Assessment Of Clinical Efficacy Research Articles

Efficacy of verdinexor for the treatment of naïve canine epitheliotropic cutaneous T-cell lymphoma: An open-label pilot study.

Verdinexor (Laverdia-CA1; Dechra Veterinary Products), a selective inhibitor of nuclear export, has been utilised for treatment of non-Hodgkin T-cell lymphoma in dogs. However, the efficacy of verdinexor has not been evaluated for cutaneous epitheliotropic T-cell lymphoma (CETL). To evaluate the efficacy of verdinexor for the treatment of CETL. Eight client-owned animals with CETL. Patients received between 1.28 and 1.45 mg/kg verdinexor per os twice weekly with a minimum of 72 h between doses until disease progression or voluntary withdrawal. Adjunctive therapy with lokivetmab or prednisone was permitted after Day (D)14. Assessment of clinical lesions (canine Response Evaluation Criteria in Solid Tumors [cRECIST v1.0] and novel Canine Epitheliotropic Lymphoma Extent and Severity Index [CELESI]), pruritus (Visual Analog Scale) and treatment efficacy (owner global assessment of treatment efficacy [OGATE]) were evaluated every 14 days for 3 months, then monthly thereafter (mean 70 ± 43.4 days). Seventy-five percent of patients achieved complete response, partial response or stable disease. The mean time to disease progression was 56 ± 41 days. There was a significant reduction (p = 0.026) in total CELESI score when the lowest score for each dog was compared to their score at D0. Verdinexor did not significantly reduce pruritus at any time point (p = 0.45), including when given as a monotherapy or concurrently with lokivetmab ± glucocorticoids. On D28, 75% of owners rated response to treatment as 'fair' to 'excellent'. The most common adverse effects included weight loss, inappetence, vomiting and lethargy. Verdinexor could be considered a safe, palliative treatment for canine CETL.

Improvement in symptoms of Rett syndrome with trofinetide beyond clinical trial efficacy assessments: case reports

Improvement in symptoms of Rett syndrome with trofinetide beyond clinical trial efficacy assessments: case reports

Percutaneous endoscopic interlaminar discectomy for high-grade migrated lumbar disc herniation: clinical efficacy and safety assessment.

This study aimed to assess the clinical effectiveness and safety of percutaneous endoscopic interlaminar discectomy (PEID) in the management of high-grade migrated Lumbar disc herniation (LDH). A total of 328 patients who underwent PEID for high-grade migrated LDH between May 2020 and January 2023 in our hospital were selected. Patients were categorized into high-grade migrated group and low-grade migrated group according to preoperative MRI findings. The preoperative and postoperative evaluations of clinical outcomes, such as Visual Analogue Scale (VAS) for lower backs and legs, Oswestry Disability Index (ODI), and modified MacNab criteria for surgical success, were compared between groups. No statistically significant differences were found in hospitalization time, surgery time, intraoperative hemorrhage, number of intraoperative fluoroscopies, or incision length between the two groups. The lower back and leg VAS scores and ODI exhibited a statistically significant decrease in both groups across all postoperative time intervals. However, the difference between the two groups was not statistically significant. Postoperative nerve root stimulation symptoms were reported in two and three cases in the high-grade migrated group and low-grade migrated group, respectively. One patient in the high-grade migrated group underwent reoperation due to re-herniation at the same segment. There was no significant difference in the rate of excellent-good cases between the two groups, with an overall rate of 94.7%. In treating high-grade migrated disc herniation, PEID offers advantages such as reduced trauma, small incision, quicker recovery and satisfactory clinical safety and efficacy.

Clinical and pathogenetic assessment of cyclosporine efficacy in the complex therapy of non-segmental vitiligo patients

BACKGROUND: Vitiligo is a chronic disease of unknown etiology, characterized by the appearance of depigmented spots on various areas of the skin, rarely on mucous membranes, and discolored hair due to destruction and reduction of melanocytes. While not life-threatening, vitiligo significantly impacts the psychoemotional aspect. Studies assessing the quality of life of vitiligo patients reveal the presence of depression in these individuals. In addition to depression, a high susceptibility to anxiety, stigmatization, sleep disturbances, adaptation, and problems in personal relationships have been identified. The prevalence of depression and anxiety among vitiligo patients is comparable to other dermatological conditions such as atopic dermatitis, acne, psoriasis, and urticaria. This underscores the need to seek new means and methods for treating this condition. AIM: Clinical assessment of the effectiveness of using cyclosporine in combination with UVB 311 nm and monotherapy with UVB 311 nm for vitiligo. MATERIALS AND METHODS: The study involved 40 patients with progressive vitiligo. All patients were randomly divided into two groups. Group 1 (20 individuals) underwent a course of cyclosporine therapy in combination with UVB therapy, while Group 2 (20 individuals) received monotherapy with UVB 311 nm. The duration of the treatment was 6 months. The extent of the affected area relative to the body surface area was evaluated using the VES index (Vitiligo extent score) on a vitiligo calculator. The impact of the disease on the quality of life was assessed using the VitiQoL scale (vitiligo-specific quality-of-life instrument). RESULTS: All patients included in the study completed the full course of treatment. Group 1 (20 individuals) underwent a course of cyclosporine therapy in combination with UVB therapy, while Group 2 (20 individuals) received monotherapy with UVB 311 nm. Patients in the combined therapy group experienced earlier stabilization of the skin process compared to those receiving monotherapy with UVB 311 nm. Additionally, Group 1 demonstrated more pronounced repigmentation of vitiligo lesions and significant improvement in quality of life compared to Group 2. CONCLUSION: Cyclosporine in combination with narrowband phototherapy at 311 nm demonstrated good clinical efficacy and significant improvement in quality of life for non-segmental vitiligo patients. Cyclosporine is well-tolerated, has a low spectrum of side effects, and can be used long-term for patients with active vitiligo.

Comparison of Clinical and Radiographic Assessment of Efficacy of Eggshell-Derived Nanohydroxyapatite (EnHA) and Demineralized Freeze-Dried Bone Allograft (DFDBA), Both Covered with Platelet-Rich Fibrin (PRF) as a Barrier Membrane in Socket Preservation: A Randomized Controlled Clinical Trial

Comparison of Clinical and Radiographic Assessment of Efficacy of Eggshell-Derived Nanohydroxyapatite (EnHA) and Demineralized Freeze-Dried Bone Allograft (DFDBA), Both Covered with Platelet-Rich Fibrin (PRF) as a Barrier Membrane in Socket Preservation: A Randomized Controlled Clinical Trial

Clinical study on forecasting the prognosis of patients with cerebellar hemorrhage based on CT radiomics models

Background and purposeWe created and verified a clinical–radiomics nomogram to forecast the prognosis of patients with cerebellar hemorrhage. Materials and MethodsEighty-eight patients with cerebellar hemorrhage from two different hospitals were retrospectively analyzed (62 cases from first hospital (training cohort) and 27 cases from second hospital (external validation cohort)). All patients underwent computed tomography scanning within 72 hours of the onset of cerebellar hemorrhage and were split into two categories based on their prognosis. Clinically independent risk factors were identified using the independent samples t-test and binary logistic regression analysis. Radiomic features were obtained using the SelectkBest, variance threshold, least absolute shrinkage, and selection operator. Radiomics scores (rad-scores) were produced from eight radiomics features of perihematomal edema (PHE) and hematoma associated with cerebellar hemorrhage prognosis. Logistic regression analyses of the rad-scores against clinical risk factors yielded clinical–radiomics column line plots. Predictive performance of the column line plots was validated using decision curve analysis analyses in both the training and external validation cohorts. ResultsTo construct rad-scores, eight radiomics traits and four clinical risk factors were combined to create clinical–radiomics models. In both the training cohort (area under the curve [AUC], 0.96 versus vs. 0.87/0.84) and the external validation cohort (AUC: 0.93 vs. 0.74/0.69), the clinical–radiomics nomogram achieved superior performance to the clinical and radiomics nomogram models. Clinical–radiomics column line plot demonstrated satisfactory calibration and clinical advantages in both cohorts. ConclusionsRadiomics features of PHE and hematoma can predict cerebellar hemorrhage prognosis. Clinical–radiomics models can help clinicians make individualized clinical treatment decisions and efficacy assessments for patients with cerebellar hemorrhage, help physicians prepare for possible deterioration, and promptly communicate treatment goals and efficacy expectations to patients and their families.

P108 Filgotinib for Rheumatoid Arthritis: an observational cohort to assess clinical effectiveness in a single centre

Abstract Background/Aims Filgotinib, a Janus-kinase (JAK) 1 preferential inhibitor, was approved for use in the UK in moderate or severe rheumatoid arthritis (RA) in 2021, as monotherapy or in combination with Methotrexate. Evidence of real-world effectiveness is currently limited. Methods Patients prescribed Filgotinib between December 2021 and August 2022 in NHS Lothian were identified from pharmacy registration data. All underwent clinical efficacy assessment at three months. Electronic patient records (EPR) were reviewed to record baseline data including previous and current treatments. Duration of Filgotinib treatment was recorded, and discontinuation reason if applicable. DAS-28 scores within six months prior to starting Filgotinib were recorded, along with available subsequent scores. Pre-existing interstitial lung disease (ILD), venous thromboembolism (VTE), major adverse cardiovascular events (MACE) and malignancy were recorded, along with incident events during treatment. Results 145 patients were prescribed Filgotinib; 106 (73.1%) females and 39 (26.9%) males, with median age 64 years. Median treatment duration was 447 days. 35 (24.1%) were treated with the reduced 100mg dose. 81 (55.9%) received conventional disease-modifying anti-rheumatic drugs (DMARDs) alongside Filgotinib. 41 (28.3%) patients discontinued treatment: 10 (6.9%) due to loss of effect; 16 (11.0%) due to lack of efficacy; six (4.1%) experienced side effects leading to cessation; five (3.4%) stopped for alternative reasons; one (0.7%) experienced a severe allergic drug reaction; three (2.1%) developed lung cancer and treatment was stopped in each case. 12 (8.3%) patients had ILD prior to treatment. 10 (6.9%) had prior major cardiovascular events, eight (5.5%) had previously treated malignancy, and six (4.1%) had previous VTE. During treatment, 1 (0.7%) patient developed ILD and two (1.4%) developed VTE. There were three (2.1%) new malignancies, all lung cancer. No new MACE occurred. 120 (82.8%) patients were previously treated with biologic or targeted synthetic DMARDs. 59 (40.7%) had failed multiple biologic DMARDs of different classes. 19 (13.1%) switched to Filgotinib from another JAK inhibitor. Pre-treatment DAS-28 scores were recorded in 55 (37.9%) patients with mean 5.1, and during treatment in 44 patients (30.3%) with mean 3.5. 17 (11.7%) patients had DAS-28 recorded both before and during treatment, with pre-treatment mean 5.0 and subsequent mean 2.9. Of these, 10 (58.8%) were classified as a good response by EULAR disease activity criteria, and four (23.5%) as a moderate response. Three (17.6%) were non-responders. Conclusion Our cohort includes 40.7% difficult-to-treat RA. Drug survival as a clinical efficacy surrogate was 71.7% at median duration 447 days, demonstrating patient acceptability and clinical effectiveness. Our service is poor at DAS-28 recording in the EPR, which may partly reflect imaging use at response assessment. Since this cohort was established, the European Medicines Agency has issued guidance advising caution using JAK inhibitors in high-risk groups to minimise the chance of serious side effects. Disclosure C.D. Box: None. S. Ramsay: None. N.D. McKay: Other; N.D.M. has received funding for conference registrations from Abbvie, UCB and Novartis, fees for lecturing from Gilead, and has taken part in advisory board meetings for UCB and Gilead.

Epithelial-Mesenchymal Transformation Promotes the Progression of Hepatocellular Carcinoma through NF-κB/MMP9 Axis.

Primary liver cancer (PHC) stands as one of the most prevalent malignant diseases in clinical settings. Studies have indicated that transcatheter arterial chemoembolization (TACE) treatment exhibits superior clinical outcomes, potentially increasing the complete necrosis rate in patients with PHC. A correlation exists between the clinical outcomes of TACE surgery and the process of epithelial-mesenchymal transition (EMT), yet the underlying mechanism remains a mystery. Hence, it is crucial to investigate the impact and mechanism of EMT on hepatocellular carcinoma (HCC). Retrospectively, patients with advanced liver cancer who underwent TACE were selected and categorized into two groups based on the assessment of clinical efficacy: the effective group and the ineffective group. The expression levels of nuclear factor-kappa B (NF-κB), matrix metalloproteinase 9 (MMP9), Ki-67, B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X (Bax), Vimentin, E-cadherin, and N-cadherin in tumor tissues were evaluated using reverse transcription-polymerase chain reaction (RT-PCR). In vitro, Huh7 cells were cultured, and lentivirus infections were utilized to inhibit the overexpression of NF-κB and MMP9. The determination of EMT and cell viability was conducted through Cell Counting Kit-8 (CCK-8) assays, RT-PCR, and Western blot. Sixty patients diagnosed with advanced liver cancer were selected for the study. Based on their clinical outcomes, 30 patients with advanced hepatocellular carcinoma were categorized into the effective group, while the remaining 30 patients were categorized into the ineffective group. The results of the Western blot analysis indicated that, in comparison to the effective group, the expression levels of NF-κB, MMP9, Ki-67, Bcl-2, Vimentin, and N-cadherin were significantly higher in the tumor tissues of the ineffective group. Conversely, the expression of Bax and E-cadherin was notably lower in the effective group. Following the individual knockdown of NF-κB and MMP9, the cell experiments revealed a remarkable decrease in the expression levels of Ki-67, Bcl-2, Vimentin, and N-cadherin, whereas the expression of Bax and E-cadherin showed significant elevation (p < 0.05). Furthermore, there was a significant increase in cell viability and a decrease in cell apoptosis after the knockdown of NF-κB and MMP9. The NF-κB/MMP9 signaling axis serves as a pivotal regulator that fosters proliferation and impedes apoptosis in Huh7 cells by modulating the process of EMT.

Tenecteplase versus Alteplase before thrombectomy: A comprehensive evaluation of clinical and angiographic impact: Insights from the ETIS registry

IntroductionData on prior use of Tenecteplase versus Alteplase in acute stroke management by mechanical thrombectomy are controversial. Our primary objective was to make a comprehensive comparative assessment of clinical and angiographic efficacy and safety outcomes in a large prospective observational study. MethodsWe included stroke patients who were eligible for intravenous thrombolysis and endovascular thrombectomy between 2019 and 2021, from an ongoing registry in twenty comprehensive stroke centers in France. We divided patients into two groups based on the thrombolytic agent used (Alteplase vs Tenecteplase). We then compared their treatment times, and their angiographic (TICI scale), clinical (mRS at three months and sICH) and safety outcomes after controlling for potential confounders using propensity score methods. ResultsWe evaluated 1131 patients having undergone thrombectomy for the final analysis, 250 received Tenecteplase and 881 Alteplase. Both groups were of the same median age (75 vs 74 respectively), and had the same baseline NIHSS score (16) and ASPECTS (8). There was no significant difference for First Pass Effect (OR 0.93, 95 % CI 0.76–1.14, p = 0.75), time required for reperfusion (OR 0.03, 95 % CI 0.09–0.16, p = 0.49), or for final reperfusion status. Clinically, functional independence at 90 days was similar in both groups (OR 0.82, 95 % CI 0.61–1.10, p = 0.18) with the same risk of sICH (OR 1.36, 95 % CI 0.77–2.41, p = 0.28). However, Tenecteplase patients had shorter imaging-to-groin puncture times (99 vs 142 min, p < 0.05). ConclusionsTenecteplase showed no better clinical or angiographic impact on thrombectomy compared to Alteplase. Nevertheless, it appeared associated with a shorter thrombolysis-to-groin puncture time.

Effectiveness of Yijinjing exercise in the treatment of early-stage knee osteoarthritis: a randomized controlled trial protocol

IntroductionKnee osteoarthritis (KOA) is still a challenging degenerative joint disease with high morbidity and disease burden. Early-stage KOA, the focus of this study, could present a Window of Opportunity to...

A label information fused medical image report generation framework

Medical imaging is an important tool for clinical diagnosis. Nevertheless, it is very time-consuming and error-prone for physicians to prepare imaging diagnosis reports. Therefore, it is necessary to develop some methods to generate medical imaging reports automatically. Currently, the task of medical imaging report generation is challenging in at least two aspects: (1) medical images are very similar to each other. The differences between normal and abnormal images and between different abnormal images are usually trivial; (2) unrelated or incorrect keywords describing abnormal findings in the generated reports lead to mis-communications. In this paper, we propose a medical image report generation framework composed of four modules, including a Transformer encoder, a MIX-MLP multi-label classification network, a co-attention mechanism (CAM) based semantic and visual feature fusion, and a hierarchical LSTM decoder. The Transformer encoder can be used to learn long-range dependencies between images and labels, effectively extract visual and semantic features of images, and establish long-term dependent relationships between visual and semantic information to accurately extract abnormal features from images. The MIX-MLP multi-label classification network, the co-attention mechanism and the hierarchical LSTM network can better identify abnormalities, achieving visual and text alignment fusion and multi-label diagnostic classification to better facilitate report generation. The results of the experiments performed on two widely used radiology report datasets, IU X-RAY and MIMIC-CXR, show that our proposed framework outperforms current report generation models in terms of both natural linguistic generation metrics and clinical efficacy assessment metrics. The code of this work is available online at https://github.com/watersunhznu/LIFMRG.

Endosonography Elastography and Magnetic Resonance Imaging in the Restaging and Response Assessment of Rectal Cancer After Neoadjuvant Therapy.

The objective of this academic research is to assess the efficacy of conventional endorectal ultrasound (ERUS), ultrasonic shear wave elastography (SWE), and magnetic resonance imaging (MRI) techniques in evaluating the impact of neoadjuvant therapy (nCRT). Forty-five patients with advanced low rectal cancer (T ≥ 3) were included. Before and after nCRT, ERUS, SWE, and MRI evaluations were conducted. The T staging of ultrasound (uT) and MRI (mT) were evaluated and compared with the pathological T staging (ypT). The accuracy of the 2 diagnostic methods for T staging, and T downstaging was evaluated. The ultrasound elasticity difference and relative elasticity before and after treatment and pathological T downstaging were compared, and its cutoff value and the area under the curve were assessed. In terms of T staging accuracy after chemoradiotherapy, the values for ERUS, ERUS combined with SWE, and MRI were 64.4%, 71.1%, and 62.2%, respectively. No significant difference was observed among these groups ( P > 0.05). The accuracy of uT downstaging was 84.4%, and that of mT downstaging was 88.9%. The receiver operating characteristic curve of uLD and elastic differences and relative elasticity of T downstaging after treatment were 0.754, 0.817, and 0.886, respectively (all P < 0.05). Both ERUS and MRI can evaluate ypT downstaging. The indicators for evaluating T downstaging are uLD, elasticity difference, and relative elasticity, providing more reference for clinical assessment of nCRT efficacy.

Efficacy of traditional Chinese medicine combined with Silibinin on nonalcoholic fatty liver disease: A meta-analysis and systematic review.

The efficacy and safety of traditional Chinese medicine (TCM) combined with Silibinin in the treatment of nonalcoholic fatty liver disease (NAFLD) are still inconclusive. This meta-analysis intends to evaluation to explore the clinical efficacy and quality assessment of traditional Chinese medicine in combination with Silymarin in the treatment of NAFLD, aiming to aims to provide evidence-based data analysis for researchers and clinical practitioners involved in TCM research for NAFLD, with the hope of facilitating wider adoption and application. In this meta-analysis, we searched PubMed, Embase, Cochrane Library, CNKI, Wanfang, CQVIP and CBM databases from the establishment of the databases to Oct 2023. The study proposed to include studies that reported combination of TCM with Silibinin and Silibinin alone in the treatment of NAFLD, excluding studies for which full text was not available or for which data extraction was not possible; studies using animal studies; reviews and systematic reviews. All data were processed by STATA15.1 statistical software. 16 randomized controlled trials (RCTs) were included in this meta-analysis. The sample size ranged from 48 to 120, with a total of 1335 patients, including 669 in the Combined treatment group and 384 in the Silibinin group. The findings indicated that the total effective rate of combined treatment group was significantly higher than that of Silibinin alone. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), total cholesterol (TC), triglycerides (TG), and gamma glutamyl transpeptidase (GGT) of combined treatment group were all significantly lower than that of western medicine alone. Additionally, after treating NAFLD with a combination of TCM and Silibinin, the TCM syndrome score were significantly lower than those observed with Silibinin alone. Traditional Chinese medicine in conjunction with Silibinin capsules has shown significant efficacy in the treatment of NAFLD, improving clinical symptoms, blood lipid levels, and liver function. Furthermore, it is essential to engage in multi-omics research, investigate iron death, and explore the gut microbiota as potential observational indicators for the diagnosis and inclusion criteria. Conducting more high-quality clinical experiments is necessary to further validate these findings.

Impact of hepatectomy and postoperative adjuvant transarterial chemoembolization on serum tumor markers and prognosis in intermediate-stage hepatocellular carcinoma.

Primary hepatocellular carcinoma (HCC) is a common malignant tumour, and its early symptoms are often not obvious, resulting in many patients experiencing middle- to late-stage disease at the time of diagnosis. The optimal time for surgery is often missed for these patients, and those who do undergo surgery have unsatisfactory long-term outcomes and a high recurrence rate within five years. Therefore, postoperative follow-up treatments, such as transhepatic arterial chemoembolization (TACE), have become critical to improving survival and reducing recurrence rates. To validate the prophylactic role of TACE after hepatic resection and to assess its impact on patient prognosis. This study investigated the efficacy of TACE in patients with intermediate-stage HCC after hepatectomy. When the post-treatment results of the observation group and the control group were compared, it was found that the inclusion of TACE significantly improved the clinical efficacy, reduced the levels of tumour markers and did not aggravate the damage to liver function. Thus, this may be an effective and comprehensive treatment strategy for patients with intermediate-stage HCC that helps to improve their quality of life and survival time. When the baseline data were analysed, no statistical differences were found between the two groups in terms of gender, age, hepatitis B virus, cirrhosis, Child-Pugh grading, number of tumours, maximum tumour diameter and degree of tumour differentiation. The assessment of clinical efficacy showed that the post-treatment overall remission rate of the observation group was significantly higher than that of the control group. In terms of changes in tumour markers, the alpha-fetoprotein and carcinoembryonic antigen levels in the patients in the observation group decreased more significantly after treatment compared with those in the control group. When post-treatment changes in liver function indicators were analysed, no statistical differences were found in the total bilirubin, alanine aminotransferase and aspartate aminotransferase levels between the two groups. In patients with intermediate-stage HCC, post-hepatectomy TACE significantly improved clinical outcomes, reduced tumour-marker levels and may have improved the prognosis by removing residual lesions. Thus, this may be an effective and comprehensive treatment strategy for patients with intermediate-stage HCC.

A Randomized, Double‐blind, Sham‐controlled, Adaptive‐Design Pivotal Trial of Sensory Stimulation in Subjects with Alzheimer’s Disease

AbstractBackgroundIn three prospective clinical trials (Overture: NCT03556280, Etude: NCT03661034, Flicker: NCT03543878) non‐invasive, visual and auditory gamma (40 Hz) sensory stimulation diminished Alzheimer’s disease (AD) symptoms, including a reduction in decline in cognitive and functional symptoms. These trials initiated the design of the Cognito Therapeutics sponsored Hope pivotal trial which examines the safety and efficacy of Cognito Therapeutics’ Sensory Stimulation System.MethodThe US‐based multicenter Hope trial will randomize (1:1) approximately 500 subjects aged 50 and older diagnosed with mild to moderate AD (MMSE 15‐26) and will stratify them to active and sham in a blinded manner across MMSE score ranges: 15‐20 and 21‐26. Subjects in both study arms will self‐administer therapy via the Sensory Stimulation System for 60 minutes daily for 12 months. An interim analysis will employ the promising zone methodology, allowing the sample size to be adjusted if the effect is trending toward success, but additional subjects are needed to maintain greater than 80% power.ResultThe primary outcome measure will be the Alzheimer’s Disease Cooperative Study – Activities of Daily Living (ADCS‐ADL) test. Changes in function and cognition will be evaluated using a combined statistical test for ADCS‐ADL and the Mini Mental State Exam (MMSE). The key secondary outcome is change in cognition using the MMSE. Other clinical efficacy assessments include instrumental activities of daily living (IADL), Zarit Burden Index (ZBI), the Clinical Dementia Rating Scale (CDR) and The Neuropsychiatric Inventory anxiety subscale (NPI – Anxiety). Key biomarker assessments include whole brain, white matter, and hippocampal volume and occipital cortical thickness. Sleep fragmentation will be assessed in a subgroup of subjects using actigraphy. Exploratory measures will include additional brain structural change, plasma biomarkers, EEG assessed coherence, and at‐home tablet‐based tasks. Safety will be evaluated via routine clinical laboratory assessments, review of adverse events, concurrent medication use, physical and neurological exams, vital signs, MRI, and a suicidality scale.ConclusionThe Hope pivotal trial is designed to demonstrate the efficacy and safety of daily in‐home gamma sensory stimulation in AD patients to support a regulatory filing with the FDA.

HIV-Related Diffuse Large B Cell Lymphoma Influences on T Cell Exhaustion

BACKGROUD HIV infection leads to T cell dysfunction, which triggers increased incidence of diffuse large B cell lymphoma (DLBCL). It has been shown that PD-1 inhibitors can better restore T cell function and effectively treat HIV-related lymphoma. However, the specific mechanism on the treatment of HIV-related DLBCL patients with PD-1 inhibitors is ambiguous, and related studies on the expression of PD-1 on T cells have not been reported. This study aimed to explore the regulatory role of altered immune function status in the microenvironment of HIV-related DLBCL and to analyze hyper-exhausted T cell subsets. METHODS Three patients with DLBCL, two patients with HIV and 11 patients with HIV-related DLBCL who were treated from September 2021 to December 2022 at the Chongqing University Cancer Hospital of were included. Single cell sequencing was used to analyze immune cell and tumor cell related genes in patients'lymph node tissues. InferCNV was used to distinguish normal and malignant B lymphocytes. Gene set enrichment analysis (GSEA) was used to find the expression of exhaustion genes and related signaling pathways in immune cells. And relevant exhausted immune cells were analyzed and validated by flow cytometry. RESULTS Compared to the HIV and DLBCL groups, the HIV-related DLBCL group had a higher level of expression of the gene PDCD1, a higher level of expression of CD23(FCER2) in normal B lymphocytes, and a greater difference in malignant B lymphocytes, with a lower percentage of TCF1-positive exhausted T cells and a higher level of CXCL13-positive exhausted T cells (Fig.1-3). Compared with the HIV group, the percentage of follicular helper T cells (T fh) was lower in the HIV-related DLBCL group. The results of the Pseudotime analysis showed two main developing directions of TCF1-positive exhausted T cells (Fig.4). The state2 was primarily the direction of TCF1-positive exhausted T cell development in the HIV group and the HIV-related DLBCL group, and the state3 was primarily the direction of TCF1-positive exhausted T cell development in the DLBCL group and the HIV-related DLBCL group. CONCLUSION Patients with HIV-related DLBCL are more at risk of T cell exhaustion. In this study, we found that HIV-related DLBCL induced T cell exhaustion has different states and shows two differentiation directions, and state2 may correlate with HIV-induced T cell exhaustion. T cell exhaustion states may be used for disease status and clinical efficacy assessment of HIV-related DLBCL.

Aesthetic Efficacy of a Novel Topical Combination Brightening Regimen to Treat Facial Hyperpigmentation

Purpose: Hyperpigmentation is a multifaceted condition that is often challenging to treat. Due to this complexity, a combination therapy providing a holistic approach of removal and prevention of pigmentation has shown greater efficacy than a monotherapy treatment. A clinical usage study was conducted to assess the cosmetic changes of a combination take-home skincare topical regimen of a novel brightening platform in subjects with mild to severe facial hyperpigmentation.&#x0D; Procedure: Participants received a take-home multimodal brightening skincare regimen (EC Regimen) that consisted of twice-daily use of EC brightening Pads and EC serum, and once-daily evening use of EC spot cream. Clinical Efficacy and tolerability assessments, and participant self-assessments of facial skin appearance were conducted.&#x0D; Results: Nineteen participants aged 31-69 years, with Fitzpatrick Skin Types I-IV, who self-identified their ethnicity as Asian, White, American Indian, and Hispanic, were included in the study. The EC Regimen provided statistically significant improvements as early as week 1 in Dark Spot Severity and Dark Spot Contrast grades with continued significant improvements through week 12 versus baseline (p&lt;0.01). There were significant improvements in Overall Hyperpigmentation and the validated Modified Melasma Area and Severity Index scores as early as week 2 with continued significant improvements through week 12 versus baseline (p&lt;0.03). Additionally, improvements in a variety of photoaging concerns such as Overall Photodamage, Tactile Roughness, Skin Tone Evenness, Fine and Coarse Lines/Wrinkles and Radiance were observed at all time points.&#x0D; The EC Regimen was highly rated by participants with an overall satisfaction of 94% by week 12. At week 12, participants stated that EC Regimen “faded the dark spots that I have had for more than 5 years” (89%), “helped prevent new dark spots” (94%), and “improved my most stubborn spots that bother me the most” (89%). At week 12, EC Regimen improved quality-of-life parameters and participants stated that EC Regimen “makes me feel happier with how I look” (83%) and “makes me more confident” (83%). EC Regimen was well-tolerated as tolerability assessments remained mild for the duration of the study.&#x0D; Conclusions: Combination therapy of EC Regimen provides a well-tolerated, effective treatment for multiple hyperpigmentation and photoaging parameters with high patient satisfaction.

Antimicrobial susceptibility of Treponema pallidum subspecies pallidum: an in-vitro study

The increasing incidence of syphilis and the limitations of first-line treatment with penicillin, particularly in neurosyphilis, neonatal syphilis, and pregnancy, highlight the need to expand the therapeutic repertoire for effective management of this disease. We assessed the in-vitro efficacy of 18 antibiotics from several classes on Treponema pallidum subspecies pallidum (T pallidum), the syphilis bacteria. Using the in-vitro culture system for T pallidum, we exposed the pathogen to a concentration range of each tested antibiotic. After a 7-day incubation, the treponemal burden was evaluated by quantitative PCR targeting the T pallidum tp0574 gene. The primary outcome was the minimum inhibitory concentration (MIC) at which the quantitative PCR values were not significantly higher than the inoculum wells. We also investigated the susceptibility of macrolide-resistant strains to high concentrations of azithromycin, and the possibility of developing resistance to linezolid, a proposed candidate for syphilis treatment. Amoxicillin, ceftriaxone, several oral cephalosporins, tedizolid, and dalbavancin exhibited anti-treponemal activity at concentrations achievable in human plasma following regular dosing regimens. The experiments revealed a MIC for amoxicillin at 0·02 mg/L, ceftriaxone at 0·0025 mg/L, cephalexin at 0·25 mg/L, cefetamet and cefixime at 0·0313 mg/L, cefuroxime at 0·0156 mg/L, tedizolid at 0·0625 mg/L, spectinomycin at 0·1 mg/L, and dalbavancin at 0·125 mg/L. The MIC for zoliflodacin and balofloxacin was 2 mg/L. Ertapenem, isoniazid, pyrazinamide, and metronidazole had either a poor or no effect. Azithromycin concentrations up to 2 mg/L (64 times the MIC) were ineffective against strains carrying mutations associated to macrolide resistance. Exposure to subtherapeutic doses of linezolid for 10 weeks did not induce phenotypic or genotypic resistance. Cephalosporins and oxazolidinones are potential candidates for expanding the current therapeutic repertoire for syphilis. Our findings warrant testing efficacy in animal models and, if successful, clinical assessment of efficacy. European Research Council.

Clinical Study and Assessment of Efficacy of Polyherbal Combination (KNDBHU) in COVID 19 Patients

Even three years after the COVID-19 pandemic initially appeared in December of the year 2019, it is still raging over the globe. There have been numerous attempts to use well-known medications in new ways to treat COVID-19 infection. Many nations, including India, implemented a series of lock downs in an effort to limit the pandemic. Sanitation practices, social seclusion, routine mask wearing, testing, and quarantining of suspected carriers were among the recommended methods for limiting the illness. Numerous treatment strategies have also been used to prevent and treat the illness, but no formal studies using well-known Ayurvedic formulations or any polyherbal combinations have been conducted. A clinical study was planned to test the noble polyherbal combination containing Withania somnifera, Tinospora cordifolia, Moringa oleifera, Adhatoda vasica, Piper longum, Glycyrrhiza glabra, Ocimum sanctum and Curcuma longa. The study checked the rate of symptom remission in individuals receiving the polyherbal combination in addition to standard of care (SoC) to that in patients with mild and moderate symptoms of COVID-19 infections receiving SoC alone. A prospective randomized interventional clinical study was planned comparing outcomes in 2 cohorts with mild to moderate COVID-19 as under. Cohort-1 was trialled with conventional treatment as per government advisory. Cohort-2 was trialled with polyherbal combination and with conventional treatment as per government advisory. With the current add-on Polyherbal regimen, an early clinical improvement in breathlessness was seen along with early ageusia and cough reduction when compared with conventional treatment. The polyherbal combination (KNDBHU) enhanced recovery in COVID-19 Patients. Given the lack of hospital beds in India, the median length of hospital stays was shortened; this development is significant. Keywords: Covid­19, Add on polyherbal combinationregimen for Corona virus, Early Clinical Improvement, Shortened hospital stays

Can the Chinese study on the normal range of FeNO in children evaluate standardized asthma treatment efficacy in 6- to 12-year-old children?

By examining fractional exhaled nitric oxide (FeNO) levels and performing pulmonary function testing, this study explored whether the multicenter study on the normal range of FeNO in children in China can be used to evaluate standardized treatment efficacy in 6- to 12-year-old children with asthma. A total of 115 children aged 6-12 years old who were first diagnosed with asthma and received standardized asthma treatment from April 2018 to July 2022 were selected. According to the FeNO level at the first visit, the subjects were divided into different high- and low-FeNO groups according to the American Thoracic Society (ATS) guidelines and the Chinese multicenter study recommendations. The consistency of the two grouping methods and the differences between the high- and low-FeNO groups were compared after standardized treatment. The grouping method that was the most suitable for children in the cross group was discussed. (i) There was fair consistency between the Chinese multicenter study recommendations and the ATS guidelines regarding the classification of high- and low-FeNO groups (Kappa = 0.338). (ii) Repeated-measures ANOVA showed that the level of improvement in FVC%, FEV1%, FEF25%, FEF50%, and FeNO in the American high- and low-FeNO groups differed with the duration of therapy (P < 0.05), however, there was no significant difference between the Chinese groups. (iii) FEV1% and FeNO improved more after treatment in the fixed high-FeNO group than in the cross group (P < 0.05). The Chinese multicenter study on the normal range of FeNO in children in China has a limited role in evaluating standardized asthma treatment efficacy in 6- to 12-year-old children. The ATS guidelines are currently recommended for clinical assessment of asthma treatment efficacy.