Impact of baseline steroids on the efficacy of neoadjuvant immunochemotherapy in locally advanced esophageal squamous cell carcinoma.

BACKGROUND: Immunochemotherapy involving the combination of programmed cell death 1/programmed cell death ligand 1 inhibitors with chemotherapy has advanced the treatment of locally advanced esophageal squamous cell carcinoma (ESCC). The use of corticosteroids as pretreatment might reduce immunotherapy efficacy. AIM: To investigate the impact of baseline corticosteroid use on neoadjuvant immunochemotherapy (nIC) outcomes in locally advanced ESCC patients. METHODS: Patients with locally advanced ESCC who received nIC at Sun Yat-sen University Cancer Center and the Third Affiliated Hospital of Sun Yat-sen University were included. Patients were divided into dexamethasone and antihistamine groups on the basis of the administered pretreatment. Antiallergic efficacy and safety were evaluated, as well as its impact on short-term efficacy [complete pathological response (pCR), major pathological response (MPR)] and long-term efficacy [overall survival (OS), progression-free survival (PFS)] of nIC. RESULTS: From September 2019 to September 2023, 142 patients were analyzed. No severe treatment-related adverse events or deaths were observed. Allergy occurrence was greater in the antihistamine group (P = 0.014). Short-term efficacy was not significantly different: The pCR rates were 29.9% and 40.0%, and the MPR rates were 57.9% and 65.7% in the dexamethasone and antihistamine groups, respectively. The long-term efficacy was not significantly different: The 2 years OS rates were 95.2% and 93.5%, and the 2 years PFS rates were 90.3% and 87.8%. Subgroup analysis revealed no difference in OS between the 20 mg dexamethasone group and the < 20 mg dexamethasone group, but PFS was significantly greater in the 20 mg dexamethasone group (93.9% vs 56.4%, P = 0.001). CONCLUSION: Dexamethasone or antihistamines can be used before nIC in locally advanced ESCC without affecting short- or long-term efficacy. Administering 20 mg dexamethasone before nIC may improve PFS in ESCC.

Efficacy of Ruxolitinib with corticosteroids in idiopathic pneumonia syndrome post-allogeneic hematopoietic stem cell transplantation: A single-center experience and systematic review.

BACKGROUND: Idiopathic Pneumonia Syndrome (IPS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a life-threatening complication with high morbidity and mortality. IPS is thought to arise from damage caused by various inflammatory mediators. This study assesses the effectiveness of Ruxolitinib, a Janus Kinase (JAK) 1 and 2 inhibitor that blocks cytokine production, in combination with corticosteroids (CS) for managing IPS after allo-HSCT, compared to the conventional use of CS alone in a case series and a systematic review of previously published literature. METHODS: The study includes a retrospective case series of three patients treated for IPS with Ruxolitinib and CS from the University of Kansas Medical Center and a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement 2020 guidelines. The systematic review encompassed seven studies involving 346 cases including three cases from the case series. Statistical analyses were conducted using SPSS v.25. RESULTS: The case series included three patients with IPS after allo-HSCT who received ruxolitinib and CS with favorable results. All patients showed substantial improvement with no IPS-associated mortality. Two of the three patients in the case series were discharged on a 2 L nasal cannula, which was later discontinued during follow-up visits, while the third was discharged on room air. There was marked improvement observed on the computed tomography (CT) following the use of ruxolitinib. Of the total 346 cases included in the systematic review, the median age was 46.6 years (Range 5-72), and 62 % were males. The primary disorders were acute leukemia (52 %), chronic myeloid leukemia (12 %), myelodysplastic syndrome (11 %), Lymphoma (10 %), and others (21 %). Stem cell sources were peripheral blood (45 %), bone marrow (49 %), and cord blood (6 %). Donor types involved match unrelated (55 %), match related (36 %), and mismatched related (4.5 %). Most patients received myeloablative conditioning (81 %). Acute GVHD was observed in 47 %, and chronic GVHD in 38 %. The primary treatment was CS (96 %), with limited use of ruxolitinib (1 %) and etanercept (9.5 %). The mortality rate was 63.3 %, whereas in our case series with the use of ruxolitinib, it was zero. CONCLUSION: The combination of Ruxolitinib and CS for treating IPS post-allo-HSCT suggested promising results in the case series, with favorable response and improved survival by blocking the cytokine production contributing to IPS. The significant mortality difference in the systematic review supports the need for innovative treatment approaches, highlighting the potential role of Ruxolitinib in CS-refractory cases. Despite the positive outcomes in the case series, the absence of randomized controlled trials emphasizes the necessity for further research.

State of the Science: LGBTQ-Affirmative Psychotherapy.

Sexual and gender minority (SGM) individuals experience significantly higher levels of depression, anxiety, and behavioral comorbidities (i.e., substance use, suicide) compared to heterosexual and cisgender individuals. LGBTQ-affirmative psychotherapy aims to ameliorate the adverse psychosocial processes, ultimately caused by stigma, that underlie this disparity. Over the past two decades, the mental health field has introduced professional guidelines and treatment protocols for LGBTQ-affirmative psychotherapy, and established their efficacy across distinct SGM populations, delivery modalities, and settings. This state of the science review outlines the history, current evidence, and future directions of LGBTQ-affirmative psychotherapy. It provides an historical account of clinically relevant research for SGM populations and outlines the factors that moved the field from pathologizing perspectives to affirmative approaches. It then discusses the current evidence for LGBTQ-affirmative psychotherapy, as well as studies identifying treatment moderators, including race/ethnicity and stigma exposure, as well as potential treatment mechanisms, including hypervigilance, shame, negative self-schemas, unassertiveness, and emotion dysregulation. SGM individuals can only benefit from LGBTQ-affirmative psychotherapy if protocols are widely available and used by therapists. To this end, the article presents current findings on implementation and dissemination, such as therapist training, and different treatment delivery modalities. Finally, the article outlines an agenda for future research to advance the field of LGBTQ-affirmative psychotherapy, including identifying treatment mechanisms, successfully implementing and disseminating treatment protocols, determining which contexts and client characteristics warrant adaptations to current protocols, and understanding how LGBTQ-affirmative psychotherapy can interact with structural and systemic conditions to exert the strongest possible impact on SGM mental health.

The State of the Science: Dialectical Behavior Therapy.

The first randomized clinical trial of dialectical behavior therapy (DBT) for women with borderline personality disorder was published in 1991. Over the past 30 years, research on DBT has proliferated along with interest by clinicians and the public. In this State of the Science review, we provide a brief description of the treatment paradigm and its conceptual and theoretical underpinnings. We also briefly review the research conducted to date on DBT across populations and settings, the vast majority of which demonstrates that it is effective at treating the behaviors that it targets. We also argue that, although DBT has been established as a "gold-standard" treatment for certain populations and behaviors, there is much more research needed to answer critical questions and improve its efficacy.

Comparative Efficacy and Safety of Neoadjuvant Immunotherapy with Nivolumab vs. Pembrolizumab in Resectable Non-Small Cell Lung Cancer: A Systematic Review.

Non-small cell lung cancer (NSCLC) remains a leading cause of cancer-related mortality worldwide. Immunotherapy has emerged as a promising treatment option due to its favorable toxicity profile. However, selecting the most appropriate immunotherapeutic agent for neoadjuvant use-aimed at curative intent in early-stage NSCLC-based on efficacy and safety remains a critical question. This review aims to compare the efficacy and safety profiles of nivolumab and pembrolizumab when used as neoadjuvant treatments in NSCLC. A systematic review was conducted across PubMed, Scopus, Wiley Online Library, ProQuest Dissertations and Theses Global, and Google Scholar, utilizing the search terms "Nivolumab OR Pembrolizumab AND Neoadjuvant Immunotherapy AND non-small cell lung cancer." Out of 1444 retrieved studies, 4 retrospective studies met the inclusion criteria by providing comparative data on nivolumab and pembrolizumab within the same study cohorts. Despite the critical risk of bias and the evidence quality ranging from moderate to very low across these studies, both nivolumab and pembrolizumab demonstrated efficacy rates exceeding 30% and maintained favorable safety profiles. There is no observed superiority between nivolumab and pembrolizumab in terms of efficacy and safety for the neoadjuvant treatment of early-stage NSCLC.

Accelerating depression intervention: identifying critical psychological factors using MCDM-MOORA technique for early therapy initiation.

BACKGROUND: A thorough psychosocial assessment is time-consuming, often requiring multiple sessions to uncover the psychological factors contributing to mental illness, such as depression. The duration varies depending on the severity of the patient's condition and how effectively the psychotherapist can establish rapport. However, prolonged assessment periods pose a significant risk of patient deterioration. METHODS: The comprehensive psychosocial intervention, led by the Multi-Criteria Decision-Making (MCDM) approach utilizing the Multi-Objective Optimization by Ratio Analysis (MOORA) method, played a pivotal role in identifying the key psychological factors contributing to the depression of the client among the 21 factors specified by BDI-II analysis. RESULTS: The integration of the MOORA strategy compared to traditional psychotherapy on 254 samples demonstrates a Jaccard similarity coefficient of 0.8, with a minimum error margin of 7% (vulnerability index = 0.57), indicating a significant agreement between the two approaches, both converging towards a similar solution. For patients with extreme depression, the number of sessions reduced from 18 ± 2 to 11 ± 2, showing a 33-35% reduction (χ2 = 6.94, p = 0.008). Severe depression patients experienced a reduction from 14 ± 2 to 8 ± 1 sessions i.e., 34-39% reduction (χ2 = 8.32, p = 0.004). Moderate depression patients saw sessions drop from 9 ± 1 to 5 ± 1, i.e., 37-43% reduction (χ2 = 0.29, p = 0.001). The accuracy for detecting dominant psychological factors improved to 82.88% for extreme, 86.74% for severe, and 90.34% for moderate depression, respectively. CONCLUSION: The implementation of MOORA facilitated the identification and prioritization of key psychosocial intervention strategies, making the process significantly faster compared to traditional methods. This acceleration greatly enhanced the precision and efficacy of the work. Additionally, critical vulnerable factors were identified through ordered statistics and correlation analysis [Pearson (r) = 0.8929 and Spearman's rank (ρ) = 0.7551] on the Beck Depression Inventory-II model. These findings were supported by other MCDM schemes such as EDAS and TOPSIS, demonstrating high stability and robustness in dynamic decision-making environments, maintaining consistency across scenarios adapted by different psychotherapists. Overall, the combined application of MCDM (MOORA) and targeted psychological interventions yielded substantial positive outcomes in enhancing the well-being of individuals with psychological illnesses, such as depression, cognitive, affective, and somatic syndromes.

Assessment of outcomes in Crohn's disease: A systematic review of randomized clinical trials to inform a multiple outcome framework.

Longstanding disease control in Crohn's disease (CD) is challenging and requires understanding treatment efficacy and outcomes assessment. With multiple novel therapeutic options, rigorous evaluation of outcomes in randomized controlled trials (RCTs) is crucial to inform clinical practice. This study systematically reviewed RCTs focusing on CD outcomes to elucidate the breadth and depth of reported outcomes and measurement instruments. A systematic search was conducted on MEDLINE and Scopus for RCTs published from 1 January 2000 to 31 January 2023. Eligible studies included full-text articles with at least 50 adult CD patients. Primary and secondary outcomes, along with their measurement instruments, were categorized according to the Outcome Measures in Rheumatology Filter 2.1 framework. From 88 included studies, 393 outcomes were analyzed. Clinical outcomes, such as clinical remission and response, were the most prevalent (50.6%); biomarkers (11.5%) and patient-reported outcomes (10.2%) were also assessed. Other outcomes included disease behavior and complications (2%), endoscopy (10.4%), histology (0.5%), radiology (1.3%), healthcare utilization (3.8%), and therapy-related safety (6.9%). Composite outcomes showed an increasing trend, reflecting a shift toward comprehensive evaluations. Coprimary endpoints, including clinical symptoms and mucosal inflammation, were reported in 21 of 88 studies. This review highlights the evolving landscape of outcome assessment in CD RCTs, emphasizing the increasing complexity of outcomes. The prominence of composite outcomes underscores efforts to capture the multidimensional nature of CD. These findings will inform the second stage of a two-round e-Delphi aimed at prioritizing key domains and outcomes for developing a multiple-component outcome for RCTs in CD research.

Introducing a specified on-line multimodal prehabilitation approach for total knee replacement surgery candidates using data from the COVID-19 pandemic: An exploratory field-based, pre-post, mixed methods implementation pilot study.

RATIONALE: Individuals waiting for total-knee-replacement surgery are at risk of developing morbidities and frailty which may affect their postoperative recovery. Multi-modal prehabilitation could mitigate these unintentional effects. AIMS AND OBJECTIVES: To implement and evaluate a specified online multi-modal prehabilitation intervention in patients waiting for total-knee-replacement surgery in a large urban acute hospital trust. METHOD: A non-randomised, pre/post analysis implementation pilot with a nested qualitative study was conducted and is reported following the standards for implementation studies (StaRI) guidance. Of 35 listed cases, 12 (34%) were eligible, recruited, and completed an 8-week multi-modal online intervention incorporating 5 modalities (i) cardiovascular exercise, (ii) strength/balance function, (iii) smoking cessation, (iv) opioid use, (v) nutritional intake. Interventions were specified using the Rehabilitation Treatment Specification System, where rehabilitation treatment theory accounts for discrete treatment components. Two participated in an online qualitative interview post-intervention. Process evaluation included intervention fidelity, eligibility/recruitment/retention rates, and clinical outcomes included knee function, frailty, gait velocity, anxiety/depression, and quality of life. RESULTS: Five participants (42%) completed the intervention and were retained at follow-up. The intervention was delivered online at specified doses, frequency/durations indicative of high respective adherence, quantity, and exposure fidelity. There was significant improvement in median oxford knee score (p = 0.015), gait velocity (p = 0.040) and anxiety (p = 0.023). The interview revealed 5 themes; surgery preconceptions, motivation, acceptability, postoperative experiences, and future recommendations confirming acceptance of the intervention by virtue of adhering to the treatment exposure delivered as planned. CONCLUSION: The specified multi-modal prehabilitation was acceptable, implementable, and demonstrated evidence of preliminary efficacy. Further experimental pilot work that represents the spectrum of frailty, obesity, quality of life, and comorbidities associated with total-knee-replacement surgery is indicated.

Advances in the Understanding and Treatment of Chronic Chagas Cardiomyopathy.

Chronic Chagas cardiomyopathy (CCC) poses significant health challenges not only in Latin America but also in non-endemic regions due to global migration. The complexity and severity of CCC call for an updated and thorough review to inform clinical practices and direct future research efforts. This review seeks to consolidate current knowledge on CCC, emphasizing diagnostic, therapeutic, and prognostic facets to facilitate better management and understanding of the disease. An exhaustive examination was conducted, analyzing peer-reviewed articles published between January 2020 and April 2024, sourced from prominent medical databases such as PubMed and Scopus. The review delineates crucial aspects of CCC pathophysiology, evaluates patient outcomes, identifies diagnostic challenges, and assesses treatment efficacy. Our findings prompt the need for revised clinical guidelines and stress the importance of continued research to enhance therapeutic strategies and disease comprehension. It is imperative that future studies address these identified gaps to advance patient care and treatment options for CCC.

Clinical and Functional Outcomes of Platelet-Rich Plasma Injection and Corticosteroid Injection in Patients With De Quervain's Tenosynovitis: A Comparative Retrospective Study.

Background and aim De Quervain's tenosynovitis (DQST) is a prevalent condition involving tendon inflammation in the wrist. This study compares the clinical and functional outcomes between patients receiving platelet-rich plasma (PRP) injections and those receiving corticosteroid injections for DQST. Methods A retrospective study conducted at Sri Devaraj Urs Academy of Higher Education and Research, Kolar, India, included 58 patients with DQST, divided into Group A (PRP injection) and Group B (corticosteroid injection). Assessments were conducted using the Visual Analogue Scale (VAS), the Disabilities of the Arm, Shoulder, and Hand (DASH) score, and the Modified Mayo Wrist Score (MMWS) at baseline, one month, three months, and six months. Statistical analyses were performed using IBM SPSS Statistics for Windows, Version 22.0 (Released 2013; IBM Corp., Armonk, NY, USA), with significance set at p < 0.05. Results Both treatment groups demonstrated a reduction in VAS scores over time. Significant improvements were observed at one month (p = 0.007) and six months (p = 0.004) post-injection. Baseline (p = 0.336) and three-month (p = 0.829) VAS scores showed no significant differences. Similarly, DASH scores were not significantly different at any measured time points: baseline (p = 0.331), one month (p = 0.592), three months (p = 0.707), and six months (p = 0.314). MMWS scores also showed no significant differences at baseline (p = 0.123), one month (p = 0.101), three months (p = 0.422), and six months (p = 0.956). Independent sample t-tests highlighted significant VAS score improvements at one month (t = 2.813, p = 0.007) and six months (t = -3.009, p = 0.004), but DASH and MMWS scores showed no significant differences at any time points. Chi-square tests indicated no significant associations between the groups at one-month, three-month, and six-month follow-ups. Conclusion Both PRP and corticosteroid injections effectively alleviate pain in DQST patients, as evidenced by significant VAS score improvements. However, functional outcomes measured by DASH and MMWS scores did not significantly differ between the treatments. These results suggest that while both treatments are effective for pain management, their short-term impact on functional improvement may be similar. To investigate long-term functional results, more research with bigger sample sizes and longer follow-up periods is required.

New staging criteria predicting m-tor inhibitors treatment effect of renal angiomyolipoma in tuberous sclerosis complex patients.

BACKGROUND: We aimed to launched new staging criteria to predict mTOR inhibitors treatment effect of renal angiomyolipomas (r-AMLs) in TSC patients. METHODS: 40 TSC patients with 69 r-AMLs were divided into two groups based on the efficacy of 6-month mTOR inhibitor treatment. Epidemiological data, therapeutic response, and predictive factors of enrolled patients were collected and analyzed. Age, sex, maximum diameter, maximum cross-sectional area (CSAmax), unenhanced mean CT value, enhanced mean CT value, and added value of enhanced CT of largest r-AML at baseline were assessed as potential influencing factors. Receiver operating characteristic (ROC) curve analysis and the area under the ROC curve (AUC) was used to estimate prediction power. RESULTS: After 6 months of mTOR inhibitor treatment, the tumor reduction rates in the two groups were 55.87% and 16.44% (P < 0.001). At the start of treatment, the maximum diameters, CSAmax, added value of enhanced CT of the target lesion in two groups were 7.70 ± 0.73 cm vs. 13.18 ± 1.23 cm(P = 0.028), 57.40 ± 10.76cm2 vs. 167.29 ± 33.09cm2 (P = 0.015), and 62.32 ± 5.03HU vs. 33.06 ± 3.13HU (P = 0.009), respectively. AUCs of CSAmax, added value of enhanced CT, and combination of both were 0.8024, 0.7672, and 0.8116, respectively (P < 0.001). Cut-off values of CSAmax combined with the added value of enhanced CT were 40cm2 and 46HU. AUCs of maximum diameters, combination of maximum diameters and added value of enhanced CT were 0.7600 and 0.8100, respectively (P < 0.001), with cut-off values of 6.6 cm and 46 HU. CONCLUSION: New staging criteria, based on CSAmax and added value of enhanced CT, can predict the treatment efficiency of m-TOR inhibitors for r-AMLs in TSC patients. A simplified version based on maximum diameter and added value of enhanced CT of lesion has also been proposed.

Combined Stromal Vascular Fraction and Fractional CO2 Laser Therapy for Hypertrophic Scar Treatment: A Systematic Review and Meta-Analysis.

BACKGROUND: Hypertrophic scars (HTSs) result from aberrant wound healing processes, leading to raised, thickened tissue with functional discomfort and cosmetic concerns. Current treatments, including corticosteroid injections and laser therapy, have limitations. Stromal vascular fraction (SVF) therapy and CO2 laser treatment offer promising avenues, with SVF therapy showing regenerative potential and CO2 laser therapy promoting precise tissue removal and wound healing. This study aims to investigate the combined application of SVF therapy and CO2 laser treatment for HTS, aiming to enhance treatment efficacy, tissue remodeling, and aesthetic outcomes, ultimately improving patient satisfaction in HTS management. METHOD: PubMed, Scopus, Embase, and Web of Science databases have been searched for relevant studies. The "R" software (version 4.3.1) along with the "tidyverse" and "meta" statistical packages utilized to analyze data related to the efficiency of this combined method. A random-effects model was fitted to the data. For each study, continuous outcomes were pooled by calculating the standardized mean difference, along with their 95% confidence intervals. The assessment of heterogeneity utilized the I2 and chi-squared tests, applying the random effect model. RESULTS: Six articles fulfilled our inclusion criteria and were included in our review. Results from the pooled analysis of Vancouver Scar Scale (VSS) scores across three included studies indicated a significant impact of the SVF+CO2 method on VSS scores post-treatment (SMD=-3.0144; 95% CI:-4.3706 to -1.6583, p<0.0001). However, analysis of transepidermal water loss levels before and after treatment showed no significant difference (SMD=-2.7603; 95% CI: -6.8729 to 1.3522; p=0.1883). Comparatively, in a pooled analysis of two studies, the combined SVF+CO2 method demonstrated superior efficacy in VSS scores compared to other methods (SMD= -1.3573; 95% CI: -2.2475 to -0.4672, p = 0.0028), with moderate heterogeneity across studies (I^2=23.0%, p = 0.2545). CONCLUSION: The combined application of SVF and CO2 laser treatment shows significant promise in improving hypertrophic scars' appearance and texture. The SVF+CO2 method demonstrates superior efficacy compared to other modalities, suggesting its potential as a valuable therapeutic approach for hypertrophic scar management. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Efficacy and Safety of Bendamustine-Rituximab as Frontline Therapy for Indolent Non-Hodgkin Lymphoma: A Real-World, Single-Center, Retrospective Study.

Background The use of bendamustine with an anti-CD20 monoclonal antibody as frontline therapy for indolent non-Hodgkin lymphoma (NHL) has become a standard of care. We aimed to evaluate the real-world efficacy and safety of bendamustine-rituximab (BR) frontline therapy for indolent NHL. Patients and methods Patients with indolent NHL treated with frontline BR therapy in Hôpital du Sacré-Coeur de Montréal, from January 2015 to August 2018 were included in this retrospective study. Results Our cohort included 42 adults with a median age of 63 years. Follicular lymphoma was the most common histology (n = 31, 74%). Most patients had advanced disease (Lugano stage III or IV, 88%). The overall response rate was 84% (complete response = 62% and partial response = 22%). Median progression-free survival (PFS) was not reached. At 30 months, PFS was 74.8% and overall survival was 90%. Grade 3-4 neutropenia occurred in 21% of patients. Infection-related adverse events were observed in 17 patients (40%). Most were grade 1 and 2 events (84%). One case of grade 5 progressive multifocal leukoencephalopathy related to John Cunningham (JC) virus reactivation was observed. The most common non-infectious-related adverse events were mild nausea and fatigue. Conclusions The efficacy and safety of BR treatment for indolent NHL were comparable in our real-life cohort compared to prior studies. This supports BR as a standard of care for indolent NHL. Future studies should assess whether the use of granulocyte-colony stimulating factors as primary prophylaxis effectively mitigates the hematological and infection-related adverse events related to BR therapy.

Efficacy and safety of dacomitinib as first-line treatment for advanced non-small cell lung cancer patients with epidermal growth factor receptor 21L858R mutation: A multicenter, case-series study in China.

Objective: To provide real-world evidence for the application of first-line dacomitinib treatment for epidermal growth factor receptor (EGFR) 21L858R mutant non-small cell lung cancer (NSCLC) patients in China and to explore the factors influencing the efficacy and safety. Methods: A longitudinal, consecutive case-series, multicenter study with mixed prospective and retrospective data was conducted. The primary endpoint was progression-free survival (PFS), and the secondary endpoints included duration of treatment (DOT), overall survival (OS), objective response rate (ORR), disease control rate (DCR) and safety. Results: A total of 155 EGFR 21L858R mutant patients treated with first-line dacomitinib were included. The median follow-up time for these patients was 20.4 months. Among 134 patients with evaluable lesions, the ORR was 70.9% and the DCR was 96.3%. The median PFS was 16.3 [95% confidence interval (95% CI), 13.7-18.9] months. Multivariate Cox regression analysis suggested that the baseline brain metastasis (BM) status [with vs. without BM: hazard ratio (HR), 1.331; 95% CI, 0.720-2.458; P=0.361] and initial doses (45 mg vs. 30 mg: HR, 0.837; 95% CI, 0.427-1.641; P=0.604) did not significantly affect the median PFS. The median DOT was 21.0 (95% CI, 17.5-24.6) months and the median OS was not reached. Genetic tests were performed in 64 patients after progression, among whom 29 (45.3%) patients developed the EGFR 20T790M mutation. In addition, among the 46 patients who discontinued dacomitinib treatment after progression, 31 (67.4%) patients received subsequent third-generation EGFR-tyrosine kinase inhibitors. The most common grade 3-4 adverse events were rash (10.4%), diarrhea (9.1%), stomatitis (7.1%) and paronychia (4.5%). The incidence of grade 3-4 rash was significantly higher in the 45 mg group than that in the 30 mg group (21.9% vs. 7.5%, P=0.042). Conclusions: First-line dacomitinib treatment demonstrated promising efficacy and tolerable adverse events among EGFR 21L858R mutant NSCLC patients in China.

Comparison of endoscopic retrograde cholangiopancreatography with laparoscopic surgery for patients with mild and moderately severe acute biliary pancreatitis.

Acute biliary pancreatitis (ABP) is an acute inflammatory reaction that occurs as a result of abnormal reflux of bile into the pancreatic duct, which activates pancreatic digestive enzymes to produce pancreatic auto-digestion. Objectives: To explore the advantages of Endoscopic Retrograde Cholangiopancreatography (ERCP) treatment compared with laparoscopic surgery in the management of patients with mild and moderately severe ABP, and to study the risk factors for recurrence of ABP and construct a risk prediction model to assist in resolving clinical decision-making and improving prognosis. Methods: Patients with mild and moderately severe ABP treated at General Hospital of Ningxia Medical University from January 1, 2019 to July 1, 2022 were reviewed. A total of 327 patients were enrolled according to the inclusion criteria and exclusion criteria. According to the different treatment modalities, they were divided into the group treated via ERCP (n = 239) and the group treated via laparoscopic surgery (n = 88). Statistical analyses were performed to compare the differences between the average levels of preoperative and postoperative blood routine and blood biochemical indexes, as well as the time of recovery from clinical symptoms, length of hospital stay, and postoperative complications between the two groups of patients. The 280 patients who participated in the follow-up were divided into the recurrence group (n = 130) and the non-recurrence group (n = 150) according to whether they had recurrence or not. Independent samples t-test and binary logistic regression were used to analyze the causative monofactors and risk factors of recurrent biliary pancreatitis, and then to construct the model and assess the predictive accuracy of the model. Results: On postoperative day 2, the incidence of local complications, Balthazar CT score, and the number of analgesia were lower in the patients in the group treated by ERCP than in the group treated by laparoscopic surgery (P < 0.001), and the duration of antibiotics, enzyme-suppressing medication, fasting, and hospital stay were shorter in the patients in the group treated by ERCP than in the group treated by laparoscopic surgery (P < 0.001). Personal history, gamma glutamyl transpeptidase (GGT), and treatment modality are risk factors for recurrence of biliary pancreatitis. The model constructed by combining GGT, personal history, and treatment modality had the best predictive ability for disease recurrence compared with the model with GGT, personal history, and treatment modality alone (area under the ROC curve 0.815). Conclusion: Compared with the laparoscopic surgery group, ERCP treatment can effectively relieve symptoms and restore gastrointestinal function in advance in patients with ABP, and reduce hospitalisation time and related complications. Personal history, GGT, and treatment modality are risk factors for recurrence of biliary pancreatitis. Patients can prevent recurrence by abstaining from smoking and alcohol, eating a healthy diet, and exercising appropriately.

The Real-World Efficacy and Safety of Direct-Acting Antivirals for Chronic Hepatitis C in Patients Active Malignancies.

BACKGROUND: Over the past years, the introduction of direct-acting antivirals (DAAs) revolutionized chronic hepatitis C treatment. We aimed to characterize and assess treatment efficacy in three specific groups of patients treated with DAAs: those with active solid malignant tumors (SMTs), hematological diseases (HDs) and hepatocellular carcinomas (HCCs). METHODS: A total of 203 patients with active oncological disease (SMT n = 61, HD = 67, HCC n = 74) during DAA treatment in 2015-2020 selected from the EpiTer-2 database were analyzed retrospectively and compared to 12,983 patients without any active malignancy. RESULTS: Extrahepatic symptoms were more frequent in HD patients (17.2% vs. SMT = 10.3%, HCC = 8.2%, without = 7.8%, p = 0.004). HCC patients characterized with the highest ALT activity (81 IU/L vs. SMT = 59.5 IU/L, HD = 52 IU/L, without = 58 IU/L, p = 0.001) more often had F4 fibrosis as well (86.11% vs. SMT = 23.3%, HD = 28.8%, controls = 24.4%, p = 0.001). A significant majority of subjects in HCC, HD and SMT populations completed the full treatment plan (HCC = 91%; n = 67, HD = 97%; n = 65, SMT = 100%; n = 62). Concerning the treatment efficacy, the overall sustained virologic response, excluding non-virologic failures, was reported in 93.6% HD, 90.16% SMT and 80.6% in HCC patients. CONCLUSIONS: As presented in our study, DAA therapy has proven to be highly effective and safe in patients with active SMTs and HDs. However, therapy discontinuations resulting from liver disease progression remain to be the major concern in HCC patients.

Unraveling the complexities of antifungal susceptibility testing in Candida spp.: Insights from design of experiments.

Our study delved into the intricate dynamics of antifungal susceptibility testing for Candida spp., employing a Design of Experiments approach. We systematically investigated the influence of pH, temperature, inoculum size, and glucose concentration on both growth patterns and inhibitory concentrations of Candida spp. Our findings underscore the nuanced interplay between these factors, revealing significant impacts on susceptibility outcomes. Notably, even minor adjustments in these parameters yielded substantial variations in growth and inhibitory concentrations, underscoring the critical importance of meticulous control over growth conditions in antifungal susceptibility testing protocols. Each Candida isolates exhibited unique susceptibility profiles, necessitating tailored culture conditions for accurate testing. Our study sheds light on the variability inherent in Candida spp. growth patterns and emphasizes the need for standardized protocols to ensure consistency across laboratories. By leveraging the design of experiments, our research provides a systematic framework for unraveling the complexities of antifungal susceptibility testing, offering valuable insights for optimizing testing protocols and informing clinical decision-making in antifungal treatment. These findings represent a significant step towards enhancing the efficacy and reliability of antifungal susceptibility testing in clinical practice.

Letter to editor: The efects of dabrafenib and/or trametinib treatment in Braf V600­mutant glioma: a systematic review and meta-analysis.

The systematic review and meta-analysis titled "The Effects of Dabrafenib and/or Trametinib Treatment in BRAF V600-Mutant Glioma" provides a critical evaluation of these targeted therapies for a challenging subset of gliomas. This review is notable for its comprehensive data integration, offering a robust assessment of the efficacy and safety of dabrafenib and trametinib. By focusing on BRAF V600 mutations, it contributes valuable insights into personalized treatment strategies. However, limitations include study heterogeneity and a lack of long-term follow-up data, which hinder the generalizability and complete understanding of treatment effects. Additionally, while the review emphasizes therapeutic potential, it requires a thorough evaluation of adverse effects. Future research should address these limitations by providing more consistent data, longer follow-up, and a balanced view of treatment risks and benefits.

Retrospective analysis of lithium treatment: examination of blood levels.

Introduction: Lithium is a key medication for treating various neuropsychiatric disorders, with a narrow therapeutic index and significant drug interactions. Monitoring lithium blood levels is crucial. This study aims to investigate the relationship between lithium blood levels and demographic characteristics such as age and gender, as well as possible drug interactions, in patients with a history of lithium use who applied to various services and outpatient clinics. Materials & methods: The files of 438 patients who were admitted to various services and outpatient clinics of Kirklareli Training and Research Hospital between January 1 and December 31, 2023, were retrospectively reviewed. Patients' blood lithium levels, gender, age, service/outpatient clinic they admitted to, other medications used, urea, creatinine, and eGFR values were recorded. Results: When the demographic characteristics of 438 patients were examined, 62% were female (270), 38% were male (168), and the average age was 46.3 ± 14.8 years, showing a normal distribution. It was found that 192 patients (71 males, 121 females) had therapeutic lithium blood levels, while 244 patients (97 males, 147 females) had levels below 0.6 mmol/L. Two female patients had blood levels above the therapeutic range (1.23 and 1.43 mmol/L). Among the clinics and services, the four most frequented were the psychiatry clinic (314 patients), internal medicine clinic (36 patients), emergency service (27 patients), and medical oncology clinic (17 patients). Of the 314 patients admitted to the psychiatry clinic, 168 had therapeutic drug levels; only 7 of the 36 admitted to internal medicine had therapeutic levels; 12 of the 27 patients in the emergency service had therapeutic levels; and all 17 patients in medical oncology had levels below therapeutic limits. Discussion: The data emphasize the importance of regular blood level monitoring to ensure lithium treatment's efficacy and patient safety. It is noteworthy that most patients in the psychiatry clinic had therapeutic drug levels, while those in other clinics had lower levels. Conclusion: In conclusion, this study highlights the importance of regular blood level monitoring to ensure the efficacy and safety of lithium treatment.

Preferences for attributes of oral antipsychotic treatments: results from a discrete-choice experiment in respondents with schizophrenia or bipolar I disorder.

BACKGROUND: Antipsychotic medications are effective treatments for schizophrenia (SZ) and bipolar I disorder (BD-I), but when presented with different treatment options, there are tradeoffs that individuals make between clinical improvement and adverse effects. As new options become available, understanding the attributes of antipsychotic medications that are valued and the tradeoffs that individuals consider when choosing among them is important. METHODS: A discrete-choice experiment (DCE) was administered online to elicit preferences across 5 attributes of oral antipsychotics: treatment efficacy (i.e., improvement in symptom severity), weight gain over 6 months, sexual dysfunction, sedation, and akathisia. Eligible respondents were aged 18-64 years with a self-reported clinician diagnosis of SZ or BD-I. RESULTS: In total, 144 respondents with SZ and 152 with BD-I completed the DCE. Of those with SZ, 50% identified themselves as female and 69.4% as White, with a mean (SD) age of 41.0 (10.1) years. Of those with BD-I, most identified themselves as female (69.7%) and as White (77.6%), with a mean (SD) age of 40.0 (10.7) years. In both cohorts, respondents preferred oral antipsychotics with better efficacy, less weight gain, no sexual dysfunction or akathisia, and lower risk of sedation. Treatment efficacy was the most important attribute, with a conditional relative importance (CRI) of 31.4% for respondents with SZ and 31.0% for those with BD-I. Weight gain (CRI = 21.3% and 23.1%, respectively) and sexual dysfunction (CRI = 23.4% and 19.2%, respectively) were adverse effects in this study that respondents most wanted to avoid. Respondents with SZ were willing to accept 9.8 lb of weight gain or > 25% risk of sedation for symptom improvement; those with BD-I were willing to accept 8.5 lb of weight gain or a > 25% risk of sedation. CONCLUSIONS: In this DCE, treatment efficacy was the most important attribute of oral antipsychotic medications among respondents with SZ and BD-I. Weight gain and sexual dysfunction were the adverse effects respondents most wanted to avoid; however, both cohorts were willing to accept some weight gain or sedation to obtain better efficacy. These results highlight features that patients value in antipsychotic medications and how they balance benefits and risks when choosing among treatments.