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Purpose: Laryngopharyngeal reflux disease (LPRD) is mainly treated with proton pump inhibitors (PPI) such as esomeprazole, which have shortcomings like delayed absorption and increased osteoporosis. Fexuprazan is a novel potent potassium-competitive acid blocker that inhibits gastric acid secretion with rapid onset and long duration of action. To assess the efficacy and safety of fexuprazan compared to esomeprazole in patients with LPRD. Methods: This prospective, randomized, double-blinded, multicenter, active-controlled trial was conducted in nine otolaryngologic clinics. Patients with reflux symptom index (RSI) ≥ 13 and reflux finding score (RFS) ≥ 7 were randomly assigned to the fexuprazan or esomeprazole groups, and received fexuprazan 40-mg or esomeprazole 40-mg once daily for 8 weeks. The outcomes were (1) mean change, change rate, and valid rate in RSI, RFS, and LPR-related questionnaires; and (2) adverse events. Results: A total of 136 patients (fexuprazan n = 68, esomeprazole n = 68) were followed up for ≥ 1 month. Each parameter significantly improved after 4 and 8 weeks in each group, with no significant differences between the two groups. For those with severe symptoms (RSI ≥ 18), the fexuprazan group (n = 32) showed more improvement in the mean change and change rate in the RSI than esomeprazole group (n = 31) after 4 weeks (p =.036 and.045, respectively). This phenomenon was especially observed in hoarseness and troublesome cough. Conclusion: Fexuprazan improved symptoms and signs without no serious adverse events in patients with LPRD. In patients with severe symptoms, fexuprazan resulted in a faster symptom improvement than PPI. Trial registration: KCT0007251, https://cris.nih.go.kr/cris/search/detailSearch.do?seq=22100. [ABSTRACT FROM AUTHOR]

• This review summarizes the history and science of LGBTQ-affirmative psychotherapy. • This review outlines a future research agenda for LGBTQ-affirmative psychotherapy. • Research is needed on LGBTQ-affirmative psychotherapy mechanisms and moderators. • Research is needed on therapy orientations beyond CBT and with diverse populations. • Future implementation efforts should embed therapy within structural interventions. 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. [ABSTRACT FROM AUTHOR]

• Describes the paradigms that inform the delivery of dialectical behavior therapy. • Provides overview of critical research on dialectical behavior therapy. • Suggests avenues for future research on 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. [ABSTRACT FROM AUTHOR]

Aim: There is no consensus on the best prophylaxis for supraventricular tachycardia (SVT) in infancy. We studied the efficacy and safety of sotalol. Method: This retrospective study comprised infants diagnosed with SVT before 1 year of age and treated with sotalol during 2002–2018 in Stockholm, Sweden. The patients' characteristics, comorbidities, sotalol dosages, QT intervals and outcomes were extracted from their medical records. Results: We studied 85 infants (65% boys) with a median age of eight (range 0–288) days at the time of diagnosis, including 78 with re‐entry tachycardia. Sotalol was completely or partially successful in the 67/75 patients who completed the treatment, as well as in four of the seven patients with other tachycardia mechanisms. The 48 infants with postnatal debut had significantly higher success rates than the 27 with foetal debut (96% vs. 78%, p = 0.04). Prolongation of corrected QT (QTc) intervals of ≥450 ms occurred in 16% of the total cohort and two patients with QTc intervals of ≥500 ms had their treatment changed. There were no cases of proarrhythmia after sotalol treatment. Conclusion: Sotalol provided effective and safe prophylaxis for SVT during infancy. QTc prolongation rarely caused treatment discontinuation and there were no cases of proarrhythmia. [ABSTRACT FROM AUTHOR]

Beauveria bassiana is an entomopathogenic fungus that has been shown to have the potential to control the potato white grub (Premnotrypes vorax), a pest that significantly affects potato production, especially in Ecuador. Therefore, the present study has focused on evaluating the effectiveness of Beauveria bassiana in the control of the potato white grub under laboratory conditions. To this end, neutrosophic statistics have been used to analyze larval mortality, by applying concentrations of and conidia of Beauveria bassiana by spraying and immersion. Among the results, it was determined that treatment at a concentration of 108 conidia per spray has proven to be the best option, with a neutrosophic coding from very effective to extremely effective in mortality in larvae. In conclusion, neutrosophic analysis has shown that Beauveria bassiana is effective in controlling white grub, especially with high concentrations and spraying. [ABSTRACT FROM AUTHOR]

Atezolizumab plus bevacizumab is a standard of care, first-line therapy for advanced hepatocellular carcinoma (HCC). Myeloid and T regulatory cells are key immunosuppressive cell types within the hepatic tumor microenvironment associated with clinical resistance to atezolizumab and bevacizumab therapy for HCC and overall poor prognosis. Therapeutic targeting of TIGIT, which is highly expressed in these cells, with tiragolumab may overcome the immunosuppressive environment and improve clinical benefit, a hypothesis supported by positive efficacy signals in the Phase Ib/II MORPHEUS-Liver study. This paper describes the rationale and design of IMbrave152/SKYSCRAPER-14, a randomized, double-blind, placebo-controlled Phase III study comparing atezolizumab and bevacizumab with tiragolumab or placebo in patients with HCC and no prior systemic treatment. Clinical Trial Registration: NCT05904886 (ClinicalTrials.gov) Plain Language Summary This research study is designed to test a new treatment combination for liver cancer, specifically for patients whose cancer cannot be removed with surgery or has spread. The treatment involves three medications: atezolizumab, bevacizumab and tiragolumab. Atezolizumab and bevacizumab are already used together as a standard treatment for liver cancer. Tiragolumab is designed to block the TIGIT receptor, which is normally involved in holding back the immune cells that would attack the tumor. Because tiragolumab may restore the immune response against the tumor, adding tiragolumab might make the treatment more effective. The study is being done worldwide and includes patients who have not received any previous systemic treatment for their advanced liver cancer. Patients participating in the study will be randomly placed into two groups. One group will receive the new combination of three medications, while the other group will receive the standard treatment of two medications plus a placebo (a treatment with no active ingredient). The main goal is to see if the new combination helps patients live longer and slows the cancer's growth compared with the standard treatment. Safety and how patients feel during the treatment are also important parts of the study. Tweetable Abstract IMbrave152/SKYSCRAPER-14: New Phase III trial tests atezolizumab, bevacizumab & tiragolumab in advanced HCC, aiming to revolutionize treatment outcomes. #HCCResearch #OncologyInnovation Article highlights Advanced hepatocellular carcinoma treatment Atezolizumab in combination with bevacizumab has become the standard first-line therapy for advanced hepatocellular carcinoma (HCC). The immunosuppressive hepatic tumor microenvironment may limit the clinical activity of this combination in patients with HCC. TIGIT, a protein often found at high levels within these immunosuppressive cells, is a potential therapeutic target to overcome this resistance. Tiragolumab is an agent that inhibits TIGIT, suggesting a possible improvement in clinical outcomes when combined with the existing therapy. IMbrave152/SKYSCRAPER-14 trial rationale The randomized Phase III trial (NCT05904886) is designed to compare the efficacy and safety of the addition of tiragolumab to the current atezolizumab and bevacizumab regimen for HCC. The trial is designed to confirm efficacy signals from the Phase Ib/II MORPHEUS-Liver study, testing the hypothesis that targeting TIGIT with tiragolumab can enhance treatment response. Study design & eligibility Approximately 650 participants with no prior systemic treatment will be assigned to receive either the triple combination of atezolizumab, bevacizumab and tiragolumab or the standard dual therapy plus placebo. Participants will be randomly divided into two groups with stratification based on geographic region, disease progression, α-fetoprotein levels and HCC etiology. Treatment & trial objectives Patients will be administered intravenous doses of the treatment every three weeks, with outcomes measured in terms of progression-free survival and overall survival. Secondary end points include safety, efficacy, pharmacokinetics, immunogenicity and quality-of-life assessments. Preliminary results & safety profile The MORPHEUS-Liver trial indicated improved outcomes with the addition of tiragolumab to the existing atezolizumab and bevacizumab treatment, suggesting a well-tolerated safety profile with manageable adverse events. Conclusions & implications for hepatocellular carcinoma treatment IMbrave152/SKYSCRAPER-14 aims to establish whether the addition of tiragolumab can redefine the standard of care for unresectable HCC. This trial's findings could significantly impact the therapeutic landscape for HCC, addressing a critical unmet medical need [ABSTRACT FROM AUTHOR]

Introduction: Little was known about the relationship between sleep disturbances and depressive and anxiety disorders, as well as the efficacy of treatment regimens. Methods: During 2021 to 2023, a total of 417 participants were screened by Hamilton Depression Rating Scale (HAMD-17) and Hamilton Anxiety Rating Scale (HAMA-14) for psychological status, and Pittsburgh sleep quality index (PSQI) assessment. 409 participants were finally enrolled, of which 188 (45.97%) were suffered from sleep disorders. All participants were received polysomnography (PSG) followed by six-week pharmacological treatment of escitalopram and zopiclone, and finally assessed by HAMD-17 and HAMA-14 for treatment efficacy. Result: PSG monitoring indicated that participants with depression experienced prolonged rapid eye movement sleep latency (REMSL) and increased wakefulness after sleep onset (WASO) (P=0.030 and P=0.002, respectively). Those with anxiety disorders demonstrated a significantly higher percentage of non-rapid eye movement sleep (NREM%) and reduced WASO (P=0.013 and P=0.001, respectively). After six-weeks pharmacological treatment, participants with or without sleep disorders exhibited with similar efficacy outcomes of depression and anxiety disorders (P>0.05). However, every point of PSQI increment at baseline would decrease 0.78 and 0.85 times of probability of effective pharmacological treatment of depression and anxiety disorders. Moreover, participants with both effective outcomes of depression and anxiety disorders were found significant shorter sleep onset latency (SOL) (P<0.001). Discussion: The insights gained underscore the necessity of considering sleep disturbances in enhancing the overall effectiveness of pharmacological treatments for depression and anxiety disorders. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The phase 3 NEURO-TTRansform trial showed eplontersen treatment for 65 weeks reduced transthyretin (TTR), halted progression of neuropathy impairment, and improved quality of life (QoL) in adult patients with hereditary TTR-mediated amyloidosis with polyneuropathy (ATTRv-PN), vs. historical placebo. Methods: NEURO-TTRansform enrolled patients with ATTRv-PN. A subset of patients were randomized to receive subcutaneous inotersen 300 mg weekly (Weeks 1–34) and subsequently switched to subcutaneous eplontersen 45 mg every 4 weeks (Weeks 37–81). Change in serum TTR and treatment-emergent adverse events (TEAEs) were evaluated through Week 85. Effects on neuropathy impairment, QoL, and nutritional status were also evaluated. Results: Of 24 patients randomized to inotersen, 20 (83%) switched to eplontersen at Week 37 and four discontinued due to AEs/investigator decision. Absolute change in serum TTR was greater after switching from inotersen (−74.3%; Week 35) to eplontersen (−80.6%; Week 85). From the end of inotersen treatment, neuropathy impairment and QoL were stable (i.e., did not progress) while on eplontersen, and there was no deterioration in nutritional status. TEAEs were fewer with eplontersen (Weeks 37–85; 19/20 [95%] patients) compared with inotersen (up to Week 35; 24/24 [100%] patients). Mean platelet counts decreased during inotersen treatment (mean nadir reduction ‒40.7%) and returned to baseline during eplontersen treatment (mean nadir reduction, ‒3.2%). Conclusions: Switching from inotersen to eplontersen further reduced serum TTR, halted disease progression, stabilized QoL, restored platelet count, and improved tolerability, without deterioration in nutritional status. This supports a positive benefit-risk profile for patients with ATTRv-PN who switch from inotersen to eplontersen. [ABSTRACT FROM AUTHOR]

Objective: This research aimed to evaluate the impact of grading and zoning nursing management on traumatic brain injury (TBI) patients' emergency treatment outcomes. Methods: This randomized controlled trial included 200 TBI patients. They were treated with a conventional care (control group, n = 100) and a novel grading and zoning approach (study group, n = 100), respectively. This innovative model organized care into levels based on urgency and complexity, facilitating targeted medical response and resource allocation. Key metrics compared included demographic profiles, consultation efficiency (time metrics and emergency treatment rates), physiological parameters (HR, RR, MAP, SpO2, RBS), and patient outcomes (hospital and ICU stays, complication rates, and emergency outcomes). Results: The study group demonstrated significantly improved consultation efficiency, with reduced times for physician visits, examinations, emergency stays, and specialist referrals (all p < 0.001), alongside a higher emergency treatment rate (93% vs. 79%, p = 0.004), notably better physiological stability, improved HR, RR, MAP, SpO2 and RBS (p < 0.001), shorter hospital and ICU stays, fewer complications, and superior emergency outcomes. Conclusion: Grading and zoning nursing management substantially enhances TBI patients' emergency care efficiency and clinical outcomes, suggesting a viable model for improving emergency treatment protocols. [ABSTRACT FROM AUTHOR]

Purpose: Stereotactic Radiosurgery (SRS) is the primary treatment for patients with limited numbers of small brain metastases. Head fixation is usually performed with framed-based (FB) fixation; however, mask-based (MB) fixation has emerged as a less invasive alternative. A comparative meta-analysis between both approaches has not been performed. Methods: Databases were searched until August 28th, 2023, to identify studies comparing MB and FB SRS in the treatment of brain metastases. Our outcomes of interest included local tumor control (LTC), radiation necrosis (RN), mortality, and treatment time (TT). Mean difference (MD), risk ratio (RR), and hazard ratio (HR) were used for statistical comparisons. Results: From 295 articles initially identified, six studies (1 clinical trial) involving 509 patients were included. LTC revealed comparable RR at 6-months (RR = 0.95[95%CI = 0.89–1.01], p = 0.12) and a marginal benefit in FB SRS at 1-year (RR = 0.87[95%CI = 0.78–0.96], p = 0.005). However, in oligometastases exclusively treated with single-fraction SRS, LTC was similar among groups (RR = 0.92 [95%CI = 0.89–1.0], p = 0.30). Similarly, in patients with oligometastases treated with single-fraction SRS, RN (HR = 1.69; 95%CI = 0.72–3.97, p = 0.22), TT (MD = -29.64; 95%CI = -80.38–21.10, p = 0.25), and mortality were similar among groups (RR = 0.62; 95%CI = 0.22–1.76, p = 0.37). Conclusion: Our findings suggest that FB and MB SRS, particularly oligometastases treated with single-fraction, are comparable in terms of LTC, RN, TT, and mortality. Further research is essential to draw definitive conclusions. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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 Kırklareli 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 patientswere examined, 62% were female (270), 38%weremale (168), and the average agewas 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), internalmedicine 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. [ABSTRACT FROM AUTHOR]

Simple Summary: In the era of direct-acting antiviral (DAA) agents, chronic hepatitis C virus (HCV) infection has become a curable disease. Eradication of the virus remains a major goal for the World Health Organization (WHO) by 2030. Main obstacles seem to be the lack of national screenings and shortage of knowledge among patients and healthcare professionals. There also remain, scarcely described in the literature, specific groups of patients who, due to their comorbidities such as malignant tumors, may not be considered as candidates eligible for DAA treatment. In our study, we aimed to characterize and present treatment efficacy in individuals with chronic hepatitis C and an active malignancy treated in Poland in years 2015–2020 with DAAs and compare their outcomes with a treated population with no active malignancy. The obtained results indicate high effectiveness and a low number of premature treatment discontinuations for the majority of patients with active malignancies, with some concerns around HCCs. We believe that data provided by this study will lead to more efficient elaboration of the standard of care in this population. 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. [ABSTRACT FROM AUTHOR]

Background: Chemotherapy‐induced anorexia is a common occurrence in patients undergoing treatment for advanced lung cancer. However, the relationship between chemotherapy‐induced anorexia and weight loss during platinum‐based chemotherapy combined with immune checkpoint inhibitors is unclear. This study explored the relationship between chemotherapy‐induced anorexia and therapeutic outcomes in patients with stage IV non‐small‐cell lung cancer undergoing platinum‐based chemotherapy combined with immune checkpoint inhibitors. Methods: The study retrospectively reviewed the medical records of 106 patients with stage IV non‐small‐cell lung cancer treated with platinum‐based chemotherapy and immune checkpoint inhibitors between January 2019 and October 2022. The incidence of weight loss and its association with treatment efficacy was assessed in the chemotherapy‐induced anorexia group. Chemotherapy‐induced anorexia, nausea, and vomiting were evaluated using Common Terminology Criteria for Adverse Events v 5.0. Progression‐free and overall survival were used to measure treatment efficacy. Results: Chemotherapy‐induced anorexia was observed in 13.2% of patients. These patients exhibited significant weight loss at 6 and 9 weeks after treatment initiation compared to those in the non‐chemotherapy‐induced anorexia group. Progression‐free and overall survival were shorter in the chemotherapy‐induced anorexia group than in the non‐chemotherapy‐induced anorexia group, but the difference was not statistically significant. Conclusions: Chemotherapy‐induced anorexia was associated with significant weight loss and reduced treatment efficacy in patients with stage IV non‐small‐cell lung cancer. These results highlight the importance of implementing robust supportive care for chemotherapy‐induced anorexia to mitigate weight loss and uphold treatment effectiveness during platinum‐based chemotherapy combined with immune checkpoint inhibitors. [ABSTRACT FROM AUTHOR]

Tyrosine kinase inhibitors (TKIs) have significantly improved the survival of patients with chronic myeloid leukemia (CML), however, older patients are often underrepresented in pivotal trials. Approximately 20% of older adults never start treatment and face significant barriers to accomplish favorable outcomes. The treatment goal is to improve survival, prevent progression, and preserve quality of life. This is achieved through optimizing TKI doses and employing discontinuation strategies to attain treatment-free remission (TFR), a goal increasingly pursued by older patients. Imatinib may be favored as the front-line option for older individuals due to its side effect profile and cost. Bosutinib's favorable cardiovascular tolerability makes it a suitable second-line agent, but lower-dose dasatinib may likewise be an attractive option. The prevalence of comorbidities can preclude the use of second generation TKIs in some older patients. Optimal care for older patients with CML centers on personalized treatment, close monitoring, and proactive support. [ABSTRACT FROM AUTHOR]

Shengyang Liu,1 Hui Zhao,2 Li Shi,1 Hongzhi Ji1 1Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University, Jinan, People’s Republic of China; 2Department of Radiology, Shandong Second Provincial General Hospital, Jinan, People’s Republic of ChinaCorrespondence: Hongzhi Ji, Department of Otorhinolaryngology Head and Neck Surgery, Shandong Provincial ENT Hospital, Shandong University, 4 Duanxing West Road, Jinan, 250000, People’s Republic of China, Email jhz_jx163@163.comAbstract: In this case report, we describe a 21-year-old man with recurrent hemangiomas in his left eye socket and nasal cavity. Traditional surgeries were unsuccessful, so we used Bevacizumab, a drug that inhibits blood vessel growth. This approach significantly reduced the tumor size and stopped frequent nosebleeds. Over two years, the tumor remained controlled without major side effects, suggesting Bevacizumab as a promising non-surgical treatment for recurrent hemangiomas.Keywords: Bevacizumab, orbital hemangioma, vascular endothelial growth factor, treatment efficacy

Abstract 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 (χ 2 = 6.94, p = 0.008). Severe depression patients experienced a reduction from 14 ± 2 to 8 ± 1 sessions i.e., 34–39% reduction (χ 2 = 8.32, p = 0.004). Moderate depression patients saw sessions drop from 9 ± 1 to 5 ± 1, i.e., 37–43% reduction (χ 2 = 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.

Background. Mycosis fungoides (MF) is classified as an orphan disease. Due to the rarity of pathology, and until recently the absence of an expert group and a specialized reference center for cutaneous lymphomas in Russia, possible treatment options for MF are presented by listing them without recommendations on the preferred indications for one or another option. This creates difficulties in choosing treatment methods and assessing their effectiveness.Aim. To characterize current treatment methods and their results in MF patients who were observed or received consultative and diagnostic care at the National Medical Research Center for Hematology.Materials and methods. The study included 210 patients: 115 with early disease stages and 95 with advanced stages.Results and conclusion. The most common treatment options were for early stages – local therapy, interferon therapy and systemic chemotherapy (CT), for advanced stages – combination therapy with interferon (+ PUVA therapy, methotrexate), interferon monotherapy and systemic CT. The frequency of systemic chemotherapy use in all lines of MF treatment was 21 %. When integrating statistical analysis using the probability of achieving an antitumor response, switching to 2nd line therapy, and accumulated incidence, the negative results of using chemotherapy in the MF treatment were clearly demonstrated.For the first time in Russia, a real practical situation of the applied MF treatment options is presented on our own large sample of patients. As the first line of therapy, the most common options were immunotherapy and phototherapy, however, in 12.4 % of cases, the use of systemic CT was registered, which is unjustified and leads to a decrease in the time to the next line of treatment and an increase in the cumulative incidence of adverse events. As a result of the use of non-chemotherapeutic approaches (interferon, etc.), the 3-year relapse-free survival rate is about 40 %, after chemotherapy – 9.4 %. Secondand third-line therapy provided more varied options, including combination treatment with interferon and methotrexate, as well as gemcitabine monotherapy, targeted therapy with brentuximab vedotin, and epigenetic therapy in the 3rd line. Studies with targeted agents in this patient population have demonstrated improved clinical outcomes, highlighting the need for their early use to achieve the best results.

Abstract 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.

Abstract Background Chemotherapy‐induced anorexia is a common occurrence in patients undergoing treatment for advanced lung cancer. However, the relationship between chemotherapy‐induced anorexia and weight loss during platinum‐based chemotherapy combined with immune checkpoint inhibitors is unclear. This study explored the relationship between chemotherapy‐induced anorexia and therapeutic outcomes in patients with stage IV non‐small‐cell lung cancer undergoing platinum‐based chemotherapy combined with immune checkpoint inhibitors. Methods The study retrospectively reviewed the medical records of 106 patients with stage IV non‐small‐cell lung cancer treated with platinum‐based chemotherapy and immune checkpoint inhibitors between January 2019 and October 2022. The incidence of weight loss and its association with treatment efficacy was assessed in the chemotherapy‐induced anorexia group. Chemotherapy‐induced anorexia, nausea, and vomiting were evaluated using Common Terminology Criteria for Adverse Events v 5.0. Progression‐free and overall survival were used to measure treatment efficacy. Results Chemotherapy‐induced anorexia was observed in 13.2% of patients. These patients exhibited significant weight loss at 6 and 9 weeks after treatment initiation compared to those in the non‐chemotherapy‐induced anorexia group. Progression‐free and overall survival were shorter in the chemotherapy‐induced anorexia group than in the non‐chemotherapy‐induced anorexia group, but the difference was not statistically significant. Conclusions Chemotherapy‐induced anorexia was associated with significant weight loss and reduced treatment efficacy in patients with stage IV non‐small‐cell lung cancer. These results highlight the importance of implementing robust supportive care for chemotherapy‐induced anorexia to mitigate weight loss and uphold treatment effectiveness during platinum‐based chemotherapy combined with immune checkpoint inhibitors.

Abstract Introduction Deucravacitinib, a novel, oral, selective allosteric tyrosine kinase 2 inhibitor, demonstrated superiority versus placebo and apremilast in the POETYK PSO-1 and PSO-2 studies. We describe patient-reported outcomes with deucravacitinib treatment versus placebo and apremilast in these studies. Methods Two multicenter, global, double-blind, placebo- and active comparator-controlled studies randomized patients with moderate-to-severe plaque psoriasis 1:2:1 to placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily. Score changes from baseline and meaningful within-patient change responses for Psoriasis Symptoms and Signs Diary (PSSD) and Dermatology Life Quality Index (DLQI) were assessed. Results In POETYK PSO-1 (n = 666) and PSO-2 (n = 1020), respectively, improvement from baseline in PSSD total score was greater with deucravacitinib (− 27.8 and − 30.1) versus placebo (− 4.4 and − 5.9) and apremilast (− 18.9 and − 22.5) at Week 16 and versus apremilast at Week 24 (deucravacitinib: − 32.8 and − 30.7; apremilast: − 21.6 and − 22.8) (nominal p

Abstract Background Many effective therapies for psoriasis are being applied in clinical practice in recent years, however, some patients still can’t achieve satisfied effect even with biologics. Therefore, it is crucial to identify factors associated with the treatment efficacy among psoriasis patients. This study aims to explore factors influencing the treatment efficacy of psoriasis patients based on decision tree model and logistic regression. Methods We implemented an observational study and recruited 512 psoriasis patients in Shanghai Skin Diseases Hospital from 2021 to 2022. We used face-to-face questionnaire interview and physical examination to collect data. Influencing factors of treatment efficacy were analyzed by using logistic regression, and decision tree model based on the CART algorithm. The receiver operator curve (ROC) was plotted for model evaluation and the statistical significance was set at P

Abstract Background Gene expression profiles in breast tissue biopsies contain information related to chemotherapy efficacy. The promoter profiles in cell-free DNA (cfDNA) carrying gene expression information of the original tissues may be used to predict the response to neoadjuvant chemotherapy in breast cancer as a non-invasive biomarker. In this study, the feasibility of the promoter profiles in plasma cfDNA was evaluated as a novel clinical model for noninvasively predicting the efficacy of neoadjuvant chemotherapy in breast cancer. Method First of all, global chromatin (5 Mb windows), sub-compartments and promoter profiles in plasma cfDNA samples from 94 patients with breast cancer before neoadjuvant chemotherapy (pCR = 31 vs. non-pCR = 63) were analyzed, and then classifiers were developed for predicting the efficacy of neoadjuvant chemotherapy in breast cancer. Further, the promoter profile changes in sequential cfDNA samples from 30 patients (pCR = 8 vs. non-pCR = 22) during neoadjuvant chemotherapy were analyzed to explore the potential benefits of cfDNA promoter profile changes as a novel potential biomarker for predicting the treatment efficacy. Results The results showed significantly distinct promoter profile in plasma cfDNA of pCR patients compared with non-pCR patients before neoadjuvant chemotherapy. The classifier based on promoter profiles in a Random Forest model produced the largest area under the curve of 0.980 (95% CI: 0.978–0.983). After neoadjuvant chemotherapy, 332 genes with significantly differential promoter profile changes in sequential cfDNA samples of pCR patients was observed, compared with non-pCR patients, and their functions were closely related to treatment response. Conclusion These results suggest that promoter profiles in plasma cfDNA may be a powerful, non-invasive tool for predicting the efficacy of neoadjuvant chemotherapy breast cancer patients before treatment, and the on-treatment cfDNA promoter profiles have potential benefits for predicting the treatment efficacy.

Introduction: Vulvovaginal candidiasis (VVC) significantly impacts women's quality of life and often shows a high recurrence rate despite conventional antifungal therapies. This study evaluates the efficacy of Limosilactobacillus fermentum (LF5), a probiotic, as an alternative treatment option to conventional miconazole therapy in managing VVC. Methods: The randomized, single-blind clinical trial involved 100 premenopausal women diagnosed with VVC. Participants were assigned to either a vaginal capsule containing LF5 probiotic strain or miconazole. Treatments were administered once daily for three consecutive days. Microbiological eradication of Candida spp. and recurrence rates were assessed at 30 days post-treatment. The trial was registered with the Italian Ministry of Health. Results: Both treatments achieved a high rate of microbiological eradication of Candida spp. within the three-day treatment period (96% for LF5 and 94% for miconazole). Recurrence rates within 2 weeks post-treatment were low and similar between the groups (10% for LF5 and 17% for miconazole). LF5 was found to have a significantly lower incidence of local adverse reactions compared to miconazole (4 vs. 12%). Discussion: LF5 presents a viable alternative to miconazole for the treatment of VVC, offering comparable efficacy with fewer side effects. The results suggest that probiotic treatments can potentially enhance patient compliance and quality of life by reducing adverse reactions and recurrence rates. Further research is needed to confirm these findings in larger and more diverse populations. [ABSTRACT FROM AUTHOR]

Aim: Angiogenesis inhibitor apatinib targets vascular endothelial growth factor receptors and improves the outcomes of patients with gynecologic malignancy. This study aimed to evaluate the efficacy and safety of angiogenesis inhibitor apatinib plus chemotherapy in recurrent platinum‐resistant ovarian cancer (RPR‐OC) patients. Methods: This study retrieved 67 RPR‐OC patients who received apatinib plus chemotherapy or chemotherapy alone and divided them into apatinib + chemo (N = 30) and chemo alone (N = 37) groups according to the actual medication. Results: Objective response rate (36.7% vs. 16.2%, p = 0.056) and disease control rate (80.0% vs. 59.5%, p = 0.072) showed an increased trend in apatinib + chemo group versus chemo alone group. The progression‐free survival (PFS) (p = 0.010) and overall survival (OS) (p = 0.042) were prolonged in apatinib + chemo group versus chemo alone group. The median (95%confidence interval [CI]) PFS was 5.9 (5.5–6.3) months in apatinib + chemo group and 3.8 (2.0–5.6) months in chemo alone group. The median (95%CI) OS was 20.5 (16.5–24.5) months in apatinib + chemo group and 13.6 (8.6–18.6) months in chemo alone group. Apatinib plus chemotherapy was independently related with better PFS (hazard ratio [HR]: 0.354, p < 0.001) and OS (HR: 0.116, p < 0.001). Subgroup analyses indicated that patients with a more serious disease condition might benefit more from apatinib plus chemotherapy. No difference was found in adverse events of all grade or grade ≥3 between the two groups (all p > 0.05). Conclusion: Angiogenesis inhibitor apatinib plus chemotherapy shows better treatment efficacy than chemotherapy alone with controllable safety profile in RPR‐OC patients. [ABSTRACT FROM AUTHOR]

Vestibular migraine (VM), a subtype of migraine characterized by vestibular symptoms, poses a significant diagnostic and therapeutic challenge. This study aimed to evaluate the effectiveness of monoclonal antibodies targeting Calcitonin Gene Related Peptide (CGRP) in the treatment of VM. Therefore, we conducted a rapid systematic review and meta-analysis following PRISMA and Cochrane guidelines. A search of databases (PubMed, Scopus, Cochrane and Google Scholar) was performed in October 2023. Inclusion criteria required original research articles focusing on patients diagnosed with VM and utilizing CGRP-targeting monoclonal antibodies. We performed qualitative assessments of study design, patient characteristics, and outcomes and, for studies with comparable outcome measures, a meta-analysis was conducted. Our search yielded four relevant studies, including cohort studies and a case report, totaling 99 patients. Proper vestibular instrumental tests were employed in half of the studies. Overall, the included studies reported significant improvements in VM symptoms. Our quantitative analysis, focused on migraine symptoms, demonstrated a substantial reduction in Monthly Days with Migraine at 6 months following treatment. No severe adverse drug reactions were reported. In conclusion, this rapid systematic review and meta-analysis provide preliminary evidence for the efficacy of CGRP-targeting monoclonal antibodies in treating Vestibular Migraine. However, the absence of randomized controlled trials and variations in study designs and diagnostic criteria introduce some limitations. Further research is needed, including controlled trials, to establish a more robust evidence base. Nonetheless, this treatment approach offers hope for the effective management of VM, potentially enhancing the well-being of affected individuals and reducing their associated disability. Key Points: Novel Therapeutic Strategy: Monoclonal antibodies targeting CGRP offer a promising new treatment avenue for Vestibular Migraine. Significant Symptom Improvement: Patients administered with these antibodies exhibited notable reductions in the frequency and severity of symptoms. Migraine-related Disability: There's a marked decrease in migraine-related disability among patients treated with monoclonal antibodies against CGRP. Research Gaps Identified: Despite the promising results, there's a lack of randomized controlled trials and a considerable heterogeneity among existing studies. Call for Further Research: High-quality, randomized controlled trials are urgently needed to solidify the role of these antibodies in clinical management of Vestibular Migraine. [ABSTRACT FROM AUTHOR]

Introduction: Deucravacitinib, a novel, oral, selective allosteric tyrosine kinase 2 inhibitor, demonstrated superiority versus placebo and apremilast in the POETYK PSO-1 and PSO-2 studies. We describe patient-reported outcomes with deucravacitinib treatment versus placebo and apremilast in these studies. Methods: Two multicenter, global, double-blind, placebo- and active comparator-controlled studies randomized patients with moderate-to-severe plaque psoriasis 1:2:1 to placebo, deucravacitinib 6 mg once daily, or apremilast 30 mg twice daily. Score changes from baseline and meaningful within-patient change responses for Psoriasis Symptoms and Signs Diary (PSSD) and Dermatology Life Quality Index (DLQI) were assessed. Results: In POETYK PSO-1 (n = 666) and PSO-2 (n = 1020), respectively, improvement from baseline in PSSD total score was greater with deucravacitinib (− 27.8 and − 30.1) versus placebo (− 4.4 and − 5.9) and apremilast (− 18.9 and − 22.5) at Week 16 and versus apremilast at Week 24 (deucravacitinib: − 32.8 and − 30.7; apremilast: − 21.6 and − 22.8) (nominal p < 0.0001). Improvement from baseline in DLQI score was also greater with deucravacitinib (− 8.5 and − 7.6) versus placebo (− 3.3 and − 3.0) and apremilast (− 5.9 and − 5.8) at Week 16 and versus apremilast at Week 24 (deucravacitinib: − 8.6 and − 7.5; apremilast: − 5.6 and − 5.5) (nominal p < 0.0001). Achievement of meaningful within-patient change in PSSD total score and in DLQI score occurred more frequently with deucravacitinib than placebo and apremilast at Week 16 and versus apremilast at Week 24. Conclusions: Deucravacitinib demonstrated meaningful improvements in patient-reported outcomes in patients with moderate-to-severe plaque psoriasis compared with apremilast and placebo. Clinical Trial Registration: NCT03624127, NCT03611751. [ABSTRACT FROM AUTHOR]

To assess the impact of budesonide-formoterol on pulmonary ventilation function and prognosis in patients with mild-to-moderate acute exacerbations of bronchial asthma. A retrospective analysis was conducted on clinical data from 232 patients with acute exacerbations of bronchial asthma. These patients were divided into 2 groups based on their treatment: a control group (n=104) receiving budesonide dry powder inhalation and an observation group (n=107) receiving budesonide-formoterol dry powder inhalation. Clinical efficacy and safety indicators were compared. The results showed that the total treatment effectiveness rate in the observation group was significantly higher than that in the control group. Following treatment, the observation group exhibited significantly higher scores in the Asthma Quality of Life Questionnaire (AQLQ), as well as improved levels of forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and peak expiratory flow (PEF), compared to the control group. Moreover, levels of tumor necrosis factor-alpha, interleukin-6, and C-reactive protein were significantly lower in the observation group. The incidence of adverse reactions between groups was comparable. Based on these findings, the application of budesonide-formoterol demonstrated significant effectiveness in patients with mild-to-moderate acute exacerbations of bronchial asthma. The combination therapy led to improved clinical outcomes, including enhanced pulmonary ventilation function and reduced inflammatory markers. Importantly, the safety profile of budesonideformoterol was comparable to that of budesonide monotherapy. These results highlight the potential benefits of using budesonide-formoterol as an alternative treatment option for patients experiencing acute exacerbations of mild-to-moderate bronchial asthma. [ABSTRACT FROM AUTHOR]

Introduction: Anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) are standard first- and second-line treatment for advanced ALK+ non-small cell lung cancer (NSCLC). We evaluated outcomes in patients with ALK+ NSCLC receiving third-line ALK TKI versus non-ALK-directed therapy. Methods: Flatiron Health OncoEMR data were extracted for patients with ALK+ NSCLC initiating first-line ALK TKI between January 2015 and March 2022 followed by second-line ALK TKI and third-line ALK TKI (group A) or non-TKI therapy (group B). Time-to-treatment discontinuation (TTD) and overall survival (OS) were analyzed using multivariate modelling. Results: Among patients receiving third-line ALK TKI (A, n = 85) or non-TKI therapy (B, n = 43), most received first-line crizotinib (A/B: 64%/60%) and second-line alectinib (36%/30%), ceritinib (24%/19%), or lorlatinib (15%/30%). Common third-line treatments were lorlatinib/alectinib (41%/33%) in A and immunotherapy, chemotherapy, or chemotherapy + immunotherapy (30%/28%/21%) in B. Group A versus B had longer TTD of first-line treatment (hazard ratio [HR] 0.62, 95% confidence interval [CI] 0.41–0.93; p = 0.020) and second-line treatment (HR 0.50, 95% CI 0.33–0.75; p < 0.001) and longer OS from start of first-line treatment (HR 0.32, 95% CI 0.19–0.54; p < 0.001) and second-line treatment (HR 0.40, 95% CI 0.24–0.66; p < 0.001). For third-line treatment, median TTD (A/B) was 6.2/2.4 months (HR 0.61, 95% CI 0.37–1.00; p = 0.049) and OS was 17.6/6.5 months (HR 0.57, 95% CI 0.33–0.98; p = 0.042). Conclusions: Patients receiving third-line non-ALK-directed therapy had suboptimal outcomes on prior TKIs. Patients with longer duration of prior ALK TKI treatment appeared to benefit from third-line ALK TKIs. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between serum prognostic nutritional index (PNI), lymphocyte/monocyte ratio(LMR), albumin/globulin ratio (ALB/GLB) and treatment efficacy and prognosis in elderly patients with non-small cell lung cancer (NSCLC). Methods: A total of 143 elderly patients with NSCLC who were treated with programmed death receptor-1 (PD-1) inhibitors in our hospital from January 2021 to January 2023 were retrospectively analyzed. Serum PNI, LMR and ALB/GLB were detected before treatment. According to the mean values of PNI, LMR and ALB/GLB, the patients were divided into low PNI group and high PNI group, low LMR group and high LMR group, low ALB/GLB group and high ALB/GLB group. According to the efficacy, they were divided into disease control(DC) and objective remission(OR), and the differences in efficacy of different PNI, LMR and ALB / GLB levels were compared. The elderly patients with NSCLC were divided into survival group and death group according to the follow-up results. Univariate and multivariate COX regression analysis were used to analyze the factors affecting the prognosis of elderly patients with NSCLC. The receiver operating characteristic(ROC) curve was used to analyze the value of PNI, LMR and ALB/GLB in predicting poor prognosis of elderly patients with NSCLC. Results: The DC rate and OR rate of low PNI group, low LMR group and low ALB / GLB group were lower than those of high PNI group, high LMR group and high ALB/GLB group(P<0.05). Distant metastasis, low PNI, low LMR and low ALB/GLB were risk factors for poor prognosis in elderly patients with NSCLC(P<0.05). The area under the curve(AUC) of PNI, LMR and ALB/GLB in predicting poor prognosis of elderly NSCLC patients were 0.792, 0.839 and 0.800, respectively. The AUC of combined prediction was 0.931, which was higher than that of single index prediction. Conclusion: Low levels of PNI, LMR and ALB/GLB are associated with poor treatment efficacy and poor prognosis of PD-1 inhibitors in elderly NSCLC patients. Combined PNI, LMR and ALB / GLB can effectively predict the risk of poor prognosis in elderly NSCLC patients. [ABSTRACT FROM AUTHOR]

Background: Gene expression profiles in breast tissue biopsies contain information related to chemotherapy efficacy. The promoter profiles in cell-free DNA (cfDNA) carrying gene expression information of the original tissues may be used to predict the response to neoadjuvant chemotherapy in breast cancer as a non-invasive biomarker. In this study, the feasibility of the promoter profiles in plasma cfDNA was evaluated as a novel clinical model for noninvasively predicting the efficacy of neoadjuvant chemotherapy in breast cancer. Method: First of all, global chromatin (5 Mb windows), sub-compartments and promoter profiles in plasma cfDNA samples from 94 patients with breast cancer before neoadjuvant chemotherapy (pCR = 31 vs. non-pCR = 63) were analyzed, and then classifiers were developed for predicting the efficacy of neoadjuvant chemotherapy in breast cancer. Further, the promoter profile changes in sequential cfDNA samples from 30 patients (pCR = 8 vs. non-pCR = 22) during neoadjuvant chemotherapy were analyzed to explore the potential benefits of cfDNA promoter profile changes as a novel potential biomarker for predicting the treatment efficacy. Results: The results showed significantly distinct promoter profile in plasma cfDNA of pCR patients compared with non-pCR patients before neoadjuvant chemotherapy. The classifier based on promoter profiles in a Random Forest model produced the largest area under the curve of 0.980 (95% CI: 0.978–0.983). After neoadjuvant chemotherapy, 332 genes with significantly differential promoter profile changes in sequential cfDNA samples of pCR patients was observed, compared with non-pCR patients, and their functions were closely related to treatment response. Conclusion: These results suggest that promoter profiles in plasma cfDNA may be a powerful, non-invasive tool for predicting the efficacy of neoadjuvant chemotherapy breast cancer patients before treatment, and the on-treatment cfDNA promoter profiles have potential benefits for predicting the treatment efficacy. [ABSTRACT FROM AUTHOR]

Background: Early intervention is essential for meaningful disease modification in Alzheimer's disease (AD). Objective: We aimed to determine the efficacy and safety of pharmacologic and nutritional interventions for early AD. Methods: PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov were searched from database inception until 1 September 2023. We included randomized controlled trials that evaluated the efficacy of interventions in early AD. Only interventions that demonstrated efficacy compared to placebo were included in the network meta-analysis (NMA). Then we performed frequentist fixed-effects NMA to rank the interventions. GRADE criteria were used to evaluate the level of evidence. Results: Fifty-eight trials including a total of 33,864 participants and 48 interventions were eligible for inclusion. Among the 48 interventions analyzed, only 6 (12.5%) treatments— ranging from low to high certainty— showed significant improvement in cognitive decline compared to placebo. High certainty evidence indicated that donanemab (standardized mean difference [SMD] –0.239, 95% confidence interval [CI] –0.343 to –0.134) and lecanemab (SMD –0.194, 95% CI –0.279 to –0.108) moderately slowed the clinical progression in patients with amyloid pathology. Additionally, methylphenidate, donepezil, LipiDiDiet, and aducanumab with low certainty showed significant improvement in cognitive decline compared to placebo. However, there was no significant difference in serious adverse events as reported between the six interventions and placebo. Conclusions: Only 12.5% of interventions studied demonstrated efficacy in reducing cognitive impairment in early AD. Donanemab and lecanemab have the potential to moderately slow the clinical progression in patients with amyloid pathology. Further evidence is required for early intervention in AD. [ABSTRACT FROM AUTHOR]

Background and aims: A single immune checkpoint inhibitor (ICI) regimen has limited value in treating advanced bile tract cancer (BTC); therefore, ICI combination therapy is often applied. This meta-analysis aimed to evaluate the effectiveness and safety of ICI combination therapy for advanced BTC. Methods: The study protocol was registered on PROSPERO (CRD42023452422). Data on the median progression-free survival (PFS), median overall survival (OS), objective response rate (ORR), disease control rate (DCR), and grade ≥3 adverse events (AEs) reported in relevant studies were pooled and analyzed to determine the efficacy and safety of ICI combination therapy. Results: In total, 15 studies with 665 patients were included in thismeta-analysis. The overallORR andDCR were 34.6% and 77.6%, respectively. The overallmedian PFS and OS were 6.06 months [95% confidence interval (CI): 4.91-7.21] and 12.11 months (95% CI: 10.66-13.55), respectively. Patients receiving ICI combination therapy in addition to other therapies had a considerablyprolongedmedianPFSandOS (z=9.69, p<0.001 and z=16.17, p<0.001). Patients treated as first-line treatment had a substantially longer median PFS and OS compared to patients treated as non-firstline treatment (z=11.19, p<0.001 and z=49.17, p<0.001). The overall pooled grade ≥3 AEs rate was 38.2% (95% CI: 0.268-0.497) and was not influenced by whether ICI therapy was combined with other treatments or not or the treatment line. Conclusion: Advanced BTC patients may benefit from ICI combination treatment without additional AEs. However, concurrent chemotherapy or radiotherapy is still needed to achieve better outcomes. [ABSTRACT FROM AUTHOR]

Abstract Background Adenocarcinoma of the ampulla of Vater (AoV) is one of the rare periampullary cancers, and due to its anatomical location, it is categorized into various histologic subtypes. Its rarity and diversity pose challenges in treatment decision-making for patients with advanced AoV carcinoma. This study investigated the efficacy and safety of the combined regimen of capecitabine and oxaliplatin (CAPOX) in a real-world clinical setting. Methods This investigation encompassed patients with advanced AoV carcinoma who underwent CAPOX treatment. Histologic phenotypes were identified through a combination of histopathological analysis and protein expression markers, including MUC1, CDX2, CK20, and MUC2. The correlation between histopathological determinants and survival outcomes was explored, in addition to an evaluation of the safety profile of CAPOX therapy. Results From January 2010 to June 2023, 42 patients received CAPOX. Of these, 14 patients (33.3%) had not received any prior palliative chemotherapy, while 28 patients (66.7%) had undergone one prior line of chemotherapy. At a median follow up of 9.0 months, the median progression-free survival (PFS) was 4.38 months (95% CI, 2.78–5.69) and the median overall survival (OS) was 9.57 months (95% CI 7.56–11.6). The objective response and disease control rates were 38.1% and 61.9%, respectively. Patients who received CAPOX as a second-line treatment had poorer PFS (HR = 2.62; 95% CI, 1.49–4.90, p = 0.003) and OS (HR = 2.82, 95% CI, 1.47–5.38, p = 0.001) compared to those who received CAPOX as a first-line chemotherapy. There were no statistically significant differences in PFS (p = 0.185) and OS (p = 0.097) between groups based on histologic subtypes. Neutropenia (14.3%) emerged as the predominant grade 3–4 toxicity. Notably, treatment cessation occurred in select instances owing to grade 3 fatigue (9.5%) and peripheral neuropathy (9.5%). Conclusions This study confirmed the therapeutic efficacy and safety of CAPOX in a real-world setting, consistent with prior phase II trial results. While CAPOX proved feasible for advanced AoV carcinoma regardless of histologic subtype, its reduced effectiveness in second-line settings necessitates further research to determine its optimal palliative use.

Abstract Background The proportion of patients with breast cancer and obesity is increasing. While the therapeutic landscape of breast cancer has been expanding, we lack knowledge about the potential differential efficacy of most drugs according to the body mass index (BMI). Here, we conducted a systematic review on recent clinical drug trials to document the dosing regimen of recent drugs, the reporting of BMI and the possible exclusion of patients according to BMI, other adiposity measurements and/or diabetes (leading comorbidity of obesity). We further explored whether treatment efficacy was evaluated according to BMI. Methods A search of Pubmed and ClinicalTrials.gov was performed to identify phase I-IV trials investigating novel systemic breast cancer treatments. Dosing regimens and exclusion based on BMI, adiposity measurements or diabetes, documentation of BMI and subgroup analyses according to BMI were assessed. Results 495 trials evaluating 26 different drugs were included. Most of the drugs (21/26, 81%) were given in a fixed dose independent of patient weight. BMI was an exclusion criterion in 3 out of 495 trials. Patients with diabetes, the leading comorbidity of obesity, were excluded in 67/495 trials (13.5%). Distribution of patients according to BMI was mentioned in 8% of the manuscripts, subgroup analysis was performed in 2 trials. No other measures of adiposity/body composition were mentioned in any of the trials. Retrospective analyses on the impact of BMI were performed in 6 trials. Conclusions Patient adiposity is hardly considered as most novel drug treatments are given in a fixed dose. BMI is generally not reported in recent trials and few secondary analyses are performed. Given the prevalence of patients with obesity and the impact obesity can have on pharmacokinetics and cancer biology, more attention should be given by investigators and study sponsors to reporting patient’s BMI and evaluating its impact on treatment efficacy and toxicity.

Juan-Manuel Sancho,1 Marc Sorigué,1 Eva Rubio-Azpeitia2 1Clinical Hematology Department, ICO-IJC-Hospital Germans Trias I Pujol. Badalona, Universitat Autònoma de Barcelona, Barcelona, Spain; 2Medical Department-Hematology, Janssen-Cilag, S.A, Madrid, SpainCorrespondence: Eva Rubio-Azpeitia, Johnson and Johnson SA, Medical Affairs Hematology, Paseo de las Doce Estrellas, 5-7, Madrid, Spain, Email eva.rubioazpeitia@gmail.comIntroduction: Mantle cell lymphoma (MCL) is an incurable disease with an aggressive clinical course, and most patients eventually relapse after chemotherapy. Targeted therapies developed for relapsed/refractory MCL have been approved based on clinical trial data. However, real-world setting data are scarce and scattered.Areas Covered: This systematic review aimed to collect, synthesize, and describe the characteristics and treatment outcomes of patients with relapsed/refractory MCL after receiving a second or subsequent line of therapy in the real-world setting.Expert Opinion: R/R MCL is clinically and biologically heterogeneous and still represents a therapeutic challenge, with high-risk and early relapsed patients remaining an unmet medical need. This systematic review is limited by the quality of the available data and the difficulty of comparing outcomes in R/R MCL due to the heterogeneity of the disease, but the results suggest that covalent BTKis should be positioned as second-line therapy, followed by CAR T-cells in BTK-i-relapsed patients. Chemo-free and combination therapies with established chemoimmunotherapy backbones in the relapsed and front-line settings have been recently developed, and front-line options are being improved to move targeted and cellular therapies to earlier lines, including front-line therapy, in elderly and younger fit patients. In the upcoming years, many new targeted agents will play an important role and will be incorporated to the routine practice as their sequence, and outcomes in unselected patients are determined.Keywords: CAR-T cells, ibrutinib, mantle cell lymphoma, real-world evidence, relapsed/refractory mantle cell lymphoma (R/R MCL), treatment efficacy

Introduction Smoking is an independent and modifiable risk factor for the onset and development of psoriasis; however, evidence on the association between tobacco smoking and psoriasis treatment efficacy is limited. This study aimed to explore the influence of smoking on treatment efficacy in a cohort of patients with psoriasis in Shanghai, China. Methods Patients with psoriasis were recruited from the Shanghai Skin Disease Hospital between 2021 and 2022. The treatment for patients with psoriasis includes acitretin, methotrexate, narrow-band ultraviolet/benvitimod, and biologics. Data were collected using a structured questionnaire, physical examination, and disease severity estimation at baseline, week four, and week eight. The achievement of a ≥75% reduction in psoriasis area and severity index (PASI 75 ) score from baseline to week 8 was set as the primary outcome for treatment efficacy estimation. Data were analyzed using SAS 9.4. Results A total of 560 patients with psoriasis were enrolled in this study, who were predominantly males (72.9%). The average age of patients was 48.4 years, and 38.8% of them were current smokers, 5.0% of them were former smokers. The median score of PASI among patients changed from 11.1 (interquartile range, IQR: 7.9–16.6) at baseline to 6.2 at week 4 and 3.1 at week 8, and 13.8% and 47.3% of patients with psoriasis achieved PASI 75 at weeks 4 and 8, respectively. Logistic regression indicated that patients without tobacco smoking had a higher proportion of PASI 75 achievement at week 8. The adjusted odds ratio (AOR) was 11.43 (95% CI: 6.91–18.89), 14.14 (95% CI: 8.27–24.20), and 3.05 (95% CI: 1.20–7.76) for non-smokers compared with smokers, current smokers, and former smokers, respectively. Moreover, former smokers had higher PASI 75 achievement than current smokers (AOR=3.37), and patients with younger smoking initiation age, longer smoking duration, and higher smoking intensity had lower PASI 75 achievement. Conclusions Tobacco smoking was negatively associated with PASI 75 achievement both in current and former smokers, and former smokers had higher PASI 75 achievement than current smokers. The implementation of tobacco control measures is beneficial for improving treatment responses.

Abstract This study developed an integrated wastewater treatment system that combines an upflow anaerobic sludge blanket (UASB), downflow hanging non-woven fabric (DHNW), and anaerobic baffled reactor (ABR) to explore the effect of treatment stages on the diversity of microeukaryotic communities. This study aimed to bridge the knowledge gap regarding the influence of integrated system stages on microeukaryotic community diversity. Through 18S rRNA amplicon sequencing, we identified unique microeukaryotic communities across different stages, with the aerobic phase hosting 35.77% of unique amplicon sequence variants (ASVs). The results of principal component analysis (PCA) and non-multidimensional scale analysis (nMDS) demonstrated the significant influence of wastewater treatment on both environmental factors and the microeukaryotic communities. Ciliophora was notably abundant in the effluent (42.09%) and sludge (17.11%). The aerobic stage was dominated by Ochrophyta, a diverse group of algae instrumental in nutrient removal, such as nitrogen and phosphorus, through biological processes. A redundancy analysis (RDA) revealed a positive correlation between chemical and biochemical oxygen demand and Cryptomycotina, highlighting its potential as a bioindicator for treatment efficacy. The detection of protozoan species, such as Acanthamoeba castellanii and Vermamoeba vermiformis, in the outlet stage poses health risks, whereas Cryptosporidium sp. was found in both the inlet and aerobic stages but not in the outlet. Our study reveals the complex nature of microeukaryotic diversity in the wastewater treatment system and its implications for treatment performance and public health.

Abstract Objectives To assess whether increasing radioactive iodine dose can increase treatment efficacy in Graves’ disease. Methods A prospective study was conducted, including 106 patients receiving 20 mCi (740 MBq) radioactive iodine (RAI), compared with a retrospective data, including 113 patients receiving 10–15 mCi (370–555 MBq) RAI. Remission and failure rates were evaluated at 6 months post-RAI. Statistical analysis was performed using logistic regression and Kaplan–Meier curves. Results Patients receiving 20 mCi RAI demonstrated a significantly higher remission rate compared to the 10–15 mCi group (82.1% vs 66.4%, p = 0.009). Median time to remission was shorter in the 20 mCI group (3 vs 4 months, p = 0.002). Hypothyroidism at 6 months was more prevalent in the 20 mCi group (67% vs 53%, p = 0.03). Larger thyroid size (> 60 g) was associated with treatment failure (p = 0.02). Conclusions Higher dosage (20 mCi) RAI showed superior efficacy in achieving remission compared to lower dosages (10–15 mCi) in Graves’ disease treatment.

Abstract Background As new migraine therapies emerge, it is crucial for measures to capture the complexities of health-related quality of life (HRQoL) improvement beyond improvements in monthly migraine day (MMD) reduction. Investigations into the correlations between MMD reduction, symptom management, and HRQoL are lacking, particularly those that focus on improvements in canonical symptoms and improvement in patient-identified most-bothersome symptoms (PI-MBS), in patients treated with eptinezumab. This exploratory analysis identified efficacy measures mediating the effect of eptinezumab on HRQoL improvements in patients with migraine. Methods Data from the DELIVER study of patients with 2–4 prior preventive migraine treatment failures (NCT04418765) were inputted to two structural equation models describing sources of HRQoL improvement via Migraine-Specific Quality-of-Life Questionnaire (MSQ) scores. A single latent variable was defined to represent HRQoL and describe the sources of HRQoL in DELIVER. One model included all migraine symptoms while the second model included the PI-MBS as the only migraine symptom. Mediating variables capturing different aspects of efficacy included MMDs, other canonical symptoms, and PI-MBS. Results In the first model, reductions in MMDs and other canonical symptoms accounted for 35% (standardized effect size [SES] − 0.11) and 25% (SES − 0.08) of HRQoL improvement, respectively, with 41% (SES − 0.13) of improvement comprising “direct treatment effect,” i.e., unexplained by mediators. In the second model, substantial HRQoL improvement with eptinezumab (86%; SES − 0.26) is due to MMD reduction (17%; SES − 0.05) and change in PI-MBS (69%; SES − 0.21). Conclusions Improvements in HRQoL experienced by patients treated with eptinezumab can be substantially explained by its effect on migraine frequency and PI-MBS. Therefore, in addition to MMD reduction, healthcare providers should discuss PI-MBS improvements, since this may impact HRQoL. Health technology policymakers should consider implications of these findings in economic evaluation, as they point to alternative measurement of quality-adjusted life years to capture fully treatment benefits in cost-utility analyses. Trial registration ClinicalTrials.gov (Identifier: NCT04418765 ; EudraCT (Identifier: 2019–004497-25; URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=2019-004497-25 ). Graphical Abstract

Shasha Zhang,1,&ast; Jianhua Wu,2,&ast; Yue Zhao,3 Jingjing Zhang,1 Xiaoyun Zhang,1 Chensi Wu,3 Zhidong Zhang,4 Zhanjun Guo1 1Department of Immunology and Rheumatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, People’s Republic of China; 2Animal Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, People’s Republic of China; 3Department of Gastroenterology and Hepatology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, People’s Republic of China; 4Department of Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050011, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhidong Zhang, Department of Surgery, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050011, People’s Republic of China, Email zzd407@163.com Zhanjun Guo, Department of Immunology and Rheumatology, The Fourth Hospital of Hebei Medical University, 12 Jiankang Road, Shijiazhuang, 050011, People’s Republic of China, Tel +86 311 86095734, Email zjguo5886@aliyun.comPurpose: Immune checkpoint inhibitors (ICIs) have significantly improved the outcomes of patients with cancer; however, these agents may initiate immune-related adverse events (irAEs). Previous studies have demonstrated a robust correlation between disease prognosis and the occurrence of irAEs, specifically skin or endocrine irAEs. Herein, we aimed to evaluate the correlation between irAE-related adrenal insufficiency (AI) and ICI treatment efficacy.Patients and methods: Patients diagnosed with gastrointestinal, respiratory, head and neck, urological, skin and gynecologic cancers treated with anti-programmed cell death 1 (PD-1)/anti-programmed cell death ligand 1 (PD-L1) antibody as monotherapy or combined therapy (combined with chemotherapy or targeted therapy) were divided into irAE-A (patients with irAE-related AI), irAE-B (patients with other irAEs) and non-irAE groups. Immunotherapy efficacy was assessed based on the disease control rate (DCR), progression-free survival (PFS), and overall survival (OS). Survival probabilities were estimated using the Kaplan–Meier method with the log–rank test.Results: Of the 192 patients enrolled in our study, 17 developed irAE-related AI and 83 developed other irAEs. The DCR of the irAE-A and irAE-B groups were higher than that of the non-irAE group (P< 0.05). Multiple extended Cox regression analyses showed that irAE status (irAE-A vs non-irAE, P=0.008; irAE-B vs non-irAE, P=0.020), Eastern Cooperative Oncology Group (ECOG) status (P=0.045), tumor-node-metastasis (TNM) stage (P=0.000), and treatment line (P=0.002) were independent predictors of PFS. Contrarily, irAE status (irAE-A vs non-irAE, P=0.009; irAE-B vs non-irAE, P=0.013), ECOG status (P=0.007), TNM stage (P=0.035), treatment line (P=0.001) and treatment modality (P=0.008) were independent predictors for OS.Conclusion: IrAE-related AI was significantly associated with ICI treatment efficacy in patients with cancer, which could be a potentially predictable marker. Due to the destruction of adrenal tissue by T cells with enhanced activity, AI reflects enhanced T cell activity to some extent.Keywords: endocrine adverse event, malignancies, monoclonal antibody therapy, immune-related side effects, treatment efficacy

Background Ustekinumab is an interleukin (IL)-12/IL-23 inhibitor for the treatment of moderate-to-severe psoriasis.Objective This real-world study compared ustekinumab and tumor necrosis factor-alpha inhibitors (TNFis) in Chinese moderate-to-severe psoriasis patients.Methods Patient health records of 110 moderate-to-severe psoriasis patients initiating or switching biologics were reviewed, with 31 patients receiving ustekinumab (ustekinumab group) and 79 patients receiving TNFis (TNFi group).Results Compared with TNFi group, psoriasis area and severity index (PASI)-75 response rate at month 6 (M6) were elevated (87.1% versus 65.8%, p = 0.026) in the ustekinumab group, whereas the rates at month 1 (M1) and month 3 (M3) and PASI-90 response rates at M1, M3, and M6 only showed an increasing trend (all p > 0.050) in the ustekinumab group than the TNFi group. By subgroup analyses, ustekinumab (versus TNFi) was more effective in patients with biologics therapy history than those without. Compared with the TNFi group, the ustekinumab group had lower dermatology life quality index scores and higher patient satisfaction scores at M3 and M6 (all p

BACKGROUND: Pulmonary arterial hypertension (PAH) is a progressive disease characterized by high mean pulmonary arterial pressure (≥ 20 mmHg) and remodeling of the vascular arteries. Approved therapies improve symptoms and delay clinical worsening in the long term, but they do not relieve acute exertional symptoms. RT234, a drug/device combination (Respira Therapeutics, Palo Alto, CA, USA) that delivers the phosphodiesterase 5 inhibitor vardenafil to the lungs via inhalation, has been shown to reduce pulmonary vascular resistance in patients with PAH. This study aims to evaluate whether RT234 can increase oxygen capacity during cardiopulmonary exercise testing (CPET) in patients with PAH. METHODS: This prospective, multi-center, open-label, two-cohort, dose-escalation, phase IIb trial in patients with PAH will evaluate the safety and efficacy of RT234 in improving exercise parameters. The trial began in September 2020 and is expected to be completed by early 2024. Patients eligible for enrollment will have a right heart catheterization-confirmed diagnosis of PAH, a 6-minute walking distance of ≥ 150 m, a minute ventilation/carbon dioxide production slope of ≥ 36, and will be on up to three stable oral and/or inhaled (not parenteral) PAH-specific background therapies. The estimated sample size is 86 patients, who will be divided into two dose cohorts. Cohort 1 will receive 0.5 mg RT234, and cohort 2 will receive 1.0 mg RT234. Each cohort will contain two subgroups based on the number of PAH background medications (up to two vs three). The trial will assess patients changes from baseline in peak oxygen consumption (VO2) during CPET 30 minutes after a single dose of 0.5 mg or 1.0 mg RT234, the change in the 6-minute walking distance, and the pharmacokinetics and safety profile of single doses of RT234. CONCLUSION: This is the first trial involving an as-needed medication for PAH. The trial will provide insights into the safety and efficacy of as-needed RT234 in treating the acute symptoms of PAH during exercise and will inform the design of further trials. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier NCT04266197.

Background: Adenocarcinoma of the ampulla of Vater (AoV) is one of the rare periampullary cancers, and due to its anatomical location, it is categorized into various histologic subtypes. Its rarity and diversity pose challenges in treatment decision-making for patients with advanced AoV carcinoma. This study investigated the efficacy and safety of the combined regimen of capecitabine and oxaliplatin (CAPOX) in a real-world clinical setting. Methods: This investigation encompassed patients with advanced AoV carcinoma who underwent CAPOX treatment. Histologic phenotypes were identified through a combination of histopathological analysis and protein expression markers, including MUC1, CDX2, CK20, and MUC2. The correlation between histopathological determinants and survival outcomes was explored, in addition to an evaluation of the safety profile of CAPOX therapy. Results: From January 2010 to June 2023, 42 patients received CAPOX. Of these, 14 patients (33.3%) had not received any prior palliative chemotherapy, while 28 patients (66.7%) had undergone one prior line of chemotherapy. At a median follow up of 9.0 months, the median progression-free survival (PFS) was 4.38 months (95% CI, 2.78–5.69) and the median overall survival (OS) was 9.57 months (95% CI 7.56–11.6). The objective response and disease control rates were 38.1% and 61.9%, respectively. Patients who received CAPOX as a second-line treatment had poorer PFS (HR = 2.62; 95% CI, 1.49–4.90, p = 0.003) and OS (HR = 2.82, 95% CI, 1.47–5.38, p = 0.001) compared to those who received CAPOX as a first-line chemotherapy. There were no statistically significant differences in PFS (p = 0.185) and OS (p = 0.097) between groups based on histologic subtypes. Neutropenia (14.3%) emerged as the predominant grade 3–4 toxicity. Notably, treatment cessation occurred in select instances owing to grade 3 fatigue (9.5%) and peripheral neuropathy (9.5%). Conclusions: This study confirmed the therapeutic efficacy and safety of CAPOX in a real-world setting, consistent with prior phase II trial results. While CAPOX proved feasible for advanced AoV carcinoma regardless of histologic subtype, its reduced effectiveness in second-line settings necessitates further research to determine its optimal palliative use. [ABSTRACT FROM AUTHOR]

Background: The proportion of patients with breast cancer and obesity is increasing. While the therapeutic landscape of breast cancer has been expanding, we lack knowledge about the potential differential efficacy of most drugs according to the body mass index (BMI). Here, we conducted a systematic review on recent clinical drug trials to document the dosing regimen of recent drugs, the reporting of BMI and the possible exclusion of patients according to BMI, other adiposity measurements and/or diabetes (leading comorbidity of obesity). We further explored whether treatment efficacy was evaluated according to BMI. Methods: A search of Pubmed and ClinicalTrials.gov was performed to identify phase I-IV trials investigating novel systemic breast cancer treatments. Dosing regimens and exclusion based on BMI, adiposity measurements or diabetes, documentation of BMI and subgroup analyses according to BMI were assessed. Results: 495 trials evaluating 26 different drugs were included. Most of the drugs (21/26, 81%) were given in a fixed dose independent of patient weight. BMI was an exclusion criterion in 3 out of 495 trials. Patients with diabetes, the leading comorbidity of obesity, were excluded in 67/495 trials (13.5%). Distribution of patients according to BMI was mentioned in 8% of the manuscripts, subgroup analysis was performed in 2 trials. No other measures of adiposity/body composition were mentioned in any of the trials. Retrospective analyses on the impact of BMI were performed in 6 trials. Conclusions: Patient adiposity is hardly considered as most novel drug treatments are given in a fixed dose. BMI is generally not reported in recent trials and few secondary analyses are performed. Given the prevalence of patients with obesity and the impact obesity can have on pharmacokinetics and cancer biology, more attention should be given by investigators and study sponsors to reporting patient's BMI and evaluating its impact on treatment efficacy and toxicity. [ABSTRACT FROM AUTHOR]