Efficacy Of Therapy Research Articles

Efficacy of Thyroid Hormone Replacement Therapy in Nasopharyngeal Carcinoma Patients with Radiation-Induced Subclinical Hypothyroidism.

Hypothyroidism is a common side effect of radiotherapy for nasopharyngeal carcinoma. However, the impact of thyroid hormone replacement therapy on patients with radiation-induced subclinical hypothyroidism has not been extensively explored. This study aimed to analyze the efficacy of thyroid hormone replacement therapy in nasopharyngeal carcinoma patients with subclinical hypothyroidism. Patients diagnosed with nasopharyngeal carcinoma who developed subclinical hypothyroidism after definitive radiotherapy between September 2019 and December 2020 were selected for inclusion in this study. Prior to thyroid hormone replacement therapy and after maintaining euthyroidism for 6-12 months through thyroid hormone replacement therapy, assessments using the SF36 Brief Health Status Scale and the Hypothyroidism-related Symptom Questionnaire were conducted via trained questionnaires. Lipid profiles were assessed at baseline and after 6-12 months of thyroid hormone replacement therapy. Statistical analyses were performed using matched samples T-test or Mann-Whitney U test. The median follow-up period was 14.5 months. The median score of hypothyroid symptoms was 5.5 out of 19 points, with the most common symptoms being chills (65.0%), fatigue (50.0%), weight gain (45.0%), and limb numbness (40.0%). Thyroid hormone replacement therapy did not significantly improve the quality of life, hypothyroidism-related symptoms, or blood lipid profile in patients. However, there was an observed downward trend in serum cholesterol levels following treatment (P=0.052). Thyroid hormone replacement therapy did not have a significant impact on alleviating hypothyroid symptoms, improving quality of life, or enhancing lipid profiles in patients with radiation-induced subclinical hypothyroidism. Nevertheless, a potential decrease in serum cholesterol levels was noted after thyroid hormone replacement therapy.

A Grant Report: Examining the Efficacy of Remote Photobiomodulation Therapy in Adolescents with Major Depressive Disorder

Major depressive disorder (MDD) is a prevalent mental health condition affecting a significant portion of the population worldwide. This condition can impact individuals of all ages, including adolescents, leading to an impact on various aspects of their lives. Adolescence is a crucial phase of human development, characterized by several neurobiological changes. The onset of MDD during this period can result in damage not only to teenagers but also might have long-lasting implications for their future as adults. Notably, the onset of MDD in adolescents is often associated with various biomarkers, such as increased levels of inflammatory cytokines (e.g., IL-6, TNF-α), oxidative stress markers, and alterations in neurotransmitter levels, indicating a complex interplay of biological factors. Therefore, early intervention is essential for addressing MDD during this phase. Photobiomodulation therapy (PBMT) emerges as an innovative and promising approach that utilizes light, especially in the near-infrared (NIR) and red spectra, to trigger biological and therapeutic effects. Notably, targeting the skull and abdomen with PBMT might explore the bidirectional communication between the intestinal system and the central nervous system in a remote and/or systemic way. In this context, we present the rationale and design of an ongoing study aiming to assess the efficacy of PBMT on depressive symptoms and biomarkers associated with oxidative stress and mitochondrial function in adolescents with MDD.

Clinical Efficacy of Music Therapy for Children with Autism Spectrum Disorder (ASD) By Bioresonance Measurement

Clinical Efficacy of Music Therapy for Children with Autism Spectrum Disorder (ASD) By Bioresonance Measurement

Future AI Will Most Likely Predict Antibody-Drug Conjugate Response in Oncology: A Review and Expert Opinion.

The medical research field has been tremendously galvanized to improve the prediction of therapy efficacy by the revolution in artificial intelligence (AI). An earnest desire to find better ways to predict the effectiveness of therapy with the use of AI has propelled the evolution of new models in which it can become more applicable in clinical settings such as breast cancer detection. However, in some instances, the U.S. Food and Drug Administration was obliged to back some previously approved inaccurate models for AI-based prognostic models because they eventually produce inaccurate prognoses for specific patients who might be at risk of heart failure. In light of instances in which the medical research community has often evolved some unrealistic expectations regarding the advances in AI and its potential use for medical purposes, implementing standard procedures for AI-based cancer models is critical. Specifically, models would have to meet some general parameters for standardization, transparency of their logistic modules, and avoidance of algorithm biases. In this review, we summarize the current knowledge about AI-based prognostic methods and describe how they may be used in the future for predicting antibody-drug conjugate efficacy in cancer patients. We also summarize the findings of recent late-phase clinical trials using these conjugates for cancer therapy.

Abstract B053: Tumor-associated macrophages diminishes IL1RAP-targeting CAR-T cell therapy efficacy in Ewing sarcoma

Abstract Ewing sarcoma (EwS) is a pediatric malignancy of soft tissue and bone with a poor prognosis, especially in its metastatic stages. We have previously identified IL1RAP as a promising target for immunotherapies like chimeric antigen receptor (CAR) T cell therapy against EwS. However, CAR-T cells, despite their success in hematological cancers, often show limited efficacy against solid tumors. In orthotopic xenograft models of Ewing sarcoma (EwS) we have observed that CD11b+ CD206+ macrophages, known as tumor-associated macrophages (TAMs), surround the primary tumor. Treatment with IL1RAP-targeting CAR-T cells specific to EwS results in T cells localizing with these macrophages and failing to infiltrate the primary tumor. This study aims to characterize the impact of TAMs on CAR-T cell efficacy in EwS. We hypothesized that TAMs, polarized by Ewing sarcoma cells, suppress IL1RAP CAR-T cell activity. To model these interactions, we co-cultured EwS cells, macrophages, and CAR-T cells, performing luciferin-based in vitro cytotoxicity assays. THP-1 monocytes were differentiated into macrophages and polarized into M1 or M2 states using cytokines (LPS + IFN-y, IL-4 + IL-13), or differentiated into TAMs by co-culture with EwS cell lines. In vitro cytotoxicity assays were conducted using luciferase-expressing EwS target cells, polarized THP-1 macrophages, and IL1RAP CAR-T effector cells, with luminescence indicating EwS cell survival. We found that M1 macrophages did not affect CAR-T cell targeting of EwS cells, whereas M2 macrophages and TAMs significantly decreased specific lysis (p < 0.001). Conditioned media from polarized macrophages had no effect on CAR-T cell performance against EwS, suggesting that physical proximity or direct contact with TAMs is necessary to suppress CAR-T cell function. Western blot analysis of polarized THP-1 macrophages revealed that M2-polarized macrophages upregulated IL1RAP expression compared to M1 macrophages. Ongoing experiments aim to determine whether elevated IL1RAP expression in M2 macrophages redirects IL1RAP CAR-T cells away from EwS cells or if M2 macrophages mediate general suppression of CAR-T cell activity. Additionally, we are investigating whether THP-1-derived TAMs and primary macrophages also upregulate IL1RAP expression when polarized and how this affects syngeneic CAR-T cell performance. Our findings indicate that TAMs can influence the efficacy of IL1RAP-targeting CAR-T cells against EwS. Further investigation into the specific mechanisms responsible for this suppressive effect could enhance CAR-T therapy for Ewing sarcoma and potentially other solid tumors. Citation Format: Yue Zhou (Joe) Huang, Melanie Rouleu, Poul Sorensen. Tumor-associated macrophages diminishes IL1RAP-targeting CAR-T cell therapy efficacy in Ewing sarcoma [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pediatric Cancer Research; 2024 Sep 5-8; Toronto, Ontario, Canada. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl):Abstract nr B053.

Development of a novel oncolytic adenovirus controlled by CDX2 promoter for esophageal adenocarcinoma therapy.

Prognosis of esophageal adenocarcinoma (EAC) is still poor. Therefore, the development of novel therapeutic modalities is necessary to improve therapeutic outcomes in EAC. Here, we report a novel promoter-controlled oncolytic adenovirus targeting CDX2 (Ad5/3-pCDX2) and its specific anticancer effect for EAC. We used OE19, OE33, HT29, MKN28, RH30, and HEL299 cell lines. To establish CDX2 overexpressing OE19 cells, pCMV-GLI1 plasmid was transfected to OE19 (OE19 + GLI1). The virus replication and cytocidal effect of replication competent Ad5/3-pCDX2 were analyzed in vitro. Antitumor effect of Ad5/3-pCDX2 was assessed in xenograft mouse models by intratumoral injection of the viruses. Finally, efficacy of combination therapy with Ad5/3-pCDX2 and 5FU was evaluated. EAC cells and HT29 showed high mRNA levels of CDX2, but not MKN28, RH30, and HEL299. We confirmed that deoxycholic acid (DCA) exposure enhanced CDX2 expression in EAC cells and OE19 + GLI1 had persistent CDX2 overexpression without DCA. Ad5/3-pCDX2 showed stronger cytocidal effect in OE19 + GLI1 than OE19, whereas Ad5/3-pCDX2 did not kill CDX2-negative cells. Ad5/3-pCDX2 was significantly replicated in EAC cells and the virus replication was higher in OE19 + GLI1 and OE19 with DCA compared to OE19 without DCA exposure. In vivo, Ad5/3-pCDX2 significantly suppressed OE19 tumor growth and the antitumor effect was enhanced in OE19 + GLI1 tumor. In contrast, Ad5/3-pCDX2 did not show significant antitumor effect in MKN28 tumor. Moreover, Ad5/3-pCDX2 significantly increased the efficacy of 5FU in vitro and in vivo. Ad5/3-pCDX2 showed specific anticancer effect for EAC, which was enhanced by bile acid exposure. Ad5/3-pCDX2 has promising potential for EAC therapy in the clinical setting.

Early goal-directed renal replacement therapy in severe pneumonia associated acute kidney injury

Introduction Severe pneumonia is a crucial issue in the development of acute kidney injury (AKI). This study evaluated the efficacy of early goal-directed renal replacement therapy (GDRRT) for the treatment of severe pneumonia-associated AKI. Methods In this real-world retrospective cohort study, we recruited 180 patients with severe pneumonia who were hospitalized and received GDRRT in a third-class general hospital in East China between January 1, 2017, and December 31, 2021. Clinical data on baseline characteristics, biochemical indicators, and renal replacement therapy were collected. Patients were divided into Early and Late RRT groups according to fluid status, inflammation progression, and pulmonary radiology. We investigated in-hospital all-cause mortality (primary endpoint) and renal recovery (secondary endpoint) between the two groups. Results Among the 154 recruited patients, 80 and 74 were in the early and late RRT groups, respectively. There were no significant differences in the demographic characteristics between the two groups. The duration of admission to RRT initiation was significantly shorter in Early RRT group [2.5(1.0, 8.7) d vs. 5.0(1.5,13.5) d, p = 0.027]. At RRT initiation, the patients in the Early RRT group displayed a lower percentage of fluid overload, lower doses of vasoactive agents, higher CRP levels, and higher rates of radiographic progression than those in the Late RRT group. The all-cause in-hospital mortality was significantly lower in the Early RRT group than in Late group (52.5% vs. 86.5%, p < 0.001). Patients in the Early RRT group displayed a significantly higher proportion of complete renal recovery at discharge (40.0% vs. 8.1%, p < 0.001). Conclusion This study clarified that early GDRRT for the treatment of severe pneumonia-associated AKI based on fluid status and inflammation progression, was associated with reduced hospital mortality and better recovery of renal function. Our preliminary study suggests that early initiation of RRT may be an effective approach for severe pneumonia-associated AKI.

Effects of Schisandrae Fructus alone or in combination in viral hepatitis treatment: A systematic review and meta-analysis of randomized controlled trials

Abstract Background Viral hepatitis causes annual deaths of 1.4 million people. Antiviral therapy rarely cures the disease, and patients are usually required to maintain lifelong medication, leading to cumulative drug toxicity. Schisandrae Fructus (SF) is efficacious in the treatment of viral hepatitis. Objective The systematic review and meta-analysis aim to examine the efficacy and safety of SF alone or in combination with specific and nonspecific treatments for treating viral hepatitis by analyzing the clinical trials performed up to date. Methods An extensive literature was searched in 7 databases from inception to May 2023. Final outcomes were divided into the primary outcomes containing the total effective rate and virological responses, as well as the secondary outcomes containing liver biochemical functions and frequencies of adverse events. RevMan 5.3 and GRADE pro 3.6 software were used for meta-analysis and assessment of evidence quality. Subgroup analysis was conducted to explore the source of the heterogeneity. Results Twenty-nine randomized controlled trials were included in the meta-analysis. SF treatment was comparable with western medicines or other traditional Chinese treatments in terms of primary and secondary outcomes. In combination with specific treatments with antiviral medicines, SF group reduced 18.45 U/L of alanine aminotransferase levels [weighted mean difference: 18.45, 95% confidence interval (CI): (16.12, 20.78), p &lt; 0.000 01] and 8.37 U/L of aspartate aminotransferase levels [weighted mean difference: 8.37, 95% CI: (1.25, 15.48), p = 0.02], and it decreased the levels of hyaluronic acid (HA) [standard mean difference (SMD): 0.92, 95% CI: (0.58, 1.27), p &lt; 0.000 01], laminin (LN) [SMD: 0.64, 95% CI: (0.38, 0.90), p &lt; 0.000 01], and procollagen type III [SMD: 0.48, 95% CI: (0.28, 0.67), p &lt; 0.000 01] while increasing the total effective rate by 24% [risk ratio: 1.24, 95% CI: (1.15, 1.32), p &lt; 0.000 01]. There were no severe adverse events during treatment. Conclusions SF was a potential adjuvant for antiviral therapy in restoring liver function. However, the poor quality of the included randomized controlled trials limited the recommendations. More long-term, randomized, and double-blind studies should be performed to assess the efficacy and safety of combination therapy.

Enzyme-responsive, multi-lock optical probes for molecular imaging and disease theranostics.

Optical imaging is an indispensable tool for non-invasive visualization of biomolecules in living organisms, thereby offering a sensitive approach for disease diagnosis and image-guided disease treatment. Single-lock activatable optical probes (SOPs) that specifically switch on optical signals in the presence of biomarkers-of-interest have shown both higher detection sensitivity and imaging quality as compared to conventional "always-on" optical probes. However, such SOPs can still show "false-positive" results in disease diagnosis due to non-specific biomarker expression in healthy tissues. By contrast, multi-lock activatable optical probes (MOPs) that simultaneously detect multiple biomarkers-of-interest could improve detection specificity towards certain biomolecular events or pathological conditions. In this Review, we discuss the recent advancements of enzyme-responsive MOPs, with a focus on their biomedical applications. The higher detection specificity of MOPs could in turn enhance disease diagnosis accuracy and improve treatment efficacy in image-guided disease therapy with minimal toxicity in the surrounding healthy tissues. Finally, we discuss the current challenges and suggest future applications of MOPs.

Bacteriophage therapy reduces Staphylococcus aureus in a porcine and human ex vivo burn wound infection model.

Burn wounds are a major burden, with high mortality rates due to infections. Staphylococcus aureus is a major causative agent of burn wound infections, which can be difficult to treat because of antibiotic resistance and biofilm formation. An alternative to antibiotics is the use of bacteriophages, viruses that infect and kill bacteria. We investigated the efficacy of bacteriophage therapy for burn wound infections, in both a porcine and a newly developed human ex vivo skin model. In both models, the efficacy of a reference antibiotic treatment (fusidic acid) and bacteriophage treatment was determined for a single treatment, successive treatment, and prophylaxis. Both models showed a reduction in bacterial load after a single bacteriophage treatment. Increasing the frequency of bacteriophage treatments increased bacteriophage efficacy in the human ex vivo skin model, but not in the porcine model. In both models, prophylaxis with bacteriophages increased treatment efficacy. In all cases, bacteriophage treatment outperformed fusidic acid treatment. Both models allowed investigation of bacteriophage-bacteria dynamics in burn wounds. Overall, bacteriophage treatment outperformed antibiotic control underlining the potential of bacteriophage therapy for the treatment of burn wound infections, especially when used prophylactically.

Enhanced platelet function through CAR-T cell therapy in relapsed/refractory multiple myeloma

The influence of chimeric antigen receptor T (CAR-T) cell therapy on platelet function in relapsed/refractory (R/R) multiple myeloma (MM) has not been thoroughly investigated. Our cohort comprised fifty MM patients treated with CAR-T cells. The mean platelet closure time (PCT) induced by collagen/adenosine diphosphate (CADP) in peripheral blood was significantly prolonged before lymphodepletion (195.24 ± 11.740 s) and notably reduced post-CAR-T cell therapy (128.02 ± 5.60 s), with a statistically significant improvement (67.22, 95% CI 46.91–87.53, P < 0.001). This post-treatment PCT was not significantly different from that of healthy controls (10.64, 95% CI 1.11–22.40, P > 0.05). Furthermore, a pronounced enhancement in PCT was observed in patients with a response greater than partial remission (PR) following CAR-T cell infusion compared to pre-treatment values (P < 0.001). An extended PCT was also associated with a less favorable remission status. In patients with cytokine release syndrome (CRS) grades 0–2, those with a PCT over 240.5 s exhibited a shorter progression-free survival (PFS), with median PFS times of 10.2 months for the PCT > 240.5 s group versus 22.0 months for the PCT ≤ 240.5 s group. Multivariate analysis revealed that a PCT value exceeding 240.5 s is an independent prognostic factor for overall survival (OS) in R/R MM patients after CAR-T cell therapy. The study demonstrates that CAR-T cell therapy enhances platelet function in R/R MM patients, and PCT emerges as a potential prognostic biomarker for the efficacy of CAR-T cell therapy.

Influence of hyperuricemia at the efficacy of hypolypidemic therapy in patients with chronic forms of ischemic heart disease

Influence of hyperuricemia at the efficacy of hypolypidemic therapy in patients with chronic forms of ischemic heart disease

The KEYVIBE program: vibostolimab and pembrolizumab for the treatment of advanced malignancies.

Vibostolimab, a humanized IgG1 monoclonal antibody, blocks the interaction between TIGITand its ligands, preventing the immunosuppressive effects of TIGIT. The addition of vibostolimab to the PD-1 inhibitor pembrolizumab has shown promising antitumor activity, warranting further exploration of vibostolimab as a potential therapeutic option. The KEYVIBE program consists of nine trials that will evaluate the safety and efficacy of vibostolimab monotherapy and vibostolimab-based combination therapy in advanced solid tumors and hematological malignancies. These studies will also evaluate coformulated immunotherapy addressing issues that occur with the sequential administration of immunotherapy. The KEYVIBE program will provide further insight into the clinical utility of vibostolimab-based therapy across multiple indications and various stages of disease.

Systematic Review and Meta-Analysis of Clinical Efficacy and Safety of Meropenem-Vaborbactam versus Best-Available Therapy in Patients with Carbapenem-Resistant Enterobacteriaceae Infections.

Antimicrobial resistance is increasingly concerning, causing millions of deaths and a high cost burden. Given that carbapenemase-producing Enterobacterales are particularly concerning due to their ability to develop structural modifications and produce antibiotic-degrading enzymes, leading to high resistance levels, we sought to summarize the available data on the efficacy and safety regarding the combination of meropenem-vaborbactam (MV) versus the best available therapy (BAT). Articles related to our objective were searched in the PubMed and Scopus databases inception to July 2024. To assess the quality of the studies, we used the Cochrane risk-of-bias tool, RoB2. The outcomes were pooled as a risk ratio (RR) and a 95% confidence interval (95%CI). A total of four published studies were involved: one retrospective cohort study and three phase 3 trials, including 432 patients treated with MV and 426 patients treated with BAT (mono/combination therapy with polymyxins, carbapenems, aminoglycosides, colistin, and tigecycline; or ceftazidime-avibactam; or piperacillin-tazobactam). No significant difference in the clinical response rate was observed between MV and the comparators at the TOC (RR = 1.29, 95%CI [0.92, 1.80], p = 0.14) and EOT (RR = 1.66, 95%CI [0.58, 4.76], p = 0.34) visits. MV was associated with a similar microbiological response as the comparators at TOC (RR = 1.63, 95%CI [0.85, 3.11], p = 0.14) and EOT assessment (RR = 1.16, 95%CI [0.88, 1.54], p = 0.14). In the pooled analysis of the four studies, 28-day all-cause mortality was lower for MV than the control groups (RR = 0.47, 95%CI [0.24, 0.92], p = 0.03). MV was associated with a similar risk of adverse events (AEs) as comparators (RR = 0.79, 95%CI [0.53, 1.17], p = 0.23). Additionally, MV was associated with fewer renal-related AEs than the comparators (RR = 0.32, 95%CI [0.15, 0.66], p = 0.002). MV was associated with a similar risk of treatment discontinuation due to AEs (RR = 0.76, 95%CI [0.38, 1.49], p = 0.42) or drug-related AEs (RR = 0.56, 95%CI [0.28, 1.10], p = 0.09) as the comparators. In conclusion, MV presents a promising therapeutic option for treating CRE infections, demonstrating similar clinical and microbiological responses as other comparators, with potential advantages in mortality outcomes and renal-related AEs.

Metapopulation model of phage therapy of an acute Pseudomonas aeruginosa lung infection.

Phage therapy is increasingly employed as a compassionate treatment for severe infections caused by multidrug-resistant (MDR) bacteria. However, the mixed outcomes observed in larger clinical studies highlight a gap in understanding when phage therapy succeeds or fails. Previous research from our team, using in vivo experiments and single-compartment mathematical models, demonstrated the synergistic clearance of acute P. aeruginosa pneumonia by phage and neutrophils despite the emergence of phage-resistant bacteria. In fact, the lung environment is highly structured, prompting the question of whether immunophage synergy explains the curative treatment of P. aeruginosa when incorporating realistic physical connectivity. To address this, we developed a metapopulation network model mimicking the lung branching structure to assess phage therapy efficacy for MDR P. aeruginosa pneumonia. The model predicts the synergistic elimination of P. aeruginosa by phage and neutrophils but emphasizes potential challenges in spatially structured environments, suggesting that higher innate immune levels may be required for successful bacterial clearance. Model simulations reveal a spatial pattern in pathogen clearance where P. aeruginosa are cleared faster at distal nodes of the bronchial tree than in primary nodes. Interestingly, image analysis of infected mice reveals a concordant and statistically significant pattern: infection intensity clears in the bottom before the top of the lungs. The combined use of modeling and image analysis supports the application of phage therapy for acute P. aeruginosa pneumonia while emphasizing potential challenges to curative success in spatially structured in vivo environments, including impaired innate immune responses and reduced phage efficacy.

The efficacy of cognitive behavioural therapy for depression and anxiety in multiple sclerosis: A systematic review and meta-analysis

Background: Adults with multiple sclerosis (MS) frequently experience symptoms of depression and anxiety, which pose significant challenges. However, psychological support for these symptoms remains a major unmet healthcare need.Objectives: To inform the evidence base for the psychological management of adults with MS, this study examined the efficacy of cognitive behavioural therapy (CBT) interventions for improving symptoms of depression and anxiety. CBT interventions teach skills for improving the relationships between an individual's thoughts, feelings, and/or behaviours. The study also examined the role of intervention and study characteristics as moderators of treatment effects.Methods: Medline, Embase, PsycINFO, and Cochrane Central Register of Controlled Trials were searched up to August 2024 for randomised control trials.Results: A meta-analysis of 15 clinical trials (1508 participants) was conducted, which found a medium significant treatment effect size for depression symptoms (g = 0.59, 95 % Confidence Interval [CI] [0.38, 0.80]) and a small significant treatment effect size for anxiety symptoms (g = 0.38 95 % CI [0.19, 0.57]). Moderator analyses revealed treatment effects for anxiety, but not depression, were significantly larger for studies conducted in non-Western countries compared to Western countries, and for those with smaller sample sizes.Conclusions: CBT-based interventions appear efficacious for the management of depression and anxiety symptoms in adults with MS. However, future clinical trials with larger samples and more rigorous methodology are warranted. Further examination of intervention characteristics, including ways in which CBT is tailored and how this relates to outcomes, may help to refine interventions for people with MS.

Acupuncture-assisted therapy for prolonged disorders of consciousness: study protocol for a randomized, conventional-controlled, assessor-and-statistician-blinded trial.

Acupuncture is a promising non-pharmaceutical complementary therapy in treating prolonged Disorders of consciousness (pDOC), but solid evidence to support its effectiveness and safety is still lacking. Thus, the purpose of this study is to investigate the efficacy and safety of acupuncture-assisted therapy for pDOC patients. A single-center, prospective, randomized, conventional-controlled, assessor-and-statistician-blinded trial has been designed and is being conducted at West China Hospital of Sichuan University. A total of 110 participants will be randomly assigned to the experimental group and the control group in a 1:1 allocation ratio and evaluated using Coma Recovery Scale-Revised (CRS-R) at 8 a.m., 12 p.m., and 4 p.m. on 2 consecutive days before enrollment to determine the consciousness level. The experimental group will receive acupuncture combined with conventional treatment, while the control group will receive only conventional treatment during the trial observation period. The treatment duration of both groups will be 20 days. Among them, the frequency of acupuncture-assisted therapy is once a day, with 10 consecutive sessions followed by a day's rest for a total of 24 days. Data will be collected separately during baseline and after the final treatment. For data analysis, both Full Analysis Set (FAS) and Per Protocol Set (PPS) principles will be performed together by applying SPSS 27.0 software. The primary outcome measures are the changes of CRS-R before and after treatment, while the secondary outcome measures are the changes of Full Outline of Unresponsiveness Scale (FOUR), the changes of Nociception Coma Scale-Revised (NCS-R), the changes of Disability Rating Scale (DRS), the changes of Mismatch Negativity (MMN) and P300 before and after treatment, respectively. This trial aims to rationally assess the consciousness level from multiple 2 perspectives through subjective evaluation and objective detection by selecting several standardized clinical scales combined with Event-Related Potential (ERP) detection technology. In this way, we will be able to reduce the subjectivity of consciousness assessment and objectively evaluate the clinical efficacy of acupuncture-assisted therapy for pDOC. The study, if proven to be effective and safe enough, will provide a favorable evidence to guide medical decision-making choices and future researches. https://www.chictr.org.cn/, identifier ChiCTR2300076180.

Tumor microenvironment-responsive manganese-based nano-modulator activate the cGAS-STING pathway to enhance innate immune system response

BackgroundManganese ions (Mn2+) combined with adjuvants capable of damaging and lysing tumor cells form an antitumor nano-modulator that enhances the immune efficacy of cancer therapy through the cascade activation of the cyclic GMP-AMP interferon gene synthase-stimulator (cGAS-STING) pathway, which underscores the importance of developing antitumor nano-modulators, which induce DNA damage and augment cGAS-STING activity, as a critical future research direction.Methods and ResultsWe have successfully synthesized an antitumor nano-modulator, which exhibits good dispersibility and biosafety. This nano-modulator is engineered by loading manganese dioxide nanosheets (M-NS) with zebularine (Zeb), known for its immunogenicity-enhancing effects, and conducting targeted surface modification using hyaluronic acid (HA). After systemic circulation to the tumor site, Mn2+, Zeb, and reactive oxygen species (ROS) are catalytically released in the tumor microenvironment by H+ and H2O2. These components can directly or indirectly damage the DNA or mitochondria of tumor cells, thereby inducing programmed cell death. Furthermore, they promote the accumulation of double-stranded DNA (dsDNA) in the cytoplasm, enhancing the activation of the cGAS-STING signalling pathway and boosting the production of type I interferon and the secretion of pro-inflammatory cytokines. Additionally, Zeb@MH-NS enhances the maturation of dendritic cells, the infiltration of cytotoxic T lymphocytes, and the recruitment of natural killer cells at the tumor site.ConclusionsThis HA-modified manganese-based hybrid nano-regulator can enhance antitumor therapy by boosting innate immune activity and may provide new directions for immunotherapy and clinical translation in cancer.Graphical

Assessing the efficacy and safety of combined buspirone and venlafaxine treatment in late-life depression accompanied by cognitive impairment: A randomized controlled trial

BackgroundLate-life depression, often accompanied by cognitive impairment, poses significant clinical challenges owing to its complex etiology and diverse manifestations. While antidepressants like venlafaxine and anxiolytics such as buspirone are effective for treating depression, their effects on cognitive function remain less well-understood. With the aging population increasingly experiencing geriatric depression, there is an urgent need for innovative treatment approaches that address both depressive symptoms and cognitive impairments. ObjectiveThis study aimed to evaluate the clinical efficacy and safety of combined buspirone and venlafaxine therapy in elderly patients diagnosed with geriatric depression accompanied by cognitive impairment. MethodsA 12-week, randomized controlled trial was conducted involving 170 elderly patients. Participants were randomized into two groups: one receiving venlafaxine alone (control group) and the other receiving a combination of venlafaxine and buspirone (experimental group). The primary analysis was performed using an Intent-to-Treat (ITT) approach with mixed-effects linear models to assess changes in depressive symptoms, cognitive function, and anxiety levels. A supplementary Per-Protocol (PP) analysis, utilizing repeated measures ANOVA, was also conducted. ResultsThe ITT analysis showed that the combination therapy significantly reduced depressive symptoms, as indicated by the HAMD-17 scores (p = 0.033 at week 12). Cognitive function, as measured by MoCA scores, also improved significantly in the experimental group by week 12 (p = 0.025). However, no statistically significant differences were observed in anxiety reduction between the groups (p = 0.127). The PP analysis confirmed these findings, demonstrating consistent improvements in depressive symptoms and cognitive function, particularly in those who completed the full course of treatment. The incidence of adverse events was comparable between groups, primarily mild and manageable symptoms like dry mouth, dizziness, and fatigue. ConclusionThe combination of buspirone and venlafaxine was found to be effective in reducing depressive symptoms and enhancing cognitive function in elderly patients with geriatric depression. However, the long-term benefits, especially regarding anxiety reduction, require further investigation. Future studies should consider larger sample sizes, longer follow-up periods, and the inclusion of placebo controls to fully assess the efficacy and safety of this treatment approach.

Bladder sparing options for muscle-invasive bladder cancer.

This review critically evaluates the current state of bladder-sparing options in muscle-invasive bladder cancer (MIBC) and provides an overview of future directions in the field. Bladder-sparing treatments have emerged as viable alternatives to radical cystectomy (RC) for selected patients with MIBC, especially in those who are unfit for RC or elect bladder preservation. Numerous studies have assessed the efficacy of trimodal therapy (TMT), with outcomes comparable to RC in a subgroup of well selected patients. Combining immunotherapy with conventional treatments in bladder-sparing approaches can yield promising outcomes. Current research is making significant progress in optimizing treatment protocols by exploring new combinations of systemic therapy agents, innovative drug delivery methods, and biomarker-based approaches. Furthermore, clinical markers of response are being tested to ensure adequate response assessment. Bladder preservation promise to offer a viable alternative to RC for selected patients with MIBC with the potential to improve patient quality of life. Careful patient selection and ongoing research are essential to optimize patient selection, response assessment, and salvage strategies. As evidence continues to evolve, the role of bladder preservation in MIBC is likely to expand, providing patients with more treatment options tailored to their needs and preferences.