Effective Melanoma Immunotherapy in Mice by the Skin-Depigmenting Agent Monobenzone and the Adjuvants Imiquimod and CpG

Background: Presently melanoma still lacks adequate treatment options for metastatic disease. While melanoma is exceptionally challenging to standard regimens, it is suited for treatment with immunotherapy based on its immunogenicity. Since treatment-related skin depigmentation is considered a favourable prognostic sign during melanoma intervention, we here aimed at the reverse approach of directly inducing vitiligo as a shortcut to effective anti-melanoma immunity. Methodology and Principal Findings: We developed an effective and simple to use form of immunotherapy by combining the topical skin-bleaching agent monobenzone with immune-stimulatory imiquimod cream and cytosine-guanine oligodeoxynucleotides (CpG) injections (MIC therapy). This powerful new approach promptly induced a melanoma antigen-specific immune response, which abolished subcutaneous B16. F10 melanoma growth in up to 85% of C57BL/6 mice. Importantly, this regimen induced over 100 days of tumor-free survival in up to 60% of the mice, and forcefully suppressed tumor growth upon re-challenge either 65- or 165 days after MIC treatment cessation. Conclusions: MIC therapy is effective in eradicating melanoma, by vigilantly incorporating NK-, B-and T cells in its therapeutic effect. Based on these results, the MIC regimen presents a high-yield, low-cost and simple therapy, readily applicable in the clini

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

How to engage children, young people and families from ethnic minority backgrounds in weight management services: a scoping review.

Childhood overweight and obesity disproportionately affect children, young people and their families from ethnic minority backgrounds, and engagement with WM services is often low due to multiple barriers. Research is limited on strategies used to support engagement with WM services amongst children, young people and their families from ethnic minority backgrounds. The objective of this scoping review is to understand the extent and type of evidence related to how weight management (WM) services support children, young people, and their families from ethnic minority backgrounds to engage

How to engage children, young people and families from ethnic minority backgrounds in weight management services: a scoping review.

Childhood overweight and obesity disproportionately affect children, young people and their families from ethnic minority backgrounds, and engagement with WM services is often low due to multiple barriers. Research is limited on strategies used to support engagement with WM services amongst children, young people and their families from ethnic minority backgrounds. The objective of this scoping review is to understand the extent and type of evidence related to how weight management (WM) services support children, young people, and their families from ethnic minority backgrounds to engage

Temporal Trends in Racial and Ethnic Disparities in Sleep Duration in the United States, 2004–2018

ABSTRACTImportanceMinoritized racial and ethnic groups are generally more likely to experience sleep deficiencies. It is unclear how these sleep duration disparities have changed over recent years.ObjectiveTo determine 15-year trends in the racial and ethnic differences in self-reported sleep duration among adults in the US.DesignSerial cross-sectional study of the National Health Interview Survey from years 2004– 2018. Analyses were performed between July 26, 2021 and February 10, 2022.SettingUS population-based.Participants429,195 non-institutionalized adults.ExposuresSelf-reported race, ethnicity, household income, and sex/gender.Main OutcomesTemporal trends and racial/ethnic differences in short- and long-sleep duration (&lt;7 and &gt;9 hours in a 24-hour period, respectively), and racial/ethnic differences in the relationship between sleep duration and age.ResultsThe study sample consisted of 429,195 individuals (mean age 46.5 [SE, 0.08] years; 51.7% female) of which 5.1% identified as Asian, 11.8% as Black, 14.7% as Latino/Hispanic, and 68.5% as White. In 2004, the adjusted estimated prevalence of short-sleep duration and long-sleep duration, respectively, were 31.3% and 2.5% among Asian individuals, 35.3% and 6.4% among Black individuals, 27.0% and 4.6% among Latino/Hispanic individuals, and 27.8% and 3.5% among White individuals. Over the study period, there was a significant increase in the short sleep prevalence among Black, Latino/Hispanic, and White individuals (P≤0.001 for each), whereas prevalence of long sleep changed significantly only among Latino/Hispanic individuals (−1.4 points, P=0.01). In 2018, compared with White individuals, short sleep prevalence among Black and Latino/Hispanic individuals was higher by 10.7 points and 2.4 points, respectively(P≤0.03 each), and long sleep prevalence was higher only among Black people (+1.4 points; P=0.01). The short-sleep disparities were the greatest among women and among those with middle/high household income. In addition, across age groups, Black individuals had a higher short- and long-sleep duration prevalence compared with White individuals of their same age. ConclusionsIn this serial cross-sectional study from 2004 to 2018, the prevalence of short and long sleep duration was persistently higher among Black individuals. The Black-White disparities in short-sleep were highest among women, individuals who had middle or high income, and among young or middle-aged adults.KEY POINTSQuestionHow have racial and ethnic differences in self-reported sleep duration among US adults changed between 2004 and 2018?FindingsIn this serial cross-sectional study that included 429,195 adults, the prevalence of both short and long sleep duration were persistently higher among Black individuals over the 15-year study period. The disparities in short sleep duration were highest for Black women, Black individuals with middle or high income, and young and middle-aged Black adults.MeaningThere were marked racial and ethnic differences in sleep duration that persisted from 2004 to 2018, which may be contributing to health disparities.</jats:sec

Successful outcome of pre-engraftment COVID-19 in an HCT patient: impact of targeted therapies and cellular immunity

AbstractCoronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has emerged as a global pandemic that upended existing protocols and practices, including those for allogeneic hematopoietic stem cell transplantation (HCT). Here, we describe the successful clinical course and multiple key interventions administered to an acute lymphoblastic leukemia patient, who tested SARS-CoV-2 positive by reverse transcriptase polymerase chain reaction on day −1 of matched unrelated donor (SARS-CoV-2 immunoglobulin G negative) T-cell-replete HCT. This experience allowed for implementing a virologic and immunomonitoring panel to characterize the impact of SARS-CoV-2 on the recipient’s nascent humoral and cellular immune response. The finding of robust, functional, and persistent levels of SARS-CoV-2-specific T cells, starting early after transplant was unexpected, and in combination with the clinical strategy, may have contributed to the favorable outcome. Additionally, it is plausible that preexisting cross-reactive endemic coronavirus immunity in the allogeneic graft reduced recipient susceptibility to COVID-19 disease. This case supports the critical role that T-cell responses may play in mitigating SARS-CoV-2 infection, even in the context of transplant immunosuppression, in which reconstitution of humoral response is commonly delayed. Interventional approaches to transfer SARS-CoV-2-specific cellular immunity such as HCT donor vaccination and adaptive cellular therapy could be of benefit.</jats:p