Efficacy Of Treatment Research Articles

Clinical Efficacy Observation of Acetylcysteine Combined with Tiotropium Bromide Inhalation for Acute Exacerbations of Chronic Obstructive Pulmonary Disease

Chronic obstructive pulmonary disease (COPD) is a common inflammatory airway disease. When acute exacerbations occur in patients, their pulmonary function (PF) and quality of life (QOL) will be adversely affected, with patient mortality closely related to the frequency and severity of the episodes. This study mainly focuses on the clinical efficacy of acetylcysteine (AC) combined with tiotropium bromide (TB) inhalation for acute exacerbations of COPD (AECOPD). First, 110 patients with AECOPD admitted between February 2019 and February 2021 were selected, of whom 51 cases treated with TB inhalation alone were set as the control group (the Con), and the other 59 cases using the combination therapy (AC+TB inhalation) were set as the observation group (the Obs). Subsequently, inter-group comparisons were performed in terms of clinical efficacy, symptom scores (e.g., cough, expectoration, and dyspnea), PF (e.g., total lung volume [TLC], forced expiratory volume in 1 s [FEV1], and peak expiratory flow [PEF]), inflammatory factors (IFs; e.g., high-sensitivity C-reactive protein [hs-CRP], interleukin-18 [IL-18], matrix metalloproteinase-2 [MMP-2]), and QOL (St. George’s Respiratory Questionnaire [SGRQ]). The Obs had higher overall treatment efficacy and lower symptom (e.g., cough, expectoration, and dyspnea) scores than the Con. Furthermore, the Obs exhibited statistically lower hs-CRP, IL-18, and MMP-2 levels and SGRQ scores and higher TLC, FEV1, and PEF than the Con after treatment. AC+TB inhalation is superior to TB inhalation alone in treating patients with AECOPD, thereby improving patients’ clinical symptoms, PF, and QOL, while inhibiting IFs, including hs-CRP, IL-18, and MMP-2.

Exploring CYP2D6 polymorphisms and angiotensin receptor blocker response in the Bai hypertensive population.

The CYP2D6 enzyme is crucial for the metabolism and disposition of a variety of drugs. This study was conducted to examine the relationship between CYP2D6 gene polymorphisms and the response to angiotensin receptor blocker (ARB)-based treatment in patients of Chinese Bai ethnicity with hypertension. Seventy-two hypertensive adults from the Chinese Bai ethnic group, exhibiting systolic blood pressure (SBP) ≥ 140 mmHg or diastolic blood pressure (DBP) ≥ 90 mmHg, were recruited. Targeted regional sequencing was utilized to genotype single nucleotide polymorphisms in the CYP2D6 gene, aiming to assess their frequency and to evaluate their influence on the therapeutic efficacy of ARB medications. Our research identified nine significant CYP2D6 polymorphisms associated with the efficacy of ARB treatment in the Bai hypertensive cohort. Specifically, patients possessing certain mutant genotype at rs111564371 exhibited substantially greater reductions in SBP and DBP, with P -values of 0.021 and 0.016, respectively, compared to those carrying the wild genotype. Additionally, these mutant genotype at rs111564371 and rs112568578 were linked to approximately 20% higher overall efficacy rates and a 10% increased achievement rate relative to the wild genotype. Our research with the Bai hypertensive group shows that certain CYP2D6 polymorphisms significantly influence ARB treatment outcomes. Mutations at rs111564371 led to better blood pressure control ( P -values: 0.021 for SBP, 0.016 for DBP), improving ARB efficacy by appromixately 20% and increasing treatment goal achievement by 10% over the wild-type genotype. Our investigation into CYP2D6 polymorphisms within the Bai hypertensive cohort marks a substantial advancement towards personalized healthcare, underscoring the pivotal influence of genetic constitution on the effectiveness of ARB therapy.

Long-term efficacy and safety of cannabidiol in patients with tuberous sclerosis complex: 3-year results from the cannabidiol expanded access program.

The cannabidiol (CBD) Expanded Access Program provided compassionate access to CBD for patients with treatment-resistant epilepsy, including tuberous sclerosis complex (TSC), at 35 US epilepsy centers. Here, we present the long-term efficacy and safety outcomes for add-on CBD treatment in patients with TSC. Patients received plant-derived, highly purified CBD (Epidiolex® 100 mg/mL, oral solution), increasing from 2 to 10 mg/kg/d to tolerance or maximum of 25-50 mg/kg/d. Efficacy endpoints were percentage change from baseline in median monthly convulsive, focal, and total seizure frequency and ≥ 50%, ≥75%, and 100% responder rates across 12-week visit windows through 144 weeks. Adverse events (AEs) are reported through 233 weeks. Thirty-four patients with confirmed TSC were included. Mean age was 12.4 years (range, 1.8-31.2), and patients were receiving a median of 3 (range, 1-7) antiseizure medications (ASMs) at baseline. Median CBD dose was 25-28 mg/kg/d for 36 weeks and then 20-50 mg/kg/d through 228 weeks. Dose reduction from baseline occurred for most ASMs, except topiramate. Median reduction in the frequency of convulsive, focal, and total seizures was 44%-81%, 51%-87%, and 44%-87%, respectively, through 144 weeks. Responder rates (≥50%, ≥75%, and 100% reduction) were 43%-71%, 14%-58%, and 0%-25% for convulsive seizures; 52%-75%, 35%-60%, and 7%-32% for focal seizures; and 46%-79%, 26%-65%, and 0%-13% for total seizures. A total of 94% of patients experienced ≥1 AE; 47% had serious AEs, considered treatment unrelated by the investigator. Treatment-related AEs (TRAEs) occurred in 71% of patients. The most frequently reported TRAEs were somnolence, diarrhea, and ataxia. Two patients experienced AEs leading to discontinuation. There were no deaths. Long-term add-on CBD use was associated with reduced seizure frequency through 144 weeks. The safety profile was consistent with previous reports. In this study, we evaluated efficacy and safety of cannabidiol (CBD) treatment in patients with tuberous sclerosis complex receiving CBD in addition to other antiseizure treatments in an Expanded Access Program. After starting CBD, 46%-79% of patients had at least 50% reduction and 26%-65% had at least 75% reduction in the number of seizures per month; up to 13% had no seizures through 144 weeks. Safety results were similar to prior studies; sleepiness and diarrhea were common treatment-related side effects. These results show that long-term CBD treatment was associated with fewer seizures and mild/moderate side effects.

Three-in-One: Molecular Engineering of D-A-π-A Featured Type I and Type II Near-Infrared AIE Photosensitizers for Efficient Photodynamic Cancer Therapy and Bacteria Killing.

Bacterial infections are closely correlated with the genesis and progression of cancer, and the elimination of cancer-related bacteria may improve the efficacy of cancer treatment. However, the combinatorial therapy that utilizes two or more chemodrugs will increase potential adverse effects. Image-guided photodynamic therapy is a highly precise and potential therapy to treat tumor and microbial infections. Herein, four donor-acceptor-π-bridge-acceptor (D-A-π-A) featured near-infrared (NIR) aggregation-induced emission luminogens (AIEgens)(TQTPy, TPQTPy, TQTC, and TPQTC) with type I and type II reaction oxygen species (ROS) generation capabilities are synthesized. Notably, TQTPy shows mitochondria targeted capacity, the best ROS production efficiency, long-term tumor retention capacity, and more importantly, the three-in-one fluorescence imaging guided therapy against both tumor and microbial infections. Both in vitro and in vivo results validate that TQTPy performs well in practical biomedical application in terms of NIR-fluorescence imaging-guided photodynamic cancer diagnosis and treatment. Moreover, the amphiphilic and positively charged TQTPy is able to specific and ultrafast discrimination and elimination of Gram-positive (G+) Staphylococcus aureus from Gram-negative (G-) Escherichia coli and normal cells. This investigation provides an instructive way for the construction of three-in-one treatment for image-guided photodynamic cancer therapy and bacteria elimination.

Effect of Stroke Etiology on Endovascular Treatment for Acute Basilar-Artery Occlusion: A Post Hoc Analysis of the ATTENTION Randomized Trial.

Stroke etiology could influence the outcomes in patients with basilar-artery occlusion (BAO). This study aimed to evaluate the differences in efficacy and safety of best medical treatment (BMT) plus endovascular treatment (EVT) versus BMT alone in acute BAO across different stroke etiologies. The study was a post hoc analysis of the ATTENTION trial (Trial of Endovascular Treatment of Acute Basilar-Artery Occlusion), which was a multicenter, randomized trial at 36 centers in China from February 2021 to September 2022. Patients with acute BAO were classified into 3 groups according to stroke etiology (large-artery atherosclerosis [LAA], cardioembolism, and undetermined cause/other determined cause [UC/ODC]). The primary outcome was a favorable outcome (modified Rankin Scale score of 0-3) at 90 days. Safety outcomes included symptomatic intracranial hemorrhage and 90-day mortality. A total of 340 patients with BAO were included, 150 (44.1%) had LAA, 72 (21.2%) had cardioembolism, and 118 (34.7%) had UC/ODC. For patients treated with BMT plus EVT and BMT alone, respectively, the rate of favorable outcome at 90 days was 49.1% and 23.8% in the LAA group (odds ratio, 3.08 [95% CI, 1.38-6.89]); 52.2% and 30.8% in the cardioembolism group (odds ratio, 2.45 [95% CI, 0.89-6.77]); and 37.5% and 17.4% in the UC/ODC group (odds ratio, 2.85 [95% CI, 1.16-7.01]), with P=0.89 for the stroke etiology×treatment interaction. The rate of symptomatic intracranial hemorrhage in EVT-treated patients with LAA, cardioembolism, and UC/ODC was 8.3%, 2.2%, and 3.2%, respectively, and none of the BMT-treated patients. Lower 90-day mortality was observed in patients with EVT compared with BMT alone across 3 etiology groups. Among patients with acute BAO, EVT compared with BMT alone might be associated with favorable outcomes and lower 90-day mortality, regardless of cardioembolism, LAA, or UC/ODC etiologies. The influence of stroke etiology on the benefit of EVT should be explored by further trials. URL: https://www.clinicaltrials.gov; Unique identifier: NCT04751708.

Acupuncture improves the live birth of patients with repeated implantation failure: a retrospective cohort study.

To explore the therapeutic efficacy of acupuncture treatment on repeated implantation failure (RIF) patients with cryo-thawed embryo transfer (CET). In a retrospective cohort study, all eligible women undergoing RIF were recruited in our center from January 1, 2018 to December 31, 2021. The patients were grouped by whether an acceptance of acupuncture treatment before CET, including the acupuncture group (Acu-group, 55 cycles) and control group (Con-group, 244 cycles). Data were analyzed by using binary logistic regression to explore the relationship of acupuncture treatment with pregnancy outcomes. The Acu-group had higher live-birth rate (LBR) [54.5% vs41.0%, respectively; odds ratio (OR) = 1.105, 95% confidence interval (CI) (1.029, 1.187), P =0.006] and ongoing pregnancy rate (OPR) [56.4% vs43.0%, respectively; OR= 1.100, 95% CI(1.025, 1.181), P =0.008] than the Con-group. There were no significant between-group differences in the rates of implantation [OR= 1.070, 95% CI(0.996, 1.149), P =0.064], clinical pregnancy [OR= 1.065, 95% CI(0.997, 1.138), P =0.061], biochemical pregnancy [OR= 1.002, 95% CI(0.903, 1.112), P =0.967], or miscarriage [OR= 0.778, 95% CI(0.551, 1.099), P =0.155]. Perinatal outcomes did not differ significantly between the two groups. Acupuncture treatment could improve the LBR and OPR in RIF patients with CET cycles, suggesting a potential adjuvant therapy of acupuncture to improve the pregnancy outcomes in RIF patients.

Evaluation of the efficacy of intrauterine treatments of twin-to-twin transfusion syndrome using myocardial performance index

Evaluation of the efficacy of intrauterine treatments of twin-to-twin transfusion syndrome using myocardial performance index

Cenobamate add-on therapy for drug-resistant focal epilepsy.

Although most people with epilepsy achieve complete seizure cessation, approximately one-third of those with the condition continue experiencing seizures despite the use of antiseizure medications (ASMs) given as monotherapy or polytherapy. In this review, we summarised the evidence from randomised controlled trials (RCTs) about cenobamate as an add-on treatment for focal epilepsy uncontrolled by one or more concomitant ASMs. To assess the efficacy and tolerability of add-on oral cenobamate for the treatment of drug-resistant focal-onset seizures, defined as seizures persisting despite treatment with one or more ASMs. We searched the Cochrane Register of Studies (CRS Web) and MEDLINE Ovid (September 2022). In addition, we contacted the manufacturer of cenobamate and experts in the field to enquire after any ongoing or unpublished studies. RCTs comparing add-on cenobamate to placebo or another ASM in people with focal epilepsy uncontrolled by one or more concomitant ASMs. Two review authors independently selected trials for inclusion, extracted data, performed risk of bias assessment, and assessed the certainty of the evidence using the GRADE approach. Our primary outcomes were at least a 50% reduction in total seizure frequency, seizure freedom, and the occurrence of adverse events. We used an intention-to-treat approach for our primary analyses. For each outcome we estimated summary risk ratios (RRs) with their 95% confidence intervals (CIs). We summarised the estimates of effects and certainty of the evidence for each outcome in a summary of findings table. We included two studies (659 adult participants, 442 allocated to cenobamate and 217 to placebo). The overall RR for at least a 50% reduction in seizure frequency for add-on cenobamate at any dose compared to placebo was 2.17 (52% versus 24%, 95% CI 1.66 to 2.84; 2 studies, 605 participants; moderate-certainty evidence). The RR for seizure freedom for add-on cenobamate at any dose compared to placebo was 4.45 (16% versus 5%, 95% CI 2.25 to 8.78; 2 studies, 605 participants; moderate-certainty evidence). The RR for the occurrence of adverse events for add-on cenobamate at any dose compared to placebo was 1.14 (77% versus 67%, 95% CI 1.02 to 1.27; 2 studies, 659 participants; moderate-certainty evidence). We judged the two included RCTs as at low or unclear risk of bias. Both studies were sponsored by the drug company that produces cenobamate. Add-on cenobamate is probably better than placebo in reducing the frequency of seizures by at least 50% and in achieving seizure freedom in adults with focal epilepsy uncontrolled by one or more concomitant ASMs (moderate level of certainty). Its use is probably associated with an increased risk of adverse events (moderate level of certainty). Further prospective, controlled trials are required to evaluate the efficacy and tolerability of add-on cenobamate compared to other ASMs. The efficacy and tolerability of cenobamate as adjunctive treatment for focal epilepsy in children should be further investigated. Finally, the long-term efficacy and tolerability of add-on cenobamate treatment in people with other epilepsy types (e.g. generalised epilepsy) or specific epilepsy syndromes, as well as its use as monotherapy, require additional study.

Brief Report: Evaluating the Efficacy of Psychobehavioral Interventions for Cardiovascular Risk Among People Living With HIV: A Systematic Review and Meta-Synthesis of Randomized Controlled Trials

Abstract: People with HIV (PWH) are disproportionately affected by cardiovascular disease (CVD). Psychobehavioral therapies are capable of targeting the pathophysiology underlying HIV-CVD comorbidity. This study synthesized findings from randomized controlled trials of psychobehavioral therapies for reducing CVD risk among PWH following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Inclusion criteria were as follows: (1) used a randomized controlled trial design, (2) evaluated a cognitive–behavioral or mindfulness-based therapy, (3) sampled adults (age ≥18 years) with HIV, (4) measured a behavioral (eg, diet) or biological (eg, immune functioning) CVD risk factor, and (5) published in an English-language peer-reviewed journal. Electronic searches were conducted in 6 databases (eg, MEDLINE) using controlled vocabulary and free-text synonyms for HIV, psychobehavioral therapy, and CVD risk. Data were independently extracted with consensus reached. Outcomes were immune activation, tobacco smoking, stress, inflammation, and physical activity from 33 studies. There were stronger effects for psychobehavioral interventions compared with controls on CD4 [Hedge g = 0.262, 95% confidence interval (CI) = 0.127 to 0.396] and tobacco-smoking abstinence (Hedge g = 0.537, 95% CI = 0.215 to 0.86). There were no differences or insufficient data for stress, inflammation, or physical activity. No eligible studies examined psychobehavioral interventions on blood pressure, lipids, or weight in PWH. There is increasing importance to further invest in broader CVD risk reduction effort for PWH that include psychobehavioral intervention strategies.

Rhythmic Effects: A Quantitative Pilot of a Pediatric Therapeutic Drumming Intervention

Abstract Date Presented 03/21/24 This study examined efficacy and instrumentation of a therapeutic drumming intervention implemented with autistic children. The study identified potentiality of an evidence-based and neurodiversity affirming intervention option for this population. Primary Author and Speaker: Dina Prisco Additional Authors and Speakers: Zahava Friedman Contributing Authors: Jorge Ochoa, Talia Nuesi, Carmen Guarino, Barbara Cheuvront

Use of Mental Practice to Reduce Severe Upper Extremity Hemiparesis: A Pilot Study

Abstract Date Presented 03/22/24 This study examined the efficacy and feasibility of a mental practice protocol to address severe upper extremity hemiparesis. The results suggest that mental practice is an efficacious, appropriate, and feasible intervention for this population. Primary Author and Speaker: Teresa M. Green Additional Authors and Speakers: Farida S. Gayle Contributing Authors: Asha Vas

In utero treatment of congenital cytomegalovirus infection with valganciclovir: an observational study on safety and effectiveness.

The treatment of congenital cytomegalovirus (CMV) infection is usually administered to neonates after birth; however, it can be anticipated during the prenatal period by treating pregnant women in order to reduce the severity of the congenital disease. The most commonly used treatment for CMV during pregnancy is valaciclovir; however, valganciclovir has a higher potency against CMV and is the first choice for neonates with congenital CMV disease. We investigated neonatal and maternal safety of tertiary prevention in infected fetuses showing ultrasound features of infection using valganciclovir. Retrospective cohort study of pregnant women and their symptomatic infected fetuses taking valganciclovir, 3 × 450 mg per day. All fetuses presented at least one prenatal feature on ultrasound. We assessed fetal/neonatal and maternal safety, as well as neonatal efficacy of treatment. The main outcome was neutropenia. Secondary outcomes included other haematological side effects, symptoms at birth and neonatal CMV-PCR was positive. Seventeen women with singleton pregnancies received valganciclovir from a median (IQR) of 27.1 (26.0-30.3) to 11.6 (6.5-12.9) weeks of gestation. No neonatal neutropenia was reported. One pregnancy was terminated for severe features. Three newborns (18%) were asymptomatic at birth, including one with negative CMV-PCR from blood and saliva. CMV-PCR was positive for 12/13 symptomatic newborns, with a median (IQR) log10 viral load of 3.36 (3.30-4.20), 4.03 (1.75-4.27) and 3.04 (0.00-3.40) log10 copies/mL in blood, urine and saliva, respectively. Tertiary prevention by valganciclovir appears to be well tolerated for both fetus and mother. However, more extensive trials accompanied by long-term follow-up are needed.

A Novel Oncogenic Role of Disulfidptosis-related Gene SLC7A11 in Anti--tumor Immunotherapy Response to Human Cancers.

The protein Solute Carrier Family 7 Member 11 (SLC7A11) plays a pivotal role in cellular redox homeostasis by suppressing disulfidptosis, which restricts tumor growth. Yet, its relevance in prognosis, immunity, and cancer treatment efficacy is not well understood. We conducted a comprehensive analysis of the expression of SLC7A11 across 33 cancer types, employing datasets from public databases. Methods, such as Cox regression and survival analyses assessed its prognostic significance, while functional enrichment explored the biological processes tied to SLC7A11. The association between SLC7A11 expression, immune cell infiltration, and immune-related gene expression was also scrutinized. Notably, SLC7A11 expression was more pronounced in cancerous compared to normal samples and correlated with higher tumor grades. Increased SLC7A11 expression was linked to poor outcomes, particularly in liver hepatocellular carcinoma (LIHC). This protein's expression also showcased significant relationships with diverse molecular and immune subtypes. Additionally, a prognostic nomogram was devised, integrating SLC7A11 expression and clinical variables. High SLC7A11 levels corresponded with cell growth and senescence pathways in various cancers and with lipid and cholesterol metabolism in LIHC. Furthermore, potential therapeutic compounds for LIHC with high SLC7A11 were identified. Real-time PCR (qPCR) and Western blot were conducted to explore the expression of SLC7A11 in tumor tissues and cancer cell lines. In summation, this study emphasizes the prognostic and immunological importance of SLC7A11, spotlighting its potential as a therapeutic target in LIHC.

Sonoanatomy of injecting botulinum neurotoxin into the facial muscles.

Ultrasonography (US) has become an essential tool for guiding botulinum neurotoxin (BoNT) injections in facial muscles, enhancing precision and safety. This narrative review explores the role of US in BoNT administration, particularly in complex anatomical regions, highlighting its impact on treatment customization, real-time visualization, and complication reduction. A comprehensive literature search was conducted using PubMed, MEDLINE, Embase, and Cochrane Library for articles published from January 2018 to December 2023. Search terms included "Botulinum neurotoxin," "facial anatomy," "ultrasonography guided injection," and "facial muscle sonoanatomy." Studies focusing on US-guided BoNT injections in facial muscles were included. Data extraction and synthesis were performed independently by two reviewers, focusing on study design, ultrasonography techniques, outcomes, and conclusions. The review found that US guidance significantly enhances the precision of BoNT injections by providing real-time visualization of facial muscles and blood vessels, thereby reducing the risk of adverse events. US enables tailored injection strategies, ensuring symmetrical facial expressions and minimizing over-treatment. The technique also offers immediate feedback, allowing for on-the-spot adjustments to improve treatment efficacy and safety. However, the review identified limitations, including potential selection bias and variability in US techniques across different studies. US guidance for BoNT injections into facial muscles offers substantial benefits in terms of precision, safety, and treatment customization. Despite the identified limitations, the integration of US into clinical practice is poised to enhance patient outcomes in aesthetic and therapeutic procedures. Further research is needed to standardize US techniques and broaden the inclusivity of studies to validate these findings comprehensively.

FGL1: a novel biomarker and target for non-small cell lung cancer, promoting tumor progression and metastasis through KDM4A/STAT3 transcription mechanism

Non-small cell lung cancer (NSCLC) is characterized by a high incidence rate and poor prognosis worldwide. A deeper insight into the pathogenesis of NSCLC and identification of novel therapeutic targets are essential to improve the prognosis of NSCLC. In this study, we revealed that fibrinogen-like protein 1 (FGL1) promotes proliferation, migration, and invasion of NSCLC cells. Mechanistically, we found that Stat3 acts as a transcription factor and can be recruited to the FGL1 promoter, enhancing FGL1 promoter activity. Lysine-specific demethylase 4A (KDM4A) interacts with Stat3 and facilitates the removal of methyl groups from H3K9me3, thereby enhancing Stat3-mediated transcription of FGL1. Furthermore, we observed that Stat3 and KDM4A promote NSCLC cell proliferation, migration, and invasion partly by upregulating FGL1 expression. Additionally, the expression of FGL1 was significantly higher in cancer tissues (n = 90) than in adjacent non-cancerous tissues (n = 90). Furthermore, patients with high FGL1 expression had a shorter overall survival (OS) compared to those with low FGL1 expression. We measured the expression levels of FGL1 on circulating tumor cells (CTCs) in 65 patients and found that patients with a dynamic decrease in FGL1 expression on CTCs exhibited a better therapeutic response. These findings suggest that the dynamic changes in FGL1 expression can serve as a potential biomarker for predicting treatment efficacy in NSCLC. Overall, this study revealed the significant role and regulatory mechanisms of FGL1 in the development of NSCLC, suggesting its potential as a therapeutic target for patients with NSCLC. Future studies should provide more personalized and effective treatment options for patients with NSCLC to improve clinical outcomes.

Bystander Effects, Pharmacokinetics, and Linker-Payload Stability of EGFR-Targeting Antibody-Drug Conjugates Losatuxizumab Vedotin and Depatux-M in Glioblastoma Models.

Antibody-drug conjugates (ADC) are targeted therapies with robust efficacy in solid cancers, and there is intense interest in using EGFR-specific ADCs to target EGFR-amplified glioblastoma (GBM). Given GBM's molecular heterogeneity, the bystander activity of ADCs may be important for determining treatment efficacy. In this study, the activity and toxicity of two EGFR-targeted ADCs with similar auristatin toxins, Losatuxizumab vedotin (ABBV-221) and Depatuxizumab mafodotin (Depatux-M), were compared in GBM patient-derived xenografts (PDX) and normal murine brain following direct infusion by convection-enhanced delivery (CED). EGFRviii-amplified and non-amplified GBM PDXs were used to determine in vitro cytotoxicity, in vivo efficacy, and bystander activities of ABBV-221 and Depatux-M. Nontumor-bearing mice were used to evaluate the pharmacokinetics (PK) and toxicity of ADCs using LC-MS/MS and immunohistochemistry. CED improved intracranial efficacy of Depatux-M and ABBV-221 in three EGFRviii-amplified GBM PDX models (Median survival: 125 to >300 days vs. 20-49 days with isotype control AB095). Both ADCs had comparable in vitro and in vivo efficacy. However, neuronal toxicity and CD68+ microglia/macrophage infiltration were significantly higher in brains infused with ABBV-221 with the cell-permeable monomethyl auristatin E (MMAE), compared with Depatux-M with the cell-impermeant monomethyl auristatin F. CED infusion of ABBV-221 into the brain or incubation of ABBV-221 with normal brain homogenate resulted in a significant release of MMAE, consistent with linker instability in the brain microenvironment. EGFR-targeting ADCs are promising therapeutic options for GBM when delivered intratumorally by CED. However, the linker and payload for the ADC must be carefully considered to maximize the therapeutic window.

Efficacy of immune-checkpoint inhibitors combined with cytotoxic chemotherapy in advanced or recurrent endometrial cancer: A systematic review and meta-analysis

BackgroundThe combination of immune checkpoint inhibitors (ICIs) and platinum-based chemotherapy has emerged as a highly promising primary option for advanced or recurrent endometrial cancer (EC). The study aimed to evaluate treatment efficacy of ICIs with cytotoxic chemotherapy in EC. MethodsWe conducted a comprehensive review of randomized controlled trials up to November 11, 2023, focusing on immunotherapy combined with chemotherapy versus chemotherapy alone for EC. The primary endpoint was the pooled hazard ratio (HR), which was further analyzed across subgroups based on mismatch repair (MMR) status, race, histology, and programmed death-ligand 1 (PD-L1) status. The protocol was registered in PROSPERO (CRD42023475669). FindingsFour trials with 2335 patients were analyzed. ICIs with chemotherapy significantly prolonged progression-free survival (PFS) (HR, 0.70; 95% CI, 0.62–0.79) and overall survival (OS) (HR, 0.75; 95% CI, 0.63–0.89) compared to chemotherapy alone. Stratification by MMR status showed substantial benefits for dMMR (PFS; HR, 0.33; 95% CI, 0.26–0.43; OS; HR, 0.37; 95% CI, 0.22–0.91) over pMMR cohorts in both PFS and OS. In the subgroup analysis, there was significant PFS advantage in Caucasian (HR, 0.63; 95% CI, 0.54–0.72) over non-Caucasian, in endometrioid histology (HR, 0.66; 95% CI, 0.56–0.78) over non-endometrioid, and in PD-L1 positive (HR, 0.39; 95% CI, 0.19–0.81) over PD-L1 negative population. InterpretationICIs combined with platinum-based chemotherapy significantly prolonged PFS and OS in patients with advanced or recurrent EC. Patients with dMMR status, Caucasians, endometrioid histology, and positive PD-L1 status showed significant PFS benefits, emphasizing the need for personalized treatment approaches to improve outcomes.

An Overview of Acupuncture Dosage in Veterinary Medicine

Acupuncture is subject to dosage considerations, similar to pharmaceuticals, that significantly influence therapeutic outcomes. In instances where the initial diagnosis is confirmed to be accurate, and results are suboptimal, consideration should be given to augmenting the acupuncture dosage and technique used. Veterinary acupuncture dosage includes size of acupuncture needles, depth of needle insertion, frequency/duration of the treatments, and type of acupuncture technique used. Larger needle size generates stronger stimulation and studies indicate that acupuncture points can have specific effects on the body based on depth of stimulation (i.e. length of needle). Optimal therapy also depends on the frequency of treatment and will vary dependent on the clinical condition and acupuncture technique. In cases where clinical improvements remain absent after 4-6 sessions of dry needle acupuncture therapy, it is prudent to reevaluate both conventional and TCVM diagnoses, as well as acupuncture dosage. Adjustments in acupuncture dosage can include the use of longer needles, the incorporation of additional acupoints or the addition of other needle stimulation techniques. The use of advanced acupuncture modalities, such as electro-acupuncture, aqua-acupuncture, acupoint embedding and scalp acupuncture, may significantly enhance therapeutic efficacy. This paper aims to explore and elucidate the various factors influencing the dosage of acupuncture in a variety of species across ten commonly used acupuncture techniques, thereby providing insights into how they can be optimized to enhance treatment efficacy.

Metastasis and basement membrane-related signature enhances hepatocellular carcinoma prognosis and diagnosis by integrating single-cell RNA sequencing analysis and immune microenvironment assessment

BackgroundHepatocellular carcinoma (HCC) is the most common type of primary liver cancer and second leading cause of cancer-related deaths worldwide. The heightened mortality associated with HCC is largely attributed to its propensity for metastasis, which cannot be achieved without remodeling or loss of the basement membrane (BM). Despite advancements in targeted therapies and immunotherapies, resistance and limited efficacy in late-stage HCC underscore the urgent need for better therapeutic options and early diagnostic biomarkers. Our study aimed to address these gaps by investigating and evaluating potential biomarkers to improve survival outcomes and treatment efficacy in patients with HCC.MethodIn this study, we collected the transcriptome sequencing, clinical, and mutation data of 424 patients with HCC from The Cancer Genome Atlas (TCGA) and 240 from the International Cancer Genome Consortium (ICGC) databases. We then constructed and validated a prognostic model based on metastasis and basement membrane-related genes (MBRGs) using univariate and multivariate Cox regression analyses. Five immune-related algorithms (CIBERSORT, QUANTISEQ, MCP counter, ssGSEA, and TIMER) were then utilized to examine the immune landscape and activity across high- and low-risk groups. We also analyzed Tumor Mutation Burden (TMB) values, Tumor Immune Dysfunction and Exclusion (TIDE) scores, mutation frequency, and immune checkpoint gene expression to evaluate immune treatment sensitivity. We analyzed integrin subunit alpha 3 (ITGA3) expression in HCC by performing single-cell RNA sequencing (scRNA-seq) analysis using the TISCH 2.0 database. Lastly, wound healing and transwell assays were conducted to elucidate the role of ITGA3 in tumor metastasis.ResultsPatients with HCC were categorized into high- and low-risk groups based on the median values, with higher risk scores indicating worse overall survival. Five immune-related algorithms revealed that the abundance of immune cells, particularly T cells, was greater in the high-risk group than in the low-risk group. The high-risk group also exhibited a higher TMB value, mutation frequency, and immune checkpoint gene expression and a lower tumor TIDE score, suggesting the potential for better immunotherapy outcomes. Additionally, scRNA-seq analysis revealed higher ITGA3 expression in tumor cells compared with normal hepatocytes. Wound healing scratch and transwell cell migration assays revealed that overexpression of the MBRG ITGA3 enhanced migration of HCC HepG2 cells.ConclusionThis study established a direct molecular correlation between metastasis and BM, encompassing clinical features, tumor microenvironment, and immune response, thereby offering valuable insights for predicting clinical outcomes and immunotherapy responses in HCC.

The relationship between trust in federal oversight of vaccine safety and willingness to participate in COVID-19 clinical trials: a repeated measures study of Philadelphia residents (September 2021 – March 2023)

BackgroundThe Coronavirus Disease 2019 (COVID-19) pandemic precipitated an urgent need for clinical trials to discover safe and efficacious treatments. We examined how COVID-19 experiences, clinical trial awareness, and trust in the vaccine safety process were associated with willingness to participate in COVID-19 clinical trials. The objective was to investigate the relationship between trust in federal oversight of vaccine safety and willingness to participate in clinical trials for COVID-19 treatment across four distinct time points over an 18-month period during the COVID-19 pandemic.MethodsWe used four waves of data collected from September 2021 to March 2023 among 582 Philadelphia residents (with a missing data rate of 0.9%). Generalized estimating equations estimated the association between willingness to participate in COVID-19 clinical trials and participants’ trust in the federal government’s oversight of COVID-19 vaccine safety, COVID-19-related variables (COVID-19 related health challenges, history of COVID-19 infection), awareness of clinical trials and how to enroll in them, and sociodemographic characteristics (age, race/ethnicity, sexual orientation, gender, parental status, education, and insurance).ResultsOn average, willingness to participate in a COVID-19 clinical trial was positively associated with greater trust in the federal government’s oversight of vaccine safety [β = 0.34, 95% confidence interval (CI): 0.15–0.53], having COVID-19 (β = 0.40, 95% CI: 0.08–0.73), awareness of clinical trials (β = 0.38, 95% CI: 0.04–0.73), and knowledge of how to enroll (β = 0.83, 95% CI: 0.44–1.23). Among sociodemographic characteristics, race/ethnicity (p = 0.001) and gender (p = 0.018) were identified as predictors for COVID-19 trial willingness.ConclusionWillingness to participate in clinical trials may be bolstered by strengthening the public’s trust in the federal government’s role within vaccine safety oversight, increasing the perceived relevance of clinical trials to individuals’ health and well-being, and offering tailored information to educate diverse communities about ongoing trials and how to enroll in them.