary embolism incidence (P = 0.52). CONCLUSION: The administration of TXA is significantly associated with reduced mortality and hemorrhage growth in patients suffering from TBI, while the need of neurosurgery, seizures, and incidence of pulmonary embolism remains comparable to that observed with placebo.

Type I Photosensitizer Targeting Glycans: Overcoming Biofilm Resistance by Inhibiting the Two-Component System, Quorum Sensing, and Multidrug Efflux.

Stubborn biofilm infections pose serious threats to human health due to the persistence, recurrence, and dramatically magnified antibiotic resistance. Photodynamic therapy has emerged as a promising approach to combat biofilm. Nevertheless, how to inhibit the bacterial signal transduction system and the efflux pump to conquer biofilm recurrence and resistance remains a challenging and unaddressed issue. Herein, a boric acid-functionalized lipophilic cationic type I photosensitizer, ACR-DMP, is developed, which efficiently generates •OH to overcome the hypoxic microenvironment and photodynamically eradicates methicillin-resistant Staphylococcus aureus (MRSA) and biofilms. Furthermore, it not only alters membrane potential homeostasis and osmotic pressure balance due to its strong binding ability with plasma membrane but also inhibits quorum sensing and the two-component system, reduces virulence factors, and regulates the activity of the drug efflux pump attributed to the glycan-targeting ability, helping to prevent biofilm recurrence and conquer biofilm resistance. In vivo, ACR-DMP successfully obliterates MRSA biofilms attached to implanted medical catheters, alleviates inflammation, and promotes vascularization, thereby combating infections and accelerating wound healing. This work not only provides an efficient strategy to combat stubborn biofilm infections and bacterial multidrug resistance but also offers systematic guidance for the rational design of next-generation advanced antimicrobial materials.

Molecular Charge and Antibacterial Performance Relationships of Aggregation-Induced Emission Photosensitizers.

Bacterial infections remain a major cause of morbidity worldwide due to drug resistance of pathogenic bacteria. Photodynamic therapy (PDT) has emerged as a promising approach to overcome this drug resistance. However, existing photosensitizers (PSs) are broad-spectrum antibacterial agents that dysregulate the microflora balance resulting in undesirable side effects. Herein, we synthesized a series of aggregation-induced emission (AIE)-active PSs with a lipophilic cationic AIE core with varying charges, named TBTCP and its derivatives. The association of the difference in their molecular charge with the antibacterial effects was systemically investigated. Among the derivatives presented, TBTCP-SF with the electronegative sulfonate group nulled its ability to bind to and ablate Gram-positive (G+) or Gram-negative (G-) bacteria. TBTCP-QY modified by electropositive quaternary ammonium facilitated binding and augmented the photodynamic antibacterial activity for both G+ and G- bacteria. TBTCP-PEG with hydrophilic neutral ligands selectively bound and inactivated G+ bacteria. Under white-light illumination, TBTCP-PEG ablated 99.9% methicillin-resistant Staphylococcus aureus (MRSA) and promoted wound healing in MRSA-infected mice, eliminating MRSA infection both in vitro and in vivo. Our work provides unprecedented insight into the utility of AIE-active PSs for highly targeted and efficient photodynamic ablation of either G+ or G- bacteria that can be translated to next-generation antibacterial materials.

Association Between Time to Endovascular Therapy and Outcomes in Patients With Acute Basilar Artery Occlusion.

OBJECTIVE: To characterize the association of onset to puncture time (OPT) with clinical outcomes among patients with acute basilar artery occlusion receiving endovascular therapy (EVT) in clinical practice. METHODS: Using the EVT for Acute Basilar Artery Occlusion (BASILAR) study, we identified consecutive patients with acute basilar artery occlusion receiving EVT in 47 comprehensive stroke centers in China from January 2014 to May 2019. The primary outcome was favorable functional outcome (defined as modified Rankin Scale score [mRS] 0-3) at 90 days. Secondary outcomes included function independence (mRS 0-2), mortality, and symptomatic intracerebral hemorrhage. The associations of OPT with clinical outcomes were analyzed using multivariable logistic regression (OPT as a categorical variable) and restricted cubic spline regression (OPT as a continuous variable). RESULTS: Among 639 eligible patients, the median age was 64 years, and median OPT was 328 minutes (interquartile range 220-490). Treatment within 4-8 hours and 8-12 hours was associated with lower rates of favorable outcome (adjusted odds ratio, 0.63 [95% confidence interval (CI), 0.40-0.98] and 0.47 [95% CI, 0.23-0.93], respectively) compared with treatment within 4 hours. Restricted cubic spline regression analysis showed that the OPT had L-shaped associations with favorable outcome (p nonlinearity = 0.028) and functional independence (p nonlinearity = 0.025), with significant benefit loss throughout the first 9 hours, but then appeared relatively flat. The odds of mortality increased relatively for OPT up to 9 hours, but then leveled off (p nonlinearity = 0.042). The association between symptomatic intracerebral hemorrhage and OPT was not significant. CONCLUSION: Among patients with acute basilar artery occlusion in routine practice, earlier treatment with EVT was associated with better outcomes throughout the first 9 hours after onset, but benefit may sustain unchanged afterwards. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with acute ischemic stroke due to basilar artery occlusion, earlier EVT is associated with better outcomes.

A multiple drug loaded, functionalized pH-sensitive nanocarrier as therapeutic and epigenetic modulator for osteosarcoma.

Osteosarcoma is a malignant condition affecting adolescents and children more than adults. Nanobiomedicine has opened up several avenues which have increased therapeutic efficiencies than the conventional treatment for the same. In the current study, a novel organic nanoparticle was devised conjugated with bisphosphonate zoledronic acid which has an affinity for bone tissues. Moreover, the nanoparticle was loaded with multiple anti-cancer drugs like gemcitabine and epirubicin. The nanoparticles were characterized by microscopic analysis, entrapment and loading efficiencies, bone affinity studies, in-vitro release studies, cytotoxicity studies and finally in-vivo tumor regression studies. Bone affinity studies depicted a high affinity of zoledronic acid towards bone powder. The nanoparticle exhibited a nanosize dimension, high entrapment and loading efficiencies with uniform symmetry devoid of agglomeration. The in-vitro release experiments showed a measured release of drugs over a longer time without any hint of burst release. However, the release was comparatively for a longer duration in acidic pH and normal physiological pH which may be excellent for therapeutic efficiency. The cytotoxicity studies revealed enhanced cytotoxic effect for MG-63 cell lines in comparison of free drug or single drug combinations. Nonetheless, they proved to be cytocompatible with primary bone cells. Additionally, cellular uptake of nanoparticle was appreciably improved. Significant tumor (250%) regression was seen upon treatment with multiple drug loaded zoledronic acid conjugated nanoparticle, along with epigenetic changes affecting microRNA expressions. The increased cytotoxicity and increased cellular uptake may be of greater advantage in systemic osteosarcoma therapy. Combining all results, our study demonstrated substantial potential towards management of osteosarcoma.

Clinical factors associated with intestinal strangulating obstruction and recurrence in adhesive small bowel obstruction: A retrospective study of 288 cases.

Postoperative adhesions are a common cause of adhesive small bowel obstruction (ASBO), and recognition of intestinal strangulation is important. The aim of this study is to analyze the clinical factors for strangulating obstruction and to identify the predictors for recurrence of ASBO.A retrospective study was conducted using the database in our department. Patients with ASBO from January 2013 to April 2016 were included in the study and were subject to follow-up. The clinical factors associated with strangulating obstruction and recurrence after treatment were analyzed by using univariate and multivariate logistic regression model.In total, 288 ASBO patients were included in the study. Of these, 37 (12.9%) patients had occurred strangulating obstructions, and 251 (87.1%) patients had simple obstructions. Four clinical parameters, including increasing heart rate (>100 bpm), increasing WBC count (>15 × 10/L), CT findings of thickening or swelling of the mesentery, and CT showing seroperitoneum were detected as independent clinical factors for intestinal strangulation. Eighty-four (29.2%) patients experienced recurrence of obstruction during the median 24 months of follow-up. Recurrence rates were reduced in patients who underwent surgical treatment compared with those who received conservative management [21.3% (26/122) vs 34.9% (58/166) (P = .010)]. Nevertheless, the recurrence rates were not significantly increased in patients with strangulating obstructions compared with those with simple ASBO [34.3% (12/35) vs 27.7% (72/253) (P = .186)].Four clinical parameters including tachycardia, leukocytosis, along with CT findings of thickening or swelling of the mesentery and CT showing seroperitoneum, associated with occurrence of intestinal strangulation in ASBO. ASBO patients who underwent surgical treatment had a reduced recurrence rate, but ASBO patients with strangulating obstructions had not increase the recurrence rates than those of patients with simple ASBO.

Incidence, risk factors and impact on outcomes of secondary infection in patients with septic shock: an 8-year retrospective study.

Secondary infection in septic patients has received widespread attention, although clinical data are still lacking. The present study was performed on 476 patients with septic shock. Time trends for mortality were analyzed using Spearman's rank correlation test. Risk factors for secondary infection were investigated by binary logistic regression. The extended Cox model with time-varying covariates and hazard ratios (HR) was performed to determine the impact of secondary infection on mortality. Differences in hospital length of stay (LOS) between patients with and without secondary infection were calculated using a multistate model. Thirty-nine percent of septic shock patients who survived the early phase of the disease developed secondary infection. There was a statistically significant increased odds ratio for secondary infection in older patients and patients with a longer LOS in the intensive care unit (ICU), a higher Sequential Organ Failure Assessment (SOFA) score, and endotracheal intubation. Secondary infection significantly reduced the rate of discharge (HR 5.607; CI95 3.612-8.704; P < 0.001) and was associated with an increased hospital LOS of 5.46 days. The present findings represent a direct description of secondary infection in septic shock patients and highlight the influence of this condition on septic shock outcomes.