Efficacy Of Treatment Research Articles

Comparison of Long-Term Outcomes in Patients with Supratentorial Spontaneous Intracerebral Hemorrhage Treated with and without Surgical Intervention.

Intracerebral hemorrhage (ICH) is associated with high mortality and morbidity. Uncertainty still exists regarding the benefit of surgery in the management of supratentorial spontaneous ICH (sICH), especially of the basal ganglia and thalamus. Studies have not shown the clinical benefit of early surgical management compared to best medical management plus delayed surgery, when necessary. Our aim was to compare the efficacy of different neurosurgical interventions with best medical management and best medical management alone. We conducted a single-center, retrospective study at a tertiary care center in India in sICH patients between January 2015 and December 2022. The primary outcome was functional disability evaluated by the modified Rankin Scale (mRS) at 3, 6, and 12 months. Time-to-event outcomes were compared using the Kaplan-Meier curve. Among 2600 stroke patients screened, 661 had sICH. Median age was 55 years, and 250 patients (37.8%) underwent neurosurgical intervention. The most common intervention was craniotomy and hematoma evacuation. The median mRS at discharge and follow-up at 3, 6, and 12 months was lower in the conservatively managed group (4, 3, 3, and 3, respectively) compared to the surgical intervention group (5, 5, 5, 4, respectively). However, the ICH score at admission was lower in the conservatively managed group and after adjustment for ICH score, there was no statistically significant difference between the two. Among the interventions, patients undergoing decompression craniectomy had the best functional outcome. Neurosurgical intervention was not associated with better functional outcome when compared to conservative management.

Escherichia coli combination with PD-1 blockade synergistically enhances immunotherapy in glioblastoma multiforme by regulating the immune cells

BackgroundGlioblastoma multiforme (GBM) is the most common and aggressive primary intracranial malignancy. It is characterized by insufficient infiltration of anti-tumor T lymphocytes within the tumor microenvironment (TME), rendering it an “immune cold” disease. This immune deficiency results in poor responses to immune checkpoint blockade (ICB) therapies. Recent studies have demonstrated that bacteria can proliferate within tumors and activate immune responses. Therefore, in this study, we employed Escherichia coli (E. coli) in combination with anti-PD-1 antibodies to treat GBM, with the aim of exploring the immune-activating potential of E. coli in GBM and its synergistic effect on anti-PD-1 therapy.MethodsThe E. coli and anti-PD-1 antibody therapy were administered intravenously and intraperitoneally, respectively. Complete blood cell count, blood biochemical analysis, hematoxylin and eosin (H&E) staining, and agar plate culture were employed to evaluate the biosafety and tumor-targeting capability of E. coli. ELISA kits were used to detect innate immune cytokines. Flow cytometry and immunofluorescence staining were used to investigate T cells. Tumor volume of tumor-bearing mice was recorded to evaluate the combined treatment efficacy. H&E staining and immunofluorescence staining were used to observe the tumor inhibition markers.ResultsE.coli can specifically target into the tumor region, and activate the innate immune response in mice. Immunofluorescence staining and flow cytometry results demonstrated that the combination treatment group exhibited a significant upregulation of cytotoxic CD8+ T cells and a marked suppression of regulatory T cells compared to the control group. The expression of Ki67 was significantly downregulated, and TUNEL staining revealed an increased number of apoptotic cells in the combination treatment group. Furthermore, the tumor growth rate in the combination treatment group was significantly slower than that in the control group.ConclusionsE. coli exhibits potential anti-tumor activity and can activate the innate immune response and further regulate immune cells in the tumor tissues to synergize the effect of anti-PD-1 therapy on GBM, providing new insights to enhance the efficacy of GBM immunotherapy.

Evaluation of the Anti-Leishmanial Activity of the Hydroalcoholic Extract of Green Algae (Spirogyra): Investigation of Weight Indicators (Lesion Size and Organ Weights) in BALB/c Mice.

Leishmaniasis remains a significant global health concern, ranking among the top ten infectious diseases and causing substantial mortality and socioeconomic burden. Effective and accessible treatments are needed. This study investigated the potential of a hydroalcoholic extract from readily available urban green algae as an anti-leishmanial agent, focusing on its impact on key weight-related indicators of Leishmania major infection in BALB/c mice. To evaluate the in vivo anti-leishmanial activity of the hydroalcoholic extract from the common green algae genus Spirogyra against Leishmania major in BALB/c mice, specifically by assessing its effects on weight loss, lesion size, liver weight, and spleen weight-key indicators of disease progression. Spirogyra algae were collected and identified in Yazd Province, Iran. A hydroalcoholic extract was prepared and administered via intraperitoneal injection into Leishmania major-infected BALB/c mice at doses of 3, 6, and 12mg/kg/day, starting after lesion development. The control groups included untreated infected mice (negative control), healthy uninfected mice (control), and infected mice treated with Glucantime (positive control). We assessed treatment efficacy by monitoring weight loss, lesion diameter, liver weight, and spleen weight. Treatment with the highest concentration of Spirogyra extract (12mg/kg/day) significantly mitigated weight loss in infected mice, demonstrating comparable efficacy to Glucantime. Both the 12mg/kg/day algae extract and Glucantime significantly controlled lesion growth. Importantly, both treatments significantly reduced liver and spleen weight compared with the negative control group, indicating a reduction in organomegaly. Specifically, the negative control and 3mg/kg extract groups exhibited the highest liver weights, whereas the negative control group showed significantly higher spleen weights than the other groups. The 12mg/kg extract and Glucantime groups showed liver and spleen sizes comparable to the healthy control group, demonstrating effective control of organ size changes associated with leishmaniasis. The hydroalcoholic extract of urban Spirogyra green algae, particularly at a dose of 12mg/kg/day, exhibited significant in vivo anti-leishmanial activity in BALB/c mice. Evaluated through weight indicators such as reduced weight loss, controlled lesion growth, and normalized liver and spleen weights, the extract showed promise in mitigating the detrimental effects of Leishmania major infection and warrants further investigation as a potential source for novel anti-leishmanial therapeutics.

Understanding Cognition, Oxytocin, and Pain in Elders (UCOPE): protocol for a double-blinded cross-over trial in chronic knee osteoarthritis pain

BackgroundOsteoarthritis (OA) is the leading cause of disability among older adults with the knee being the most affected joint. Specifically, there is an urgent need to develop better analgesics for individuals with OA-related pain, since currently used analgesics frequently fail to provide adequate relief or must be discontinued owing to adverse effects. A promising treatment is the neuropeptide oxytocin (OT), which has been shown to play a role in endogenous analgesia with human and animal studies demonstrating anti-nociceptive effects. The primary aims of the study are to examine preliminary analgesic effects of a chronic OT intervention in community-dwelling older individuals with chronic knee osteoarthritis pain.MethodsIn this article, we describe the rationale and design of the Understanding Cognition, Oxytocin, and Pain in Elders (UCOPE) study, a double-blinded intervention in which 80 participants over 45 years of age with knee osteoarthritis pain will be recruited to participate in a cross-over trial of 4 weeks of intranasal oxytocin or placebo administration. Primary study outcomes include preliminary changes in pain intensity and interference as well as multi-modal assessment batteries including circulating biomarkers and neuroimaging measures. Self-reported and quantitative outcomes will be assessed at baseline, post-intervention periods, and up to a 6-month follow-up period.DiscussionThis study will establish preliminary effectiveness of a novel intervention in middle to older aged adults with knee osteoarthritis pain. Achievement of these aims will provide a rich platform for future intervention research targeting improvements in pain and disability among geriatric populations and will serve as a foundation for a fully powered trial to examine treatment efficacy and potential mechanisms of the proposed intervention.Trial registrationClinicalTrials.gov NCT03878589. Registered on March 18th, 2019.

The Current State of Breast Cancer Genetics in Populations of African Ancestry

Breast cancer (BC) constitutes a significant global health burden, particularly among women, with disparities observed across populations. Notably, women of African ancestry often experience BC at earlier ages and in more aggressive forms, with a higher prevalence of metastasis. Genetic studies, including those focused on BRCA1 and BRCA2 genes, have revealed population-specific variations in BC susceptibility. Despite efforts to investigate BC genetics in African and African-descendant populations, research remains limited compared to studies conducted in populations of European descent. Socioeconomic factors further compound the challenges faced by marginalized populations, influencing disease outcomes and treatment efficacy. This review explores the BC literature in African and African-descendant populations, highlighting population-specific genetic variants associated with the disease’s subtypes, treatment response, and disease evolution. Limited sample sizes and lack of data on genetic ancestry hinder the development of precise risk stratification and treatment strategies. Efforts to expand research, improve data collection, and enhance genetic analyses in diverse populations are crucial steps toward addressing racial disparities and advancing BC care on a global scale.

Analysis of efficacy of picosecond laser treatment for nevus of Ota.

To analyze the efficacy, safety, and influencing factors of 1064nm picosecond Nd: YAG laser(PSAL)treatment for Nevus of Ota. From January 2018 to March 2024, 212 patients with Nevus of Ota were treated with 1064nm picosecond Nd: YAG laser at the Guangzhou Dermatology Hospital. The study analyzed the impact of patient gender, age, Tanino classification of skin lesions, color of skin lesions, Fitzpatrick classification of skin, and number of treatments on efficacy, while also documenting any adverse reactions to the treatment. Overall, out of the 212 patients who underwent 1 to 11 treatment sessions, 80 cases (37.73%) achieved complete clearance, 42 cases (19.81%) showed excellent outcomes, 45 cases (21.22%) had good outcomes, 37 cases (17.45%) saw fair outcomes, and 8 cases (3.77%) had minimal effect, resulting in an overall effective rate of 78.77%. The study revealed a correlation between treatment efficacy, age, and the number of laser treatments (P < 0.05). Multifactorial logistic regression analysis demonstrated a positive association with treatment effectiveness (odds ratio 3.324; 95% confidence interval 2.110-5.238). Other variables such as gender, Tanino classification of skin lesions, color of skin lesions, and Fitzpatrick skin type showed no significant correlation with efficacy (P > 0.05). Among the patients, two experienced temporary post-inflammatory effects, while three exhibited folliculitis. Notably, there were no reported cases of persistent erythema, scarring, or hypopigmentation. The treatment of Nevus of Ota using 1064nm picosecond Nd: YAG laser has been demonstrated to be both safe and effective, with treatment efficacy impacted by patient age and the number of treatment sessions. Early intervention and higher frequency of treatment sessions are associated with improved treatment outcomes.

What Prognostic Indicators and Treatment Mechanisms Exist for Efficacious Treatments in People With Patellofemoral Pain? A Secondary Meta-Regression With an Updated Search

OBJECTIVE: To investigate the prognostic and mechanistic variables associated with efficacious treatments in people with patellofemoral pain (PFP). DESIGN: Updated intervention systematic review with de novo meta-regression. LITERATURE SEARCH: We searched MEDLINE, Web of Science, and Scopus from inception until October 2023 for randomised controlled trials (RCTs) involving people with PFP. STUDY SELECTION CRITERIA: High-quality RCTs (scoring ≥7 on the PEDro scale) involving participants with PFP and at least one treatment arm involving an efficacious intervention. DATA SYNTHESIS: We extracted homogenous pain and function data to calculate effect sizes to regress with baseline prognostic (e.g., symptom duration) and mechanistic (e.g., strength change) data. RESULTS: Thirty-four high-quality RCTs involving 1,526 people with PFP were included. For knee-targeted exercise, we identified symptom duration (R2 = 0.68), older age (R2 = 0.31), and low baseline knee extensor strength (R2= 1.0) as significant prognostic variables. For hip-and-knee-targeted exercise, we identified older age (R2= 0.37), greater mass (R2= 0.28), and greater baseline hip abduction torque (R2= 1.0) as significant prognostic variables. We also identified a significant mechanistic association between pain and increased knee extensor torque (R2= 0.99). For hip-targeted exercise, we identified lower height as a significant prognostic variable (R2= 0.96-0.99) and a significant mechanistic association between both pain and function and increased hip abduction (R2= 0.93-0.96) and hip external rotation (R2= 0.96-0.97) strength. CONCLUSIONS: Prolonged symptom duration, older age, and greater mass are prognostic variables for people with PFP. Increasing hip and knee muscle strength may be mechanisms underpinning positive responses to exercise therapy.

A Brief Biofeedback Training, Integrated with Breathing and Relaxation Exercises, in Treating Tinnitus Disorders within Routine Medical Care.

Tinnitus, a distressing condition, significantly impacts psycho-social functioning. While medical interventions have been the norm for treating tinnitus, few studies have explored the efficacy of psychological treatments and their enduring effects. This study aims to evaluate the effectiveness of a brief biofeedback training program in alleviating perceived tinnitus handicap severity over a 3-month follow-up period. Engaging 431 tinnitus outpatients from a medical center, the study allocated the control group to treatment as usual, involving monthly visits to an otolaryngologist and specific pharmacological interventions. Concurrently, the experimental group participated in a brief biofeedback training, using Procomp Infinity by Thought Technology Ltd., an eight-channel computer-operated encoder, integrated with breathing and relaxation exercises. No biofeedback booster sessions were provided to the experimental group during the 3-month follow-up period. Changes in tinnitus severity were assessed using the Tinnitus Handicap Inventory (THI). The analysis, conducted via ANCOVA, demonstrated that biofeedback, integrated with relaxation training and breathing exercises, had a positive impact on both the follow-up THI total score and its three sub-scales (Functional, Emotional, Catastrophic). Notably, the experimental group displayed reduced psycho-physiological parameters in all aspects compared to their baseline measurements at 3-month follow-up. This study's findings underline the effectiveness of non-pharmacological intervention in treating tinnitus. It had a positive impact on the emotional, functional, and physical dimensions of daily life affected by tinnitus.

Osteosarcoma Cells and Undifferentiated Human Mesenchymal Stromal Cells Are More Susceptible to Ferroptosis than Differentiated Human Mesenchymal Stromal Cells

Current research suggests that promoting ferroptosis, a non-apoptotic form of cell death, may be an effective therapy for osteosarcoma, while its inhibition could facilitate bone regeneration and prevent osteoporosis. Our objective was to investigate whether the susceptibility to and regulation of ferroptosis differ between undifferentiated (UBC) and differentiated (DBC) human bone marrow stromal cells, as well as human osteosarcoma cells (MG63). Ferroptosis was induced by either inhibiting glutathione peroxidase 4 (GPX4) using RSL3 or blocking all glutathione-dependent enzymes through inhibition of the glutamate/cysteine antiporter with Erastin. Lipid peroxidation was assessed using the fluorescent probe BODIPY™581/591C11, while Ferrostatin-1 was used to inhibit ferroptosis. We demonstrate that neither Erastin nor RSL3 induces ferroptosis in DBC. However, both RSL3 and Erastin induce ferroptosis in UBC, while Erastin predominantly induces ferroptosis in MG63 cells. Our data suggest that ferroptosis induction in undifferentiated hBMSCs is primarily regulated by GPX4, whereas glutathione S-Transferase P1 (GSTP1) plays a key role in controlling ferroptosis in osteosarcoma cells. In conclusion, targeting the key pathways involved in ferroptosis across different bone cell types may improve the efficacy of cancer treatments while minimizing collateral damage and supporting regenerative processes, with minimal impact on cancer therapy.

Impact of Single-Incision Sling Placement on Female Sexual Function in Women with Stress Urinary Incontinence.

Stress urinary incontinence (SUI) is a common condition among women of childbearing age, often requiring surgical intervention. The midurethral sling (MUS), including first-generation tension-free vaginal tapes (TVT) and second-generation transobturator tapes (TOT, TVT-O), has long been the standard treatment. However, both approaches have associated risks, prompting the development of single-incision slings (SIS) as a third option. SIS have proven their efficacy in SUI treatment, but the impact of these slings on female sexual function specifically remains underexplored. A literature search was conducted using PubMed using the keywords "stress urinary incontinence," "midurethral slings," "single-incision slings," "female sexual function," and "dyspareunia." The reviewed studies demonstrated that SIS generally maintain or improve sexual function postoperatively, but with varying impact on specific aspects of sexual function. While coital urinary incontinence often improved or resolved, new or worsened dyspareunia was reported in a significant number of patients. SIS placement for SUI generally preserves or enhances sexual function, though individual aspects, such as dyspareunia, may worsen for some patients. Given that an important goal of SUI treatment is to improve quality of life, it is crucial to identify preoperative factors that will identify patients at risk of developing dyspareunia after surgery or are more likely to experience an improvement in sexual function. Further research is needed to better understand these predictors and optimize surgical outcomes for women undergoing SUI treatment with SIS.

Antibody-Dependent Cellular Cytotoxicity of iPS Cell-Derived Natural Killer T Cells by Anti-GD2 mAb for Neuroblastoma.

While antibody-dependent cellular cytotoxicity (ADCC) by anti-disialoganglioside GD2 monoclonal antibody (mAb) has succeeded in increasing the survival rate of high-risk patients with neuroblastoma, approximately 40%-50% of patients die from the disease. Recently, we developed induced pluripotent stem cell-derived natural killer T (iPS-NKT) cells, which exhibit NK-like cytotoxicity. However, whether iPS-NKT cells can induce ADCC function is unclear. Here, we investigated the ADCC of iPS-NKT cells and the efficacy of the combination treatment of anti-GD2 mAb and iPS-NKT cells against neuroblastoma. Anti-GD2 mAb enhanced the cytotoxicity and secretion of cytokines and cytotoxic granules of iPS-NKT cells, which expressed CD16 to GD2-expressing neuroblastoma cell lines. We also examined which Fcγ receptors contribute to ADCC of iPS-NKT cells. CD16 stimulation against iPS-NKT cells caused cytotoxicity and secretion of interferon-gamma, tumor necrosis factor, and granzyme B. In contrast, CD32 and CD64 stimulation did not. Invivo, the intratumor administration of anti-GD2 mAb and iPS-NKT cells significantly inhibited tumor growth compared with the other treatment groups: no treatment, anti-GD2 mAb alone, and iPS-NKT cells alone. In conclusion, iPS-NKT cells exhibit CD16-mediated ADCC, and the addition of iPS-NKT cells to anti-GD2 mAb therapy may be a potential approach for immunotherapy against neuroblastoma.

Weight Management for Fertility-Preservation Therapy in Endometrial Cancer: Opportunities and Challenges.

Obesity is increasingly recognized as a significant factor impacting the outcomes of fertility-preserving therapies for endometrial cancer (EC). This review explores the effects of glycolipid metabolism on EC and its relationship with body weight. We will examine how excess body weight influences the effectiveness of fertility-preserving treatments and discuss potential mechanisms for effective weight management. Additionally, the review highlights the importance of comprehensive weight management as an adjunct strategy to enhance the efficacy of fertility-preserving interventions, providing insights into how to integrate metabolic health into clinical treatment protocols. Weight management can modify the tumor microenvironment by depriving the tumor of nutrients, whereas exercise can enhance immunity, potentially leading to tumor cell death. In addition, progesterone therapy may impede the proliferation of EC cells. Comprehensive weight management can serve as an essential adjuvant treatment for patients undergoing fertility-preserving therapies for EC. In this review, we highlight that comprehensive weight management can serve as a crucial adjuvant treatment for patients undergoing fertility-preserving therapies for endometrial cancer. Targeting glycolipid metabolism and addressing adiposity can improve hormonal balance, reduce inflammation, and enhance fertility outcomes. Further research is necessary to establish specific protocols and evaluate the effectiveness of these strategies in clinical practice.

Enhanced Photothermal Tumor Ablation Using Polypyrrole-Gold Nanocomposites Activated by Polarized Polychromatic Low-Energy Light: An InVivo Study.

Photothermal therapy (PTT) offers a minimally invasive approach for cancer treatment, using light energy to selectively heat and destroy cancer cells. Success in PTT depends on efficient, stable, and biocompatible photothermal agents. This study investigates polypyrrole@gold nanocomposites (PPy@Au NCs) as photothermal agents combined with polarized polychromatic low-energy light (PPLEL) to target tumors and limit disease progression. Invivo experiments on Ehrlich carcinoma-bearing female Swiss albino mice demonstrated that PPy@Au NCs selectively accumulated in tumor tissue and, when activated by PPLEL, generated sufficient heat for effective tumor ablation. This approach enhanced treatment efficacy and presented a cost-effective solution due to the affordability of both the nanocomposite and light source. Histopathological analysis confirmed significant tumor reduction, suggesting that this synergistic combination offers a promising cancer treatment strategy. Findings support further research and potential clinical applications in photothermal cancer therapy.

Synergistic action of mucoactive drugs and phages against Pseudomonas aeruginosa and Klebsiella pneumoniae.

N-acetylcysteine (NAC) and ambroxol hydrochloride (AMB) are commonly prescribed alongside antibiotics to alleviate sputum retention in lower respiratory tract infections, which are often caused by bacterial pathogens. With the rising threat of antibiotic resistance, phage therapy has emerged as a promising alternative alongside. However, no studies have explored the potential interactions between phages and these mucoactive agents despite their frequent concurrent use during phage therapy. Therefore, investigating the potential synergy and its subsequent impact on phage infection dynamics could enhance clinical strategies for treating bacterial infections with phages. Our study utilized Pseudomonas aeruginosa strain ZS-PA-35 and Klebsiella pneumoniae strain Kp36, alongside their respective phages, to investigate their interactions in the presence of NAC or AMB. Our findings indicate that, under specific conditions, these mucoactive agents can function as adjuvants to lytic phages, enhancing bacterial susceptibility to phage infection and facilitating subsequent phage proliferation. Our study revealed that these synergistic interactions are strongly influenced by the physiological characteristics of the phages, the surrounding microenvironments, and the physiology of host tissues, as varying outcomes of phage-host interactions were observed among different phages and across distinct media. Taken together, our results emphasize the complexity of interactions between phages and NAC or AMB, underscoring the need for caution when using combination treatments.IMPORTANCEN-acetylcysteine (NAC) and ambroxol hydrochloride (AMB) are used in medical treatment of patients with acute and chronic bronchitis. Often, the choice of NAC or AMB is empirically determined by physicians. However, the potential impact of combining NAC or AMB with phage therapy remains unclear. To address this gap, a comprehensive understanding of their interplay is crucial to determine any potential synergistic effects. This study aims to elucidate how NAC or AMB influence phages targeting different receptors, thereby affecting their antibacterial activity against Pseudomonas aeruginosa and Klebsiella pneumoniae. Our results suggest that, under certain conditions, NAC or AMB provides an adjuvant effect by rendering the cells more susceptible to phage infection. These results contribute to advancing our understanding of the clinical combination of mucoactive agents and phage therapy, offering insights for optimizing treatment efficacy.

Modeling critical dosing strategies for stromal-induced resistance to cancer therapy

Complex interactions between stromal cells, tumor cells and therapies can influence environmental factors that in turn impact anticancer treatment efficacy. Disentangling these phenomena is critical for understanding treatment response and designing effective dosing strategies. We propose a mathematical model for a common tumor-stromal interaction motif where stromal cells secrete factors that promote drug resistance. We demonstrate that the presence of this interaction modulates the therapeutic dose window of efficacy and can lead to nonmonotonic treatment response. We consider combination strategies that target stromal cells and their secretome, and identify strategies that constrain drug concentrations within the efficacious window for long-term response. We explore an experimental dataset from colorectal cancer cells treated with anti-EGFR targeting therapy, cetuximab, where cancer-associated fibroblasts increase epidermal growth factor secretion under treatment. We apply our general approach to identify a critical drug concentration threshold and study effective dosing regimens for single-drug and combination therapies.

Relevant markers for overactive bladder laser therapy: nitric oxide and urinary nerve growth factor

To investigate the potential of nitric oxide (NO) and urinary nerve growth factor (NGF) as indicators of therapeutic outcomes in overactive bladder (OAB) patients undergoing low-level laser therapy (LLLT) via a prospective randomized controlled trial. Fifty OAB patients participated in the study and were subjected to LLLT using 650-nm laser irradiation. The study employed a prospective randomized controlled trial design. Nitric oxide and urine NGF levels were assessed before and after the LLLT intervention to evaluate their correlation with therapeutic outcomes. The study provided evidence supporting the effectiveness of LLLT as a treatment modality for OAB. Analysis of NO and urine NGF levels revealed significant changes following LLLT intervention suggesting their potential as biomarkers for assessing therapeutic response in OAB patients. These biomarkers hold promise for aiding clinicians in evaluating treatment response and personalizing therapy approaches for OAB patients. This study highlights the utility of LLLT in managing OAB and underscores the importance of exploring biomarkers such as nitric oxide and urinary nerve growth factor to enhance treatment efficacy assessment. The findings suggest that NO and urine NGF levels may serve as valuable indicators of therapeutic outcomes in OAB patients undergoing LLLT. Further research is warranted to elucidate the underlying mechanisms and optimize the clinical application of LLLT in OAB management.

Imaging in clinical trials for psoriatic arthritis: a scoping review.

Psoriatic arthritis (PsA) is a chronic inflammatory condition principally affecting the skin and musculoskeletal system, associated with comorbidities and decreased quality of life. Imaging is crucial for diagnosis, monitoring progression, and evaluating treatment efficacy; therefore, it plays an important role in PsA clinical trials. In this review, we aimed to characterize how imaging modalities and advances in imaging techniques are being used specifically in the PsA clinical trial literature. Following the Arksey and O'Malley framework for scoping reviews, we conducted a comprehensive search of multiple literature databases, from January 1, 2000, to June 27, 2024. We captured 1961 articles and after deduplication, title and abstract screening, and full-text review, 53 studies were included. Radiographs were the most used imaging modality (n = 32/53, 60%), and radiographic progression was frequently measured using the PsA-modified Sharp/van der Heijde score. MRI (n = 16/53, 30%) was used in evaluating peripheral and axial disease, with more recent adoption of validated scoring systems (PsAMRIS and SPARCC). Ultrasound (n = 11/53, 21%), including power Doppler, was used to assess soft tissue inflammation. Standardized scoring systems (e.g. GLOESS) were used in a minority of ultrasound-based studies. Multimodality imaging (n = 7/53, 13%) and CT (n = 2/53, 4%) was uncommon. The development of PsA-specific scoring systems for radiographs and MRI has been instrumental in advancing imaging assessment in PsA. However, their application remains limited, particularly in ultrasound, where further standardization is needed. Future clinical trials should focus on increasing the adoption of PsA-specific scoring systems, exploring advanced techniques (e.g. DCE-MRI), and multi-modal imaging to improve PsA disease monitoring.

Capturing the Additional Cardiovascular Benefits of SGLT2 Inhibitors and GLP-1 Receptor Agonists Beyond the Control of Traditional Risk Factors in People with Diabetes.

This study aimed to quantify the additional cardioprotective effects of sodium-glucose cotransporter 2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) beyond the traditional risk factors control in individuals with type 2 diabetes (T2D). This helps calibrate the BRAVO diabetes simulation model to capture the total cardiovascular benefits of new diabetes medications accurately. We extracted patient characteristics and treatment efficacy data from four cardiovascular outcomes trials (CVOTs) of SGLT2is and four CVOTs of GLP-1RAs completed before May 2023. Using the BRAVO diabetes simulation model, we translated reductions in traditional risk factors (i.e., glycated hemoglobin; systolic blood pressure; low-density lipids; body mass index) from the newer drugs into risk reductions in cardiovascular outcomes (i.e., myocardial infarction (MI), stroke, congestive heart failure (CHF), and mortality) assuming the drug-associated risk reductions are only driven by traditional risk factors. Then we compared the simulated risk-factor-driven risk reductions of cardiovascular outcomes with observed risk reductions from the trials and calculated drug-specific incremental benefits (DIB). After accounting for the cardiovascular effects from traditional risk factors control, SGLT2is was associated with an additional 19% risk reduction in CHF (DIB: 0.81, 95% CI: 0.72-0.90). Furthermore, the uncalibrated model predicted a risk reduction in stroke with SGLT2is, which was not observed in CVOTs. This discrepancy highlights the need for an SGLT2i-specific calibrator to align the simulation results with the observed outcomes. In contrast, no additional cardiovascular benefit was associated with GLP-1RAs after controlling for traditional risk factors. Our study revealed that SGLT2is could further reduce CHF risks beyond the control of traditional risk factors but may offer additional pathways to offset overall benefits from traditional risk factor control in stroke risks. No additional cardiovascular benefits were observed for GLP-1RAs beyond traditional risk factor control. The BRAVO model calibration enhances cardiovascular outcome prediction with these newer antidiabetic therapies.

Multifunctional nanodrug for simultaneously combating chemoresistance and immunosuppression in Fusobacterium nucleatum-associated colorectal cancer.

Fusobacterium nucleatum (Fn) infection in colorectal cancer (CRC) induces chemoresistance and creates an immunosuppressive tumor microenvironment, compromising the efficacy of conventional chemotherapy. To address these challenges, a multifunctional MPLO@HA nanodrug was developed by conjugating metformin (Met), oxaliplatin (OxPt), and lauric acid (LA) onto oligomethyleneimine, subsequently complexed with hyaluronic acid (HA). The MPLO@HA nanodrug is designed to target Fn-infected CRC, offering multiple mechanisms for enhanced therapeutic outcomes. The nanodrug features a multi-stimuli responsive structure that enables precise and controlled release at the tumor site, responsive to pH, glutathione, and hyaluronidase levels. The enhanced positive charge of self-assembled nanodrug combined with Met effectively eradicates both extracellular and intracellular Fn, overcoming Fn-induced chemoresistance. Furthermore, incorporating Met improves the efficacy of chemotherapy by sensitizing CRC cells to treatment. The immunomodulatory properties of the MPLO@HA nanodrug promote immunogenic cell death, repolarize macrophages from the M2 to the M1 phenotype, and reduce the levels of regulatory T cells and myeloid-derived suppressor cells. By integrating antimicrobial, chemotherapeutic, and immunomodulatory capabilities, the MPLO@HA nanodrug offers a promising and comprehensive approach to combating Fn-induced chemoresistance and immunosuppression in CRC. This strategy could also provide a foundation for developing treatments for other cancers associated with bacterial infections. STATEMENT OF SIGNIFICANCE: Fusobacterium nucleatum (Fn) infection in colorectal cancer (CRC) induces chemoresistance and creates an immunosuppressive tumor microenvironment, severely compromising treatment efficacy. Current therapies face challenges in addressing these issues due to the complex interactions between bacterial infection and tumor development. Our study introduces a multifunctional nanodrug, MPLO@HA, which integrates metformin, oxaliplatin, lauric acid, and hyaluronic acid into a multi-responsive nanodrug system. This nanodrug simultaneously combats bacterial infection, chemoresistance, and immunosuppression in Fn-associated CRC. MPLO@HA demonstrates synergistic effects by eradicating both extracellular and intracellular Fn, enhancing chemosensitivity, and modulating the tumor immune microenvironment. This comprehensive approach offers a promising strategy to overcome Fn-induced treatment barriers, potentially improving outcomes for patients with Fn-infected CRC and opening new avenues in bacteria-associated cancer therapy.

Interactions Between Mesenchymal Stem Cells and Microorganisms: Unraveling the Paradox for Enhanced Mesenchymal Stem Cell-Based Therapy.

Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic tool in stem cell-based therapy due to their immunomodulatory or regenerative characteristics. Nowadays, controlled application of nonpathogenic bacterial cells and their derivatives has shown promise in preconditioning and manipulating MSC behavior. This approach is being explored in various fields, including immunotherapy, tissue engineering, and cell therapy. However, recent discoveries have elucidated the complex interactions between MSCs and microorganisms, especially bacteria and viruses, raising concerns regarding the utility of MSCs in clinical applications. In this review, we discussed the interactions between MSCs and microorganisms and highlighted both positive and negative aspects. We also examined the use of bacterial-derived compounds in MSCs-mediated interventions. The balanced colonization of the microbiome in organs, such as the oral cavity, not only does not hinder therapeutic interventions but also could be crucial for achieving desirable outcomes. On the contrary, disturbances in the microbiome have been found to disturb the biological potential of MSCs, such as migration, osteogenic differentiation, and cell proliferation. Evidence also suggests that commensal bacteria, following certain interventions, can transition to a pathogenic state when interacting with MSCs, leading to acute inflammation. Indeed, the maintenance of homeostasis through various approaches, such as probiotic application, results in an optimal equilibrium during MSCs-based therapies. However, further investigation into this matter is imperative to identify efficacious interventions.