Similar Efficacy Research Articles

Screening for colorectal cancer by full colonoscopy in first-degree relatives of colorectal cancer patients: a multicentric study by the Italian League for the Fight against Cancer.

Colorectal cancer currently presents the third-highest incidence of cancers worldwide, making secondary prevention through screening programs for colorectal cancer, usually by Fecal Occult Blood Testing, an essential preventive medicine intervention. First-degree relatives of colorectal cancer patients are a particularly at-risk group, with indications to consider direct screening by full colonoscopy. Colonoscopy is considered the gold standard for diagnosing colorectal cancer, as it has high sensitivity and specificity, and is both a diagnostic and therapeutic tool. However, it requires significant organizational and financial resources, and has a small but relatively higher risk of complications as opposed to fecal occult blood testing. The present study aimed to assess the appropriateness of a screening program without age restrictions of CRC by full colonoscopy in asymptomatic, first-degree adult relatives of patients with colorectal cancer, aiming both to actively increase screening coverage and to determine the detection rate of precancerous lesions and colorectal cancer in this population. Uncontrolled interventional study - colorectal cancer screening by full colonoscopy for at-risk population. The Italian League for the Fight against Cancer started a colorectal cancer screening program by full colonoscopy for first-degree relatives of colorectal cancer patients in 1998 in the province of Latina, Lazio Region, Italy. The program was expanded to the provinces of Rieti, Lazio Region, and Sassari, Sardinia Region, in 2014 and 2016 respectively, and was concluded in 2018. Subjects were actively and voluntarily recruited by the study's working group. Subjects that had already been subjected to a full colonoscopy in the preceding 5 years were excluded from this study. Identified neoplastic lesions were treated either directly or referred to the Day Hospital setting, and histologically diagnosed following World Health Organization guidelines. In total, 2,288 subjects (age range 15-88, mean 52.3 yrs, M/F = 946/1,204) were screened by colonoscopy, of which 103 (4.5%) were incomplete and 2,173 (95.0%) complete, with data on colonoscopy performance missing for 12 participants. Out of 468 positive outcomes on colonoscopy, diagnosis for 422 (204M/173F), 19.4% of total subjects, was adenomatous polyps and 46 (20M/20F), 2.1% of total subjects, was colorectal cancer. Female sex was a protective factor against a positive test outcome, with a 35% reduction compared to male sex, with OR=0.64 95%CI (0.52-0.80). On the other hand, being over 50 years of age was found to be a risk factor, making a positive outcome more than twice as likely, with OR=2.3 95%CI (1.8-2.9). Subjects over 50 also had significantly more instances of multiple adenomas being found, however the size distribution of found adenomas was not significantly different between subjects under and over 50, despite size being a predictor of risk of neoplastic progression. Given the high detection rate of precancerous lesions and colorectal cancer in the studied population, it is our opinion that guidelines should continue to recommend earlier and more frequent screening in first-degree relatives of patients with colorectal cancer, and, barring the introduction of more cost-effective and/or lower risk procedures with a similar efficacy profile, maintain the use of colonoscopy as the main screening option.

Aerobic exercise training and zolpidem have similar efficacy for reducing insomnia severity

Aerobic exercise training and zolpidem have similar efficacy for reducing insomnia severity

Efficacies of anlotinib monotherapy versus gemcitabine-based chemotherapy for patients with advanced soft tissue sarcoma after the failure of anthracycline-based chemotherapy

ObjectiveThe purpose of this study was to compare the antitumor efficacy of anlotinib with gemcitabine-based chemotherapy as subsequent treatment regimens in patients with advanced non-specific soft tissue sarcoma (STS) after the failure of anthracycline-based chemotherapy.MethodsPatients diagnosed with advanced STS who were treated with either anlotinib or gemcitabine-based chemotherapy between May 2009 and May 2023 in our center were eligible. All patients experienced disease progression or recurrence after the anthracycline-based chemotherapy. The primary endpoint was progression-free survival (PFS). Secondary endpoints were disease control rate (DCR), overall survival (OS) and safety.ResultsWe included 49 patients receiving anlotinib and 45 patients receiving gemcitabine-based chemotherapy. The median follow-up time was 76.9 weeks (range 2.9–678.9 weeks). The DCR (65.3% vs. 57.8%; p = 0.610), PFS (24.0 weeks vs. 18.6 weeks; p = 0.669) and OS (79.4 weeks vs. 87.0 weeks; p = 0.471) of anlotinib and gemcitabine-based chemotherapy indicated similar clinical efficacy. Moreover, exploratory subgroup analyses showed that patients with STS originating from limbs and trunk were inclined to benefit from anlotinib treatment (median PFS: 31.3 weeks vs. 12.4 weeks; p = 0.045). ECOG PS was an independent predictor of the PFS [Hazard Ratio (HR) 0.31; 95% confidence interval (CI) 0.11–0.85; p = 0.023] and OS (HR 0.26, 95%CI 0.10–0.70; p = 0.008) in the anlotinib group. While neutrophil-to-lymphocyte ratio (NLR) was an independent prognostic factor of the PFS (HR 0.33, 95%CI 0.11–0.98; p = 0.045) in the gemcitabine-based chemotherapy group. The incidence of grade 3 or higher related AEs in anlotinib and gemcitabine-based chemotherapy was 20.4% (n = 10) and 20.0% (n = 9), respectively.ConclusionOur research suggested that anlotinib and gemcitabine-based chemotherapy showed similar clinical efficacy and safety in the subsequent treatment of advanced STS after the failure of anthracycline-based chemotherapy.

Percutaneous endoscopic lumbar discectomy for single and double segment lumbar disc herniation with sciatic scoliosis in adults: a retrospective study

ObjectiveSciatic scoliosis can be seen in patients with lumbar disc herniation. Percutaneous endoscopic lumbar discectomy (PELD) is a common surgical method for the treatment of lumbar disc herniation. The difference between single-segment lumbar disc herniation and double-segment lumbar disc herniation with Sciatic Scoliosis in adults after PELD needs further study. The aim of this study was to compare the imaging features of single-segment and double-segment lumbar disc herniation with Sciatic Scoliosis in adults and to further explore the clinical outcomes of functional improvement and scoliosis imaging parameters of the two groups after PELD.MethodsAdult patients with lumbar disc herniation with sciatic scoliosis who received PELD from January 2019 to June 2022 were analyzed retrospectively. According to the number of operative segments, the patients were divided into a single-segment group and a double-segment group. Perioperative parameters were observed and compared between the two groups. The Visual Analogue Scale (VAS) score, Oswestry dysfunction index (ODI), Japanese Orthopaedic Association scores (JOA) and imaging parameters of the two groups were recorded and compared before the operation and during the follow-up.ResultsA total of 53 patients with single segments and 21 patients with double segments were included in this study. During the follow-up, the VAS score, ODI index and JOA score of the two groups were significantly improved as compared with those before the operation(P < 0. 05). Ninety-two point five percent of single-segment patients and 90.5% of double segment patients returned to normal scoliosis within 12 months after the operation. The operation time, number of intraoperative fluoroscopy times and the amount of intraoperative blood loss in single-segment patients were better than those in double-segment group(P < 0. 05). At the last follow-up, the AVT, CBD and SVA in the double-segment group were 5.2 ± 2.3, 5.1 ± 1.0 and 12.2 ± 3.0 mm, respectively, which were higher than those in the single-segment group (1.9 ± 0.4, 1.1 ± 1.6 and 3.9 ± 2.1 mm) (P < 0. 05).ConclusionPELD is an effective treatment for single-segment and double-segment lumbar disc herniation with Sciatic scoliosis. Double-segment patients can enjoy similar clinical efficacy to single-segment patients, avoiding complications caused by decompression, fusion, and internal fixation. Scoliosis was corrected spontaneously within 12 months after operation, and the sagittal curve was significantly improved in both groups. The improvement of coronal and sagittal balance in double -segment patients may take longer.

Clinical evaluation of a novel protocol for supportive periodontal care: A randomized controlled clinical trial.

The aim of this study was to compare the clinical efficacy and the patient perception of subgingival debridement with either guided biofilm management (GBM) or conventional scaling and root planing (SRP) during supportive periodontal care (SPC). Forty-one patients in SPC were randomly assigned to either treatment with GBM or SRP every 6 months. The primary outcome was the percentage of bleeding on probing (BoP) at 1 year. Moreover, pocket probing depths (PPD), recession, and furcation involvements were also measured. Full-mouth and specific site analyzes were performed at baseline, 6 and 12 months of SPC. Patient comfort was evaluated using a visual analogue scale (VAS) at 12 months. At 1 year, mean BoP percentage decreased from 12.2% to 9.0% (p=0.191) and from 14.7% to 7.9% (p=0.004) for the GBM and SRP groups, respectively. Furcation involved multirooted teeth but no through-and-through lesions were significantly fewer in the GBM than in the SRP group after 12 months (p=0.015). The remaining parameters showed slight improvement in both groups without any statistically significant differences between the two groups after 1 year. Pain evaluation as patient reported outcome measures (pain evaluation) was in favor (p=0.347) of the SRP group, while overall satisfaction was similar for both groups. Treatment time was not statistically significantly different between the two groups (p=0.188). In well-maintained SPC patients, SRP protocols resulted in significant clinical improvements in terms of BoP; however, for the other clinical improvements, similar efficacy for both GBM and SRP was observed.

Efficacy of an oral suspension containing xyloglucan and pea proteins on a murine model of gastroesophageal reflux disease.

Gastroesophageal reflux disease (GERD) is the most common foregut disease, affecting about 20% of the adult population. Esophageal epithelial barrier plays a fundamental role in the pathophysiology of GERD; however, pharmacological therapies mainly aim to reduce the acidity of the gastroesophageal environment rather than to protect esophageal tissue integrity. This study aims to evaluate the efficacy of an oral solution containing xyloglucan and pea proteins (XP) in reestablishing gastroesophageal tissue integrity and biochemical markers. To induce GERD, C57BL/6 mice were alternatively overfed and fasted for 56 days and then treated with XP, sodium alginate, omeprazole, or omeprazole+XP twice daily for 7 days. Gastric pain and inflammatory markers were evaluated after 3 and 7 days of treatment. After sacrifice, the esophagi and stomachs were surgically removed for macroscopic and histological examination. Gastric pain was significantly reduced at days 3 and 7 by XP, omeprazole, and omeprazole+XP, while alginates were ineffective at day 3. XP was able to diminish gastric macroscopic damage and demonstrated the same efficacy as omeprazole in reducing esophageal damage. XP significantly reduced histological damage, with an efficacy comparable to that of omeprazole, but superior to alginates. Inflammatory markers were significantly reduced by XP, with superior efficacy compared with alginates at day 7. Interestingly, XP was also able to significantly increase gastric pH. This study demonstrated that XP restored gastric homeostasis, improved esophageal integrity, and decreased inflammation and pain with a similar efficacy to omeprazole and greater than alginates.

Comparing Outcomes of Banana-Shaped and Straight Cages in Transforaminal Lumbar Interbody Fusion for Lumbar Degenerative Diseases: A Systematic Review and Meta-Analysis.

This meta-analysis aims to refine the understanding of the optimal choice between different cage shapes in transforaminal lumbar interbody fusion (TLIF) by systematically comparing perioperative data, radiological outcomes, clinical results, and complications associated with banana-shaped and straight bullet cages. A meticulous literature search encompassing PubMed, Embase, Scopus, Web of Science, China Knowledge Network, and Wanfang Data was executed up to October 5, 2023. Inclusion criteria focused on studies comparing banana-shaped and straight bullet cages in TLIF. The quality of included studies was assessed using appropriate tools such as the Newcastle-Ottawa Scale (NOS) for nonrandomized studies. Rigorous evaluations were performed for radiographic outcomes, including disc height (DH), segmental lordosis (SL), lumbar lordosis (LL), subsidence, and fusion rates. Clinical outcomes were meticulously evaluated using visual analogue scale (VAS), Oswestry Disability Index (ODI), and complications. The analysis incorporated 7 studies, involving 573 patients (297 with banana-shaped cages, 276 with straight cages), all with NOS ratings exceeding 5 stars. No statistically significant differences were observed in operative time, blood loss, or hospitalization between the 2 cage shapes. Banana-shaped cages exhibited greater changes in DH (p = 0.001), SL (p = 0.02), and LL (p = 0.01). Despite statistically higher changes in ODI for straight cages (26.33, p < 0.0001), the actual value remained similar to banana-shaped cages (26.15). Both cage types demonstrated similar efficacy in VAS, complication rates, subsidence, and fusion rates. Although banana-shaped cages can excel in restoring DH, SL, and LL, straight bullet cages can provide comparable functional improvements, pain relief, and complication rates.

Medical therapy has similar hemostatic efficacy with endoscopic treatment for PUB patients with adherent clot (FIIb ulcers).

Currently, there is no clear consensus on whether medical treatment or endoscopic treatment should be used for peptic ulcer bleeding patients with adherent clot. The aim of this study is to investigate the hemostatic effects of medical treatment, single endoscopic treatment, and combination endoscopic treatment for peptic ulcer bleeding (PUB) patients with adherent clot. We retrospectively analyzed PUB patients with adherent clot who underwent endoscopic examination or treatment in our center from March 2014 to January 2023 and received intravenous administration of proton pump inhibitors. Patients were divided into medical treatment (MT) group, single endoscopic treatment (ST) group, and combined endoscopic treatment (CT) group. Subsequently, inverse probability of treatment weighting (IPTW) was performed to calculate the rebleeding rate. A total of 605 eligible patients were included in this study. After IPTW, the rebleeding rate in the MT group on days 3, 7, 14, and 30 were 13.3 (7.3), 14.2 (7.8), 14.5 (7.9), and 14.5 (7.9), respectively; the rebleeding rates in the ST group were 17.4 (5.1), 20.8 (6.1), 20.8 (6.1), and 20.8 (6.1), respectively; the rebleeding rates in the CT group were 0.4 (0.9), 1.7 (3.3), 2.3 (4.5), and 2.3 (4.5), respectively. Although the rebleeding rate in the medical treatment group was higher, there was no significant difference among the three groups on days 3, 7, 14, and 30 (P = 0.132, 0.442, 0.552, and 0.552). Medical therapy has similar hemostatic efficacy with endoscopic treatment for PUB patients with adherent clot (FIIb ulcers). However, for patients with more risk factors and access to well-equipped endoscopy centers, endoscopic treatment may be considered. The choice of treatment approach should be based on the individual conditions of the patient, as well as other factors such as medical resources available.

Clinical Trial: Efficacy of Mosapride Controlled-release and Nortriptyline in Patients With Functional Dyspepsia: A Multicenter, Double-placebo, Double-blinded, Randomized Controlled, Parallel Clinical Study.

Prokinetic agents and neuromodulators are among the treatment options for functional dyspepsia (FD), but their comparative efficacy is unclear. We aimed to compare the efficacy of mosapride controlled-release (CR) and nortriptyline in patients with FD after 4 weeks of treatment. Participants with FD were randomly assigned (1:1) to receive mosapride CR (mosapride CR 15 mg and nortriptyline placebo) or nortriptyline (mosapride CR placebo and nortriptyline 10 mg) in double-placebo, double-blinded, randomized controlled, parallel clinical study. The primary endpoint was defined as the proportion of patients with overall dyspepsia improvement after 4 weeks treatment. The secondary endpoints were changes in individual symptom scores, anxiety, depression, and quality of life. One hundred nine participants were recruited and assessed for eligibility, and 54 in the mosapride CR group and 50 in the nortriptyline group were included in the modified intention-to-treat protocol. The rate of overall dyspepsia improvement was similar between groups (53.7% vs 54.0%, P = 0.976). There was no difference in the efficacy of mosapride CR and nortriptyline in a subgroup analysis by FD subtype (59.3% vs 52.5% in postprandial distress syndrome, P = 0.615; 44.4% vs 40.0% in epigastric pain syndrome, P = > 0.999; 50.0% vs 59.1% in overlap, P = 0.565; respectively). Both treatments significantly improved anxiety, depression, and quality of life from baseline. Mosapride CR and nortriptyline showed similar efficacy in patients with FD regardless of the subtype. Both treatments could be equally helpful for improving quality of life and psychological well-being while also relieving dyspepsia.

Efficacy and safety of piclidenoson in plaque psoriasis: Results from a randomized phase 3 clinical trial (COMFORT-1).

A3 adenosine receptor (A3AR) is overexpressed in the skin and peripheral blood mononuclear cells of psoriasis patients. We investigated the efficacy/safety of piclidenoson (CF101), an orally bioavailable A3AR agonist that inhibits IL-17 and IL-23 production in keratinocytes, in moderate-to-severe plaque psoriasis. The randomized, placebo- and active-controlled, double-blind phase 3 COMFORT-1 trial randomized patients (3:3:3:2) to piclidenoson 2 mg BID, piclidenoson 3 mg BID, apremilast 30 mg BID or placebo. At Week 16, patients in the placebo arm were re-randomized (1:1:1) to piclidenoson 2 mg BID, piclidenoson 3 mg BID or apremilast 30 mg BID. The primary end point was the proportion of patients achieving ≥75% improvement in Psoriasis Area and Severity Index (PASI) from baseline (PASI-75) at Week 16 versus placebo. A total of 529 patients were randomized and received ≥1 dose of study medication (safety population). The efficacy analysis population for the primary end point included 426 patients (piclidenoson 2 mg BID, 127; piclidenoson 3 mg BID, 103; apremilast, 118; placebo, 78). Piclidenoson at 2 and 3 mg BID exhibited similar efficacy. The primary end point was met with the 3 mg BID dose: PASI 75 rate of 9.7% versus 2.6% for piclidenoson versus placebo, p = 0.037. The PASI responses with piclidenoson continued to increase throughout the study period in a linear manner. At week 32, analysis in the per-protocol population showed that a greater proportion of patients in the piclidenoson 3 mg BID arm (51/88, 58.0%) achieved improvement from baseline in Psoriasis Disability Index (PDI) compared to apremilast (59/108, 55.1%), and the test for noninferiority trended towards significance (p = 0.072). The safety/tolerability profile of piclidenoson was excellent and superior to apremilast. Piclidenoson demonstrated efficacy responses that increased over time alongside a favourable safety profile. These findings support its continued clinical development as a psoriasis treatment (ClinicalTrials.gov identifier: NCT03168256).

Pulsed field ablation and cryoballoon ablation for pulmonary vein isolation: insights on efficacy, safety and cardiac function.

Pulmonary vein isolation (PVI) has become the cornerstone treatment of atrial fibrillation (AF). While in cryoablation cell damage is caused by thermal effects, lately, pulsed field ablation (PFA) has been established as a novel non-thermal tissue-specific ablation modality for PVI. However, data comparing outcomes of patients undergoing either PFA or cryoballoon ablation (CBA) for primary PVI are sparse. Consecutive patients with AF undergoing PVI by either CBA or PFA were included in the analysis. The primary outcome was the time to AF/AT recurrence. For secondary outcomes, clinical and periprocedural parameters were compared. In total, outcomes of 141 AF patients treated by PFA (94 patients) or CBA (47 patients) were compared. After 365 days, 70% of patients in the PFA group and 61% of patients in the CBA group were free from AF/AT (HR 1.35, 95% CI 0.60-3.00; p = 0.470). No deaths occurred. While symptoms alleviated in both groups, only after PFA, we observed significant improvement of left atrial volume index (PFA group baseline: 40 [31;62] ml/m2, PFA group follow-up: 35 [29;49] ml/m2; p = 0.015), NT-pro BNP levels (PFA group baseline: 1106 ± 2479 pg/ml, PFA group follow-up: 1033 ± 1742 pg/ml; p = 0.048), and left ventricular ejection fraction (LVEF) (PFA group baseline: 55 [48;60] %, PFA group follow-up: 58 [54;63] %; p = 0.006). PVI by PFA was the only independent predictor of LVEF improvement. In our study, we show that CBA and PFA for PVI are of similar efficacy when it comes to AF recurrence. However, our findings suggest that PFA rather than CBA might induce left atrial reverse remodeling thereby contributing to left ventricular systolic function.

Exploring the Clinical Applications of Lemongrass Essential Oil: A Scoping Review.

Lemongrass is a medicinal plant that produces essential oil with a variety of therapeutic properties. Although lemongrass essential oil (LGEO) is promising in clinical applications, the existing knowledge on the efficacy and safety of LGEO remains limited. This scoping review aimed to identify, summarize, and synthesize existing literature related to the clinical applications of LGEO to provide an overview of its potential therapeutic benefits for patients. Three databases (PubMed, Web of Science, Scopus) were used following the PRISMA-ScR guidelines to find articles published between 1 January 2013, and 1 November 2022. A total of 671 records were identified and 8 articles were included in this scoping review. The majority of patients received oromucosal and topical treatment. The results of the studies suggest that LGEO might be a useful tool in the treatment of periodontitis, gingivitis and oral malodour, with similar efficacy to chlorhexidine (anti-gingivitis effect) and doxycycline (periodontitis). Additionally, LGEO has the potential for treating pityriasis versicolor and preventing skin aging and may have anti-dandruff effects. These findings not only underscore the diverse clinical potential of LGEO but also emphasize its comparable efficacy to established treatments. Further research is imperative to comprehensively evaluate LGEO's effectiveness, safety, mechanisms of action, potential interactions with other medications, and its long-term tolerability across diverse populations.

Enzalutamide versus Abiraterone Plus Prednisolone for Nonmetastatic Castration-Resistant Prostate Cancer: A Sub-Analysis from the ENABLE Study for PCa

Enzalutamide (ENZ) and abiraterone plus prednisolone (ABI) can improve the survival of patients with castration-resistant prostate cancer (CRPC). However, the agent that is more effective against nonmetastatic CRPC remains unclear. To evaluate the agent that can be used as the first-line treatment for CRPC, an investigator-initiated, multicenter, randomized controlled trial (ENABLE Study for PCa) including both metastatic and nonmetastatic CRPC was conducted in Japan. The prostate-specific antigen (PSA) response rate, overall survival, some essential survival endpoints, and safety of patients with nonmetastatic CRPC were also analyzed. In this subanalysis, 15 and 26 patients in the ENZ and ABI arms, respectively, presented with nonmetastatic CRPC. There was no significant difference in terms of the PSA response rate between the ENZ and ABI arms (80% and 64%, respectively; p = 0.3048). The overall survival did not significantly differ between the two arms (HR: 0.68; 95% CI: 0.22–2.14, p = 0.5260). No significant differences were observed in terms of radiographic progression-free survival and cancer-specific survival between the ENZ and ABI arms (HR: 0.81; 95% CI: 0.35–1.84; p = 0.6056 and HR: 0.72; 95% CI: 0.19–2.73; p = 0.6443, respectively). Only four and six patients in the ENZ and ABI arms, respectively, had ≥grade 3 adverse events. ABI and ENZ had similar efficacy and safety profiles in patients with nonmetastatic CRPC.

P558 Clinical Effectiveness and Safety of Vedolizumab vs. Infliximab in Biologic-Naïve Ulcerative Colitis Patients: A Brazilian Real-World Multicentric Observational Study

Abstract Background Vedolizumab (VDZ) and infliximab (IFX), are considered first-line agents in the treatment of moderate to severe Ulcerative Colitis (UC). However, there are no head-to-head studies comparing the relative effectiveness of the two agents, and Real-world data on the effectiveness and safety of VDZ and IFX in UC are lacking in the Brazilian population. We aimed to compare effectiveness and safety of VDZ to IFX in Biologic-naïve UC patients. Methods We conducted a multicenter retrospective cohort study, including patients with moderate to severe UC (Total Mayo score 6-12, with an endoscopic subscore of 2 or 3) who treated with VDZ or IFX. The primary endpoints were: clinical remission, defined as a partial Mayo score (PMS) ≤2, endoscopic remission (endoscopic Mayo subscore of 1 or 0) and steroid-free clinical remission at week 52. Secondary endpoints included; clinical response at weeks 12 and 26, need for drug optimization, adverse events (AEs), need for hospitalization and colectomy, loss of response and biochemical remission (C-reactive protein [CRP] ≤ 0.5 mg/dl and/or fecal calprotectin [FC] ≤ 150 mcg/g) at week 52. Results A total of 174 UC (79 VDZ and 95 IFX) patients were included. Clinical remission and endoscopic remission at week 52 were achieved by 56 (70.8% vs 68.4%, p= 0.44) and 46 (58.2% vs 55.7%, p=0.18) of VDZ and IFX patients, respectively. Steroid-free clinical remission at week 52 was 84.2% and 54.1% in the VDZ and IFX group, respectively (p = 0.03). Clinical response at weeks 12 and 26 was reached in 80.0% vs 76.2%, p = 0.74 and in 71.4% vs 77.3%, p = 0.71 in the VDZ and IFX group, respectively. The need for drug optimization was higher for IFX than for VDZ (36.8% vs. 21.5%, p = 0.03). The incidence of AEs (26.3% vs 12.6%, p=0.03) and need for hospitalization (26.3% vs 11.4%, p=0.02) were higher for IFX than to VDZ patients. Secondary loss of response was similar in the two groups (16.4 % for VDZ and 16.8% for IFX, p = 1.00). Biochemical remission at week 52 was 75.0% for VDZ, and 63.9% for IFX, respectively (p=0,42). Conclusion In this real-world study VDZ and IFX had similar efficacy in inducing clinical remission, endoscopic remission, clinical response and biochemical remission at week 52. Compared to IFX, VDZ was superior in inducing steroid-free remission, in addition to having a better safety profile and less need for dose escalation. Both VDZ and IFX were effective treatment options in bio-naïve UC patients.

P134 Characterization for the similarity assessment between proposed biosimilar SB17 and ustekinumab reference product using state-of-the-art analytical method

Abstract Background SB17 is being developed as a proposed biosimilar to ustekinumab reference product (RP), a human monoclonal antibody (IgG1 kappa immunoglobulin) that binds to the common p40 subunit of cytokines interleukin (IL)-23 and IL-12. Binding to this subunit prevents interaction with their receptor, resulting in modulation the immune system responses which play a key role in the inflammatory disease. The objective of this study was to demonstrate structural, physicochemical, and biological similarity between ustekinumab RP and SB17 using various state-of-the-art analytical methods. Methods Comprehensive analytical characterization was conducted with side-by-side comparison of SB17 with the EU and US ustekinumab RP using various analytical methods. Comparisons included purity, product-related impurity, charge heterogeneity, primary structure, post-translational modification, higher order structure, quantity, Fab-related biological activities (potency and binding activity), and Fc-related biological activities. Results Based on the analytical similarity assessment, the structural, physicochemical, and biological characterization results demonstrated that SB17 is highly similar to the EU and US ustekinumab RP. In the structural aspects, it was confirmed that there is no clinically meaningful difference between post-translational modification profiles and higher order structures of SB17 compared to the ustekinumab RP. Product-related impurities in the form of aggregates were also confirmed to be similar. SB17 has a lower of acidic and basic peaks compared with ustekinumab RP, due to the difference in producing cell line. Ustekinumab RP is expressed in an Sp2/0 cell line, whereas SB17 is expressed in CHO cell line. However, the difference between SB17 and ustekinumab RP in the charge variants is not considered clinically meaningful since equivalent biological activity was observed. In case of mechanism of action (MoA)-related biological activities, SB17 is highly similar to the EU and US ustekinumab RP with respect to overall critical and non-critical quality attributes analyzed. Moreover, similarity or lack of activity in Fc-related biological activities was also confirmed. Based on these results, SB17 is expected to have highly similar safety and efficacy as compared to ustekinumab RP. Conclusion In summary, the overall analytical characterization and similarity assessment results show that SB17 is highly similar to the EU and US ustekinumab RP in terms of structural, physicochemical, biophysical, biological attributes.

P1044 Mirikizumab Pharmacokinetics and Exposure-Response in a Phase 2 Study in Patients With Moderately to Severely Active Crohn’s Disease

Abstract Background Mirikizumab (miri) is a humanized anti–interleukin-23-p19 monoclonal antibody approved for the treatment of ulcerative colitis (UC) and under development for Crohn’s disease (CD). This analysis characterises miri pharmacokinetics (PK) and the relationship between miri exposure and efficacy response using data from a phase 2 trial in adults with moderately to severely active CD. Methods AMAG was a randomised, double-blind, placebo-controlled trial conducted in 14 countries. Patients received placebo, miri 200 mg, 600 mg, or 1000 mg as induction regimens administered intravenously (IV) every 4 weeks (Q4W) through Week 12, followed by 36 weeks of maintenance treatment with continuous treatment of miri 200 mg, 600 mg, or 1000 mg IV or miri 300 mg administered subcutaneously (SC) Q4W. PK parameters were analysed by non-linear mixed-effects modelling. Covariate effects on miri exposure were evaluated using simulation-based estimations. Exposure-response (ER) for patients achieving endoscopic response by Simple Endoscopic Score for Crohn’s Disease (SES-CD) at Weeks 12 and 52 were assessed using logistic regression models. Results 186 patients were included. The estimated systemic clearance (CL), central volume of distribution (V), and SC bioavailability (F) were 0.022 L/hr, 3.31 L, and 33.4%, respectively. Lower baseline values for SES-CD (indicative of a less severe CD) were associated with reduced CL. Lower body weight and higher albumin levels were also associated with reduced CL. Higher body weight was associated with higher V and lower baseline body mass index correlated with higher SC F. Impacts on PK parameters were small relative to random variability and not considered clinically relevant. The model-based ER analyses for endoscopic response probability at Week 12 detected a significant treatment effect relative to placebo (p&amp;lt;0.001) and a significant ER (p=0.001) in a dose range of 200-1000 mg. The ER analyses indicated near maximal efficacy for IV dose between 600 mg and 1000 mg during the Induction Period. There was no significant relationship between miri exposure and the probability of achieving endoscopic response by SES-CD at Week 52, indicating exposures produced by the maintenance doses provided similar efficacy. Conclusion Miri PK characteristics in adults with active CD were consistent with miri UC studies. Overall, none of the covariates identified as being significantly correlated with miri PK parameters were considered clinically relevant. No patient factors evaluated in this analysis justify dose adjustment. These findings support the miri induction dose 900 mg IV Q4W and maintenance dose 300 mg SC Q4W selected for phase 3 CD study.

Growth inhibition of Salmonella by Leuconostoc species isolated from buffalo milk curd

Traditional fermented products are considered to be a niche for microbial diversity. Probiotics offer a unique approach for addressing the threat of antibiotic resistance. Therefore, the aim of the present study was to isolate Leuconostoc spp. from Buffalo milk curd, an artisanal fermented dairy product in Bangladesh and assess their growth inhibition competence against Salmonella sp. A total of 50 isolates were isolated and purified from five freshly prepared buffalo milk curd samples using two different media, with glucose or sucrose as the carbon source. Among these pure isolates, 37 were identified as presumptive Leuconostoc spp. The biochemical identification using the VITEK 2 system confirmed that 59.5% of the isolates were Leuconostoc mesenteroides ssp. cremoris, while 40.5% were Leuconostoc pseudomesenteroides. Out of the identified isolates, twelve had a similarity of over 97%, and twenty-five had a similarity of less than 96%. Consequently, these twelve isolates were tested for their antimicrobial activity against Salmonella sp. using two in vitro methods, agar well diffusion and microbroth. The isolate M1L1 exhibited the highest inhibitory zone (15 mm) and showed 55.6% growth inhibition by the agar well diffusion and microbroth assay, respectively, suggesting a similar efficacy between the two methods. Notably, five other isolates also displayed inhibitory zones ranging from 13 to 15 mm and growth inhibition percentages of 37 to 52%. Overall, the isolated Leuconostoc spp. could be utilized as probiotics to combat pathogenic microorganisms. Ann. Bangladesh Agric. (2023) 27 (1): 93-104

Very high-power and short-duration radiofrequency ablation for atrial fibrillation in a Latin American low-volume private center.

Center volume and operator experience/training are important factors impacting outcomes in AFib CA. Setting for RF delivery (power, duration, and contact force) associated with better outcomes remains to be determined. This is an observational, longitudinal, and retrospective study. All consecutive procedures performed between December 12, 2013, and March 9, 2023, in a low-volume private center in Latin America were analyzed. Procedure characteristics and outcomes were compared between STD and vHPSD. Two hundred ten procedures were performed on 194 patients. Median annual number of procedures was 19 (7-29). Median age was 62 (52-68), and majority were male (71%). Median procedure duration was 155 (125-195) min, mean fluoroscopy time 32.8 ± 15min and mean fluoroscopy dose 373.5 ± 208.9 mGray. Median follow-up was 27months, significantly longer in STD compared with vHPSD group (43 [31-68] vs. 13 [8-19], respectively; P ≤ 0.001). The recurrence rate was 33.2% and major complications 8.6%. Compared with STD, vHPSD resulted in a significantly shorter procedure duration (125 vs. 180min, P ≤ 0.001), shorter fluoroscopy time (22.7 ± 9.5 vs. 39.2 ± 14.3min, P ≤ 0.001), and lower fluoroscopy dose (283.8 ± 161.1 vs. 438.3 ± 216.1 mGray, P ≤ 0.001). No long-term recurrence difference was observed when the follow-up periods were comparable. No difference in complication rate was observed (8.5% vs. 8.6%, P = 0.988). Outcomes in AFib CA in a Latin American low-volume private center can be considered acceptable, with efficacy and safety similar to those reported in the literature. Compared with STD ablation, vHPSD showed higher efficiency with similar efficacy and safety.

Outcomes of 3-year follow up with induction vs first line chemotherapy in oral cancer patients: An observational hospital-based study.

Our study aims to analyse and compare the efficacy, adverse effect profile and survival among the Paclitaxel/Cisplatin/5-Flurouracil (TPF) induction chemotherapy and Paclitaxel/carboplatin (PC) first line or cisplatin chemotherapy in a high-volume tertiary care cancer centre. 215 patients with oral cavity cancer were recruited in this study. Patients with stages I-IIc underwent surgical resection or radiation therapy 66-74 GY/fraction. Patients of Stages III-IV were administered with either induction chemotherapy TPF or PC or cisplatin regimen. Treatment responses were assessed by CT and MRI. Response rates, survival and adverse effects data were tabulated and analysed. The mean age was 49.2 ± 11.68 years. Symptoms were ulceration (33.5%), growth (20.5%), pain (13%), ulcer-proliferative growth (8.4%) and swelling (13, 6%). The tumour site was found at the base of the tongue, C01 (42.2%) followed by C06 (35.8%), C08 (6.5%), C07 (5.2%) and C05 (4.6%). There were no significant differences ( P > 0.05) in efficacy and survival outcomes between the different groups of treatment. Median survival was achieved within 36 months. The major side effect observed were anaemia (15.81%), diarrhoea (36.2%), dyspepsia (28.8%), fever (33.95%), mucositis (28.85%), myalgia (33.95%) and nausea (7.9%). Survival among the responder categories (CR, PR and NR) was significantly different as per Log-rank analysis ( P = 0.015). TPF induction therapy and PC first line chemotherapy showed similar efficacy, safety profile and survival whereas cisplatin shows poor efficacy and safety and survival in Indian oral cancer patients.

Comprehensive molecular characteristics of clinical responses to PD-1 inhibitors plus anti-angiogenic agents (PA) in metastatic HER2-negative gastric adenocarcinoma.

279 Background: Anti-angiogensis agents were reported to enhance the efficacy of PD-1 inhibitor by inhibiting the infiltration of suppressive immune cell populations. Clinical studies indicated the synergistic anti-tumor effect of the combination of PD-1 inhibitors and anti-angiogenesis agents (PA). We aim to assess the efficacy of PA versus chemo-PA regiment in mGC, as well as the potential predictive biomarkers. Methods: A total of 55 GC tumors were analyzed using the next-generation sequencing (NGS), immunohistochemistry (IHC), and the tumor immune microenvironment (TIME) by multiplex immunofluorescence (mIHC). Clinical outcomes [Disease Control Rate (DCR), Progression-free survival (PFS) and overall survival (OS)] were compared between patients receiving PA treatment (n=32) and chemo-PA (n=23) treatment. Exploratory biomarker analyses were conducted for the prediction for the efficacy of PA/chemo-PA treatment. Results: Patients receiving PA regiment had comparable DCR (69% vs 50%, P =0.25) and PFS (median PFS: 6.53 vs 4.73 months, HR=0.70, 95%CI: 0.27-1.78, P =0.52), compared with those treated with combination of chemo-PA regiment as second or later-line treatment in mGC. Patients with HMCN1 wild-type showed significant improvements in DCR (77% vs 0%, P =0.023) and PFS (median PFS: 6.53 vs 1.17 months, P =0.0017), versus those with HMCN1 mutations in PA treatment cohort. HMCN1 mutations are associated with lower infiltration of endothelial cells and lower score of VEGF ligand-receptor interaction, according to the EPIC and pathway enrichment analysis ( P &lt; 0.05). In addition, analysis of TIME by mIHC revealed that the fraction of CD68+ tumor-associated macrophages in the tumor center was higher in responders than non-responders before treatment (median: 17.59% vs 2.45%, P=0.016). Conclusions: PA regiment and chemo-PA regiment had similar efficacy in second or later line treatment of mGC. HMCN1 mutations maybe a predictive marker for PA regiment in HER2-negative mGC, which should be further validated in a large cohort.