Efficacy Of Therapy Research Articles

Efficacy of Continuous Positive Airway Pressure Therapy in a Patient With Saber-Sheath Trachea on Dilated Central and Peripheral Airways: A Case Report

Efficacy of Continuous Positive Airway Pressure Therapy in a Patient With Saber-Sheath Trachea on Dilated Central and Peripheral Airways: A Case Report

Lead implantation in the late activation zone of the left ventricle determined by preoperative noninvasive mapping to improve the efficacy of cardiac resynchronization therapy

Lead implantation in the late activation zone of the left ventricle determined by preoperative noninvasive mapping to improve the efficacy of cardiac resynchronization therapy

Remolding the tumor microenvironment by bacteria augments adoptive T cell therapy in advanced-stage solid tumors

The intricate tumor microenvironment presents formidable obstacles to the efficacy of adoptive T cell therapy in the management of solid tumors by limiting the infiltration and inducing exhaustion of the transferred T cells. Here, we developed a bacterial-based adjuvant approach that augments the efficacy of adoptive T-cell therapy for solid tumor treatment. Our study reveals that intratumor injection of E. coli MG1655 normalizes tumor vasculatures and reprograms tumor-associated macrophages into M1 phenotype that produce abundant CCL5, together facilitating tumor infiltration of adoptively transferred T cells. The depletion of tumor-associated macrophages or CCL5 neutralization in vivo leads to the significantly decreased solid tumor infiltration of adoptive T cells in the presence of bacteriotherapy. This combinatorial therapy, consisting of E. coli adjuvant and adoptive T-cell therapy, effectively eradicates early-stage melanoma and inhibits the progression of pancreatic tumors. Notably, this dual strategy also strengthened the distal tumor control capabilities of adoptive T-cell therapy through the induction of in situ tumor vaccination. This dual therapeutic approach involving bacterial therapy targeting the interior of solid tumors and adoptive T-cell therapy attacking the tumor periphery exhibits potent therapeutic efficacy in achieving the eradication of advanced-stage tumors, including melanoma and hepatocellular carcinoma, by converging attacks from both inside and outside the tumor tissues.

Low level laser therapy and rheumatoid arthritis: a systematic review and meta-analysis study.

This systematic review and meta-analysis aimed to evaluate the efficacy of Low-Level Laser Therapy (LLLT) in the treatment of Rheumatoid Arthritis (RA), focusing on its effects on pain relief, grip strength, and morning stiffness. A comprehensive search was conducted across PubMed, Scopus, and Web of Science, yielding 3,111 articles. After eliminating duplicates and screening titles and abstracts, 94 full-text articles were assessed, and 23 studies met the eligibility criteria for inclusion in the systematic review. Of these, 22 studies were included in the meta-analysis. Data were extracted and analyzed using a random-effects model, with pooled Mean Differences (MD) calculated for the primary outcomes. The meta-analysis revealed that LLLT did not significantly reduce pain compared to placebo (MD = 0.00, 95% CI [-0.09, 0.09], p = 0.97). However, LLLT significantly improved grip strength (MD = -12.38, 95% CI [-17.42, -7.34], p < 0.01) and reduced morning stiffness (MD = -0.84, 95% CI [-1.33, -0.36], p < 0.01), despite substantial heterogeneity in these outcomes. LLLT shows promise in improving grip strength and reducing morning stiffness in RA patients, though it does not significantly impact pain relief. These findings highlight the potential role of LLLT as an adjunctive treatment for RA, with further research needed to optimize treatment protocols and clarify underlying mechanisms.

Neural therapy in notalgia paresthetica.

Notalgia Paresthetica (NP) is a type of chronic sensory neuropathy characterized by localized itching, pain and dysesthesias including numbness, tingling, burning, coldness, hypo- and hyperesthesia. It is frequently underdiagnosed and thus, there is no established standard of care for treatment. The objective of our study was to evaluate the efficacy of neural therapy in patients with NP. Patients aged 30-60 years with a diagnosis of NP for at least 6 months were included in our study. Intralesional and segmental neural therapy was administered to the patients in five sessions, with one-week intervals between each session. Patients were evaluated with numeric rating scale (NRS) for pain, the PainDETECT Questionnaire for neuropathic pain, the Short Form-12 (SF-12) for quality of life and the 5-D Itch Scale for pruritus. A total of 12 patients diagnosed with NP were included in the study. The median age of the patients included in the study was 45 years (33-59). 58.3% (n = 7) of the patients were female and 41.7% (n = 5) were male. The median duration of pain was 24 (6-60) months. Itching was observed in 75% (n = 9) and hypoesthesia was present in 58.3% (n = 7) of the patients. Comparisons were made with assessment scales before and 3 months after treatment. There was a significant difference in the pre-treatment NRS, PainDETECT Questionnaire, physical component of SF-12 and 5-D itch scale scores compared to post-treatment. Neural therapy represents a promising complementary treatment method for the reduction of pain, neuropathic pain, and pruritus in patients with NP. Furthermore, it has been demonstrated to enhance quality of life.

A Comparative Analysis of Alpha and Beta Therapy in Prostate Cancer Using a 3D Image-Based Spatiotemporal Model.

In treating prostate cancer, distinguishing alpha and beta therapies is vital for efficient radiopharmaceutical delivery. Our study introduces a 3D image-based spatiotemporal computational model that utilizes MRI-derived images to evaluate the efficacy of 225Ac-PSMA and 177Lu-PSMA therapies. We examine the impact of tumor size, diffusion, interstitial fluid pressure (IFP), and interstitial fluid velocity (IFV) on the absorbed doses. An MRI-based geometric model of the tumor and its surrounding environment is initially developed. Subsequently, COMSOL Multiphysics software is utilized to solve convection-diffusion-reaction equations and conduct numerical analyses of blood pressure distribution. This computational methodology provides valuable insights into interstitial fluid patterns and the spatiotemporal distribution of extracellular and intracellular concentrations of 225Ac-PSMA and 177Lu-PSMA. In addition, our study investigates the impacts of increasing tumor size on absorbed doses and mechanisms involved in radiopharmaceutical transport and delivery. Larger tumors have diminished absorbed doses, highlighting the need for customized treatments according to tumor size. Diffusion significantly influences the transport and delivery of radiopharmaceuticals. Additionally, alpha therapy was observed to consistently yield higher absorbed doses within the tumor than beta therapy. This study reveals the complex interplay between radiopharmaceutical properties, the tumor microenvironment, and treatment outcomes. It highlights the potential of 225Ac-PSMA in prostate cancer treatment, advocating for personalized treatment strategies tailored to the specific characteristics of each patient and their tumor.

Growth Hormone Therapy in Chronic Heart Failure: a Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Guideline-directed medical therapy of heart failure (HF) primarily targets neurohormonal activation. However, growth hormone (GH) has emerged as a potential treatment for the multiple hormonal deficiency syndrome, which is associated with worse outcomes in HF. This study evaluates the efficacy and safety of GH therapy in HF. A systematic search was conducted in PubMed, Cochrane Library, and ClinicalTrials.gov, according to PRISMA guidelines. Randomized, placebo-controlled trials studying GH therapy in adult HF patients were included. Of the 1,184 initially identified records, 17 studies (1.4%) met the inclusion criteria. Two independent authors conducted the search, with any disagreements resolved by a third author. Study quality was assessed using predefined criteria, including randomization, blinding, and the presence of a placebo group. A random-effects model was applied due to heterogeneity across studies. GH therapy significantly improved left ventricular ejection fraction (3.34%, 95% CI: 1.09% to 5.59%, p=0.0037), peak oxygen consumption (2.84 mL/kg/min, 95% CI: 1.32 mL/kg/min to 4.36 mL/kg/min, p=0.0002), and New York Heart Association class (-0.44, 95% CI: -0.08 to -0.81, p=0.023). GH therapy also reduced the composite of death, worsening HF or ventricular tachycardia by 41% (95% CI: 0.39-0.90, p=0.013). Subgroup analyses indicated that patients with ischemic cardiomyopathy, baseline ejection fraction ≥30% and longer treatment duration experienced greater benefits. GH therapy may improve cardiac function, exercise capacity, and HF symptoms, with a trend towards improvement in hard endpoints, such as worsening HF. Event-driven trials are necessary to validate these findings.

Synthesis of Closely-Contacted Cu2O-CoWO4 Nanosheet Composites for Cuproptosis Therapy to Tumors With Sonodynamic and Photothermal Assistance.

Cuproptosis offers a promising and selective therapeutic strategy for cancer therapy. To fully realize its potential, the development of novel cuproptosis therapeutic agents and the achievement of efficient copper release are critical steps forward. Herein, closely-contacted Cu2O-CoWO4 nanosheet heterojunctions (CCW-NH) are successfully synthesized using an in-situ process for cuproptosis therapy. The efficient release of copper ions from CCW-NH can be triggered by ultrasound irradiation, primarily due to the generation of superoxide radicals as the sonodynamic agents via the Z-scheme charge transfer mechanism. When subjected to the combined effects of ultrasound and laser irradiation, the effective release of copper ions is increased by 1.7 times compared to the untreated group, significantly enhancing the efficiency of cuproptosis. And the incorporation of CCW-NH and L-arginine into the temperature-sensitive injectable hydrogel (HP-CCW@LA) ultimately achieved a tumor inhibition rate of up to 95.1%. L-arginine, serving as a reducing agent, enabled the sustained release of highly active Cu+ during treatment. Notably, after treating tumors with HP-CCW@LA, the tumor microenvironment is leveraged to promote copper ion conversion, which offers the potential for monitoring tumor therapy efficacy through magnetic resonance imaging. This work offers a novel integrated strategy for the development of new cuproptosis agents and therapeutic evaluation.

Oncolytic virus encoding 4-1BBL and IL15 enhances the efficacy of tumor-infiltrating lymphocyte adoptive therapy in HCC.

Previous studies have found that oncolytic virus (OVs) can improve the efficacy of TIL adoptive therapy in oral cancer, colon cancer, and pancreatic cancer. However, the curative effect in hepatocellular carcinoma (HCC) is still unclear. Therefore, this study aims to explore the therapeutic effect and mechanism of OVs encoding 4-1BBL and IL15 (OV-4-1BBL/IL15) combined with TIL adoptive therapy on HCC. In this study, the role and immunological mechanism of armed OVs combined with TILs were evaluated by flow cytometry and ELISA in patient-derived xenograft and syngeneic mouse tumor models. Co-culturing with TILs can up-regulate the expression of antigen-presenting cell (APC) markers on the surface of OV-infected primary HCC cells, and promote the specific activation ability and tumor-killing ability of TILs. OV-4-1BBL/IL15 combined with TIL adoptive therapy could induce tumor volume reduction and anti-tumor immune memory in patient-derived xenograft and syngeneic mouse tumor models. Furthermore, OV combined with TIL adoptive therapy can endow tumor cells with aAPC characteristics, activate T cells at the same time, and reprogram tumor macrophages into anti-tumor phenotype. OV-4-1BBL/IL15 can stimulate the anti-tumor potential of TIL therapy in HCC, and possess broad clinical application prospects.

Interpersonal Psychotherapy for the Treatment of Depression in Parkinson's Disease: Results of a Randomized Controlled Trial.

Depression is a common nonmotor complication in Parkinson's disease (PD). However, few studies have evaluated the efficacy of first-line psychological therapies for depression in this patient population. This randomized controlled trial evaluated the efficacy of interpersonal psychotherapy (IPT), an empirically validated intervention for depression that focuses on the bidirectional relationship between mood disturbance and interpersonal and social stressors. A secondary aim was to assess maintenance of treatment gains at 6-month follow-up. Participants with PD stages I to III and a comorbid depressive disorder were randomly assigned to 12 sessions of IPT (n = 32) or supportive therapy (ST) (n = 31), our active control intervention. The primary outcome was the Hamilton Depression Rating Scale (HAM-D) administered blindly by telephone. Secondary outcomes included self-report depression and anxiety, quality of life, clinician-rated motor symptom, interpersonal relationships, and attachment style. IPT compared to ST resulted in a greater reduction in posttreatment HAM-D scores (least square mean difference = -3.77, 95% confidence interval [CI]: -6.19 to -1.34, P = 0.003) and was associated with a greater odds of meeting remission (odds ratio = 3.23, 95% CI: 1.10-9.51, P = 0.034). The advantage of IPT over ST on HAM-D scores and remission rates was not sustained at the 6-month follow-up. Both treatments improved self-report depression, anxiety, quality of life, and aspects of interpersonal functioning. This trial demonstrates the benefits of acute treatment with IPT in reducing depressive symptoms in PD. Clinicians should consider psychotherapy, alone or in combination with medication, as an important treatment option for PD depression. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

MAGE-A4 pMHC-targeted CAR-T cells exploiting TCR machinery exhibit significantly improved in vivo function while retaining antigen specificity

BackgroundThe development of chimeric antigen receptor (CAR)-T cell therapies for solid tumors has attracted considerable attention, yet their clinical efficacy remains limited. Therefore, various efforts have been made to improve...

Clinical outcomes of endovascular interventions for cerebral venous thrombosis in Japan: a nationwide retrospective study

IntroductionCerebral venous thrombosis (CVT) is a rare but serious disease. Despite anticoagulation being the cornerstone therapy, some patients experience worsening disease, necessitating alternative treatment. Endovascular treatment is an anticipated option...

Emerging Role of Extracellular pH in Tumor Microenvironment as a Therapeutic Target for Cancer Immunotherapy.

Identifying definitive biomarkers that predict clinical response and resistance to immunotherapy remains a critical challenge. One emerging factor is extracellular acidosis in the tumor microenvironment (TME), which significantly impairs immune cell function and contributes to immunotherapy failure. However, acidic conditions in the TME disrupt the interaction between cancer and immune cells, driving tumor-infiltrating T cells and NK cells into an inactivated, anergic state. Simultaneously, acidosis promotes the recruitment and activation of immunosuppressive cells, such as myeloid-derived suppressor cells and regulatory T cells (Tregs). Notably, tumor acidity enhances exosome release from Tregs, further amplifying immunosuppression. Tumor acidity thus acts as a "protective shield," neutralizing anti-tumor immune responses and transforming immune cells into pro-tumor allies. Therefore, targeting lactate metabolism has emerged as a promising strategy to overcome this barrier, with approaches including buffer agents to neutralize acidic pH and inhibitors to block lactate production or transport, thereby restoring immune cell efficacy in the TME. Recent discoveries have identified genes involved in extracellular pH (pHe) regulation, presenting new therapeutic targets. Moreover, ongoing research aims to elucidate the molecular mechanisms driving extracellular acidification and to develop treatments that modulate pH levels to enhance immunotherapy outcomes. Additionally, future clinical studies are crucial to validate the safety and efficacy of pHe-targeted therapies in cancer patients. Thus, this review explores the regulation of pHe in the TME and its potential role in improving cancer immunotherapy.

Integrin Targeting and Beyond: Enhancing Cancer Treatment with Dual-Targeting RGD (Arginine-Glycine-Aspartate) Strategies.

Integrins, an important superfamily of cell adhesion receptors, play an essential role in cancer progression, metastasis, and angiogenesis, establishing them as prime targets for both diagnostic and therapeutic applications. Despite their significant potential, integrin-targeted therapies have faced substantial challenges in clinical trials, including variable efficacy and unmet high expectations. Nevertheless, the consistent expression of integrins on tumor and stromal cells underscores their ongoing relevance and potential. Traditional RGD-based imaging and therapeutic agents have faced limitations, such as inconsistent target expression and rapid systemic clearance, which have reduced their effectiveness. To overcome these challenges, recent research has focused on advancing RGD-based strategies and exploring innovative solutions. This review offers a thorough analysis of the latest developments in the RGD-integrin field, with a particular focus on addressing previous limitations. It delves into new dual-targeting approaches and cutting-edge RGD-based agents designed to improve both tumor diagnosis and therapeutic outcomes. By examining these advancements, this review illuminates new pathways for enhancing the specificity and efficacy of integrin-targeted therapies, paving the way for more effective cancer diagnosis and treatment strategies.

Systemic and transcriptional response to intermittent fasting and fasting-mimicking diet in mice

BackgroundDietary restriction (DR) has multiple beneficial effects on health and longevity and can also improve the efficacy of certain therapies. Diets used to instigate DR are diverse and the corresponding response is not uniformly measured. We compared the systemic and liver-specific transcriptional response to intermittent fasting (IF) and commercially available fasting-mimicking diet (FMD) after short- and long-term use in C57BL/6 J mice.ResultsWe show that neither DR regimen causes observable adverse effects in mice. The weight loss was limited to 20% and was quickly compensated during refeeding days. The slightly higher weight loss upon FMD versus IF correlated with stronger fasting response assessed by lower glucose levels and higher ketone body, free fatty acids and especially FGF21 concentrations in blood. RNA sequencing demonstrated similar transcriptional programs in the liver after both regimens, with PPARα signalling as top enriched pathway, while on individual gene level FMD more potently increased gluconeogenesis-related, and PPARα and p53 target gene expression compared to IF. Repeated IF induced similar transcriptional responses as acute IF. However, repeated cycles of FMD resulted in blunted expression of genes involved in ketogenesis and fatty acid oxidation.ConclusionsShort-term FMD causes more pronounced changes in blood parameters and slightly higher weight loss than IF, while both activate similar pathways (particularly PPARα signalling) in the liver. On individual gene level FMD induces a stronger transcriptional response, whereas cyclic application blunts transcriptional upregulation of fatty acid oxidation and ketogenesis only in FMD. Hence, our comparative characterization of IF and FMD protocols renders both as effective DR regimens and serves as resource in the fasting research field.

Efficacy and Safety of Systemic Thrombolysis and Catheter-Directed Therapy in Pulmonary Embolism: A Narrative Review

Efficacy and Safety of Systemic Thrombolysis and Catheter-Directed Therapy in Pulmonary Embolism: A Narrative Review

Enhancing localized chemotherapy with anti-angiogenesis and nanomedicine synergy for improved tumor penetration in well-vascularized tumors

Intratumoral delivery and localized chemotherapy have demonstrated promise in tumor treatment; however, the rapid drainage of therapeutic agents from well-vascularized tumors limits their ability to achieve maximum therapeutic efficacy. Therefore, innovative approaches are needed to enhance treatment efficacy in such tumors. This study utilizes a mathematical modeling platform to assess the efficacy of combination therapy using anti-angiogenic drugs and drug-loaded nanoparticles. Anti-angiogenic drugs are included to reduce blood microvascular density and facilitate drug retention in the extracellular space. In addition, incorporating negatively charged nanoparticles aims to enhance diffusion and distribution of therapeutic agents within well-vascularized tumors. The findings indicate that, in the case of direct injection of free drugs, using compounds with lower drainage rates and higher diffusion coefficients is beneficial for achieving broader diffusion. Otherwise, drugs tend to accumulate primarily around the injection site. For instance, the drug doxorubicin, known for its rapid drainage, requires the prior direct injection of an anti-angiogenic drug with a high diffusion rate to reduce microvascular density and facilitate broader distribution, enhancing penetration depth by 200%. Moreover, the results demonstrate that negatively charged nanoparticles effectively disperse throughout the tissue due to their high diffusion coefficient. In addition, a faster drug release rate from nanoparticles further enhance treatment efficacy, achieving the necessary concentration for complete eradication of tumor compared to slower drug release rates. This study demonstrates the potential of utilizing negatively charged nanoparticles loaded with chemotherapy drugs exhibiting high release rates for localized chemotherapy through intratumoral injection in well-vascularized tumors.

Combination Effect of Radiotherapy and Targeted Therapy with NK Cell-Based Immunotherapy in head and Neck Squamous Cell Carcinoma

ABSTRACT Background Head and neck squamous cell carcinoma (HNSCC) has a poor prognosis, and current treatments are limited by high toxicity and low survival rates, highlighting the need for new therapeutic approaches. Natural killer (NK) cells can identify and eliminate cancer cells without prior antigen exposure. Radiotherapy directly targets tumors and increases activating ligands on tumor cells, promoting NK cell interactions. Cetuximab, an EGFR-targeting antibody, enhances NK cell cytotoxicity. Additionally, anti-PD-1 antibodies may further boost NK cell function by blocking inhibitory signals. The study aimed to enhance HNSCC treatment efficacy by combining radiotherapy and targeted therapy with expanded NK cells. Methods NK cells were isolated, activated, and expanded from healthy donors. The FaDu and SCC-47 cell lines were inoculated into NOD/SCID mice. The mice were treated with PD-1 inhibitors, cetuximab, and radiation, followed by intravenous injection of NK cells. Results Radiation increased ligands that regulate NK cell sensitivity. The combination of cetuximab, radiotherapy, and expanded NK cells significantly suppressed cancer progression and improved survival rates. However, adding anti-PD-1 antibodies did not further enhance outcomes. Conclusion This study suggests that a multimodal approach combining cetuximab, radiotherapy, and NK cells can significantly improve HNSCC therapy efficacy, offering a novel and promising treatment strategy.

Risk factors for lenvatinib-induced hypertension in patients with hepatocellular carcinoma: A retrospective study.

Lenvatinib mesylate (LEN) is an orally administered tyrosine kinase inhibitor used to treat various cancers, including hepatocellular carcinoma (HCC). LEN therapy for HCC is associated with a high incidence of adverse events, including hypertension (HTN). However, the risk factors associated with LEN therapy remain unclear. This study investigated the incidence of LEN-induced HTN (LENiHTN), and the relationship between HTN incidence and patient demographics in patients with HCC receiving LEN therapy. This was a single-centre, retrospective study of patients with HCC who received LEN therapy between 19 April 2018 and 30 September 2020. The observation period was from 1week before the start to 1month after the end of LEN administration. Seventy-five patients with HCC were enrolled. Any grade LENiHTN was found in 74.7% of patients. Among patients with LENiHTN, the use of 2 or more antihypertensive agents before starting LEN was less common (P=.007); serum potassium (K) and albumin-bilirubin score (ALBI) were lower (P=.013 and 0.038, respectively); and albumin (Alb) was higher (P=.025). The cut-off values of K, Alb and ALBI for HTN were estimated at 4.1mEq L-1, 3.1g dL-1 and -1.736, respectively. In the multivariable analysis, low K (adjusted HR: 2.078) and low ALBI (adjusted HR: 2.845) were independent risk factors for LENiHTN. Low K, high Alb and low ALBI were independent risk factors for LENiHTN. Systematic evaluation of HTN risk and early intervention for HTN prevention among high-risk patients can markedly enhance LEN therapy efficacy and use.

The Efficacy of Metacognitive Therapy on Social Avoidance and Distress, and Academic Persistence Among Students with Exam Anxiety

Background: Attendance in educational settings such as schools is often accompanied by varying levels of anxiety for many students. One of the most significant types of anxiety in educational environments is exam anxiety. Objectives: This study aimed to investigate the efficacy of metacognitive therapy on social avoidance, distress, and academic persistence among students with exam anxiety in 2023. Methods: This quasi-experimental study utilized a pretest-posttest design to assess the efficacy of metacognitive therapy for female students with exam anxiety. All female second-grade high school students in Ahvaz city who reported experiencing exam anxiety during the 2022 - 2023 academic year were included in the study sample. A purposive sample of 36 female students was randomly divided into two groups: An experimental group receiving metacognitive therapy and a control group. The experimental group participated in seven 60-minute sessions of metacognitive therapy, conducted twice a week. The control group did not receive any intervention during the study period. The Social Avoidance and Distress Scale (SADS) and Academic Persistence Scale (APS) were administered to both groups before and after the intervention. Data were analyzed using analysis of covariance to control for baseline differences. Results: Metacognitive therapy was effective in reducing social avoidance and distress, as well as in improving academic persistence in high school students (P &lt; 0.001). Specifically, the mean social avoidance and distress score decreased significantly from 19.67 ±1.68 to 10.11 ±2.13 in the metacognitive therapy group. Additionally, the mean academic persistence score increased significantly from 9.39 ±1.78 to 23.72 ±3.10 in the metacognitive therapy group. Conclusions: Metacognitive therapy effectively reduced social avoidance and distress while increasing academic persistence in female students with exam anxiety. This study highlights the therapy's potential as a valuable intervention for improving the overall well-being and academic performance of students facing similar challenges.