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Aim: This post-marketing surveillance study evaluated the safety and effectiveness of lenvatinib as first-line treatment for unresectable hepatocellular carcinoma in Korea. Materials & methods: Adverse drug reactions (ADRs) and other safety and effectiveness end points were assessed in patients who initiated lenvatinib according to the approved label in republic of Korea. Results: Among 658 lenvatinib-treated patients, ADRs were reported in 57.8%; ADRs grade ≥3 in 13.5%. The most common grade ≥3 ADRs were asthenia (1.2%) and hepatic encephalopathy (1.2%). Physician-reported tumor responses (n = 511) were complete (1.0%) or partial (12.9%) response and stable (45.2%) or progressive disease (40.9%); objective response rates were higher with longer lenvatinib treatment duration (p < 0.001). Conclusion: Lenvatinib was generally well tolerated and effective in real-world clinical practice in Korea. Clinical trial registration:ClinicalTrials.govNCT05225207 Article highlights Since 2018, lenvatinib has been available in several countries as first-line treatment for patients with unresectable hepatocellular carcinoma (uHCC). This was a prospective, multicenter, observational, post-marketing surveillance of the safety and effectiveness of lenvatinib as first-line treatment for uHCC in routine clinical practice in republic of Korea. Among 700 case report forms of patients who initiated lenvatinib according to the approved label in republic of Korea at 29 institutions, 658 were included in the safety analysis and 511 in the effectiveness analysis. None of the safety population (median age 64 years, 85% male) had received prior chemotherapy, 64.1% had received non-chemotherapy treatment, and 42.1% had a history of hypertension treatment. Among 658 lenvatinib-treated patients, the incidence of adverse drug reactions (ADRs) was 57.8% and the incidence of ADRs grade ≥3 was 13.5%. The most common ADRs were hypertension (14.4%) diarrhea (10.5%), palmar-plantar erythrodysesthesia syndrome (10.0%) and decreased appetite (7.6%); the most common grade ≥3 ADRs were asthenia (1.2%) and hepatic encephalopathy (1.2%). Factors significantly associated with adverse events were history of non-chemotherapy treatment, hypertension treatment; and the average daily dose of lenvatinib (12 mg/day compared with <8 mg/day and 8 – <10 mg/day). Physician-reported tumor responses evaluated by RECIST v1.1 or mRECIST criteria were: complete response (1.0%); partial response (12.9%); stable disease (45.2%); and progressive disease (40.9%). Objective response rates were significantly higher with longer (≥3 months to >9 months) lenvatinib treatment duration compared with <3 months. This PMS study shows that lenvatinib has a manageable tolerability profile and provides clinically meaningful effectiveness as first-line treatment for patients with uHCC in the real-world clinical setting in Korea. [ABSTRACT FROM AUTHOR]

The purpose of this article is to introduce a design-based research (DBR) approach developed in the field of vocational and continuing education, which is grounded in a pragmatic and phenomenologically inspired enactivist approach to activity. As a design-based methodology, our activity-centered and enactive DBR approach aims to generate knowledge related to design and to identify relevant design principles. After detailing the particularities of an activity-centered and enactive DBR approach, we focus on the results pertaining to design knowledge by identifying two broad design principles for vocational education and training, and five enactivist inspired principles for training design. A significant practical implication for researchers and practitioners in vocational and continuing education and training is that these enactivist inspired design principles provide promising pathways to enhance the connectivity between (i) work experiences, (ii) work and training practices, and (iii) learning contexts. [ABSTRACT FROM AUTHOR]

Objective: There is currently no consensus over whether neoadjuvant immunochemotherapy is more effective in young patients than in elderly patients with IIA–IIIB non-small-cell lung cancer (NSCLC). In this study, we compare the efficacy and safety of neoadjuvant immunochemotherapy in young and elderly patients with IIA–IIIB NSCLC. Methods: This retrospective study consecutively included IIA–IIIB NSCLC patients who received 2–4 cycles preoperative immunochemotherapy at the Department of Thoracic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine from 2019 to 2022. The 1:1 propensity score match analysis was conducted to balance the confounding factors between the young patient group (< 65 years old) and elderly patient group (≥ 65 years old). The follow-up period would not end until at least 1 year after surgery or patient's decision to abandon treatment. The primary endpoint was pathological response, while the secondary endpoints were objective response rate (ORR), adverse events (AEs), disease-free survival (DFS) and overall survival (OS). Results: A total of 179 patients were included in our study: <65 years group (71 patients) and ≥ 65 years group (108 patients). After a 1:1 propensity score matching,132 patients (66 pairs) were analyzed to compare the efficacy and safety between the two groups. The ORR in the young patient group and elderly patient group was 72.7% and 71.2% (P = 1.000), respectively. The incidence of grade 3–4 AEs in the elderly patient group was similar to the young patient group (13.6% vs. 16.7%, P = 0.627). About 62.1% (41/66) in the young patient group and 54.5% (36/66) in the elderly patient group eventually underwent surgery. The rate of major pathological response (MPR) in the young patient group and elderly patient group was 68.3% and 55.6% (P = 0.903), respectively. The rate of pathological complete response (pCR) in the young patient group was significantly higher than that in the elderly patient group (46.3% vs. 22.2%, P = 0.027). The median DFS in the young patient group was not reached and 32.2 months in the elderly patient group (P = 0.071). The 1-year DFS rate, 2-year DFS rate and 3-year DFS rate in the young patient group were 90.2%, 85.4% and 80.5%, with that in the elderly patient group 86.1%, 69.4% and 66.7%. The median OS in the young patient group was 42.4 months and not reached in the elderly patient group (P = 0.067). The 1-year OS rate, 2-year OS rate and 3-year OS rate in the young patient group were 97.6%, 90.2% and 90.2%, with that in the elderly patient group 88.9%, 80.6% and 72.2%. Conclusions: For IIA–IIIB NSCLC, neoadjuvant immunochemotherapy in young patients can produce a higher percentage of patients with a pCR than in elderly patients. However, the survival benefits and incidence of AEs are similar in young and elderly patients. [ABSTRACT FROM AUTHOR]

Abstract Objective There is currently no consensus over whether neoadjuvant immunochemotherapy is more effective in young patients than in elderly patients with IIA–IIIB non-small-cell lung cancer (NSCLC). In this study, we compare the efficacy and safety of neoadjuvant immunochemotherapy in young and elderly patients with IIA–IIIB NSCLC. Methods This retrospective study consecutively included IIA–IIIB NSCLC patients who received 2–4 cycles preoperative immunochemotherapy at the Department of Thoracic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine from 2019 to 2022. The 1:1 propensity score match analysis was conducted to balance the confounding factors between the young patient group (

Background: To identify predictive factors associated with successful transition to conversion therapy following combination therapy with atezolizumab and bevacizumab in the treatment of unresectable hepatocellular carcinoma (HCC). Methods: In total, 188 patients with HCC, who received atezolizumab plus bevacizumab combination therapy as the first‐line chemotherapy, were studied. Patients who achieved complete response (CR) with systemic chemotherapy alone were excluded. Clinical factors possibly linked to successful transition to conversion therapy and the achievement of cancer‐free status were identified. Results: Fifteen (8.0%) patients underwent conversion therapy. In the conversion group, there was a significantly higher proportion of patients with Barcelona Clinic Liver Cancer (BCLC) stage A or B (73.3% versus [vs.] 45.1%; p =.03) and tended to have lower Child‐Pugh scores and alpha‐fetoprotein levels. Multivariate analysis revealed that BCLC stage was a predictive factor for the implementation of conversion therapy (A or B; odds ratio 3.7 [95% CI: 1.1–13]; p =.04). Furthermore, 10 (66.7%) patients achieved cancer‐free status and exhibited a smaller number of intrahepatic lesions at the start of treatment (3.5 vs. 7; p <.01), and a shorter interval between systemic chemotherapy induction and conversion therapy (131 vs. 404 days; p <.01). In addition, the rate of achieving cancer‐free status by undergoing surgical resection or ablation therapy was significantly higher (p =.03). Conclusion: BCLC stage was the sole predictive factor for successful transition to conversion therapy when using combination therapy with atezolizumab and bevacizumab to treat HCC. Furthermore, a small number of intrahepatic lesions and early transition to conversion therapy were associated with the achievement of cancer‐free status. [ABSTRACT FROM AUTHOR]

Simple Summary: Immune checkpoint inhibitors have become widely used against malignant tumors. The neutrophil-to-lymphocyte ratio, an index focusing on immune cells, has been reported as a marker to predict the efficacy and side effects of anti-tumor drugs. In the present study, we found that the neutrophil-to-lymphocyte ratio shows an altered predictability of anti-tumor efficacy and side effects due to changes in nutritional status. Patients with carcinoma in situ are prone to changes in nutritional status depending on the progression of the cancer and the age of the patient. We believe that the results of this study are important findings in predicting the course of treatment for cancer patients. The neutrophil -to-lymphocyte ratio (NLR) is useful for predicting the effectiveness of treatment with immune checkpoint inhibitors (ICIs) and immune-related adverse events (irAEs). Because a growing body of evidence has recently shown that the number of lymphocytes that comprise NLR fluctuates according to nutritional status, this study examined whether the usefulness of NLR varies in ICI treatment due to changes in nutritional status. A retrospective analysis was performed on 1234 patients who received ICI treatment for malignant tumors at our hospital. Progression-free survival (PFS) was significantly prolonged in patients with NLR < 4. Multivariate analysis revealed that the factors associated with the occurrence of irAE were NLR < 4 and the use of ipilimumab. However, when limited to cases with serum albumin levels <3.8 g/dL, lymphocyte counts significantly decreased, and the associations between NLR and PFS and between NLR and irAE occurrence disappeared. In contrast, when limited to the cases with serum albumin levels ≥3.8 g/dL, the associations remained, with significantly prolonged PFS and significantly increased irAE occurrence at NLR < 4. NLR may be a good predictive tool for PFS and irAE occurrence during ICI treatment when a good nutritional status is maintained. [ABSTRACT FROM AUTHOR]

Abstract Aims The current European Society of Cardiology (ESC) guidelines provide clear indications for the treatment of acute and chronic heart failure (HF). Nevertheless, there is a constant need for real‐world evidence regarding the effectiveness, adherence, and persistence of drug therapy. We investigated the use of sacubitril/valsartan for the treatment of HF with reduced ejection fraction in real‐world clinical practice in Italy. Methods and results An observational, retrospective, non‐interventional cohort study based on electronic medical records from nine specialized hospital HF centres in Italy was carried out on patients with prescription of sacubitril/valsartan. Overall, 948 patients had a prescription of sacubitril/valsartan, with 924 characterized over 6 months and followed up for 12 months. Pharmacoutilization data at 1 year of follow‐up were available for 225 patients {mean age 69.7 years [standard deviation (SD) = 10.8], 81.8% male}. Of those, 398 (45.2%) reached the target dose of sacubitril/valsartan of 97/103 mg in a mean time of 6.9 (SD = 6.2) weeks. Blood pressure and hypotension in 61 patients (65%) and worsening of chronic kidney disease in 10 patients (10.6%) were the main reasons for not reaching the target dose. Approximatively 50% of patients had a change in sacubitril/valsartan dose during follow‐up, and 158 (70.2%) were persistent with the treatment during the last 3 months of follow‐up. A sensitivity analysis (persistence during the last 4 months of follow‐up) showed persistence for 162 patients (72.0%). Adherence data, available for 387 patients, showed full adherence for 205 (53%). Discontinuation (102/717 patients, 14.2%) was mainly due to hypotension and occurred after a mean time of 34.3 (SD = 28.7) weeks. During follow‐up, out of 606 patients with available data, 434 patients (71.6%) had an HF add‐on drug or drugs concomitant with sacubitril/valsartan. HF‐related hospitalization during follow‐up was numerically higher in non‐persistent (16/67 patients, 23.9%) vs. patients persistent to sacubitril/valsartan (30/158, 19%) (P = 0.405). Conclusions Real‐world data on the use of sacubitril/valsartan in clinical practice in Italy show a rapid titration to the target dose, high therapeutic adherence enabling a good level of therapeutic management in line with ESC guidelines for patients with reduced ejection fraction.

Open in new tab Download slide OBJECTIVES To assess the current practice of pulmonary metastasectomy at 15 European Centres. Short- and long-term outcomes were analysed. METHODS Retrospective analysis on patients ≥18 years who underwent curative-intent pulmonary metastasectomy (January 2010 to December 2018). Data were collected on a purpose-built database (REDCap). Exclusion criteria were: previous lung/extrapulmonary metastasectomy, pneumonectomy, non-curative intent and evidence of extrapulmonary recurrence at the time of lung surgery. RESULTS A total of 1647 patients [mean age 59.5 (standard deviation; SD = 13.1) years; 56.8% males] were included. The most common primary tumour was colorectal adenocarcinoma. The mean disease-free interval was 3.4 (SD = 3.9) years. Relevant comorbidities were observed in 53.8% patients, with a higher prevalence of metabolic disorders (32.3%). Video-assisted thoracic surgery was the chosen approach in 54.9% cases. Wedge resections were the most common operation (67.1%). Lymph node dissection was carried out in 41.4% cases. The median number of resected lesions was 1 (interquartile range 25–75% = 1–2), ranging from 1 to 57. The mean size of the metastases was 18.2 (SD = 14.1) mm, with a mean negative resection margin of 8.9 (SD = 9.4) mm. A R0 resection of all lung metastases was achieved in 95.7% cases. Thirty-day postoperative morbidity was 14.5%, with the most frequent complication being respiratory failure (5.6%). Thirty-day mortality was 0.4%. Five-year overall survival and recurrence-free survival were 62.0% and 29.6%, respectively. CONCLUSIONS Pulmonary metastasectomy is a low-risk procedure that provides satisfactory oncological outcomes and patient survival. Further research should aim at clarifying the many controversial aspects of its daily clinical practice. [ABSTRACT FROM AUTHOR]

Aims: The current European Society of Cardiology (ESC) guidelines provide clear indications for the treatment of acute and chronic heart failure (HF). Nevertheless, there is a constant need for real‐world evidence regarding the effectiveness, adherence, and persistence of drug therapy. We investigated the use of sacubitril/valsartan for the treatment of HF with reduced ejection fraction in real‐world clinical practice in Italy. Methods and results: An observational, retrospective, non‐interventional cohort study based on electronic medical records from nine specialized hospital HF centres in Italy was carried out on patients with prescription of sacubitril/valsartan. Overall, 948 patients had a prescription of sacubitril/valsartan, with 924 characterized over 6 months and followed up for 12 months. Pharmacoutilization data at 1 year of follow‐up were available for 225 patients {mean age 69.7 years [standard deviation (SD) = 10.8], 81.8% male}. Of those, 398 (45.2%) reached the target dose of sacubitril/valsartan of 97/103 mg in a mean time of 6.9 (SD = 6.2) weeks. Blood pressure and hypotension in 61 patients (65%) and worsening of chronic kidney disease in 10 patients (10.6%) were the main reasons for not reaching the target dose. Approximatively 50% of patients had a change in sacubitril/valsartan dose during follow‐up, and 158 (70.2%) were persistent with the treatment during the last 3 months of follow‐up. A sensitivity analysis (persistence during the last 4 months of follow‐up) showed persistence for 162 patients (72.0%). Adherence data, available for 387 patients, showed full adherence for 205 (53%). Discontinuation (102/717 patients, 14.2%) was mainly due to hypotension and occurred after a mean time of 34.3 (SD = 28.7) weeks. During follow‐up, out of 606 patients with available data, 434 patients (71.6%) had an HF add‐on drug or drugs concomitant with sacubitril/valsartan. HF‐related hospitalization during follow‐up was numerically higher in non‐persistent (16/67 patients, 23.9%) vs. patients persistent to sacubitril/valsartan (30/158, 19%) (P = 0.405). Conclusions: Real‐world data on the use of sacubitril/valsartan in clinical practice in Italy show a rapid titration to the target dose, high therapeutic adherence enabling a good level of therapeutic management in line with ESC guidelines for patients with reduced ejection fraction. [ABSTRACT FROM AUTHOR]

BackgroundHeart failure (HF) significantly affects the morbidity, mortality, and quality of life of patients. New therapeutic strategies aim to improve the functional capacity and quality of life of patients while controlling HF-related risks. Real-world data on both the functional and cardiopulmonary exercise capacities of patients with HF with reduced ejection fraction upon sacubitril/valsartan use are lacking.MethodsA multicenter, retrospective, cohort study, called REAL.IT, was performed based on the data collected from the electronic medical records of nine specialized HF centers in Italy. Cardiopulmonary exercise testing was performed at baseline and after 12 months of sacubitril/valsartan therapy, monitoring carbon dioxide production (VCO2) and oxygen consumption (VO2).ResultsThe functional capacities of 170 patients were evaluated. The most common comorbidities were hypertension and diabetes (i.e., 53.5 and 32.4%, respectively). At follow-up, both the VO2 peak (from 15.1 ± 3.7 ml/kg/min at baseline to 17.6 ± 4.7 ml/kg/min at follow-up, p

Aim. To study the real-world efficacy and safety of netakimab in the treatment of ankylosing spondylitis (AS) and psoriatic arthritis (PsA). Materials and methods. The retrospective analysis included 23 patients (13 males; 56.5%) aged 23 to 73 years (median 42, interquartile range 28 to 52 years) with AS (n=12) or PsA (n=11) who received netakimab therapy from February 2021 to April 2023. Disease activity was assessed every 3-6 months based on the C-reactive protein (CRP) level for all patients according to the BASDAI and ASDAS-CRP indices for AS, DAPSA and PASI for PsA. These indicators were analyzed before therapy and at the last visit to assess the effectiveness of treatment. The results are presented as median (interquartile range). Results. In all patients treated with netakimab (median duration of treatment 11 months), the CRP level decreased from 10.6 (3.1; 17.3) to 3.1 (1.9; 8.9) mg/L (absolute difference -7.5 mg/L, median relative reduction -60%; p=0.008), and the proportion of patients with elevated CRP decreased from 70 to 41%; p=0.039. In patients with AS (median duration of treatment 9 months), BASDAI score decreased from 5.8 (4.7; 6.5) to 3.0 (1.9; 3.8) points (absolute difference -2.8 points, median relative reduction of -45%; p=0.008) and ASDAS-CRP score decreased from 2.8 (1.9; 3.9) to 1.9 (1.7; 2.6) points (absolute difference -0.9 points, median relative reduction -21%; p=0.007). The proportion of patients with high AS activity (BASDAI≥4) decreased from 90% to 20% (p=0.031); however, there was no significant change in the CRP level (absolute difference -4.9 mg/L, median relative reduction -57%; p=0.110). In patients with PsA (median duration of treatment 18 months), the CRP level decreased from 12.0 (4.5; 17.3) to 3.3 (2.0; 7.8) mg/L (absolute difference -8.7 mg/L, median relative reduction -80%; p=0.041), the DAPSA score decreased from 23.0 (19.0; 30.5) to 6.3 (5.2; 13.5) points (absolute difference -16.7 points, median relative reduction -69%; p=0.018). Three (13%) patients reported mild to moderate adverse events. Conclusion. The obtained data confirm the effectiveness and safety of netakimab in treating AS and PsA in real-world practice.

Abstract Background and Aims The IMbrave 150 trial revealed the usefulness of atezolizumab plus bevacizumab therapy in patients with unresectable hepatocellular carcinoma (HCC), making it now considered the first‐line systemic chemotherapy agent for HCC. The present study investigated factors associated with early tumor progression of atezolizumab plus bevacizumab in patients with advanced HCC in real‐world clinical practice. Methods A total of 184 HCC patients who received atezolizumab plus bevacizumab therapy were studied. We investigated the frequency of early progressive disease (e‐PD; PD within 9 weeks) and analyzed the risk factors for e‐PD. Results There were 47 patients (25.5%) diagnosed as e‐PD. Patients with e‐PD had a worse performance status (PS) and albumin–bilirubin (ALBI) and Child‐Pugh (C‐P) scores and a significantly higher rate of a systemic therapy than those with non‐e‐PD. A multivariate analysis showed that PS ≥1 (odds ratio [OR] = 4.5, 95% confidence interval [CI] = 1.9–10, p

New treatment options for advanced ovarian cancer have the potential to significantly change the treatment pathway in the UK. Understanding the structures and responsibilities of multidisciplinary teams/tumour boards (MDT) and regional variations will enable services to adapt more effectively to these changes. The KNOW-OC survey was conducted in 2020 to understand the views of a selected group of 66 healthcare professionals (HCPs) involved in advanced ovarian cancer care in UK hospitals. The results showed that MDT involvement in the management of advanced ovarian cancer varied depending on pathway stage and line of relapse, with 98.5% of HCPs responding that the MDT was involved in decisions at initial presentation, but only 40.9% for patients with multiple relapses. The MDT was mostly responsible for determining whether the patients would undergo primary or interval cytoreductive surgery according to 75.8% of respondents, and most HCPs (80.3%) stated that tumour dissemination patterns were the most important factor influencing this decision. The most commonly assessed biomarkers at the time of the survey were CA125, gBRCA and tBRCA. Homologous recombination deficiency was viewed as the second most important factor for determining prognosis, but few centres had access to testing at the time of survey completion. The use of active surveillance was expected to decrease in favour of first-line targeted therapies. Nearly all (98.5%) HCPs agreed there is a role for secondary cytoreductive surgery for the treatment of recurrence (for carefully selected patients). The results highlighted UK-specific geographical variation in the views of HCPs on MDT involvement and specific practices, such as molecular biomarker testing, and the overall treatment approach. Together, these findings improve the understanding of reported clinical practice across the UK for ovarian cancer and provide insight into decision-making associated with updates to recommendations for best practice (e.g. European Society for Medical Oncology/European Society of Gynaecological Oncology consensus statements) and the introduction of new treatment options. • The survey describes real-world management of advanced ovarian cancer in the UK. • Multidisciplinary team input into treatment decisions decreases later in the pathway. • HCPs anticipate a shift from active surveillance to first-line targeted therapies. • Secondary cytoreductive surgery viewed as a plausible option in the recurrent setting. • There is geographical variation in practices and views across UK centres. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Peginterferon β-1a (PEG-IFN-β-1a) is the most recent interferon beta formulation approved for treating relapsing-remitting multiple sclerosis (RRMS). We aim to describe the real-world utilization of PEG-IFN-β-1a in RRMS and compare it with other injectable disease-modifying therapies (DMTs). PATIENTS AND METHODS: In this population-based study, we used 2015-2019 routinely collected healthcare data of the Campania region of Italy from National Healthcare System DMT prescriptions, inpatient and outpatient clinical records of hospitals in Campania, and the Federico II University MS clinical registry for a subset of patients. We included individuals with RRMS receiving new prescriptions of PEG-IFN-β-1a [n=281; age = 38.8±12.3 years; females=70.5%; disease duration = 8 .4±8.3 years; Expanded Disability S tatus Scale (EDSS) at baseline=2.0 (1.0-6.5)], glatiramer acetate [n=751; age = 46.0±11.4 years; females= 67.1%; disease duration = 9.8±8.2 years; EDSS=4.0 (1.5-8.5)], and subcutaneous (SC) IFN-β-1a [n=1,226; a ge = 3 9.7±11.7 y ears; f emales= 66.5%; disease duration = 8.2±6.5 years; EDSS 2.5 (1.5-6.5)]. Adherence [medication possession ratio (MPR)], escalation to more effective DMTs, hospitalization rates and costs were measured. We used mixed-effect linear regression models (for adherence, hospitalization rates and costs) and Cox regression models (for escalation) to assess differences between PEGIFN-β-1a (statistical reference), glatiramer acetate, and SC IFN-β-1a. All models included age, sex, previous treatment/untreated, year of treatment initiation, treatment duration, and adherence as covariates. RESULTS: Adherence was lower in glatiramer acetate (MPR = 0.91±0.1; Coeff=-0.11; p<0.01), and IFN-β-1a (MPR = 0.92±0.1; Coeff=-0.08; p<0.01), compared with PEG-IFN-β-1a (MPR = 1.01±0.1). The probability of escalating to more effective DMTs was higher for glatiramer acetate (14.9%; HR=4.09; p<0.01) and IFN-β-1a (9.1%; HR=3.35; p=0.01), compared with PEG-IFN-β-1a (4.9%). No differences in annualized hospitalization rates were identified between glatiramer acetate [annualized hospitalization rates (AHR) = 0.05±0.30; Coeff=0.02; p=0.31), IFN-β-1a (AHR = 0.02±0.21; Coeff=0.01; p=0.97], and P EG-IFN-β-1a (AHR = 0 .02±0.24); h owever, monthly costs for MS admissions were higher for glatiramer acetate (€49.45±€195.27; Coeff=-29.89; p=0.03), compared with IFN-β-1a (€29.42±€47.83; Coeff=6.79; p=0.61), and PEGIFN-β-1a (€23.91±€43.90). CONCLUSIONS: SC PEG-IFN-β-1a and IFN-β-1a were used in relatively similar populations, while glatiramer acetate was preferred in older and more disabled patients. PEG-IFN-β-1a was associated with higher adherence and lower escalation rates toward more effective (and costly) DMTs. [ABSTRACT FROM AUTHOR]

Introduction: Carfilzomib plus dexamethasone (Kd) is widely used in patients with relapsed and/or refractory multiple myeloma (RRMM). However, the treatment outcomes of Kd, especially in trial-unfit patients, have not been extensively studied in the real-world setting. Methods: We analyzed the outcomes of 152 RRMM patients who received Kd at our hospitals from April 2018 to March 2022. Results: At the commencement of Kd, patients received a median of two (range 1–7) lines of prior anti-myeloma therapy. According to the ENDEAVOR study criteria, 93 (61.2%) and 59 (38.8%) patients were classified as the trial-fit and the trial-unfit group, respectively. The overall response (OR) rate for the entire cohort was 71.1% (95% CI 63.2–78.1%). Progression-free survival (PFS) and overall survival (OS) were 5.6 months (95% CI 3.9–6.9 months) and 24.0 months (95% CI 13.4–38.0 months), respectively. There was no significant difference in the OR rate between the trial-fit and the trial-unfit groups (76.3% vs. 62.7%; P = 0.105). However, the median PFS (3.6 months vs. 7.3 months; P < 0.001) and OS (15.0 vs. 36.8 months; P = 0.009) were significantly shorter in the trial-unfit group. On multivariate analysis, trial-fitness (unfit vs. fit) remained a significant covariate influencing the TRM (HR: 4.84, 95% CI 1.66–14.06; P = 0.004) and PFS (HR: 1.82, 95% CI 1.27–2.62; P = 0.001). Conclusion: Our data suggest that the treatment outcomes of Kd are acceptable in the real-world setting with significant differences between the trial-fit and the trial-unfit groups, although they are relatively inferior to those of a pivotal trial. [ABSTRACT FROM AUTHOR]

Aim. To conduct a meta-analysis of population-based observational studies of dapagliflozin compared with therapy without iNGLT-2 to assess its effect on the risk of cardiovascular events in patients with type 2 diabetes mellitus in real-world practice. Materials and methods. A systematic search was carried out in 3 bibliographic databases PubMed (Medline), Embase and eLibrary. According to the search results, 1,451 records were identified. 3 studies were selected for inclusion in the meta-analysis: CVD-REAL Nordic, EASEL Population-Based Cohort Study and CARDIA-MOS. The criteria for evaluating the effectiveness were the frequency of major adverse cardiovascular events (MACE) and cardiovascular mortality. The meta-analysis was carried out in the RevMan 5.4.1. Results. According to the results of the meta-analysis, there was a statistically significant association between the use of dapagliflozin and a decrease in the risk of MACE: relative risk 0.73, 95% confidence interval 0.650.82, as well as a decrease in cardiovascular mortality: relative risk 0.67, 95% confidence interval 0.480.92. Conclusion. Our results demonstrated that the use of dapagliflozin is associated with a reduction in the risk of developing MACE and cardiovascular mortality in patients with type 2 diabetes mellitus with cardiovascular diseases or cardiovascular risk factors.

Introduction: To investigate the safety and effectiveness of insulin degludec (IDeg) in a real-world population of Korean patients with diabetes requiring insulin therapy. Methods: This was a multicenter, prospective, single-arm, open-label, non-interventional study. Patients aged ≥ 12 months and treated with previous glucose-lowering medications were eligible to switch to IDeg. The primary endpoint was the incidence of adverse events (AEs), and the secondary endpoints were changes in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), postprandial glucose (PPG), and target HbA1c < 7.0%. Results: In total, 3225 and 2450 patients were included in the safety analysis set (SAS) and effectiveness analysis set (EAS), respectively. The mean baseline HbA1c and duration of diabetes were 9.4% and 13.0 years, respectively. Adverse events were reported in 740 patients (22.9%); the majority were mild and resolved. Significant improvements were observed in HbA1c, FPG, and PPG at week 26 (all p < 0.0001). The target of HbA1c < 7% was achieved in 22.2% of patients at week 26. Conclusion: In real-world clinical practice, 26 weeks of IDeg treatment resulted in significant reductions in glycemic parameters with a low incidence of AEs in Korean patients with diabetes. No new safety signals were observed. Clinical Trials Registry and Registration Number: This trial is registered under ClinicalTrials.gov (NCT02779413) and the universal trial number is [U1111-1176-2287]. [ABSTRACT FROM AUTHOR]

Background and Aims: The IMbrave 150 trial revealed the usefulness of atezolizumab plus bevacizumab therapy in patients with unresectable hepatocellular carcinoma (HCC), making it now considered the first‐line systemic chemotherapy agent for HCC. The present study investigated factors associated with early tumor progression of atezolizumab plus bevacizumab in patients with advanced HCC in real‐world clinical practice. Methods: A total of 184 HCC patients who received atezolizumab plus bevacizumab therapy were studied. We investigated the frequency of early progressive disease (e‐PD; PD within 9 weeks) and analyzed the risk factors for e‐PD. Results: There were 47 patients (25.5%) diagnosed as e‐PD. Patients with e‐PD had a worse performance status (PS) and albumin–bilirubin (ALBI) and Child‐Pugh (C‐P) scores and a significantly higher rate of a systemic therapy than those with non‐e‐PD. A multivariate analysis showed that PS ≥1 (odds ratio [OR] = 4.5, 95% confidence interval [CI] = 1.9–10, p < 0.001), ALBI score ≥−2.30 (OR = 2.1, 95% CI = 1.0–4.5, p = 0.044) and the history of a systemic therapy (OR = 3.0, 95% CI = 1.4–6.4, p = 0.0038) were significant and independent determinants of e‐PD. When examining the liver function trends in e‐PD patients, the ALBI scores at 3 and 6 weeks after starting therapy were significantly higher than before the treatment (p < 0.001). Conclusions: The liver function and systemic therapy are useful predictors of e‐PD in HCC patients treated with atezolizumab plus bevacizumab in real‐world clinical practice. [ABSTRACT FROM AUTHOR]

Background: This study evaluates the real-world safety and discontinuation rate of Zadiva® (generic product of dimethyl fumarate (DMF)) in Iranian patients with relapsing–remitting multiple sclerosis (RRMS), supplementing existing clinical evidence from randomized controlled trials. Methods: This retrospective observational study evaluated the real-world safety and discontinuation rate of DMF in RRMS patients from Amir A'lam referral hospital's neurology clinic. Data on safety, discontinuation rate, and clinical disease activity were collected retrospectively. The study aimed to assess the discontinuation rate, safety, and reasons for discontinuation, as well as the number of patients experiencing a relapse, MRI activity, and EDSS scores. Results: In total, 142 RRMS patients receiving DMF were included in the study, with 15 discontinuing treatment due to adverse events, lack of efficacy, or pregnancy. Notably, a significant reduction in relapse rates was observed, with 90.8% of patients remaining relapse-free throughout the study period. After 1 year of treatment with Zadiva®, only 17.6% of patients experienced MRI activity, whereas the EDSS score remained stable. Conclusions: This study provides important real-world data on the safety and tolerability of Zadiva® in RRMS patients. The results indicate that Zadiva® is generally well tolerated and safe, with a low discontinuation rate due to adverse events or lack of efficacy. These findings suggest that Zadiva® is an effective and safe treatment option for RRMS patients in real-world practice. [ABSTRACT FROM AUTHOR]

This paper explores the nature of reflection that qualified physiotherapists use in their day-to-day practice. This is an area in which there is a dearth of research. With a grounded theory approach purposive sampling was used to recruit seven qualified physiotherapists for photo-elicitation interviews exploring whether they did reflect and if so, what their reflection was like. The findings were that they did reflect but that it occurred outside of working hours. Four conceptual categories were identified: Personal Concept, Personal Process, Time and Head-Space. Practitioners had their own ideas of what reflection was, own ways of reflecting and personal strategies for making the head space to reflect in. Typically, they used thinking modes of reflection, with occasional dialogical modes; written reflection was rare. Of novel significance was the use of strategies to complete reflection to their satisfaction, most frequently walking but also preparing vegetables, driving and showering, typically outside of work hours. The use of such cognitively non-demanding, routinised activities to aid reflection has not been widely explored in the literature on reflection and may suggest a need to rethink approaches to support the teaching of reflection which would have high validity for its place in the real world of practice. [ABSTRACT FROM AUTHOR]

Background: Tildrakizumab, an anti-IL-23, showed promising efficacy and safety profiles in two randomized clinical-trials (reSURFACE-1 and reSURFACE-2), comparing tildrakizumab superiority to placebo and etanercept. Due to its recent availability in clinical-practice, real-life data are still limited. Objective: To assess the efficacy and safety of tildrakizumab in a real-world-practice in patients suffering from moderate-to-severe psoriasis. Methods: A 52-week observational retrospective study enrolled patients suffering from moderate-to-severe plaque-psoriasis, starting tildrakizumab treatment. Results: A total of 42 patients were included in the study. Mean PASI showed a significant reduction at each follow-up (p< 0.001), reducing from 13.5± 5.9 at baseline, 2.8± 3.8 at week-28, resulting stable up to week-52. High rates of patients reached both PASI90 and PASI100 responses at both week 16 (PASI90: 52.4%, PASI100: 33.3%) and week 28 (PASI90: 76.1%, PASI100: 61.9%), maintaining these up to week 52 (PASI90: 73.8%, PASI100: 59.5%). The impact of treatment on patient's quality of life has been evaluated with DLQI, which showed a significant reduction during follow-ups. Conclusion: Our data confirm tildrakizumab as an effective and generally safe treatment for the management of moderate-to-severe psoriasis, with high rates of both PASI90 and PASI100 responses, and very few reported adverse events, up to 52 weeks of follow-up. [ABSTRACT FROM AUTHOR]

Objectives: To obtain information on the frequency of using preloaded IOL delivery system, the time of the IOL implantation procedure, the convenience of using various preloaded systems, the incidence of complications and the overall level of satisfaction during the work by ophthalmologists during a survey of experts.Methods. A survey was conducted among 14 Russian experts from different regions who already have practical experience with the following preloaded IOL implantation systems: RayOne® Aspheric (RAO600C), iSert® (250/251), iTec (Tecnis®1) and AutonoMe™ (Clareon®). The evaluation was carried out on a 10-point scale for parameters related to IOL implantation safety when using preloaded systems, convenience and intuitive operation, the level of control over the IOL implantation process, and the overall total time required to complete the entire IOL implantation procedure.Results. Among all the parameters, the experts gave the highest safety rating of the IOL implantation when using preloaded systems; in general, quite high scores were also assigned to the other parameters, reflecting satisfaction with the work by the experts. In a comparative analysis of the parameters of IOL implantation safety, convenience and intuitive operation, the level of control over the IOL implantation process, as well as the total time required for the entire IOL implantation procedure, depending on the type of preloaded systems, significant differences were obtained (p = 0.012, p = 0.001, p = 0.003, p = 0.014, p = 0.004, respectively). Frow the 4 analyzed system types, AutonoMe™ (Clareon®) achieved the highest scores across all dimensions (10.0, 9.0, 10.0, 9.0 and 9.5, respectively).Conclusion. This experts’ survey is the first Russian experience of evaluating the real practice of working with different types of preloaded systems for implanting IOLs. The survey indicated that the greatest application experience currently exists with the preloaded AutonoMe™ (Clareon®) system, which scored higher across all analyzed parameters when compared to systems from other manufacturers.

Background: In clinical studies, some patients who achieve deep molecular response (DMR) can successfully discontinue tyrosine kinase inhibitor (TKI). TKI dose reduction is also an important aspect of alleviating adverse effects and improving quality of life. This study aimed to explore the outcome after drug withdrawal in Chinese CML patients. Methods: Weconducted a retrospective analysis of the outcome of 190 patients who stopped TKI. 27 patients experienced dose reduction before TKI discontinuation. The median duration of TKI treatment and MR4 before discontinuation was 82 months and 61 months. Results: With median follow-up after stopping TKI treatment of 17 months, the estimated TFR (Treatment Free Remission) were 76.9% (95%CI, 70.2%-82.4%), 68.8% (95%CI, 61.3%-75.2%), and 65.5% (95%CI, 57.4%-72.5%) at 6, 12 and 24 months. For full-dose and low-dose TKI groups, the TFR at 24 months was 66.7% and 55.8% (p = 0.320, log-rank). Most patients (56/57) quickly achieved MMR after restarting TKI treatment. Multivariable analysis showed that patients with TKI resistance had a higher risk of molecular relapse than patients without TKI resistance (p < 0.001). Conclusion: TFR rates were not impaired in patients experiencing dose reduction before TKI discontinuation compared to patients with full-dose TKI. Our data on Chinese population may provide a basis for the safety and feasibility of TKI discontinuation, including discontinuation after dose reduction, in clinical practice. [ABSTRACT FROM AUTHOR]

Sacubitril/valsartan reduces heart failure (HF)-related hospitalizations and cardiovascular mortality in PARADIGM-HF and has become a foundational treatment for HF with reduced ejection fraction (HFrEF). However, data of its routine real-world use are limited, and evidence from Italian settings is lacking. The REAL.IT study aimed to characterize the demographics, pharmacotherapy, clinical characteristics and outcomes of sacubitril/valsartan-treated Italian patients with HFrEF. Electronic medical records of patients initiating sacubitril/valsartan from October 2016 to June 2019 at nine specialized hospital outpatient HF centers across Italy were reviewed. Overall, 924 adults (mean age 64.5 years, 84.6% male) were included. At baseline, 38.7% had an ischemic HF etiology, 45.9% hypertension, 23.2% atrial fibrillation, 25.4% diabetes mellitus, 26.1% an implantable cardioverter-defibrillator and 31.9% coronary artery bypass grafting. There were no clear patterns of patient selection over time. During follow-up, NYHA class improved in 37.5% of patients after a mean of 5.3 ± 3.8 months; 36.1% and 16.7% of patients were in NYHA class III during characterization and after one year of follow-up, respectively. Left ventricular ejection fraction (LVEF) improved ≥5% in 56.3% of patients at one year; 39.7% had ≥30% reduction of N-terminal pro-B-type natriuretic peptide; 2.2% had hyperkalemia during characterization and 2.6% during follow-up; and 3.8% had hypotension during characterization and 12% during follow-up. A total of 50 (5.8%) of patients had device implantation (ICD/CRT) during follow-up. HF-related hospitalization was recorded in 19.6% of patients during follow-up; 3.8% of patients died, approximately 1.3% from cardiovascular causes. Our real-world data confirm the favorable effectiveness and tolerability of sacubitril/valsartan observed in pivotal randomized controlled trials. [ABSTRACT FROM AUTHOR]

Radium-223 dichloride (223Ra) is an α-emitter approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC) with bone metastases, but without visceral involvement. Despite being a life-prolonging therapy (LPT), 223Ra remains underutilized. A large body of real-world evidence (RWE) for 223Ra has been published in the decade since the pivotal phase 3 ALSYMPCA study, a period during which the treatment landscape has continued to evolve. How to optimize 223Ra use, including how to integrate it into the mCRPC management pathway amongst other current LPTs (i.e., with respect to timing and concurrent, layered, or sequential use), is therefore of considerable interest. RWE studies lack the conventional restraints of clinical trials and can therefore help to build an understanding of how treatments may be best used in routine practice. Here we review RWE studies investigating the efficacy and safety of 223Ra in mCRPC [including in sequence with the recently approved 177-Lutetium conjugated to the ligand prostate-specific membrane antigen (177Lu-PSMA)], as well as response marker development, imaging techniques, and current clinical practice recommendations.

Summary: Measurable residual disease (MRD) negativity is a strong prognostic indicator in multiple myeloma (MM). However, the optimal use of MRD in daily clinical practice has been hampered by the limited feasibility of MRD testing. Therefore, we examined the clinical relevance of commercially available MRD modalities based on clonality assays by fragment analysis with IdentiClone® (n = 73 patients) and next‐generation sequencing (NGS) with LymphoTrack® (n = 116 patients) in newly diagnosed patients with MM who received autologous stem cell transplantation (ASCT). MRD was assessed at the end of induction (pre‐ASCT) and/or at 100 days after ASCT (post‐ASCT). MRD could not predict survival when assessed by fragment analysis. However, NGS‐based MRD negativity at pre‐ or post‐ASCT was beneficial in terms of progression‐free and overall survival. Moreover, NGS‐based MRD negativity was independently associated with improved progression‐free and overall survival, and MRD‐positive patients both pre‐ and post‐ASCT had worst outcome. Indeed, initial adverse prognostic features by high‐risk cytogenetics could be mitigated upon achieving MRD negativity by NGS. We demonstrate the feasibility and clinical benefit of achieving MRD negativity by commercially available clonality‐based MRD assays in MM and support incorporating NGS, but not fragment analysis, to tailor therapeutic strategies in real‐world practice. [ABSTRACT FROM AUTHOR]

Interleukin (IL)-23 inhibitors, guselkumab, risankizumab, and tildrakizumab, represent the latest class of biologics approved for the treatment of moderate-to-severe psoriasis. Since their approval numerous real-life studies were published on anti-IL-23 use in routine clinical practice. Indeed, real-life data are important to improve the dermatological decision-making process, including patients who are typically excluded from clinical trials, such as subjects suffering from several comorbidities, subjects on polypharmacy, as well as multifailure patients. Herein, we performed a comprehensive literature review about real-life data available on guselkumab, risankizumab, and tildrakizumab. Real-life data of anti-IL-23 seem to confirm the promising results of IL-23 shown by clinical trials, highlighting the efficacy and safety profiles of this new class of biologics also in clinical practice. [ABSTRACT FROM AUTHOR]

BackgroundData related to adverse drug reactions (ADRs), specifically immune-related adverse events (irAEs), in long-term treatment with immunotherapy in real-world practice is scarce, as is general information regarding the management of ADRs.ObjectivesTo characterize and describe the incidence of ADRs in patients who began immunotherapy treatment in clinical practice.MethodsIn a prospective observational study cancer patients ≥18 years of age who were treated with a monotherapy regime of PD-1/PD-L1 inhibitors were evaluated. The study period was from November 2017 to June 2019 and patients were followed up until June 2021. Patients were contacted monthly by telephone and their electronic health records were reviewed. Each ADR was graded according to the Common Terminology Criteria for Adverse Events (CTCAE 5.0).ResultsOut of 99 patients, 86 met the inclusion criteria. Most were male (67.4%), with a median age of 66 (interquartile range, IQR: 59–76). The most frequent cancer was non-small cellular lung cancer (46 cases, 53.5%), followed by melanoma (22, 25.6%). A total of 74 patients (86%) were treated with anti-PD-1 drugs and 12 (14%) were treated with anti-PD-L1 drugs. The median treatment durations were 4.9 (IQR: 1.9–17.0) and 5.9 months (IQR: 1.2–12.3), respectively. Sixty-three patients (73%) developed from a total of 156 (44% of the total number of ADR) irADRs, wherein the most frequent were skin disorders (50 cases, 32%, incidence = 30.5 irADRs/100 patients per year [p-y]), gastrointestinal disorders (29, 19%, 17.7 irADRs/100 p-y), musculoskeletal disorders (17, 11%, 10.4 irADRs/100 p-y), and endocrine disorders (14, 9%, 8.6 irADRs/100 p-y). A total of 22 irADRs (14%) had a latency period of ≥12 months. Twelve irADRs (7.7%) were categorized as grade 3–4, and while 2 (1.3%) were categorized as grade 5 (death). Sixty-one irADRs (39.1%) in 36 patients required pharmacological treatment and 47 irADRs (30.1%) in 22 patients required treatment with corticosteriods.ConclusionThe majority of patients treated with anti-PD1/PDL1-based immunotherapy experienced adverse reactions. Although most of these reactions were mild, 11.5% were categorized as grade 3 or above. A high percentage of the reactions were immune-related and occurred throughout the treatment, thereby indicating that early identification and close monitoring is essential.

Background. Mantle cell lymphoma (MCL) is a rare and clinically aggressive lymphoma subtype. Current approaches have greatly improved patients outcomes, but relapse is inevitable. In phase IIIII clinical trials, ibrutinib has shown significant activity in patients with relapsed or refractory (R/R) MCL. Aim. To assess efficacy and toxicity of ibrutinib monotherapy in patients with R/R MCL in routine practice outside of clinical trials. Materials and methods. The study enrolled patients with confirmed R/R MCL who had received at least one line of previous chemotherapy. ECOG 24, cytopenia, infectious complications, hemorrhagic syndrome were not exclusion criteria. Patients received daily oral ibrutinib 560 mg until progression or unacceptable toxicity. Results. From May 2015 to September 2020 ibrutinib therapy was started in 106 patients with R/R MCL in 16 regions of Russia. The median age was 66 years; ECOG2 18%, blastoid variant (or Ki6740% or WBC50109/l) 43%. The median number of previous treatment lines was 2 (111). The ORR was 78.4% (CRR 27.4%). The median PFS was 13.6 months and OS 23.2 months. In the blastoid group the median PFS was 4.4 months vs 36.5 months in the alternative group (p0.001), the median OS 9.0 vs 41.0 (p=0.001). The median OS of patients after progression on ibrutinib was 3.2 months. The common complications are hemorrhages (63%), diarrhea (62%), myalgia and muscle cramps (60%), infections (31%), skin and nail toxicity 15%, arrhythmia 8%. None of recipients had to completely discontinue ibrutinib therapy due to complications. Conclusion. Ibrutinib is effective and well tolerated in routine practice of R/R MCL treatment and our results are consistent with international clinical trials. The favorable toxicity profile and the high response rate made it possible to prescribe ibrutinib in severe somatic status, cytopenia, and even in the presence of infectious complications.

Background: Lenvatinib has been recently approved as a first-line treatment option for patients with unresectable hepatocellular carcinoma (HCC) in Korea. We aimed to study the efficacy and safety of lenvatinib therapy in a real-world practice and to find prognostic factors related to survival and disease progression. Methods: A hospital-based retrospective study was conducted on 111 consecutive patients who had unresectable HCC and were treated with lenvatinib at Samsung Medical Center from October 2018 to March 2020. Efficacy was determined using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria in 111 patients who completed 1st tumor assessment. Safety was evaluated in 116 HCC patients including 5 patients who discontinued lenvatinib due to adverse events (AEs) before 1st tumor assessment using Common Terminology Criteria for AEs version 5.0. Results: A total of 111 patients with a median age of 59 years were analyzed during a median follow-up duration of 6.2 (4.4–9.0) months. The Kaplan-Meier estimate of overall survival was 10.5 months, and the median progression-free survival was 6.2 months. Based on mRECIST criteria, the objective response rate was 18.9% and disease control rate was 75.7%. AEs developed in 86/116 (74.1%) patients, and grade ≥3 AEs developed in 16/116 (13.8%) patients. Diarrhea, hand-foot skin rash, abdominal pain, hypertension, and anorexia were identified as the AEs with the highest frequencies of any grade. REFLECT eligibility criteria including tumor extent ≥50% liver occupation or inadequate bone marrow function and occurrence of anorexia were prognostic factors for survival, and occurrence of diarrhea was a favorable factor for disease progression. Conclusion: Lenvatinib therapy showed a favorable efficacy and safety in a real-world practice. The REFLECT eligibility criteria and specific AEs could be one of the prognostic markers.

Background: Colorectal cancer is the third most common cancer and second leading cause of cancer mortality in Australia, thus carrying a significant disease burden. Aims: This analysis aims to explore real‐world treatment landscape of metastatic colorectal cancer in the third‐line setting. Methods: We retrospectively analysed treatment of recurrent and advanced colorectal cancer (TRACC) registry database from 2009 onwards. Patients treated with palliative intent who progressed after two lines of therapies were included. One treatment line was defined as any combination of systemic therapy given until progression. Results: Out of 1820 patients treated palliatively, 32% (590 patients) met study criteria. Of these, 43% (254 patients) proceeded to third‐line therapy, equating to 14% of all metastatic patients. In KRAS mutant or unknown tumours (97 patients), fluoropyrimidine (FP)‐oxaliplatin combination was the most common choice (51%), followed by FP‐irinotecan (15%), trifluridine/tipiracil (11%), mono‐chemotherapy (10%), regorafenib (5%) and others (7%). Majority of FP‐doublet (83%) was given as rechallenge. In 157 patients with KRAS wildtype disease, monotherapy with EGFR inhibitor was most commonly used (41%), followed by EGFR inhibitor with chemotherapy (20%), FP‐doublet (18%), mono‐chemotherapy (6%), trifluridine/tipiracil (6%), regorafenib (1%) and others (8%). Median overall survival was 7.1 months (range 0.4‐41.2), and median time on third‐line treatment was 3 months (range 0.1‐40). Conclusions: In real‐world Australian population, treatment choices differed based on KRAS status and will likely change with the availability of newer drugs on the pharmaceutical benefits scheme. Survival outcomes are comparable to newer agents in clinical trials for select patients. [ABSTRACT FROM AUTHOR]

Background: T-cell/NK-cell non-Hodgkin's lymphoma (T/NK-NHL) is an uncommon heterogeneous group of diseases. The current classification of T/NK-NHL is mainly based on histopathology and immunohistochemistry. In practice, however, the lack of unique histopathological patterns, overlapping cytomorphology, immunophenotypic complexity, inadequate panels, and diverse clinical presentations pose a great challenge. Flow cytometric immunophenotyping (FCI) is a gold standard for the diagnosis, subtyping, and monitoring of many hematological neoplasms. However, studies emphasizing the role of FCI in the diagnosis and staging of T/NK-NHL in real-world practice are scarce. Methods: We included T-cell non-Hodgkin's lymphoma (T-NHL) patients evaluated for the diagnosis and/or staging of T/NK-NHL using FCI between 2014 and 2020. We studied the utility of FCI in the diagnosis and subtyping of T/NK-NHL and correlated the FCI findings with the results of histopathology/immunohistochemistry. For correlation purposes, patients were categorized under definitive diagnosis and subtyping, inadequate subtyping, inadequate diagnosis, and misdiagnosis based on the findings of each technique. Results: A total of 232 patients were diagnosed with T/NK-NHL. FCI findings provided definitive diagnoses in 198 patients and subtyping in 187/198 (95.45%) patients. The correlation between FCI and histopathological/immunohistochemistry results (n = 150) demonstrated an agreement on the diagnosis and subtyping in 69/150 (46%) patients. Of the remaining cases, the diagnosis and subtyping were inadequate in 64/150 (42.7%), and 14/150 (9.33%) were misdiagnosed on histopathology/immunohistochemistry results. FCI provided definitive diagnosis and subtyping in 51/64 (79.7%) patients. Among these, 13 patients diagnosed with peripheral T-cell lymphoma not-otherwise-specified were reclassified (angioimmunoblastic T-cell lymphoma (AITL)-11 and prolymphocytic leukemia-2) on FCI. It corrected the diagnosis in 14 patients that were misdiagnosed (6 B-cell NHL (B-NHL), 3 Hodgkin's lymphoma, 1 acute leukemia, and 1 subcutaneous panniculitis-like T-cell lymphoma) and misclassified (3 T-NHL) on histopathological results. AITL was the commonest T-NHL misclassified on histopathological results. FCI also confirmed the definite involvement in 7/83 (8.4%) and 27/83 (32.5%) bone marrow (BM) samples reported as suspicious and uninvolved, respectively, on histopathological evaluation. Conclusion: AITL was the most frequently diagnosed T/NK-NHL in this study. FCI provided a distinct advantage in detecting BM involvement by T/NK-NHL, especially in patients with low-level involvement. Overall, our study concluded that FCI plays a critical role in the diagnosis, subtyping, and staging of T/NK-NHL in real-world practice. [ABSTRACT FROM AUTHOR]

Purpose: Application of hypofractionated radiotherapy (HFRT) is growing in patients with breast cancer (BC). This study aimed to explore a real-world practice of HFRT in early and locally advanced BC. Methods: Patients with invasive BC between 2015 and 2019 were retrospectively reviewed. Radiotherapy (RT) was delivered by HFRT and conventionally fractionated radiotherapy (CFRT). Locoregional recurrence-free survival (LRRFS) and disease-free survival (DFS) were calculated by Kaplan–Meier curve and compared by Log-rank test. The effect of treatment modality on DFS was estimated by univariate and multivariable analyses. Results: A total of 1,010 patients were included in this study, and 903 (89.4%) were treated with HFRT. At a median follow-up of 49.5 months, there was no significant difference in a 4-year cumulative incidence of LRRFS in HFRT group (1.5%) and in CFRT group (3.8%) (p = 0.23), neither in different nodal stages nor in N2–3 patients with different molecular subtypes. The 4-year DFS was 93.5% in HFRT group compared with 89.9% in CFRT group with no significant difference either (p = 0.17). Univariate and multivariable analyses also showed no significant difference in DFS between HFRT and CFRT group. However, DFS of HFRT group tended to be lower in N2–3 patients with triple negative BC compared with that of CFRT group (76.2% versus 100%). Conclusion: HFRT can achieve similar cumulative incidence of LRRFS and DFS in patients with BC after lumpectomy or mastectomy, and also in different nodal stage, and in locally advanced stage with different molecular subtypes. [ABSTRACT FROM AUTHOR]

BackgroundT-cell/NK-cell non-Hodgkin’s lymphoma (T/NK-NHL) is an uncommon heterogeneous group of diseases. The current classification of T/NK-NHL is mainly based on histopathology and immunohistochemistry. In practice, however, the lack of unique histopathological patterns, overlapping cytomorphology, immunophenotypic complexity, inadequate panels, and diverse clinical presentations pose a great challenge. Flow cytometric immunophenotyping (FCI) is a gold standard for the diagnosis, subtyping, and monitoring of many hematological neoplasms. However, studies emphasizing the role of FCI in the diagnosis and staging of T/NK-NHL in real-world practice are scarce.MethodsWe included T-cell non-Hodgkin’s lymphoma (T-NHL) patients evaluated for the diagnosis and/or staging of T/NK-NHL using FCI between 2014 and 2020. We studied the utility of FCI in the diagnosis and subtyping of T/NK-NHL and correlated the FCI findings with the results of histopathology/immunohistochemistry. For correlation purposes, patients were categorized under definitive diagnosis and subtyping, inadequate subtyping, inadequate diagnosis, and misdiagnosis based on the findings of each technique.ResultsA total of 232 patients were diagnosed with T/NK-NHL. FCI findings provided definitive diagnoses in 198 patients and subtyping in 187/198 (95.45%) patients. The correlation between FCI and histopathological/immunohistochemistry results (n = 150) demonstrated an agreement on the diagnosis and subtyping in 69/150 (46%) patients. Of the remaining cases, the diagnosis and subtyping were inadequate in 64/150 (42.7%), and 14/150 (9.33%) were misdiagnosed on histopathology/immunohistochemistry results. FCI provided definitive diagnosis and subtyping in 51/64 (79.7%) patients. Among these, 13 patients diagnosed with peripheral T-cell lymphoma not-otherwise-specified were reclassified (angioimmunoblastic T-cell lymphoma (AITL)-11 and prolymphocytic leukemia-2) on FCI. It corrected the diagnosis in 14 patients that were misdiagnosed (6 B-cell NHL (B-NHL), 3 Hodgkin’s lymphoma, 1 acute leukemia, and 1 subcutaneous panniculitis-like T-cell lymphoma) and misclassified (3 T-NHL) on histopathological results. AITL was the commonest T-NHL misclassified on histopathological results. FCI also confirmed the definite involvement in 7/83 (8.4%) and 27/83 (32.5%) bone marrow (BM) samples reported as suspicious and uninvolved, respectively, on histopathological evaluation.ConclusionAITL was the most frequently diagnosed T/NK-NHL in this study. FCI provided a distinct advantage in detecting BM involvement by T/NK-NHL, especially in patients with low-level involvement. Overall, our study concluded that FCI plays a critical role in the diagnosis, subtyping, and staging of T/NK-NHL in real-world practice.

PurposeApplication of hypofractionated radiotherapy (HFRT) is growing in patients with breast cancer (BC). This study aimed to explore a real-world practice of HFRT in early and locally advanced BC.MethodsPatients with invasive BC between 2015 and 2019 were retrospectively reviewed. Radiotherapy (RT) was delivered by HFRT and conventionally fractionated radiotherapy (CFRT). Locoregional recurrence-free survival (LRRFS) and disease-free survival (DFS) were calculated by Kaplan–Meier curve and compared by Log-rank test. The effect of treatment modality on DFS was estimated by univariate and multivariable analyses.ResultsA total of 1,010 patients were included in this study, and 903 (89.4%) were treated with HFRT. At a median follow-up of 49.5 months, there was no significant difference in a 4-year cumulative incidence of LRRFS in HFRT group (1.5%) and in CFRT group (3.8%) (p = 0.23), neither in different nodal stages nor in N2–3 patients with different molecular subtypes. The 4-year DFS was 93.5% in HFRT group compared with 89.9% in CFRT group with no significant difference either (p = 0.17). Univariate and multivariable analyses also showed no significant difference in DFS between HFRT and CFRT group. However, DFS of HFRT group tended to be lower in N2–3 patients with triple negative BC compared with that of CFRT group (76.2% versus 100%).ConclusionHFRT can achieve similar cumulative incidence of LRRFS and DFS in patients with BC after lumpectomy or mastectomy, and also in different nodal stage, and in locally advanced stage with different molecular subtypes.

Background: There is currently no consensus on whether intensive cycles of neoadjuvant immunochemotherapy provide greater benefit than do less intensive cycles (two cycles) in esophageal cancer (EC). Therefore, in this study, we assessed the efficacy and safety of three to four cycles of neoadjuvant immunochemotherapy compared to two cycles for treating patients with locally advanced esophageal squamous cell carcinoma (ESCC)., Methods: This is a retrospective study of patients enrolled on previous clinical studies involving locally/regionally advanced ESCC (St. II-IVA) who received preoperative immunochemotherapy at the Department of Thoracic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine from 2019 to 2021. In this study, patients were planned to receive 2-4 cycles of chemoimmunotherapy. In this secondary analysis, patients who received three to four cycles of neoadjuvant immunochemotherapy were compared to those receiving two cycles in terms of safety and oncologic outcomes. The follow-up duration required for inclusion was at least one year following surgery, or until the patient died or independently elected to cease treatment if less than one year., Results: Our study identified a total of 142 participants, who were categorized into two groups based on the number of neoadjuvant treatment cycles: the two cycles group (2 cycles) (n=65) and the three to four cycles group (3-4 cycles) (n=77). Regarding the rate of major pathologic response (MPR), the rates for the 3-4 cycles and 2 cycles groups were 22.1% and 20.0%, respectively, although this difference was not statistically significant (P=0.25). Similarly, the rate of pathologic complete remission (pCR) was higher in the 3-4 cycles group at 14.3% compared to 7.7% in the 2 cycles group, but the difference did not reach statistical significance (P=0.07). However, the incidence of adverse events (AEs) classified as grade 3 or 4 was significantly higher in the 3-4 cycles group than in the 2 cycles group (36.4% vs. 18.5%; P=0.02). The median disease-free survival (DFS) for the 3-4 cycles group was 30.8 months [95% confidence interval (CI): not reached to not reached] and was not reached in the 2 cycles group (hazard ratio 2.35, 95% CI: 1.134-4.86; P=0.02). The 2 cycles group did not reach the median overall survival (OS) (hazard ratio 2.47, 95% CI: 1.08-5.53; P=0.045), with that in the 3-4 cycles group 34.9 months (95% CI: 24.5 to not reached). Interestingly, the survival outcomes were more favorable in the 2 cycles group for certain subgroups of patients: those who were male, those with a history of smoking, those with a history of drinking, and those who did not achieve MPR., Conclusions: Two cycles of neoadjuvant immunochemotherapy can be considered in locally advanced ESCC at high risk of developing toxicity with 3-4 cycles with similar oncologic outcomes., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-24-1365/coif). J.M.P. received honoraria from ASTELLAS and J&J Worldwide, and payment for participation in Advisory Board from Ferranova, and serves as the Chair of the Florida Chapter of the American College of Surgeons (FCACS) Surgical Education Committee. The other authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Background: A large prospective multicenter cohort study with systematic follow-up recently reported a 2.3% 2-year cumulative incidence of chronic thromboembolic pulmonary hypertension (CTEPH) after acute pulmonary embolism (PE)., Objectives: The present investigation aimed to determine the reported prevalence and incidence of CTEPH diagnosis after acute PE in real-world practice over a 12-year period., Methods: This study was based on nationwide ambulatory billing claims and drug prescription data of all residents with public health insurance in Germany from 2010 to 2021., Results: A total of 573 972 patients with acute PE (median age, 71 years; 57.4% women) were identified between 2010 and 2021. Prevalence of CTEPH among patients with history of PE increased during the period from 0.4% in 2010 to 0.9% in 2021. CTEPH was diagnosed in 2556 patients after acute PE, with most (17.6%) diagnoses reported within the first 3 months after the index PE event. The cumulative incidence rate after 3 months (first quarter) was calculated at 0.08% and after the first 2 years (eighth quarter) at 0.36%; it was 0.75% over the entire (90-month) follow-up period. Patients with CTEPH diagnosis during follow-up more often had right ventricular dysfunction at the index acute PE (14.9% vs 8.3%; P < .001)., Conclusion: The low CTEPH incidence rate after acute PE in the present analysis suggests low awareness of CTEPH. It further suggests a lack of systematic follow-up protocols for acute PE survivors in the real world. Improved implementation of existing recommendations on follow-up strategies after PE is warranted., Competing Interests: Declaration of competing interests L.H. received lecture/consultant fees from Johnson & Johnson, Inari Medical, MSD, and Boston Scientific, outside the submitted work. L.M.P. reports no conflict of interest. I.F. declares no conflict of interest. S.B. received lecture/consultant fees from Bayer HealthCare, Concept Medical, BTG Pharmaceuticals, INARI, Boston Scientific, and LeoPharma; institutional grants from Boston Scientific, Bentley, Bayer HealthCare, INARI, Medtronic, Concept Medical, Bard, and Sanofi; and economic support for travel/congress costs from Daiichi Sankyo, BTG Pharmaceuticals, and Bayer HealthCare, outside the submitted work. S.P. reports no conflict of interest. T.M. reports no conflict of interest. S.K. reports institutional grants and personal lecture/advisory fees from Bayer AG, Daiichi Sankyo, and Boston Scientific; institutional grants from Inari Medical; and personal lecture/advisory fees from MSD and Bristol-Myers Squibb/Pfizer. K.K. reports no conflict of interest. M.B. reports no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

To estimate costs of pharmacotherapy of recurrent depressive disorder (RDD) in a hospital-based care. In the study, we analyzed the real-world practice in hospital-based care and the costs of RDD pharmacotherapy. A total of 119 case histories of patients who received a diagnosis of RDD and were hospitalized in 2017 were retrospectively analyzed. The study examined sociodemographic data, clinical and economic data, the frequency of prescribing medications, and medical expenses per 1 hospitalization and per day. The sample (N = 119) was divided into 3 groups according to the International Classification of Diseases-10th Revision code and the severity of the disease. The cost conversion factor was 1 euro equals 89.92 rubles. Antidepressants and antipsychotic drugs prevailed in the structure of prescriptions (32% and 36%, respectively). Antidepressants had the largest share in the total cost structure (about 41%), while the total cost of antidepressants and antipsychotics reached a total of 70%. Less than half of the costs were drugs included in the Russian RDD hospital treatment standard. The most expensive group in terms of pharmacotherapy costs per patient was the group "patients with RDD of moderate severity" (F33.1)—€61.1 ± 92.0 per case of hospitalization; this diagnosis was made in 80% of hospitalized patients. Assessment of real-world practices and costs of treatment of patients with RDD allows for more widespread implementation of management methods that allow making a choice in favor of more cost-effective drugs for the treatment of RDDs in Russia. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease and is associated with obesity and metabolic comorbidities. Liver steatosis can progress to nonalcoholic steatohepatitis (NASH) exhibiting a relevant risk of fibrosis and ultimately liver failure. To date, no approved treatment for NASH to reduce its clinical and humanistic burden has been developed. We undertook a literature review to identify English language, national and international clinical guidelines for NAFLD regarding diagnosis, assessment and management, and determined their points of agreement and difference. Additionally, we investigated published literature relating to real-world management of NAFLD and NASH. National (China, England/Wales, Italy, the USA) and international society (Asia-Pacific, Europe, World Gastroenterology Organization) guidelines were identified and analyzed. All guidelines addressed identifying and diagnosing subjects with likely NAFLD, as well as assessment and management of individuals with risk factors for advanced disease, including fibrosis. Real-world practice reveals widespread suboptimal awareness and implementation of guidelines. In the absence of proven therapeutics, such gaps risk failure to recognize patients in need of specialist care and monitoring, highlighting the need for clear, easy-to-apply care pathways to aid in reducing the clinical and humanistic burden of NAFLD and NASH. [ABSTRACT FROM AUTHOR]

Aims: This study evaluated primary treatment modalities in advanced ovarian cancer according to sociodemographic characteristics and characterized chemotherapy regimens used. Methods: This was a retrospective study of newly diagnosed advanced ovarian, tubal or peritoneal cancer patients at two hospitals from 2011 to 2016. Results: Of 175 women, 41% received neoadjuvant chemotherapy and 59% received primary cytoreductive surgery. Within the neoadjuvant chemotherapy group, 23% did not have a surgical consultation prior to initiating treatment. Women receiving neoadjuvant chemotherapy lived closer to an academic center and more frequently received carboplatin/paclitaxel every 3 weeks. Cytoreductive surgery patients more frequently received intraperitoneal chemotherapy. Conclusion: The authors identified disparities in age, insurance, distance from treatment center and chemotherapy choice in the primary treatment for ovarian cancer. [ABSTRACT FROM AUTHOR]

Summary: Purpose Despite the established activity of regorafenib in metastatic colorectal cancer (CRC), gastrointestinal stromal tumor (GIST), and hepatocellular carcinoma (HCC), its toxicity profile has limited clinical use. We aimed to evaluate the pharmacokinetics of regorafenib and its active metabolites M-2/M-5, and to clarify the relationships between total drug-related exposure and clinical outcomes in real-world practice. Methods Blood samples at steady state were obtained during Cycle 1 from patients treated with regorafenib. Plasma concentrations of regorafenib and its metabolites were measured by liquid chromatography–tandem mass spectrometry. The efficacy and safety endpoints were progression-free survival (PFS) and dose-limiting toxicities (DLTs), respectively. The exposure–response relationships were assessed. Results Thirty-four Japanese patients with advanced cancers were enrolled (CRC, n = 26; GIST and HCC, each n = 4). Nine patients started regorafenib treatment at the recommended dose of 160 mg once daily (3 weeks on / 1 week off), while the other patients received a reduced starting dose to minimize toxicities. The median PFS was significantly longer in patients achieving total trough concentrations (Ctrough) of regorafenib and M-2/M-5 ≥2.9 µg/mL than those who did not (112 vs. 57 days; p = 0.044). Furthermore, the cumulative incidence of DLTs during the first 2 cycles was significantly higher in patients with summed Ctrough levels ≥4.3 µg/mL than in others (p = 0.0003). Conclusions Dose titration of regorafenib to achieve drug-related Ctrough levels between 2.9 and 4.3 µg/mL in Cycle 1 may improve efficacy and safety, warranting further investigation in a larger patient population. Clinical trial registry: Not applicable. [ABSTRACT FROM AUTHOR]

Although the number of antihyperglycemic agents has expanded significantly, sulfonylureas (in particular gliclazide MR) remain an important option in the treatment algorithms of type 2 diabetes mellitus (DM2). A large observational international study EASYDia in real clinical practice, assessing effectiveness of gliclazide MR 60 mg in patients with long-term DM2 on standard glucose-lowering therapy, showed that step-by-step intensification of therapy with gliclazide MR 60mg allows to achieve and maintain the target values of glycemia, with good tolerability even in maximum doses, low risk of hypoglycemia and no weight gain.

Abstract Aims/Introduction The prevalence and risk of vaginal candidiasis before and after initiating sodium–glucose cotransporter 2 (SGLT2) inhibitors, although some clinical trials have been carried out, have not been adequately shown in real‐world practice. We investigated the incidence of vaginal Candida colonization and symptomatic vaginitis, and the clinical risk factors including diabetic microvascular complications. Materials and Methods The participants were 114 women with type 2 diabetes who were free of vaginitis symptoms and started SGLT2 inhibitors. Vaginal candidiasis tests through self‐administered swabs were carried out at baseline, 6 and 12 months. Results Before starting SGLT2 inhibitors, 17 participants (14.9%) had positive vaginal Candida colonization. Younger age and the presence of microangiopathy were significantly associated with the positive colonization in multivariate analysis. Among all participants, 23 (20.2%, 8 because of vaginitis and 15 for other reasons) discontinued SGLT2 inhibitors before reaching the 6‐month test. Of 65 participants who were negative for Candida at baseline and received the 6‐month test, 24 (36.9%) converted to a positive culture, and multivariate analysis showed older age as an independent risk for developing Candida colonization. There were 18 participants (15.8%) who developed symptomatic vaginitis, and they showed similar characteristics to the 24 participants. Most of those with negative cultures at 6 months showed negative results at 12 months and vice versa. Conclusions The rates of developing positive colonization and symptomatic vaginitis after starting SGLT2 inhibitors appear to be higher in real‐world practice than the rates of 31% and 5–10% in clinical trials, respectively. Risk factors of vaginal Candida colonization might be different before and after taking SGLT2 inhibitors.

Background: The expenses of multiple myeloma (MM) represent a real economic and societal burden for patients and health authorities. However, very little is known about the situation in Algeria. Therefore, the aim of this study is to evaluate the costs generated by the management of MM and its complications in Algerian patients., Materials and Methods: An observational retrospective study conducted on patients diagnosed with MM, from January 1st, 2019 to April 31st, 2023, at the Establishment Hospitalier Universitaire November 1st, Oran. A bottom-up costing methodology was used to assess the phase-specific cost and the complication burden., Results: In total, 249 qualified for the study. For autologous stem cell transplantation (ASCT) eligible patients, the mean per patient cost of treating myeloma was estimated at: induction regimen ($4072); ASCT ($2899); consolidation ($1538); and maintenance ($355.76). The mean drug cost for ASCT-ineligible patients was $1421. The use of generic bortezomib and generic melphalan has led to a reduction in expenses of $1,075,181 ($5,024 per patient; 55.35%) and $10,864 ($487 per patient; 15.07%), respectively. Another cost-saving adaptation was ASCT using non-cryopreserved (NC) stem cells. The cost of managing MM complications was $177,782 per year., Conclusion: A number of adjustments have been implemented to the management of MM over time to improve clinical efficacy and reduce costs in Algeria. However, this may have come with a startlingly high cost of complications., (Copyright © 2024 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.)

Background: In recent years, the emergence of multiplex technology that can simultaneously measure multiple anti-islet autoantibodies has become particularly valuable for the staging and early diagnosis of immune-mediated type 1 diabetes (T1D). While it has been established that 20%-30% of T1D patients suffer from autoimmune thyroid disease (AITD), there is limited available data regarding the presence of anti-islet autoantibodies in AITD patients. Among commercially available anti-islet autoantibodies, glutamic acid decarboxylase 65 autoantibodies (GADAs) are often the first marker measured in general clinical practice., Aim: To investigate the frequency of anti-islet autoantibodies in AITD patients., Methods: Our study involved four hundred ninety-five AITD patients, categorized into three distinct groups: AITD with T1D ( n = 18), AITD with phenotypic type 2 diabetes (T2D) ( n = 81), and AITD without diabetes ( n = 396), and the enzyme-linked immunosorbent assay (ELISA) was employed to determine the frequencies of 3 Screen Islet Cell Autoantibody (3 Screen ICA), GADA, insulinoma-associated antigen-2 autoantibodies (IA-2As), and zinc transporter 8 autoantibodies (ZnT8As) within these groups., Results: The frequency of 3 Screen ICA in AITD patients with T1D, T2D, and those without diabetes were 88.9%, 6.2%, and 5.1%, respectively, with no significant difference seen between the latter two groups. Notably, the frequency of 3 Screen ICA was 11.1% higher in AITD patients with T1D, 1.3% higher in AITD patients with T2D, and 1.1% higher in AITD patients without diabetes compared to GADA, respectively. Furthermore, 12.5%, 20.0%, and 20.0% of the 3 Screen ICA-positive patients were negative for GADA. Additionally, 1.3% of the AITD patients who tested negative for 3 Screen ICA in both the AITD with T2D and non-diabetic AITD groups were found to be positive for individual autoantibodies. Among the 3 Screen ICA-positive patients, there was a significantly higher proportion of individuals with multiple autoantibodies in AITD patients with T1D compared to those without diabetes (37.5% vs 5.0%, P < 0.05). However, this proportion was similar to that in AITD patients with T2D (20.0%). Nevertheless, there was no significant difference in 3 Screen ICA titers between AITD patients with T1D and those without diabetes (436.8 ± 66.4 vs 308.1 ± 66.4 index). Additionally, no significant difference in 3 Screen ICA titers was observed between Graves' disease and Hashimoto's thyroiditis in any of the groups., Conclusion: Our findings reveal that some AITD patients without diabetes exhibit 3 Screen ICA titers comparable to those in AITD patients with T1D. Thus, 3 Screen ICA outperforms GADA in identifying latent anti-islet autoantibody-positive individuals among AITD patients., Competing Interests: Conflict-of-interest statement: The authors declare no conflicts of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Lenvatinib has been recently approved as a first-line treatment option for patients with unresectable hepatocellular carcinoma (HCC) in Korea. We aimed to study the efficacy and safety of lenvatinib therapy in a real-world practice and to find prognostic factors related to survival and disease progression. Methods: A hospital-based retrospective study was conducted on 111 consecutive patients who had unresectable HCC and were treated with lenvatinib at Samsung Medical Center from October 2018 to March 2020. Efficacy was determined using the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria in 111 patients who completed 1st tumor assessment. Safety was evaluated in 116 HCC patients including 5 patients who discontinued lenvatinib due to adverse events (AEs) before 1st tumor assessment using Common Terminology Criteria for AEs version 5.0. Results: A total of 111 patients with a median age of 59 years were analyzed during a median follow-up duration of 6.2 (4.4–9.0) months. The Kaplan-Meier estimate of overall survival was 10.5 months, and the median progression-free survival was 6.2 months. Based on mRECIST criteria, the objective response rate was 18.9% and disease control rate was 75.7%. AEs developed in 86/116 (74.1%) patients, and grade ≥3 AEs developed in 16/116 (13.8%) patients. Diarrhea, hand-foot skin rash, abdominal pain, hypertension, and anorexia were identified as the AEs with the highest frequencies of any grade. REFLECT eligibility criteria including tumor extent ≥50% liver occupation or inadequate bone marrow function and occurrence of anorexia were prognostic factors for survival, and occurrence of diarrhea was a favorable factor for disease progression. Conclusion: Lenvatinib therapy showed a favorable efficacy and safety in a real-world practice. The REFLECT eligibility criteria and specific AEs could be one of the prognostic markers. [ABSTRACT FROM AUTHOR]

Background: Esophageal cancer is one of the most fatal and difficult-to-treat cancer. Multi-modality management is the key to success of improving outcomes, however, which modality is the most proper is difficult to determine. Objective: To evaluate the overall survival (OS) of patients with early or locally-advanced (E/LA) esophageal carcinoma treated in Vajira Hospital. The outcomes of the multi-modality management among patients with E/LA diseases were evaluated. Materials and Methods: The retrospective analyses of esophageal carcinoma patients who attended at Vajira Hospital between January 1, 2012 and December 31, 2016 were performed. Results: There were 86 patients with complete medical records. The median age was 60.5 years (IQR 52 to 66). Sixty-five patients (75.6%) presented with E/LA diseases. Most of the patients had primary site at thoracic part of esophagus (58 patients, 67.4%) and had squamous cell carcinoma histology (84 patients, 97.7%). Tri-modality treatment including neoadjuvant chemoradiation and esophagectomy for clinically fitted patients without evidence of mediastinal involvement and non-regional lymph node metastasis resulted in the best survival outcome [28.56 months (IQR 10.64 to 46.47)]. The OS of patients with E/LA disease was only 9.15 months (IQR 4.49 to 23.02). Male patients, non-cervical site, and non-surgical treatment were associated with the worse OS. Conclusion: The outcomes of patients with esophageal carcinoma treated in a real-world practice is still not impressive. Tri-modality management would be the best paradigm; however, it is suitable for well-selected patients. [ABSTRACT FROM AUTHOR]

Objectives: To characterize real-world prescribing patterns and their clinical and healthcare resource utilization (HRU) implications in patients with metastatic renal cell carcinoma (mRCC) treated in Germany. Methods: Eligible individuals were enrolled in the "Bundesverband der Betriebskrankenkassen" claims database and received targeted mRCC therapy between 1 January 2008 and 31 December 2016. Prescribing patterns and HRU were characterized by treatment line and summarized by descriptive statistics. Proxy progression-free survival (PFS) and overall survival (OS) were estimated using Kaplan-Meier curves. Results: 536 patients receiving mRCC treatment were included. The median treatment duration was 4.2 months (interquartile range [IQR]: 1.7–9.3) for first-line therapy and 3.8 months (IQR: 1.7–9.1) for second-line therapy. Median PFS and OS estimates were similar for the first- and second-line treatments: PFS, 7.4 versus 7.2 months; OS, 14.9 versus 13.6 months. Mean HRU costs were higher for patients receiving first-line therapy (€7,253.2) compared with those receiving second-line therapy (€6,242.9). Exploratory stratification of outcomes by centre expertise suggested a possible trend towards improved OS in the 10 most experienced centres versus all -others: first-line, 18.4 versus 13.2 months; second-line, 16.4 versus 12.4 months. Conclusions: In routine care, German clinicians make rational prescribing decisions; possible variations in outcomes between centres warrant further investigation. [ABSTRACT FROM AUTHOR]

Summary: Weight‐loss maintenance and lifestyle behaviour necessary to manage weight are undisputedly challenging. We evaluated a secondary prevention weight‐loss maintenance programme for participants (n = 490) with weight‐related chronic disease in the Australian private health insurance setting. This study investigated the impact of the maintenance programme on anthropometric and lifestyle risk behaviour changes after 6 and 12 months, and trends in weight‐loss maintenance after 1 year. Using a pre‐ and post‐test design, data were analysed with generalized linear mixed models for repeated measures to determine the effect of the programme on weight loss and lifestyle behaviour outcomes. After initially losing a clinically significant amount of weight (mean 9.1 kg), maintenance‐programme participants maintained clinically significant weight loss (mean 7.6 kg) at 12 months. Rates of discontinuation in the programme were high (47% at 6 months and 73% at 12 months). Weight‐loss maintenance was achieved by 76% of participants at 3 months and 62% at 6 months, stabilizing at 55% and 56% at 9 and 12 months, respectively. Greater initial weight loss was associated with weight‐loss maintenance at 12 months. Participants <55 years demonstrated consistent weight‐loss maintenance over this time but the odds for successful weight‐loss maintenance for those ≥55 years continued to decrease over time. At maintenance‐baseline, 68.3% of participants had sufficient physical activity for health; 61.4% and 19.8% met recommended fruit and vegetable consumption, respectively. All lifestyle risk behaviours were maintained at 12 months. A programme extending support strategies for maintaining weight‐related behaviour shows promise to successfully support these changes over 12 months. There is a potentially important opportunity for targeted intervention at 6 to 9 months. [ABSTRACT FROM AUTHOR]