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Early termination does not negatively impact the outcome of adjuvant immunotherapy in melanoma
No full textBackground:
Adjuvant treatment with anti-PD1 antibodies has been shown to effectively reduce the risk of recurrence in patients with resected metastatic melanoma. Whether a full 12-month duration of treatment is needed to achieve full clinical benefit is not known. This study investigated the survival outcome depending on the duration of adjuvant anti-PD1 therapy.
Methods:
From the prospective multicentre real-world skin cancer registry ADOREG data of 620 patients who finished adjuvant treatment with nivolumab or pembrolizumab for AJCCv8 stage III/IV resected melanoma was analyzed. Recurrence-free survival (RFS) and overall survival (OS) were compared between patients with regular treatment duration (52 ± 4 weeks; n = 229) and no disease recurrence during therapy (A1) and patients with a premature end of treatment (<48 weeks; n = 214, B). Patients with disease recurrence during adjuvant treatment were included in cohort A2.
Results:
The median duration of follow-up was 26.0 months [interquartile range (IQR) 18.0–34.0] in group A1 [median treatment duration 51.3 weeks (IQR 50.0–52.1) and 19.0 months (IQR 13.0–29.0)] in group B [median treatment duration 22.2 weeks (IQR 10.0–34.8)]. Reasons for early discontinuation were treatment-related side effects in 45.3% (n = 97) and other reasons than toxicity in 54.7% (n = 117). The 2-year rate of RFS was 72.4% (95% CI, 68.5–76.3) for patients in group B and 51.5% (95% CI, 48.8–54.2) in patients with regular and intended regular treatment duration (A1 plus A2). When analysing the patients who did not relapse during adjuvant treatment (A1), there was a significantly higher RFS rate of 84.1% (95% CI, 81.5–86.7). When only assessing patients with a recurrence after more than 12 months after initiation of therapy, there was a trend towards better RFS in patients with regular treatment duration.
Conclusions:
In patients with resected metastatic melanoma, shorter treatment duration with anti-PD1 antibodies is not associated with a worse outcome
Accuracy of full arch scans performed with nine different scanning patterns– an in vitro study
No full textDiscrepancies between physician-assessed and patient-reported complications after cystectomy – a prospective analysis
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Effect of A Patient Reminder Program on Adherence in Postmenopausal Women with Osteoporosis Receiving Oral Bisphosphonate Treatment: A Randomized Clinical Control Trial
No full textPoor adherence to oral bisphosphonate therapy remains a major challenge in the treatment of osteoporosis, substantially reducing therapeutic efficacy. While reminder interventions have been proposed as a method to enhance adherence, evidence remains limited. This study aimed to evaluate the impact of written and verbal reminders on medication adherence compared to standard patient care over a 12-month period in a real-world clinical setting. In this randomized controlled study, 180 postmenopausal women diagnosed with osteoporosis were assigned to one of three groups: standard care (control), written reminder, or verbal reminder. Interventions were administered at five standardized time points. Adherence was defined as intake of ≥80% of prescribed weekly doses (≥42 out of 52 doses) and a ≥35% reduction in serum C-terminal telopeptide of type I collagen (CTX) levels from baseline to 12 months. No significant differences in adherence rates were observed between groups: 53.2% in the control group, 52.0% in the written reminder group, and 52.7% in the verbal reminder group (χ2 = 0.014; p = 0.993). Changes in bone mineral density and serum CTX levels were also comparable across groups. The implementation of standardized written or verbal reminder strategy did not result in a statistically significant improvement in adherence to oral bisphosphonate therapy. Further studies are needed to investigate the reasons for low adherence to treatment
Novel Tet3 enzymes for next-generation epigenetic sequencing
No full textEpigenetic regulation of gene expression is essential for cellular development and differentiation processes in higher eukaryotes. Modifications of cytosine, in particular 5-methylcytosine (5mdC), in DNA play a central role through impacting chromatin structure, repressing transposons, and regulating transcription. DNA methylation is actively installed by DNA methyltransferases and reversed through Tet-dioxygenase-mediated oxidation of 5mdC to 5-hydroxylmethylcytosine (5hmdC), 5-formylcytosine (5fdC), and 5-carboxycytosine (5cadC). It is crucial to understand the role of these epigenetic DNA modifications in cellular differentiation and developmental processes, as well as in disease state mapping and tracing of 5mdC and its oxidized forms. In bisulfite sequencing, which has been the benchmark for mapping 5mdC for the last few decades, degradation of the majority of genetic material occurs through harsh chemical treatment. Alternative sequencing methods often utilize Tet-enzyme-mediated oxidation of 5mdC to locate 5mdC and 5hmdC in genomic DNA. Herein, we report the development of novel Tet3-variants for oxidation-based bisulfite-free 5mdC- sequencing
Experimental investigations of social exclusion among adolescents with psychiatric disorders: a systematic review
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