Treatment Discontinuation Research Articles

NIMG-77. MRI PHENOMENON OF PUNCTATE ENHANCING LESIONS IN PATIENTS TREATED WITH IDH INHIBITORS

Abstract BACKGROUND Magnetic Resonance Imaging (MRI) response assessment is essential in isocitrate dehydrogenase (IDH)-mutant gliomas and provides evidence of treatment efficacy. Ivosidenib, a mutant IDH1 inhibitor, and vorasidenib, a pan-mutant IDH inhibitor, may induce imaging stabilization or improvement. We describe an imaging phenomenon of punctate enhancing lesions in patients receiving ivosidenib or vorasidenib. METHODS From October 2020 to December 2023, we identified patients treated with IDH inhibitors who developed punctate enhancing lesions on imaging during their treatment course. We report their clinical and imaging characteristics. RESULTS In our cohort (n=5), patients age range was 29-47 years. Diagnoses included astrocytoma grades 2 (n=2) or 3 (n=1), and oligodendroglioma grades 2 (n=1) or 3 (n=1). Beside all having a prior resection, two had prior radiation therapy and temozolomide, one had prior temozolomide only and two were treatment-naïve. Before initiation of IDH inhibitor, all patients had some evidence of enhancement, albeit small (<1 cm) for most. Four patients received ivosidenib (500mg daily) and one received vorasidenib (40mg daily). The median time to develop punctate lesions from treatment initiation was 16 months (range 1-28 months). All but one lesion was < 1 cm and adjacent to the original tumor locations. Four had FLAIR correlation, and two had high DWI signal without associated restricted diffusion. Punctate lesions resolved on subsequent imaging, within 1-2 months, for all grade 2 tumors. Punctate lesions persisted in the grade 3 tumors, without further progression. Four patients remain on therapy. One discontinued treatment due to this enhancement, which resolved on subsequent imaging. CONCLUSIONS Punctate enhancing lesions may develop in patients on IDH inhibitors. We advocate for close interval imaging monitoring in these cases since they may not universally require treatment discontinuation. Future advanced imaging and tissue evaluations of punctate enhancement, to differentiate between inflammatory response and progression, would be of interest.

CTIM-07. A PHASE II, OPEN LABEL, SINGLE ARM STUDY OF NIVOLUMAB FOR RECURRENT OR PROGRESSIVE IDH MUTANT GLIOMAS WITH PRIOR EXPOSURE TO ALKYLATING AGENTS

Abstract BACKGROUND Somatic mutations in isocitrate dehydrogenase 1 (IDH1) are an important prognostic factor in patients with gliomas. IDH-mutant gliomas are prone to develop hypermutation after exposure to alkylating agents; in other solid tumors, hypermutation may be a predictive biomarker for PD-1 inhibitor response. In this study, we hypothesize that this specific subgroup of patients would clinically benefit from nivolumab as measured by overall response rate (ORR), duration of response (DOR), median progression-free survival (PFS), and overall survival (OS). METHODS Patients aged 18 years and older with recurrent/progressive IDH-mutant (WHO Grades 2-4) gliomas and prior exposure to alkylating agents were included. Nivolumab was given 240 mg q2w for 8 cycles, then 480 mg q4w until progression, toxicity, study withdrawal, or completion at 2 years. Efficacy was evaluated by ORR of partial (PR) and complete responses (CR) per RANO criteria; low-grade glioma RANO criteria was used for patients with non-enhancing disease. Secondary endpoints included median PFS, median OS, DOR. Toxicity and survival were followed every 3 months until death/study completion. RESULTS Thirty-three patients (66.7% male) were evaluable at study completion. Histology consisted of oligodendroglioma (N=11; 55% Grade 3) and astrocytoma (N=22; 36% Grade 3, 32% Grade 4). Median number of prior lines of systemic therapy was 1 (range 1-6). Median dexamethasone dose at screening was 0 mg (range 0-4). ORR was 9% with two PR and one CR, median DOR 33 months. 11 (32%) patients had stable disease (7 stable for 6+ months) with median PFS 2.2 months and median OS 29.1 months. There were two treatment-related Grade 3 adverse events (lymphopenia and hypotension). One patient discontinued treatment for Grade 2 transaminitis. CONCLUSIONS Though the primary endpoint was not met, three patients have ongoing CR and PR at 54+, 33+ and 24+ months. Future combination therapies with PD-1 inhibitors may increase efficacy in recurrent IDH-mutant gliomas.

HIV-related outcomes among migrants living in Europe compared with the general population: a systematic review and meta-analysis

Compared with the general population, international migrants arriving in Europe face severe socioeconomic challenges that result in higher HIV prevalence and limited access to health care, potentially leading to negative outcomes. In this systematic review and meta-analysis, we aimed to investigate the incidence of HIV-related outcomes among international migrants arriving in Europe compared with the incidence among the general population. We did a systematic review and meta-analysis to identify studies investigating HIV-related outcomes in migrants and the general population living with HIV in Europe. Six authors (EDV, VP, VS, SDG, MC, and RN) independently searched PubMed, Scopus, and Web of Science from database inception until July 22, 2023 (with an update on March 3, 2024), then screened titles and abstracts of all potentially eligible articles. Studies were included if they were observational studies; investigated clinical, virological, or immunological outcomes in migrants living with HIV; were conducted in Europe; had at least one control group of non-migrants living in a European country; and were in English. Titles and abstracts were screened for eligibility followed by a full-text assessment by two authors (EDV, VP, VS, SDG, MC, or RN). Data were extracted from articles using a structured Redcap form. Primary outcomes of our systematic review were (1) mortality, (2) AIDS-defining condition, (3) combined outcome of AIDS or death, (4) treatment discontinuation, (5) rate of loss to follow-up, (6) virological failure, and (7) immunological failure. Data were reported as relative risks (RRs) or odds ratios with their 95% CIs. The study is registered with PROSPERO, CRD42024501191. Of the 1316 articles identified (1297 in the initial search and 19 in the updated search), 19 were included in our systematic review, consisting of 104 676 participants who were followed up for a mean of 79·3 months. The meta-analysis, adjusted for potential confounders, showed that migrants present similar mortality risk (RR 0·88, 95% CI 0·75-1·04), but higher risk for AIDS-defining conditions (1·23, 1·14-1·34), treatment discontinuation (2·39, 1·49-3·29), loss to follow-up (2·53, 1·41-4·53), virological failure (1·80, 1·25-2·60), and immunological failure (3·70, 2·17-12·50) compared with the general population. In subanalyses for WHO regions, people originally from the African region had higher risk for HIV-related adverse outcomes. Compared with the non-migrant population, migrants living in Europe with HIV face higher risks for progression to AIDS, loss to follow-up, treatment discontinuation, and virological and immunological failure. Interventions aimed to improve HIV care among migrants living in Europe are urgently needed. None.

Phase 3 Open-Label Study Evaluating the Efficacy and Safety of Mavacamten in Japanese Adults With Obstructive Hypertrophic Cardiomyopathy - The HORIZON-HCM Study.

Mavacamten, a cardiac myosin inhibitor, significantly improved symptoms and cardiac function vs. placebo in patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM) in EXPLORER-HCM. However, the efficacy and safety profiles of mavacamten in Japanese patients are unclear. HORIZON-HCM is a Phase 3 single-arm study in Japanese patients with symptomatic obstructive HCM. The mavacamten starting dose was 2.5 mg; individualized dose titration occurred in Weeks 6-20 based on Valsalva left ventricular outflow tract (LVOT) gradient and resting left ventricular ejection fraction (LVEF). Overall, 38 patients were treated; 36 completed the 30-week primary treatment analysis period. Clinically significant improvements in postexercise LVOT gradient were observed after 30 weeks of treatment (mean change from baseline -60.7 mmHg). Improvements in N-terminal pro B-type natriuretic peptide, New York Heart Association class, and Kansas City Cardiomyopathy Questionnaire-23 Clinical Summary Score were observed over 30 weeks, and mean LVEF was ≥74% at all visits. Treatment-emergent adverse events (TEAEs) and serious TEAEs were reported in 63.2% and 7.9% of patients, respectively; none resulted in treatment discontinuation. One patient experienced a transient asymptomatic reduction in LVEF to <50%. No deaths occurred during the study. In Japanese patients with obstructive HCM, mavacamten was associated with similar improvements in LVOT gradients, cardiac biomarkers, and symptoms to those observed in EXPLORER-HCM. Treatment was well tolerated with no new safety concerns.

Differences in immune-related toxicity between PD-1 and PD-L1 inhibitors: a retrospective cohort study in patients with advanced cancer

Immunotherapy with PD-1 or PD-L1 inhibitors has become an essential treatment strategy for a growing number of malignancies. These treatments have a risk for immune-related adverse events (IRAEs). Pooled analyses based on clinical trials show a favorable toxicity profile for treatment with PD-L1 compared to PD-1 inhibitors. This study aimed to investigate differences in IRAEs between patients with advanced solid malignances treated with PD-L1 and PD-1 inhibitors in a real-world setting. We conducted a retrospective cohort study at four Swedish Regions. Patients (n = 605) treated for advanced cancer with a PD-L1 or PD-1 inhibitor in monotherapy between June 2016 and August 2022 were included. Non-small cell lung cancer (NSCLC) was the most common malignant disease (n = 251; 41.5%), followed by malignant melanoma (n = 173; 28.6%), renal cell carcinoma (n = 71; 11.7%) and urothelial carcinoma (n = 35; 5.8%). Among patients receiving PD-L1 inhibitors, NSCLC (94.4%) was the predominant malignancy, whereas for those treated with PD-1 inhibitor, malignant melanoma constituted the most prevalent malignancy (34.5%). Discontinuation of treatment due to IRAEs overall and IRAEs grade ≥ 2 were significantly less common in patients treated with PD-L1 compared to PD-1 inhibitors [Odds Ratio (OR): 0.38 (95% Confidence Interval (CI) 0.16–0.88) and OR: 0.63 (95% CI 0.35–0.98) respectively]. Any grade IRAE, IRAE grade ≥ 3 and multiple IRAEs were numerically more frequent in patients treated with PD-1 inhibitors.In conclusion, our study of patients with advanced solid malignancies in a real-world setting supports the results from clinical trials demonstrating a favorable toxicity profile for PD-L1 inhibitors versus PD-1 inhibitors.

Treatment sequences and survival outcomes in advanced HR + HER2- breast cancer patients: a real-world cohort.

Palliative treatment options for HR + HER2- advanced breast cancer (ABC) patients have increased, but data is lacking about the optimal treatment sequence. We used real-world data from a comprehensive cancer center to describe applied treatment sequences and we determined treatment-related and survival outcomes. Patients aged 18 years and older with HR + HER2- ABC treated with systemic treatment were included in this historic cohort study. Sequential treatment schedules, time to treatment discontinuation, time to chemotherapy, and overall survival (OS) were determined, stratified by first-line treatment. 202 patients were included. They received a total of 650 treatment lines (median 3; range: 1-11). 91 (45%), 25 (12%), 24 (12%), 28 (14%), 22 (11%) and 12 (6%) patients started first-line treatment with non-steroidal aromatase inhibitors (NSAI), NSAI + cyclin dependent kinase 4/6-inhibitors (CDK4/6i), fulvestrant + CDK4/6i, tamoxifen, chemotherapy and other treatment, respectively. 10, 13, and 14 different treatment regimens were given in first, second and third-line, respectively. Of the patients who started first-line NSAI monotherapy (n = 91), 3 (3%) died before receiving second-line treatment. In this real-world cohort, we observed a wide variety of different treatment sequences applied in daily clinical practice, some of which were in discordance with the current guidelines. Fear that patients may never get around to treatment with CDK4/6i if a patient did not start with a CDK4/6i was not supported by our study results.

Durable improvements in atopic dermatitis in the head and neck and across other anatomic regions with rocatinlimab

In a randomized phase 2b trial (NCT03703102) for adult patients with moderate-to-severe atopic dermatitis (AD), treatment with the T cell rebalancing anti-OX40 receptor antibody rocatinlimab (AMG 451/KHK4083) led to significant improvements in clinical measurements versus placebo including whole-body Eczema Area and Severity Index (EASI) score. AD manifestations can impact variable anatomic regions, and involvement of the head and neck, a sensitive, hard-to-treat area, can negatively impact quality of life. In this post hoc analysis, we investigated response to rocatinlimab treatment across anatomic regions, including the head and neck. Least squares mean change from baseline to Week 56 in EASI score was analyzed by anatomic region (head and neck, trunk, upper extremities, or lower extremities) for patients with baseline moderate-to-severe AD in the respective anatomic region, using mixed models for repeated measures. Rocatinlimab groups were compared with placebo at Week 16. The proportion of patients achieving at least 75% reduction from baseline in EASI (EASI-75) was calculated. Probability of relapsing in EASI-75 during the off-treatment follow-up period (Weeks 36–56) was estimated using a Kaplan − Meier approach. At Week 16, decrease from baseline in mean EASI score was greater with all rocatinlimab regimens versus placebo across all anatomic regions for patients with baseline moderate-to-severe AD in the respective region (all P < 0.001). EASI scores continued to improve on treatment after Week 16 and were maintained during the off-treatment period across all regions. Among patients with baseline moderate-to-severe AD in the head and neck (n = 219; rocatinlimab, n = 174; placebo, n = 45), mean difference (rocatinlimab vs placebo) at Week 16 in LS mean percent change in head and neck EASI score ranged from − 30.4% to − 42.6% across treatment regimens. In patients who received rocatinlimab from the start of the trial, 47% − 71% achieved EASI-75 in the head and neck at Week 36. Among EASI-75 responders at Week 36, the probability of relapsing in EASI-75 in any region was low (< 25% in the head and neck) 20 weeks after treatment discontinuation until Week 56.Rocatinlimab treatment led to durable improvements in AD across multiple anatomic regions, including the sensitive head and neck region.Graphical abstract

Heterogeneity in Reported Side Effects Following Initiation of Elexacaftor-Tezacaftor-Ivacaftor: Experiences at a Quaternary CF Care Center.

The benefits of Elexecaftor-Tezacaftor-Ivacaftor (ETI) therapy on the health and wellbeing of people with CF (pwCF) are well documented. Since approval, however, a growing number of potential side effects have emerged in reports from clinical practice. With current understanding of ETI tolerability limited to data from clinical trials, the prevalence of side effects and their impact on care decision making remains poorly categorized. A 10-question survey was developed and distributed to patients 18 years or older who were treated at the Massachusetts General Hospital CF centers. Reports of side effects were measured across 12 distinct categories, and dose adjustments and discontinuation due to side effects were collected. If a patient reported no side effects, they did not have to complete the entire survey. Among 92 respondents initiated on ETI, 51 respondents (55.4%) reported potential side effects and 41 (44.5%) respondents reported no adverse events. The most commonly reported side effects were mental health, changes in appearance, and gastrointestinal complaints, which were reported by 22.8%, 30.4%, and 21.7% of patients, respectively. Eighteen (19.6%) respondents modified their dosing in response to side effects, and six discontinued treatment permanently (6.52%) due to persistent side effects. Responses demonstrated marked heterogeneity, with most respondents reporting at least one side effect following initiation. Dose modification was commonly utilized to mitigate adverse effects, however few respondents had to discontinue treatment. These findings demonstrate the importance of monitoring for potential drug-related side effects of ETI in clinical settings.

Chronic pain among primary fentanyl users: The concept of self-medication.

Chronic pain is among the leading causes of disability worldwide, of which only a small percentage of patients receive adequate treatment for. Non-prescribed opioid analgesics are commonly sought out in effort to alleviate unrelieved pain. This study assesses the prevalence and correlates of chronic pain among primary fentanyl users. A cross-sectional and structured survey was conducted with 200 adults who reported fentanyl as their drug of choice from a Vancouver acute care hospital. Presence and levels of chronic pain were determined through self-report. The majority of participants (n = 130, 72.6%) reported having chronic pain in the past 6 months, with the mean level of pain on a typical day to be 7.6 out of a scale of 10 (SD = 1.9). Majority (n = 85, 65.4%) reported using street opioids to self-medicate, while only 9 (6.9%) reported that their chronic pain was unrelated. Regression analysis indicated that increasing age and co-use of cannabis and opioids were independent associated factors of chronic pain. Higher levels of reported pain on a typical day were further associated with age and self-medication. The findings of this study demonstrate a significant association between self-medication and chronic pain among primary fentanyl users in British Columbia. For these individuals, inadequate pain relief may drive continued opioid use, which in turn may increase risks of treatment discontinuation and overdose. Appropriate pain management strategies are crucial to avoid opioid misuse and decrease the large societal burden caused by chronic pain. Our work points to the high prevalence of self-reported chronic pain among individuals who primarily use fentanyl. Among those with self-reported fentanyl use and chronic pain, self-medication with street opioids was found to be common and associated with higher reported pain levels on a typical day. This highlights the need for pain management strategies to be integrated into opioid dependence treatment and more research in the overlap of pain and fentanyl use.

A transformer-based deep learning model for identifying the occurrence of acute hematogenous osteomyelitis and predicting blood culture results

BackgroundAcute hematogenous osteomyelitis is the most common form of osteomyelitis in children. In recent years, the incidence of osteomyelitis has been steadily increasing. For pediatric patients, clearly describing their symptoms can be quite challenging, which often necessitates the use of complex diagnostic methods, such as radiology. For those who have been diagnosed, the ability to culture the pathogenic bacteria significantly affects their treatment plan.MethodA total of 634 patients under the age of 18 were included, and the correlation between laboratory indicators and osteomyelitis, as well as several diagnoses often confused with osteomyelitis, was analyzed. Based on this, a Transformer-based deep learning model was developed to identify osteomyelitis patients. Subsequently, the correlation between laboratory indicators and the length of hospital stay for osteomyelitis patients was examined. Finally, the correlation between the successful cultivation of pathogenic bacteria and laboratory indicators in osteomyelitis patients was analyzed, and a deep learning model was established for prediction.ResultThe laboratory indicators of patients are correlated with the presence of acute hematogenous osteomyelitis, and the deep learning model developed based on this correlation can effectively identify patients with acute hematogenous osteomyelitis. The laboratory indicators of patients with acute hematogenous osteomyelitis can partially reflect their length of hospital stay. Although most laboratory indicators lack a direct correlation with the ability to culture pathogenic bacteria in patients with acute hematogenous osteomyelitis, our model can still predict whether the bacteria can be successfully cultured.ConclusionLaboratory indicators, as easily accessible medical information, can identify osteomyelitis in pediatric patients. They can also predict whether pathogenic bacteria can be successfully cultured, regardless of whether the patient has received antibiotics beforehand. This not only simplifies the diagnostic process for pediatricians but also provides a basis for deciding whether to use empirical antibiotic therapy or discontinue treatment for blood cultures.

Olaparib-associated toxicity in cancer patients: a systematic review and meta-analysis.

To investigate the characteristics of olaparib-associated adverse events (AEs) in cancer patients. Databases were searched for phase II and III randomized controlled trials (RCTs) involving olaparib treatment up to March 2024. A systematic assessment was performed. Twenty-seven RCTs involving 9542 patients were included. This meta-analysis indicates that olaparib could significantly increase the risk of developing any all-grade (RR, 1.08; 95% CI, 1.03-1.13; p = 0.001) and high-grade (RR, 1.45; 95% CI, 1.19-1.77; p = 0.0003) AEs in cancer patients. Olaparib could increase the risk of dose reduction (RR, 3.00; 95% CI, 1.59-5.70; p = 0.0007) and treatment discontinuation (RR, 2.00; 95% CI, 1.28-3.14; p = 0.002). Hematologic toxicities and gastrointestinal toxicities commonly occur in patients receiving olaparib. Anemia, nausea, and fatigue were the most frequent AEs, with olaparib increasing the risk of both all-grade and high-grade occurrences of these events. Patients with longer treatment durations tend to have a higher risk of anemia. Patients with urinary system tumors tend to have a higher risk of nausea, while those with breast cancer tend to have a higher risk of fatigue. Olaparib maintenance therapy may be associated with a higher risk of fatigue. Olaparib could increase other AEs such as diarrhea, vomiting, decreased appetite, dyspepsia, dysgeusia, dizziness, headache, back pain, urinary tract infection, dyspnea, and cough. Olaparib-containing therapy could increase the occurrence of specific AEs in patients with cancer. Clinicians should be aware of these risks and conduct regular monitoring.

Predicting dropout and non-response to psychotherapy for personality disorders: A study protocol focusing on therapist, patient, and the therapeutic relationship

BackgroundThe abandonment of psychotherapeutic treatments is influenced by various factors, including patient characteristics, therapist traits, and the therapeutic relationship. Despite the well-documented importance of these factors, limited empirical research has focused on the role of the therapeutic relationship and the characteristics of therapist-patient dyads in predicting treatment dropout. This study protocol outlines a longitudinal research project aimed at predicting dropout and non-response in psychotherapy for individuals with personality disorders. The research seeks to identify predictive factors related to psychotherapy outcomes, focusing on patient, therapist, and dyadic elements. Specifically, the study will examine the influence of therapist characteristics (e.g., personality traits, countertransference, responsiveness) on treatment outcomes, explore the impact of relational factors (e.g., treatment expectations, epistemic trust, therapeutic alliance) on therapy effectiveness, and assess how the therapeutic alliance within therapist-patient dyads affects the likelihood of dropout and non-response.MethodsThe longitudinal study will include 100 therapist-patient dyads (200 participants) recruited from various Mental Health Services in Milan, Italy. Validated instruments will be administered to both patients and therapists at four-time points: T0 (baseline), T1 (3 months), T2 (6 months), and T3 (1 year). Data will be collected at baseline and at the one-year mark to evaluate the relationships between therapist, patient, and dyadic factors and treatment outcomes.DiscussionIdentifying predictive variables associated with high dropout rates can help preempt treatment discontinuation, reducing the financial and operational burdens on mental health services. Understanding these factors will enable the development of targeted interventions to improve treatment engagement and reduce attrition. This approach could enhance outcomes for individuals with personality disorders and lead to more efficient resource allocation and sustainable delivery of mental health care.

Eculizumab in refractory myasthenia gravis: a real-world single-center experience.

Immunosuppressive treatment is effective in most Myasthenia gravis patients, but 10-15% of patients areconsidered refractory due to inadequate response or intolerance to therapy. Eculizumab, a humanized monoclonalantibody directed against C5 complement protein, was approved in Italy to treat Ab-AchR generalized refractoryMG (rMG) in October 2022. We aim to describe a real-world Italian experience in a population of refractory myasthenia gravis patients with oneyear follow up. A retrospective data analysis was conducted on patients with refractory generalized MG treated with eculizumabbetween November 2022 and May 2024. Clinical assessment through specific scales (MG ADL - QMG - MGFA -PIS), rescue, and background therapy was recorded after one, three, six, and twelve months. 21 rMG patients were treated with eculizumab with a medium follow up of 10.4 months and 14 patients had at leastone year follow up. A clinically meaningful reduction in total MG-ADL and QMG scores was achieved in the firstmonth. It was maintained throughout the first, third, sixth, and twelfth month along with concomitant reduction ofimmunosuppressive treatments. A drastic reduction of myasthenic exacerbations and crisis was observed duringfollow up and intravenous immunoglobulin treatment was discontinued in all patients except one. The total dailydose of prednisone was significantly reduced. This single-center real-world study confirmes safety and effectiveness of eculizumab. Eculizumab improved rapidlyall clinical outcome measures, leading to discontinuation of intravenous immunoglobulin treatment and remarkable immunosuppressant-sparing benefits.

The journey of patients affected by metastatic hormone receptor-positive/HER2-negative breast cancer from CDK 4/6 inhibitors to second-line treatment: A real-world analysis of 701 patients enrolled in the GIM14/BIOMETA study

PurposeThe aim of this study was to evaluate the effectiveness of CDK 4/6 inhibitors (CDK 4–6i) according to HER2 status (low/zero), and endocrine resistance/sensitivity, as well as the efficacy of second-line treatments, in a large real-world cohort. MethodsThe GIM14/BIOMETA study (NCT02284581) is a retrospective/prospective study of the Gruppo Italiano Mammella evaluating treatment patterns and survival outcomes in patients with metastatic breast cancer (MBC). We retrieved data on patients with hormone receptor-positive/HER2-negative MBC receiving first-line CDK 4/6i. ResultsAmong 3832 patients enrolled in the GIM14-BIOMETA study, 701 were eligible. At a median follow-up of 24.80 months, no significant differences were found between HER2-zero and HER2-low subgroups in terms of first-line time to treatment discontinuation (TTD) (26.16 months [IQR 12.84-NR] vs. 27.60 months [IQR 12.12–64.44], p = 0.972) or overall survival (OS) (mOS>60 months for both groups, p = 0.398). Median TTD was 33.24 months (IQR 16.32-NR) for the endocrine sensitive subgroup, 19.92 months (IQR 8.88–51.24) for the secondary endocrine resistant subgroup and 17.40 months (IQR 7.44–24.72) for the primary endocrine resistant subset, respectively (p < 0.001). Among 239 patients receiving second-line treatment, no significant difference (p = 0.188) was found in terms of second-line TTD between those treated with capecitabine (6.11 months, IQR 2.96–11.47), taxane-based chemotherapy (5.06 months, IQR 2.99–9.99), everolimus plus exemestane (5.39 months, IQR 2.53–9.03) or fulvestrant (6.44 months, IQR 3.38-NR). ConclusionsEndocrine therapy plus CDK 4/6i represents an effective treatment, regardless of HER2 status (low/zero). Second-line agents did not differ significantly in terms of TTD. Endocrine resistant cancers exhibit poor response to CDK 4/6i.

A comprehensive review of immune checkpoint inhibitor-related diabetes mellitus: incidence, clinical features, management, and prognosis

Immune checkpoint inhibitor-related diabetes mellitus (ICI-DM) is a rare complication that medical oncologists seldom encounter in routine practice. The sporadic nature and intrinsic complexity of ICI-DM make it challenging to analyze comprehensively in experimental settings. In this review, we examine phase 3 clinical trials on ICIs and published case reports of ICI-DM, aiming to summarize its incidence, clinical features, management, and prognosis. Phase 3 clinical trials reveal that the incidence of ICI-DM is higher with combination therapies, such as anti-PD-1 and anti-CTLA-4 or anti-PD-L1, compared to anti-PD-1 monotherapy. ICI-DM typically presents as severe hyperglycemia with a fulminant onset and is often associated with diabetic ketoacidosis, accompanied by unexpectedly low HbA1c and C-peptide levels. ICI-DM shares similarities with classic type 1 diabetes, particularly in terms of autoimmunity and genetic predisposition. This includes a high prevalence of islet autoantibodies and susceptibility to certain HLA haplotypes, often with concurrent endocrine gland dysfunction. This suggests that genetic susceptibility and exposure to ICIs may both be necessary for triggering islet autoimmunity and inducing ICI-DM. Notably, patients with positive islet autoantibodies, such as glutamic acid decarboxylase antibody and islet-associated antigen 2 antibody, tend to experience rapid onset of ICI-DM after ICI exposure. Although patients with ICI-DM generally show a high objective response rate to immunotherapy, a significant proportion also face the need to permanently discontinued treatment. Further research is urgently needed to determine whether permanent discontinuation of immunotherapy is necessary and whether this discontinuation negatively impacts overall survival.

Global Research Trends on Factors Affecting Tuberculosis (TB) Adherence and Dropout: A Bibliometric Study

ABSTRACT Tuberculosis (TB) remains one of the significant global health challenges, especially in resource-limited countries. Adherence to TB treatment is key to successful therapy and preventing the emergence of drug resistance. However, dropout rates or discontinuation of treatment before completion remains a major problem that needs to be addressed. This study aims to analyze global trends in research focusing on factors affecting TB treatment adherence and dropout through a bibliometric approach. Using the Publish or Perish application, relevant scientific articles with keywords such as treatment adherence, tuberculosis, treatment dropout, and influencing factors were searched from 2017 to 2024. A total of 50 articles from Google Scholar were further analyzed to identify by publication year, country, publisher, citation, and article type. The data was then processed using VOSviewer to visualize the relationship between keywords and research trends through Network Visualization, Overlay Visualization, and Density Visualization. The results of the analysis showed that Indonesia is the country with the highest number of publications, demonstrating a great commitment in addressing the TB challenge. Articles published in reputable journals, especially those adopting systematic and meta-analysis approaches, show great impact with a high number of citations. Bibliometric visualizations reveal that the focus of research lies on factors such as treatment, adherence, health workers, and access. In addition, family and community support was also found to be an important element in ensuring treatment adherence. In conclusion, this study emphasizes the need for a comprehensive and collaborative approach in improving TB treatment adherence and preventing dropouts. Further research in this area is needed to address existing gaps and develop more effective strategies in the fight against TB. Keywords: Treatment Adherence, Tuberculosis, Dropout, Influencing Factors, Health Worker

Sotalol prophylaxis was efficient and safe for supraventricular tachycardia in early infancy.

There is no consensus on the best prophylaxis for supraventricular tachycardia (SVT) in infancy. We studied the efficacy and safety of sotalol. 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. 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. Sotalol provided effective and safe prophylaxis for SVT during infancy. QTc prolongation rarely caused treatment discontinuation and there were no cases of proarrhythmia.

Pharmacologic properties and results of a clinical study of oxybutynin hydrochloride lotion (APOHIDE® Lotion 20%) as a novel treatment for primary palmar hyperhidrosis

APOHIDE® Lotion 20% is a topical agent for treating primary palmar hyperhidrosis that contains the active ingredient oxybutynin hydrochloride. Oxybutynin hydrochloride has anticholinergic effects and inhibits sweating by binding to the M3 receptor, a subtype of the muscarinic acetylcholine receptor, in eccrine sweat glands. The clinical response to oxybutynin hydrochloride treatment also involves N-desethyloxybutynin, an active metabolite of oxybutynin. A clinical study in Japanese patients with primary palmar hyperhidrosis showed superiority of APOHIDE® Lotion 20% over placebo, i.e., there were significantly more responders (i.e., patients with a reduction in sweat volume ≥50% from baseline) in the APOHIDE® Lotion 20% group (APOHIDE® Lotion 20% group: 52.8%, placebo group: 24.3%; treatment difference: 28.5%; P < 0.001, Fisher's exact test). This and other clinical studies reported some adverse events (AEs) associated with the drug's anticholinergic effects and some application site AEs, but most of the AEs were mild. Clinical response did not decrease with long-term (52-week) treatment, and only a few patients (2 of 125) discontinued treatment because of AEs. Taken together, study results indicate that APOHIDE® Lotion 20% may be an effective and safe new treatment option for patients with primary palmar hyperhidrosis.

Treatment of atopic dermatitis with abrocitinib in real practice in Spain: efficacy and safety results from a 24-week multicenter study.

Abrocitinib, a selective JAK 1 inhibitor, was recently approved in Europe. Despite its approval, real-world data on its efficacy and safety in treating moderate-to-severe atopic dermatitis (AD) remains limited. This study aimed to evaluate the short-term effectiveness and safety of abrocitinib in a real-life setting for patients with moderate-to-severe AD. We conducted a retrospective multicenter study involving adult patients with moderate-to-severe AD who started abrocitinib treatment between May 1, 2023, and September 30, 2023, in 15 Spanish hospitals. Treatment doses were 100 or 200 mg daily, based on clinical assessment. Data collection included patient demographics, AD history, comorbidities, previous treatments, and disease severity indicators such as SCORing atopic dermatitis (SCORAD), Eczema Area and Severity Index (EASI), body surface area, and Peak Pruritus NRS scores at baseline, 4, 12, and 24 weeks. Quality of life was measured using the Dermatology Life Quality Index (DLQI), and safety was assessed by monitoring adverse reactions and various biochemical parameters. The cohort comprised 76 patients with an average age of 33.93 years; 57.89% were male. Before abrocitinib, 36.84% were naïve to advanced therapies. The baseline mean scores were SCORAD 47.04, EASI 21.79, and DLQI 15.01. At Week 24, there were significant improvements: EASI was reduced to 2.81, and 70.58% of the patients achieved EASI 75. However, 18.42% discontinued treatment mainly due to inefficacy or adverse effects. The safety profile was favorable, with 22.37% reporting mild adverse events (AEs) and one serious case of cutaneous lymphoma. This first Spanish series assessing abrocitinib in real-world conditions reveals a significant improvement in AD symptoms and quality of life in a range of severity and prior treatment failures. Abrocitinib was well-tolerated, with few serious AEs, highlighting its potential as an effective treatment option for AD.

Abatacept and tofacitinib in refractory sarcoidosis: drug survival, safety, and treatment response.

To describe drug survival, safety and treatment response in sarcoidosis patients treated with abatacept or tofacitinib in routine care. We identified 41 sarcoidosis patients treated with abatacept and 12 patients treated with tofacitinib. Of the patients treated with tofacitinib 83% had previously been treated with abatacept. Drug survival and reasons for discontinuation of treatment was investigated. Treatment response was evaluated at least once within the first 6 months of treatment by at least one trained clinician and classified as responder or non-responder. No direct comparison of drugs was made. Median (range) disease duration was 3.5 (1-27) and 3 (1-16) years for abatacept and tofacitinib. The patients had previously received a median of 1 DMARD and 1 biological DMARD in both groups. Nearly all patients had been treated with at least one TNFi (95%/92 %). After 6 months, 90% (95%CI 85-90%) of the 41 patients in the abatacept group and 89% (79-99%) of the 12 patients in the tofacitinib group-maintained treatment. At 12 months, it was 80% (73-87%) and 74% (58-90%). No serious adverse events were recorded. For abatacept and tofacitinib 71% and 67% of patients were characterised as responders. In both treatment groups, there was a significant reduction in prednisolone dosage and levels of soluble IL2-receptor at all time points. Sarcoidosis patients treated with abatacept and tofacitinib had long drug survival, achieved high response rates. Both drugs represent good and safe therapeutic options in sarcoidosis patient's refractory to previous TNFi therapy.