Assessment Of Clinical Efficacy Research Articles

Comparative efficacy of lidocaine and bupivacaine in epidural anesthesia in sheep

The issues of anesthesia during surgical operations in farm animals require the improvement and application of modern methods of both general and local anesthesia. The method of epidural anesthesia and the choice of the optimal anesthetic for its implementation are becoming increasingly widespread in veterinary practice, its dosage determines the adequacy of anesthesia. The present study was conducted in order to conduct a comparative assessment of clinical efficacy when using modern local anesthetics for epidural anesthesia of sheep. A series of 60 tests were conducted on sheep using 2% lidocaine hydrochloride (group I), 2% lidocaine hydrochloride with adrenaline (group II) and 0,5% bupivacaine hydrochloride (group III) at the Department of General, Private and Operative Surgery of St. Petersburg State University of Veterinary Medicine in the period from January to July in 2024. Each of the groups consisted of 20 healthy sheep aged from 1 to 2 years. The effect of anesthetics on heart rate, respiration, respiratory volume, minute ventilation and rectal temperature was monitored. During epidural anesthesia with 0.5% bupivacaine solution, there was a significant decrease in heart rate, a slight decrease in respiration and a decrease in rectal temperature. The heart rate and respiration rate increased significantly when using 2% lidocaine and when using 2% lidocaine with adrenaline. The use of adrenaline in the second experimental group allowed to increase the duration of action of 2% lidocaine. The duration of anesthesia with 0,5% bupivacaine in the third group was the longest in comparison with other groups. Drowsiness, tympania and trembling were observed in some cases when using 0,5% bupivacaine. It follows from the present study that the use of 2% lidocaine is most reasonably in epidural anesthesia in sheep.

COMPARATIVE CHARACTERISTICS OF MODERN PROTON PUMP INHIBITORS IN THE TREATMENT AND PROPHYLAXIS OF HEMORGIC GASTRITIS AND DUODENAL ULCER

Resume. Purpose. To study factors that significantly alter the pharmacokinetics and pharmacodynamics of proton pump inhibitors in patients with chronic gastritis and duodenal ulcer. Introduction. The problem of comparative assessment of pharmacodynamics and clinical efficacy of various proton pump inhibitors, including representatives of other pharmacological groups that affect acid production, is relevant. For such an analysis in patients suffering from various variants of acid-dependent pathology of the stomach and duodenum, it is necessary to conduct a comparative characterization of modern proton pump inhibitors in the treatment and prevention of hemorrhagic gastritis and duodenal ulcer. Material and methods. The work was carried out in the Department of Gastrointestinal and Esophageal Surgery of the State Institution «V. T. Zaitsev Institute of Gastrointestinal Medicine of the National Academy of Medical Sciences of Ukraine» with the presentation of the results of the study of the most frequently used proton pump inhibitors: omeprazole (Omez, 20 mg capsules, «Dr. Reddy’s Laboratories, Ltd», India), lansoprazole (Lancerol, 30 mg capsules, PJSC «KYIVMEDPREPARAT», Kyiv, Ukraine), esomeprazole (Nexium, film-coated tablets, «ASTRAZENECA», Great Britain), rabeprazole (Pariet, film-coated tablets, «Janssen Pharmaceutica N. V.», Belgium). Two groups of patients were studied: the main group — with gastrointestinal pathology (31 patients) and the comparison group, which was represented by 25 relatively healthy individuals. Research results. Two-time studies of the pharmacokinetics of proton pump inhibitors were conducted in patients with incomplete remission of peptic ulcer disease, since it was proven on the example of lancerol that the decrease in the bioavailability of proton pump inhibitors persists after ulcer healing, and conducting a two-time pharmacokinetic study, with the exception of taking antiulcer drugs between them during exacerbation, is unethical. When studying resistance to acid production blockers using the virtual NBI-chromoendoscopy method, it was shown that in non-operated patients with peptic ulcer disease on the background of taking proton pump inhibitors, a single case of resistance (to lancerol) was observed. At the same time, when using famotidine, resistance was observed in 13 out of 50 patients. In operated patients, we did not observe cases of resistance to proton pump inhibitors (esomeprazole). Conclusions. Esomeprazole and rabeprazole have higher clinical efficacy in the treatment of chronic gastritis compared to omeprazole and lancerol. In duodenal ulcer, the rate of ulcer healing is the same with omeprazole, lancerol, esomeprazole and rabeprazole and exceeds the rate of healing with famotidine.

Clinical efficacy and safety assessment of tedizolid using therapeutic drug monitoring.

Thrombocytopenia derived from tedizolid (TZD) has been reported but less frequently than that from linezolid. Only a few reports have investigated the relationship between the efficacy and safety of TZD administration. This study aimed to measure TZD concentration and investigate the relationship between efficacy and safety. The study was conducted at the Aichi Medical University Hospital. All patients administered TZD were included; the serum trough concentration (Cmin) of TZD was measured using LM1010 high-performance liquid chromatography. Efficacy was assessed as clinical and microbiological efficacy. Clinical efficacy was defined as no recurrence and no need for additional treatment until 2 weeks after the end of TZD therapy. Microbiological efficacy was defined as the absence of bacteria during and after TZD therapy. Safety was assessed using thrombocytopenia. Thrombocytopenia was defined as a decrease in platelet count of ≥25% compared with baseline levels and a minimum count of <10 × 104/μL. Seventeen patients were included. The Cmin in 16 patients was <0.5 μg/mL; one patient had a Cmin of 1.01 μg/mL complicated by hepatic cirrhosis. Clinical and microbiological efficacy was found in >80% of the patients. Thrombocytopenia occurred in 14.3% (2/14) of the patients. The Cmin in two patients with thrombocytopenia were 0.14 and 0.28 μg/mL, respectively. The serum concentration of TZD might increase in patients with hepatic cirrhosis; therapeutic drug monitoring may be required. Thrombocytopenia due to TZD could occur regardless of its serum concentration, necessitating monitoring for platelet count.

TMOD-02. PATIENT-DERIVED GLIOBLASTOMA ORGANOIDS AS REAL-TIME AVATARS FOR ASSESSING RESPONSES TO CLINICAL CAR-T CELL THERAPY

Abstract Patient-derived tumor organoids have been increasingly leveraged for disease modeling and preclinical studies, but rarely in real-time to aid with the interpretation of patient treatment responses in the clinical setting. Whether tumor organoids can be applied to mirror clinical activity in patients and even to predict responses for personalized medicine remains uncertain. We recently demonstrated promising early efficacy signals in a first-in-human, phase 1 study of dual-targeting chimeric antigen receptor T cells (EGFR-IL13Rα2 CAR-T cells) in patients with recurrent glioblastoma (clinical trial identifier: NCT05168423). Determination of meaningful clinical efficacy, in particular for CAR-T cell therapy, may take months to manifest. Given this challenge, real-time analysis of patient-derived glioblastoma organoids (GBOs) could help to provide early assessment of clinical efficacy and guide patient management. We analyzed six sets of GBOs generated on the same timeline as the production of patients’ CAR-T cell products. GBOs demonstrated the presence and retention of both targeted tumor-associated antigens EGFR and IL13Rα2 by immunohistochemistry. These GBOs were then treated with the same autologous CAR-T cell products received by patients in our phase 1 study in parallel with patient treatment. CAR-T cell treatment led to target antigen reduction assessed by immunohistochemistry and flow cytometry. Furthermore, we confirmed cytolysis of tumor cells in GBOs by cleaved caspase-3 immunostaining and by co-culture in the Axion Maestro Cellular Impedance platform. Importantly, the degree of cytolysis ex vivo significantly correlated with CAR-T cell engraftment detected in patients’ cerebrospinal fluid (CSF) for all six patients. Furthermore, cytotoxic activity of CAR-T cells as measured by TNFα, IL-2, and IFNγ release kinetics in GBOs mirrored cytokine levels in patient CSF samples over time. Our findings highlight a unique trial design and suggest GBOs as a valuable platform for real-time assessment of CAR-T cell bioactivity and for insights into immunotherapy efficacy.

Assessment of clinical efficacy and safety of ICL implantation in patients with relatively shallow anterior chamber depth in early and midterm postoperative time

ObjectiveTo investigate the clinical effect and safety of Implantable Collamer Lens (ICL) implantation in myopic patients with relatively shallow anterior chamber depth (ACD). MethodsRetrospective analysis, comparative, non-interventional case series. Patients with myopia who underwent ICL implantation were included in the study and were categorized into two groups: one with a relatively shallow ACD (2.60 mm ≤ ACD ＜ 2.80 mm) and the other with a normal ACD (ACD ≥2.80 mm). Each group comprised 51 eyes and were reviewed for at least 6 months. To evaluate preoperative and postoperative visual acuity, intraocular pressure (IOP), central vault, ACD, endothelial cell density (ECD) and anterior chamber angle parameters [ trabecular iris angle (TIA), angle opening distance at 500 μm and 750 μm (AOD500, AOD750), trabecular iris space area at 500 μm and 750 μm (TISA500, TISA750) ]. Analyze the trend of postoperative data changes of 1 week, 1 month, 3 months, and at least 6 months. Patients in relatively shallow ACD with vault <100 μm or >1000 μm were performed detailed follow-up. ResultsThe postoperative uncorrected distance visual acuity (UDVA) and best corrected visual acuity (BCVA) surpassed the preoperative BCVA in two groups. The group differences of effectiveness index (EI) was p = 0.409 and of safety index (SI) was p = 0.563. The EI were 1.07 and 1.09, SI were1.10 and 1.21. Postoperative vision and refractive error were effectively corrected. The preoperative and postoperative IOP and ECD values of the two groups were within the normal range, and the preoperative and postoperative differences and the group differences of IOP and ECD were p = 0.649, p = 0.501, p = 0.222, p = 0.276. The ACD in two groups were reduced by approximately 25 % and 26 %, the nasal and temporal TIA were reduced to 45 % and 50 % approximately. The nasal and temporal AOD500, AOD750, TISA500, and TISA750 in the relatively shallow ACD group were reduced 40 % approximately and in the normal ACD group were reduced to 30 % approximately. All the preoperative and postoperative differences and the group differences of anterior segment parameters were statistically significant (all p < 0.01), with more significant anterior segment changes in normal ACD group.The postoperative data in two groups showed that when the follow-up time was prolonged, the central vault was decreasing, and the postoperative ACD was increasing, the postoperative TIA increased slowly in relatively shallow ACD group and decreased slowly in normal ACD group, temporal TIA were greater than nasal TIA, with no significant variation. There were four eyes in the relatively shallow ACD group in the remarkable abnormal postoperative central vault. Three eyes had second operation: one eye had an ICL alignment, and two eyes had ICL replacement. ConclusionPatients with relatively shallow ACD who underwent ICL implantation had fine postoperative clinical efficacy and safety.

Right ventricular-pulmonary artery coupling and clinical outcomes after mitral transcatheter edge-to-edge repair: A meta-analysis

Abstract Introduction Mitral transcatheter edge-to-edge repair (TEER) has gained prominence in the realm of cardiovascular care, as it has been proven to improve patient prognosis and quality of life. While the primary focus of such interventions is the mitral valve itself, understanding the broader impact of right ventricular function and pulmonary artery dynamics is crucial for a comprehensive assessment of clinical efficacy and patient outcomes. A newly recognized index, right ventricular-pulmonary artery (RV-PA) coupling, reflects the RV's ability to handle pulmonary afterload and is associated with adverse outcomes. Purpose This meta-analysis consolidates findings from diverse studies to systematically evaluate the association between RV-PA coupling parameters and the success of mitral TEER. Methods We conducted a systematic literature search for studies assessing RV-PA coupling indices at baseline in patients undergoing mitral TEER. We recorded the year of publication, method of RV-PA assessment, and the proposed cutoffs. The primary outcome of interest was the combined primary endpoint of included studies at maximal follow-up and the adjusted hazard ratios of RV-PA uncoupling were extracted if they were available. Secondary outcomes included mortality and post-operative mitral regurgitation at follow-up. Pooling of the hazard ratios was conducted according to a random effects model. I2 was chosen as the measure of between-study heterogeneity, with values exceeding 50% being significant. Results We identified a total of 316 studies, of which 8 were ultimately selected for data extraction and inclusion in the meta-analysis after screening of title/abstract/full-text. All but one study utilized the Tricuspid Annular Plane Systolic Excursion/Pulmonary artery systolic pressure (TAPSE/PASP) as the method of RV-PA assessment. According to the results of the meta-analysis, the presence of baseline RV-PA uncoupling was associated with a 2.3-fold increased risk of facing the combined primary endpoint at maximal follow-up (Figure, Panel A). All-cause mortality was also approximately 2.2-fold higher in cases of RV-PA uncoupling (Figure, Panel B). Finally, post-operative MR was 1.4-fold higher in cases of RV-PA uncoupling (Figure, Panel C). Significant between-study heterogeneity was detected in all the examined endpoints. Conclusion: This meta-analysis indicates that RV-PA uncoupling at baseline represents an important prognostic marker in patients undergoing mitral TEER.Figure

Clinical efficacy of combined goserelin and anastrozole in neoadjuvant endocrine therapy for premenopausal women with hormone receptor-positive breast cancer

ObjectiveThe objective of this study is to assess the efficacy and safety of combining goserelin with anastrozole in neoadjuvant endocrine therapy (NET) for patients diagnosed with premenopausal breast cancer.MethodsA retrospective analysis was conducted on the clinicopathological data of 34 patients diagnosed with premenopausal breast cancer who underwent NET in the Department of Breast Surgery at Baotou Cancer Hospital between March 2016 and December 2019. Additionally, the feasibility of using goserelin combined with anastrozole for premenopausal endocrine therapy was assessed.ResultsThe duration of NET ranged from 6 to 72 months, with a mean of 22.5 months and a median of 18 months. In patients with progressive disease, endocrine therapy was assessed over a period of 6 to 18 months, with a mean of 13.1 months and a median of 13 months. Among the 28 patients assessed, 12 (42.86%) were found to have stable disease, subsequently receiving chemotherapy. Of these, seven patients demonstrated good compliance, and 5 achieved a pathological complete response. Including the 2 patients who responded favorably to NET alone, a total of 7 patients attained a pathological complete response. Additionally, 16 patients achieved complete cell cycle arrest following treatment. A significant correlation was observed between the clinical efficacy assessment and the pathological assessment of NET (P < 0.05).ConclusionAlthough NET was safe for patients diagnosed with premenopausal breast cancer, it should not be considered in isolation from chemotherapy. Transitioning to chemotherapy in a timely manner can significantly enhance treatment outcomes. The duration of NET should be guided by clinical assessment rather than being constrained by a predetermined time frame.

AML-VAC-XS15-01: protocol of a first-in-human clinical trial to evaluate the safety, tolerability and preliminary efficacy of a multi-peptide vaccine based on leukemia stem cell antigens in acute myeloid leukemia patients.

Acute myeloid leukemia (AML) has a dismal prognosis, mostly due to minimal residual disease-driven relapse, making an elimination of persisting therapy-resistant leukemia progenitor/stem cells (LPCs) the main goal for novel therapies. Peptide-based immunotherapy offers a low-side-effect approach aiming to induce T cell responses directed against human leukocyte antigen (HLA) presented tumor antigens on malignant cells by therapeutic vaccination. Mass spectrometry-based analysis of the naturally presented immunopeptidome of primary enriched LPC and AML samples enabled the selection of antigens exclusively expressed on LPC/AML cells, which showed de novo induction and spontaneous memory T cell responses in AML patients, and whose presentation and memory T cell recognition was associated with improved disease outcome. Based on these data the therapeutic vaccine AML-VAC-XS15 was designed, comprising two mutated HLA class I-restricted peptides from the common AML-specific mutation in NPM1 and seven HLA class II-restricted peptides (six non-mutated high-frequent AML/LPC-associated antigens and one mutated peptide from the AML-specific mutation R140Q in IDH2), adjuvanted with the toll like receptor 1/2 ligand XS15 and emulsified in Montanide ISA 51 VG. A phase I open label clinical trial investigating AML-VAC-XS15 was designed, recruiting AML patients in complete cytological remission (CR) or CR with incomplete blood count recovery. Patients are vaccinated twice with a six-week interval, with an optional booster vaccination four months after 2nd vaccination, and are then followed up for two years. The trial's primary objectives are the assessment of the vaccine's immunogenicity, safety and toxicity, secondary objectives include characterization of vaccine-induced T cell responses and assessment of preliminary clinical efficacy. The AML-VAC-XS15-01 study was approved by the Ethics Committee of the Bavarian State medical association and the Paul-Ehrlich Institut (P01392). Clinical trial results will be published in peer-reviewed journals.

A Prospective Observational Study on Assessment of Risk Factors, Complications and Clinical Efficacy of Hepatoprotectives and Antimicrobials in Treatment of Liver Diseases at Tertiary Care Teaching Hospital in Telangana

A Prospective Observational Study on Assessment of Risk Factors, Complications and Clinical Efficacy of Hepatoprotectives and Antimicrobials in Treatment of Liver Diseases at Tertiary Care Teaching Hospital in Telangana

Frequency of Asymptomatic Optic Nerve Enhancement in 203 Patients With MOG Antibody-Associated Disease.

Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a distinct CNS demyelinating disease. The rate of asymptomatic optic nerve enhancement on MRI has not been explored in patients with MOGAD. An improved understanding of this would guide clinical practice and assessment of treatment efficacy. We aimed to determine the frequency of asymptomatic optic nerve enhancement in MOGAD. This was a retrospective review of patients evaluated at Mayo Clinic with MOGAD between January 1, 2000, and August 1, 2021 (median follow-up 1.6 [range 1-19] years). MRI studies were reviewed by masked neuroradiologists. Scans performed within 30 days of ON attack were classified as attack scans. Images obtained for routine surveillance, before ON attack, or at the time of non-ON attack were classified as interattack scans. Five hundred sixty-six MRIs (203 unique patients, 53% female) were included. Interattack MRIs represented 341 (60%) of the scans (median 36 days post-ON [range -1,032 to 6,001]). Of the interattack scans, 43 of 341 (13%), 30 unique patients, showed optic nerve enhancement. The enhancement was located at prior sites of ON in 35 of 43 (81%). Among the 8 patients with enhancement in new optic nerve areas, 6 had acute disseminated encephalomyelitis without an eye examination at the time of the MRI and 2 had preceding ON without imaging. Long-term visual outcomes showed no significant difference between those with and without asymptomatic enhancement, with improved visual acuity in most patients. Asymptomatic optic nerve enhancement occurred in 13% of interattack MRIs, the majority in patients with prior ON and occurring at prior sites of optic nerve enhancement. New asymptomatic optic nerve enhancement in areas without prior ON was rare. These findings are important for understanding the natural history of MOGAD, the interpretation of symptoms or response to treatment, and the adjudication of attacks in clinical trials.

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.

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

Evaluation of Dihydroartemisinin-Piperaquine Efficacy and Molecular Markers in Uncomplicated Falciparum Patients: A Study across Binh Phuoc and Dak Nong, Vietnam.

Background and Objectives: Malaria continues to be a significant global health challenge. The efficacy of artemisinin-based combination therapies (ACTs) has declined in many parts of the Greater Mekong Subregion, including Vietnam, due to the spread of resistant malaria strains. This study was conducted to assess the efficacy of the Dihydroartemisinin (DHA)-Piperaquine (PPQ) regimen in treating uncomplicated falciparum malaria and to conduct molecular surveillance of antimalarial drug resistance in Binh Phuoc and Dak Nong provinces. Materials and Methods: The study included 63 uncomplicated malaria falciparum patients from therapeutic efficacy studies (TES) treated following the WHO treatment guidelines (2009). Molecular marker analysis was performed on all 63 patients. Methods encompassed Sanger sequencing for pfK13 mutations and quantitative real-time PCR for the pfpm2 gene. Results: This study found a marked decrease in the efficacy of the DHA-PPQ regimen, with an increased rate of treatment failures at two study sites. Genetic analysis revealed a significant presence of pfK13 mutations and pfpm2 amplifications, indicating emerging resistance to artemisinin and its partner drug. Conclusions: The effectiveness of the standard DHA-PPQ regimen has sharply declined, with rising treatment failure rates. This decline necessitates a review and possible revision of national malaria treatment guidelines. Importantly, molecular monitoring and clinical efficacy assessments together provide a robust framework for understanding and addressing detection drug resistance in malaria.

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.

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.