Favorable Treatment Research Articles

Subclonal TP53 and KRAS variants combined with poor treatment response identify ultra-high-risk pediatric T-ALL patients.

Variations in the TP53 and KRAS genes indicate a particularly adverse prognosis in relapsed pediatric T-ALL. We hypothesized that these variations might be subclonally present at disease onset and contribute to relapse risk. To test this, we examined two cohorts of children diagnosed with T-ALL: one with 81 patients who relapsed and 79 matched non-relapsing controls, and another with 226 consecutive patients, 30 of whom relapsed. In cohort 1, targeted sequencing revealed TP53 clonal and subclonal variants in 6 of 81 relapsing patients but none in the non-relapsing group (p=0.014). KRAS alterations were found in 9 of 81 relapsing patients compared to 2 of 79 non-relapsing patients (p=0.032). Survival analysis showed that none of the relapsed patients with TP53 and/or KRAS alterations survived, whereas 19 of 67 relapsed patients without such variants did with a minimum follow-up time of 3 years (p=0.023). In cohort 2, none of the relapsing patients but 10 of 196 non-relapsing patients carried TP53 or KRAS variants, indicating that mutation status alone does not predict poor prognosis. All ten non-relapsing patients with mutations had a favorable early treatment response. Among the total cohort of 386 patients, 188 showed poor treatment response of whom 69 relapsed. Nine of these poor responders harbored TP53 or KRAS variants. In conclusion, subclonal TP53 and KRAS alterations identified at the time of initial diagnosis, along with a poor treatment response, characterize a subset of children with T-ALL who face a dismal prognosis and may benefit from alternative treatment approaches.

Orthodontic treatment for preserving periodontally hopeless teeth in a middle-aged patient: a case report.

In this case report, we show a strategic approach to prolonging the lifespan of pathologically migrated maxillary canines with a hopeless prognosis in a 57-year-old female patient, highlighting the potential of orthodontic management for middle-aged patients to enhance both occlusion and facial esthetics while minimizing the need for extensive prosthetic treatment. According to the visual treatment objective, the nonextraction treatment plan showed advantages in the type of orthodontic tooth movement and final occlusal relationship. Therefore, considering the favorable periodontal treatment results and single-root teeth, the hopelessly migrated maxillary canines were relocated, eliminating the existing trauma from occlusion. Segmental tooth movement was performed, and orthodontic temporary skeletal anchorage devices were used to support strategic orthodontic tooth movement. After 27 months of treatment, proper occlusion was established with a significant improvement in facial esthetics. The periodontally compromised teeth were preserved with adequate periodontal support. The patient expressed satisfaction with the results, and the 30-month follow-up records confirmed the stability of treatment outcomes.

Feasibility and resource utilization of nurse-administered subcutaneous immunoglobulin therapy in antibody deficiency: A cross-sectional study.

Primary and secondary antibody deficiencies (PAD and SAD) are amongst the most prevalent immunodeficiency syndromes, often necessitating long-term immune globulin replacement therapy (IRT). Both intravenous immunoglobulin (IVIG) and subcutaneous immunoglobulin (SCIG) have demonstrated efficacy in antibody deficiency. Comparative analyses of these two routes of administration are limited to nurse-administered IVIG and home therapy with self-administered SCIG. A third programmatic approach, SCIG administered by nurses in hospital-based outpatient infusion clinics, combines certain advantages of IVIG and home SCIG such as the provision of nursing support and the reduced risk of systemic reactions associated with the subcutaneous route. This cross-sectional study aimed to compare the viability and resource utilization of nurse-administered SCIG with IVIG in patients with antibody deficiency. We hypothesized that nurse-administered SCIG would require a similar amount of infusion clinic time per month as IVIG, despite more frequent dosing, due to shorter individual appointments, while maintaining high patient satisfaction. Information on infusion duration, time in the infusion chair, direct nursing time, and treatment satisfaction using the Life Quality Index was collected. Time measures for each patient were expressed as minutes/4 weeks to account for the more frequent dosing of nurse-administered SCIG compared to IVIG. We determined that the total time, infusion time, and nursing time needed to provide nurse-administered SCIG was comparable to IVIG. The more frequent dosing of SCIG was offset by the shorter times required per infusion. Patients reported favorable treatment satisfaction with both nurse-administered SCIG and IVIG. We conclude that nurse-administered SCIG may be a useful treatment modality for well-selected individuals.

High-throughput drug screening identifies SMAC mimetics as enhancers of NK cell cytotoxicity in chronic myeloid leukemia.

Natural killer (NK) cells have proven to be safe and effective immunotherapies, associated with favorable treatment responses in chronic myeloid leukemia (CML). Augmenting NK cell function with oncological drugs could improve NK cell-based immunotherapies. Here, we used a high-throughput drug screen consisting of over 500 small-molecule compounds to systematically evaluate the effects of oncological drugs on primary NK cells against CML cells. We identified SMAC mimetics as potent enhancers of NK cell cytotoxicity in both cell lines and primary patient samples. In contrast, several drug classes, including glucocorticoids and tyrosine kinase inhibitors such as dasatinib, inhibited NK cell cytotoxicity. Single-cell RNA sequencing revealed drug-induced transcriptomic changes in both NK and target CML cells. SMAC mimetics upregulated NF-κB target genes in NK cells, potentially contributing to their enhanced cytotoxicity. Inhibitory drugs dexamethasone, dasatinib, and sotrastaurin prevented NK cell transition to an activated state and suppressed the expression of IFN-γ by NK cells, thus preventing IFN-γ mediated target cell transcriptomic response. In conclusion, we discovered that SMAC mimetics sensitize cancer cells to NK cell mediated killing, with potential clinical applications especially in patients with advanced phase CML.

Treatment outcomes of primary salivary gland squamous cell carcinoma: A multi-institutional retrospective study in Japan.

Primary salivary gland squamous cell carcinoma (SCC) is extremely rare, accounting for 0.3-10.4 % of all salivary gland malignancies. Due to this rarity, the clinical characteristics of primary salivary gland SCC remain unelucidated. In the present study, we conducted a multi-institutional retrospective analysis-including a large number of cases compared with that of previous studies-to reveal the prognosis, treatment outcomes, and prognostic factors of primary salivary gland SCC. The clinical course of patients with primary salivary gland SCC between January 2012 and December 2022 was retrospectively investigated. Thirteen university hospitals and cancer centers in Japan participated in this study. The diagnosis of primary salivary gland SCC was based on the following criteria: 1) pathological diagnosis of SCC and exclusion of other histological types and 2) exclusion of metastatic SCCs from other organs. Progression-free and overall survival rates were compared using Kaplan-Meier curves and log-rank tests. Treatment outcomes were assessed using univariate and multivariate analyses with Cox proportional hazards models. In total, 723 patients with salivary gland cancer were admitted to the participating institutions. Among them, 63 patients (8.7 %) were diagnosed with primary salivary gland SCC. The clinical courses of the 58 patients that received definitive treatment and had complete data were analyzed. Primary treatments included surgery in 35 patients (60.3 %), chemoradiotherapy in 16 (27.6 %), radiotherapy in 5 (8.6 %), and chemotherapy in 2 (3.4 %). Complete response and objective response rates to chemoradiotherapy were 62.5 % and 93.8 %, respectively. Five-year progression-free and overall survival rates were 30.1 % and 60.1 %, respectively. Five-year progression-free survival rates for each treatment were 37.7 % (surgery), 33.0 % (chemoradiotherapy), 0 % (radiotherapy), and 0 % (chemotherapy). Overall survival rates were 71.5 % (surgery), 39.5 % (chemoradiotherapy), 53.3 % (radiotherapy), and 0 % (chemotherapy). Multivariate analysis revealed that age ≥70 years, N classification ≥1, and surgery were independent predictors of progression-free (hazard ratios: 3.75, 2.46, and 0.33, respectively) and overall survival (hazard ratios: 3.11, 6.24, and 0.32, respectively). Adjuvant radiotherapy significantly improved progression-free and overall survival in patients with stage Ⅳ cancer or positive surgical margins. Log-rank tests revealed no significant difference between patients with or without elective neck dissection in progression-free and overall survival; however, a relatively high percentage of occult lymph node metastasis (50.0 %) was observed. Surgical resection is a favorable first-line treatment option in salivary gland SCC, and definitive chemoradiotherapy would show acceptable complete and objective response rates.

Serum metabolomic profiling for predicting therapeutic response and toxicity in breast cancer neoadjuvant chemotherapy: a retrospective longitudinal study

Serum metabolomic profiling for predicting therapeutic response and toxicity in breast cancer neoadjuvant chemotherapy: a retrospective longitudinal study

Implementing Tariff Commitments in the EVFTA

The study introduces the process of implementing tariff commitments in free trade agreements (FTAs) and applying tariffs in implementing Vietnam’s international trade policies. At the same time, evaluates the Factors affecting these tariffs in the context of Vietnam’s extensive participation in international integration and signing of bilateral and multilateral trade agreements. Along with modernizing customs procedures to meet the FTAs, Vietnam’s tariff policies are also promptly completed to be compatible with commitments. The authors use qualitative research methods to collect data in ‘non-numerical’ form to evaluate the research object, which are new types of preferential tariffs and special incentives. Data is collected from government agencies and businesses that directly enforce import tariffs. Within the framework of the research, the author has delved into the fundamental legal principles of the WTO: favoured nation, national treatment, market openness and fair competition, practicality on Vietnam’s import tax policy, thereby serving as a basis for comparing promulgated tax policies and proposing perfect solutions implementation of preferential tariffs and special preferential tariffs for trade agreements.

Cost–utility analysis of MR imaging-guided transurethral ultrasound ablation for the treatment of low- to intermediate-risk localised prostate cancer

BackgroundMagnetic resonance-guided transurethral ultrasound ablation (MR-TULSA) is a new focal therapy for treating localised prostate cancer that is associated with fewer adverse effects (AEs) compared with established treatments. To support...

Novel Clinical Manifestation and Favorable Treatment Outcome of Cochlear Implant in a Chinese Family With Likely Pathogenic Variant of the P2RX2 Gene.

The rapid development and clinical application of sequencing technologies enable the genetic diagnosis of inherited deafness. P2RX2, as the gene responsible for autosomal dominant non-syndromic deafness-41 (DFNA41), has been proven to be essential for life-long normal hearing and for the protection of noise-induced hearing loss (NIHL). Our present study reports a missense variant in the P2RX2 gene (c.178G > T (p.V60L)), for the second time worldwide, in a five-generation kindred living in Henan, China. Despite carrying the same variant, the affected members in this family appear to present with earlier-onset hearing loss and poorer hearing compared to the original DFNA41 families. In addition, this study supplements some content that was not covered in previous reports. We quantitatively evaluated the pain perception ability of some members using the Pain Vision PS-2100 system, and further found an interesting clinical manifestation, that is, hyperalgesia, in heterozygotes for P2RX2 p.V60L. The cochlear implant (CI) was also provided for the proband of profound deafness, resulting in satisfactory clinical outcomes. Finally, we carried out a systematic review of recently published articles on the P2RX2 gene, which is beneficial for better understanding the role of the P2RX2 gene in the auditory system and the pathogenic mechanisms in sensorineural hearing loss (SNHL).

Influence of CYP2C8*3 and ABCG2 C421A genetic polymorphisms on trough concentration and molecular response of imatinib in Egyptian patients with chronic myeloid leukemia.

The treatment landscape for chronic myeloid leukemia (CML) has been revolutionized by the introduction of imatinib, a tyrosine kinase inhibitor, which has transformed the disease from a fatal condition into a manageable chronic illness for a substantial number of patients. Despite this, some individuals do not respond adequately to the treatment, and others may experience disease progression even with continued therapy. This study examined how CYP2C8*3 (G416A; rs11572080) and ABCG2 C421A (rs2231142) single nucleotide polymorphisms (SNPs) affect the plasma trough concentration and therapeutic response of imatinib in Egyptian CML patients. The study included fifty patients with chronic-phase CML, who were categorized into two groups: responders (n = 26) and non-responders (n = 24), according to their BCR-ABL1 transcription levels after 12 months of imatinib treatment. Genotyping of the CYP2C8*3 and ABCG2 C421A polymorphisms was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), while plasma trough concentrations were determined through high-performance liquid chromatography with ultraviolet-diode array detection (HPLC-UV/DAD). Patients with the CA genotype of ABCG2 C421A showed significantly higher mean plasma trough concentrations of imatinib (CA: 1731 ± 424.7 ng/mL; CC: 1294 ± 381.3 ng/mL; p = 0.0132) and demonstrated a better molecular response compared to those with the CC genotype (p = 0.0395). The ABCG2 C421A polymorphism significantly influenced imatinib plasma trough concentrations and molecular responses in Egyptian chronic-phase CML patients. Genotyping of this polymorphism in these patients could assist in optimizing imatinib therapy, predicting more favorable treatment outcomes, and enabling the development of more personalized treatment plans.

Effectiveness and Treatment Persistence of Vedolizumab Compared to Anti-Tumour Necrosis Factor-α in Patients With Crohn's Disease: A Systematic Literature Review and Meta-Analysis.

Vedolizumab is approved for the treatment of moderately to severely active Crohn's disease (CD). Real-world evidence is essential for understanding the effectiveness and benefit-risk profile of vedolizumab outside clinical trial settings. To identify, systematically review and assess the real-world effectiveness and treatment persistence of vedolizumab in patients with CD, particularly over long-term follow-up periods and among populations with differing treatment experience, and to compare with the treatment persistence of anti-tumour necrosis factor (TNF)-α treatment. Literature searches were conducted to identify studies published from 2014 to 2022. Relevant congress searches were conducted (2015-2022) using Embase or by hand. Data on adults with CD treated with vedolizumab or anti-TNFα treatment in a real-world setting were extracted for meta-analysis. Data from 73 studies, including 29,894 patients with CD, reported ≥ 1 outcome of interest for this analysis. Vedolizumab treatment persistence rate was 65.3% (95% confidence interval [CI] 60.2-70.1) at 1year and 54.8% (95% CI 43.9-65.3) at 2years. The treatment persistence rate with vedolizumab versus anti-TNFα treatment was 84.6% (95% CI 70.2-92.8) versus 75.3% (95% CI 69.7-80.2) at 1year and 70.6% (95% CI 60.7-78.8) versus 64.6% (95% CI 56.7-71.8) at 2years. The mucosal healing rate at 1year was 40.6% (95% CI 34.2-47.3). Clinical remission rates were 39.4% (95% CI 33.9-45.1) at 1year and 34.3% (95% CI 18.1-55.2) at 2years. Corticosteroid-free clinical remission rates were 33.2% (95% CI 28.5-38.3) at 1year and 20.4% (95% CI 12.5-31.5) at 2years. All clinical outcome rates were higher in biologic-naive than in biologic-experienced patients. Real-world use of vedolizumab was associated with favourable long-term effectiveness and treatment persistence. Vedolizumab is a suitable first-line biological option for biologic-naive patients with CD.

TGFβ signaling sensitizes MEKi-resistant human melanoma to targeted therapy-induced apoptosis

The TGFβ signaling pathway is known for its pleiotropic functions in a plethora of biological processes. In melanoma, TGFβ signaling promotes invasiveness and metastasis formation. However, its involvement in the response to therapy is controversial. While several studies have linked TGFβ signaling to elevated resistance to targeted therapy in melanoma, separate findings have indicated a favorable treatment response through TGFβ-mediated increase of cell death. We now found that the outcome of TGFβ signaling in the context of targeted therapy is dose dependent. Unlike low doses, high levels of TGFβ signal activation induce apoptosis upon simultaneous MAPK pathway inhibition, even in targeted therapy resistant melanoma cell lines. Using transcriptomic analyses, combined with genomic target identification of the critical TGFβ signaling effector SMAD4, we demonstrate that parallel activation of TGFβ signaling and MAPK pathway inhibition causes a complete switch of TGFβ target genes from promoting pro-invasive processes to fueling pro-apoptotic pathways. Investigations of underlying mechanisms identified a novel apoptosis-inducing gene signature. Functional validation of signature members highlighted a central role of the pro-apoptotic BCL2 family member BCL2L11 (BIM) in mediating apoptosis in this condition. Using a modified, synthetic version of the TGFB1 mRNA for intra-tumoral injections, we additionally showcase a potential therapeutic application of this treatment combination.

Semaglutide vs. dulaglutide for glycemic and weight control in patients with type 2 diabetes mellitus: A systematic review and meta‑analysis.

The present systematic review and meta-analysis aimed to evaluate the effectiveness of semaglutide and dulaglutide for glycemic control and weight loss in patients with type 2 diabetes mellitus (T2DM). A thorough literature search was conducted using several databases from inception until the end of July 2024. The primary outcome was the difference in glycated hemoglobin levels from the initial measurement between the groups. By contrast, the secondary outcome was the effect of the medications on body weight loss (change in body weight from baseline) during the treatment period. Appropriate statistical tests were employed to reach study endpoints. The results showed no statistically significant difference in glycemic control achievement between the two medications in patients with T2DM. Semaglutide demonstrated higher efficacy in inducing weight loss; however, sensitivity analysis indicated that the weight loss efficacy results should be interpreted cautiously. The study acknowledges the high heterogeneity and low quality among the studies included in the meta-analysis and the potential impact of individual studies on the outcome. Despite these limitations, the findings suggested that semaglutide may be a more favorable treatment option for patients with T2DM requiring weight management and glycemic control. Further research is needed to investigate the long-term benefits of glucagon-like peptide-1 receptor agonists and individual factors that may influence treatment response and outcomes.

Ultrasound guided microwave ablation treatment of uterine fibroids: Clinical response and patient acceptability.

The objective of this study was to evaluate the effectiveness and acceptability of ultrasound guided microwave ablation for treating symptoms related to uterine fibroids. This was a prospective interventional study. Patients with symptomatic uterine fibroids were included at Danderyd Hospital, Sweden, from January 2020 to August 2023. All patients were treated with percutaneous or vaginal ultrasound guided microwave ablation. Primary outcome was reduction of fibroid symptoms evaluated by the validated uterine fibroid symptom and quality of life (UFS-QoL) questionnaire at 6 months post-treatment. Location of each fibroid was noted. Secondary outcomes included reduction of menstruation blood loss, change in hemoglobin, ferritin and Anti-Müllerian hormone, fibroid volume difference, hospitalization, acceptability, and postoperative pain. Clinical trials registration number NCT04240262. Symptoms from uterine fibroids decreased by 37% (p < 0.001) on the symptom severity scale and health-related quality of life increased by 74% (p < 0.001). Menstrual blood loss decreased by 38% (p < 0.001) according to the Pictorial Bleeding Assessment Chart and median fibroid shrinkage of the three largest treated fibroids was 64% (p < 0.001). Highest median shrinkage rate (82) was seen in submucous fibroids. A total of 110 of 113 (97%) patients left the hospital on the day of treatment. We experienced one adverse event (0.8%) Clavien Dindo grade 3. Acceptability was high and postoperative pain was mild to moderate. Microwave ablation is a highly acceptable minimally invasive method for treating symptoms related to uterine fibroids in patients who desire uterus preservation. Submucosal fibroids showed more favorable treatment results.

Rapid and sustained response of stubborn guttate psoriasis to ustekinumab: A 52-week, two-center, one-arm, observational study.

Ustekinumab showed significant and prolonged efficacy in treating stubborn GP patients, particularly for those patients with SDD. The CARD14: rs11652075C>T may serve as a predictor of favorable treatment response.

Treatment success prediction in patients with methicillin-resistant coagulase-negative staphylococci infections, using vancomycin AUC24/MIC ratio: a multicentre retrospective cohort study.

Although vancomycin is commonly used to treat methicillin-resistant coagulase-negative staphylococci (MRCoNS) infections, there are no clear guidelines for the optimal 24 h AUC24/MIC ratio. This study aimed to determine the target AUC24/MIC ratio associated with vancomycin-treated MRCoNS infection outcomes. This multicentre retrospective cohort study included adult patients who received vancomycin for ≥5 days for bloodstream infections caused by MRCoNS between January 2018 and December 2023. Primary outcome was treatment success, defined as a composite of survival beyond 30 days, clinical success and microbiological eradication. Secondary outcomes included 30-day mortality, clinical success, microbiological eradication and nephrotoxicity. Receiver operating characteristic (ROC) curve analysis was used to identify the AUC24/MIC cut-off for treatment success. Multivariate regression analysis was used to determine the association between AUC24/MIC and outcomes. This study included 147 patients. ROC analysis identified a target AUC24/MIC ≥373 for treatment success. The overall treatment success rate (70.1%) was significantly higher in the above-average AUC24/MIC cut-off group (83.1%) than that in the below AUC24/MIC cut-off group (57.9%). Multivariate analysis confirmed that AUC24/MIC ≥373 was an independent predictor (adjusted OR = 10.227; 95% CI = 3.585-29.171). The 30-day mortality and microbiological eradication rates differed significantly between the below- and above-cut-off groups, whereas nephrotoxicity rates were comparable among the groups. In treating MRCoNS infections, vancomycin AUC24/MIC ratio ≥373 was independently associated with favourable treatment outcomes. However, further prospective studies are required to confirm this target owing to the retrospective nature of this study.

The evolution of telehealth in early-onset scoliosis care throughout the COVID-19 pandemic.

To investigate the adoption and sustained use of telehealth for managing early-onset scoliosis (EOS) during and after the COVID-19 pandemic. A 35-question anonymous survey was emailed to 191 physician members of an international pediatric spine research group. Ninety seven clinicians completed the survey (51%). Of the 78% who reported that they currently use telehealth for EOS patients, 44% do so rarely; 21% do not use telehealth at all for EOS patients. Pre-pandemic, 37% used telehealth, increasing to 93% during the pandemic, with 40% using telehealth for most visits and 33% for a quarter of visits (p<0.001). Post-pandemic usage was significantly higher than pre-pandemic levels (p<0.001). Bracing was the favored treatment to monitor via telehealth (61% of respondents). Minor curves and initial post-op visits were ranked as the most suitable for remote care (77% of respondents). Geography and transport issues were the most cited drivers of telehealth (71% and 57% of respondents, respectively). No specific subset of EOS was particularly suitable for telehealth. The most common exam techniques used via telehealth included back inspection (88%), observing gait/posture (58%), and Adams test (46%). The COVID-19 pandemic saw a significant increase in telehealth services for EOS patients (p<0.001). While most patients returned to in-person visits post-pandemic, a significant number continued to use telehealth, especially when compared to pre-pandemic (p<0.001). This persistent use, particularly for patients treated with bracing and to monitor minor curves, highlights the opportunity to optimize EOS care by strategically blending telemedicine with conventional clinic visits.

Predicting lymph node metastasis of clinical T1 non-small cell lung cancer: a brief review of possible methodologies and controversies

Non-small cell lung cancer (NSCLC) is a major subtype of lung cancer and poses a serious threat to human health. Due to the advances in lung cancer screening, more and more clinical T1 NSCLC defined as a tumor with a maximum diameter of 3cm surrounded by lung tissue or visceral pleura have been detected and have achieved favorable treatment outcomes, greatly improving the prognosis of NSCLC patients. However, the preoperative lymph node staging and intraoperative lymph node dissection patterns of operable clinical T1 NSCLC are still subject to much disagreement, as well as the heterogeneity between primary tumors and metastatic lymph nodes poses a challenge in designing effective treatment strategies. This article comprehensively describes the clinical risk factors of clinical T1 NSCLC lymph node metastasis, and its invasive and non-invasive prediction, focusing on the genetic heterogeneity between the primary tumor and the metastatic lymph nodes, which is significant for a thoroughly understanding of the biological behavior of early-stage NSCLC.

A pilot study of tofacitinib citrate with 308-nm excimer laser for the treatment of vitiligo.

Vitiligo is a clinically prevalent acquired skin disorder characterized by depigmentation. Currently, the therapeutic options for vitiligo are restricted, and numerous issues exist, such as a prolonged treatment course, unsatisfactory therapeutic efficacy, adverse reactions, and a high propensity for recurrence after treatment cessation. To assess the safety and efficacy of combined treatment involving oral tofacitinib citrate (TC) and a 308-nm excimer laser (EL), with the aim of discovering a rapid and effective treatment approach to minimize the side effects of various drugs. A total of 63 patients with progressive vitiligo and a Vitiligo Disease Activity Score (VIDA) score of four from January 2022 to January 2024 were enrolled and divided into three groups. The three groups were the TC combined with 308-nm EL and methylprednisolone treatment group, the TC and 308-nm EL treatment group, and the methylprednisolone treatment alone group. The treatment was continued for 24 weeks. Finally, assessment of therapy outcomes was performed. When TC was combined with 308-nm EL and methylprednisolone treatment, the effect was more rapid. When TC was combined with 308-nm EL, it had a more favorable treatment effect than that of methylprednisolone alone, despite having a slower effect onset. After 24 weeks of treatment, there was no significant difference between the two groups in terms of the total response rate or significant efficiency. However, when only methylprednisolone treatment was applied, the effect is relatively slow and inefficient. This study confirmed the rapid and efficient treatment of vitiligo through the combination of TC and 308-nm EL, and no serious adverse reactions were reported, which could offer an optimal treatment plan for patients with vitiligo.

Zanubrutinib Versus Bendamustine and Rituximab in Patients With Treatment-Naïve Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: Median 5-Year Follow-Up of SEQUOIA.

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.SEQUOIA (ClinicalTrials.gov identifier: NCT03336333) is a phase III, randomized, open-label trial that compared the oral Bruton tyrosine kinase inhibitor zanubrutinib to bendamustine plus rituximab (BR) in treatment-naïve patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). The initial prespecified analysis (median follow-up, 26.2 months) and subsequent analysis (43.7 months) found superior progression-free survival (PFS; the primary end point) in patients who received zanubrutinib compared with BR. At a median follow-up of 61.2 months, median PFS was not reached in zanubrutinib-treated patients; median PFS was 44.1 months in BR-treated patients (hazard ratio [HR], 0.29; one-sided P = .0001). Prolonged PFS was seen with zanubrutinib versus BR in patients with mutated immunoglobulin heavy-chain variable region (IGHV) genes (HR, 0.40; one-sided P = .0003) and unmutated IGHV genes (HR, 0.21 [95% CI, 0.14 to 0.33]; one-sided P < .0001). Median overall survival (OS) was not reached in either treatment arm; estimated 60-month OS rates were 85.8% and 85.0% in zanubrutinib- and BR-treated patients, respectively. No new safety signals were detected. Adverse events were as expected with zanubrutinib; rate of atrial fibrillation was 7.1%. At a median follow-up of 61.2 months, the results supported the initial SEQUOIA findings and suggested that zanubrutinib was a favorable treatment option for untreated patients with CLL/SLL.