Nyborghemmingsen2020

[177Lu]Lu-BL02 showed high uptake in MCL xenografts. Therapy studies with a single dose in the Z138 model showed tumor regression and improved survival compared with a control group. Upon regrowth, the treated mice experienced concurrent metastasis alongside localized xenograft regrowth, and recurrent lesions showed enhanced CXCR4 signaling.

CXCR4 is an independent factor of poor prognosis for MCL and a promising target for imaging and radioligand therapy. [68Ga]Ga-BL02 showed high contrast to visualize CXCR4-expressing xenografts for PET imaging and [177Lu]Lu-BL02 induced rapid tumor regression in a preclinical model of MCL.

CXCR4 is an independent factor of poor prognosis for MCL and a promising target for imaging and radioligand therapy. [68Ga]Ga-BL02 showed high contrast to visualize CXCR4-expressing xenografts for PET imaging and [177Lu]Lu-BL02 induced rapid tumor regression in a preclinical model of MCL.

Therapy-related myelodysplastic syndrome and acute leukemias (t-MDS/AL) are a major cause of nonrelapse mortality among pediatric cancer survivors. Although the presence of clonal hematopoiesis (CH) in adult patients at cancer diagnosis has been implicated in t-MDS/AL, there is limited published literature describing t-MDS/AL development in children.

We performed molecular characterization of 199 serial bone marrow samples from 52 patients treated for high-risk neuroblastoma, including 17 with t-MDS/AL (transformation), 14 with transient cytogenetic abnormalities (transient), and 21 without t-MDS/AL or cytogenetic alterations (neuroblastoma-treated control). We also evaluated for CH in a cohort of 657 pediatric patients with solid tumor.

We detected at least one disease-defining alteration in all cases at t-MDS/AL diagnosis, most commonly TP53 mutations and KMT2A rearrangements, including involving two novel partner genes (PRDM10 and DDX6). Backtracking studies identified at least one t-MDS/AL-associatelication in high-risk pediatric patients.

Vismodegib is approved for the treatment of locally advanced basal cell carcinoma (laBCC), but some cases demonstrate intrinsic resistance (IR) to the drug. We sought to assess the frequency of IR to vismodegib in laBCC and its underlying genomic mechanisms.

Response to vismodegib was evaluated in a cohort of 148 laBCC patients. Comprehensive genomic and transcriptomic profiling was performed in a subset of five intrinsically resistant BCC (IR-BCC).

We identified that IR-BCC represents 6.1% of laBCC in the studied cohort. Prior treatment with chemotherapy was associated with IR. Genetic events that were previously associated with acquired resistance (AR) in BCC or medulloblastoma were observed in three out of five IR-BCC. However, IR-BCCs were distinct by highly rearranged polyploid genomes. Functional analyses identified hyperactivation of the HIPPO-YAP and WNT pathways at RNA and protein levels in IR-BCC. In vitro assay on the BCC cell line further confirmed that YAP1 overexpression increases the cell proliferation rate.

IR to vismodegib is a rare event in laBCC. IR-BCCs frequently harbor resistance mutations in the Hh pathway, but also are characterized by hyperactivation of the HIPPO-YAP and WNT pathways.

IR to vismodegib is a rare event in laBCC. IR-BCCs frequently harbor resistance mutations in the Hh pathway, but also are characterized by hyperactivation of the HIPPO-YAP and WNT pathways.

Paramedics are frequently called to attend seizures in children. High-quality evidence on second-line treatment of benzodiazepine (BZD)-refractory convulsions with parenteral long-acting antiepileptic drugs in children has become available from the ED. In order to address the potential need for an alternative agent, we set out to determine the association of BZD use prehospital and the need for respiratory support.

We conducted a retrospective observational study of state-wide ambulance service data (Ambulance Victoria in Victoria, Australia, population 6.5 million). Children aged 0-17 years assessed for seizures by paramedics were analysed for demographics, process factors, treatment and airway management. We calculated adjusted ORs (AOR) of the requirement for respiratory support in relation to the number of BZD doses administered.

Paramedics attended 5112 children with suspected seizures over 1 year (1 July 2018 to 30 June 2019). Overall, need for respiratory support was low (n=166; 3.2%). Before ambulance arrival, 509 (10.0%) had already received a BZD and 420 (8.2%) were treated with midazolam by paramedics. Of the 846 (16.5%) patients treated with BZD, 597 (70.6%) received 1 BZD dose, 156 (18.4%) 2 doses and 93 (11.0%) >2 doses of BZD. Patients who were administered 1, 2 and >2 doses of BZD received respiratory support in 8.9%, 32.1% (AOR 4.6 vs 1 dose, 95% CI 2.9 to 7.4) and 49.5% (AOR 10.3 vs 1 dose, 95% CI 6.0 to 17.9), respectively.

Increasing administration of BZD doses was associated with higher use of respiratory support. Alternative prehospital antiepileptic drugs to minimise respiratory depression should be investigated in future research.

Increasing administration of BZD doses was associated with higher use of respiratory support. Alternative prehospital antiepileptic drugs to minimise respiratory depression should be investigated in future research.Emergency physicians use diagnostic and prognostic tests on a daily basis to assess for life-threatening illness and to inform clinical decisions. Current and new tests must be scientifically evaluated for their diagnostic utility. We discuss the evaluation of diagnostic and prognostic tests using the Bayesian likelihood ratio (LR) and logistic regression diagnostic odds ratio (OR) frameworks. These approaches can be applied to a single test in isolation using univariate techniques, or to a group of tests as commonly applied in clinical practice using multivariate methods. We compare and contrast the relative benefits and challenges of the LR and OR approaches, and assess their interchangeability. The concepts of diagnostic multivariate testing also underlie the framework of clinical decision rules which have gained acceptance in emergency medicine. Clinical decision rules can be viewed as a subanalysis within the joint LR framework. Ultimately, a variety of approaches may be acceptable and even complementary to assess a diagnostic test, each with its own merits and limitations.

People with psychiatric disorders have increased risk of premature death partly due to diabetes. This study aims to explore the quality of diabetes care, diabetes management, diabetes support and well-being of people with psychiatric disorders and diabetes.

A total of 107 participants aged ≥18 years with diabetes and psychiatric disorders treated at psychiatric outpatient clinics in Denmark were recruited from August 2018 to June 2019. This descriptive cross-sectional study includes data from medical records on quality of diabetes care (eg, level and annual examination of hemoglobin A1c (HbA

)) and questionnaires on diabetes management (measured on items from the Summary of Diabetes Self-Care Activities Scale and diabetes distress based on Problem Areas in Diabetes Scale (PAID-5)), diabetes support (no, some or high support from eight potential support persons and experience of care actions measured on items from Patient Assessment of Chronic Illness Care) and well-being (WHO 5-Item Scale and self-rated ights a need for improved diabetes support in people with psychiatric disorders and diabetes. Although a high proportion received appropriate diabetes care, we found high levels of diabetes distress, moderate levels of optimal self-management behaviors, low well-being and low diabetes support from psychiatric health professionals, while one-third of the population found it relevant to receive diabetes support from psychiatric health professionals.

To evaluate the general population's awareness of and attitudes toward

(HP) screening and health behaviours.

Cross-sectional study.

Hengyang, Hunan Province, China.

Using stratified cluster random sampling, a pretested structured questionnaire was used to interview members of the general population aged ≥18 years.

Knowledge of and attitudes toward HP screening and associated health behaviours, sociodemographic factors associated with HP knowledge, and screening behaviours.

This study featured 1042 participants. The average knowledge score was 11 (Q

=4, Q

=20, range 0-29). Approximately 68.9% of the participants said they had heard of HP, but 67.5% had never had an HP test. The most common reasons for not undergoing screening were 'no symptoms' (55.7%) and 'lack of knowledge regarding the benefits of the test' (21.1%). Independent factors related to knowledge included age, education level, occupation, HP infection, frequency of drinking unboiled water (p<0.05). Factors independently associacreened. These results highlight the urgent need for educational activities to raise awareness, enhance screening rates for HP, and encourage people to adopt a healthy lifestyle.

There is a strong theoretical rationale for combining checkpoint blockade with cytotoxic chemotherapy in pleural mesothelioma and other cancers. Two recent single-arm, phase 2 trials [DuRvalumab with chEmotherapy as first-line treAtment in advanced pleural Mesothelioma (DREAM) and Phase II multicenter study of anti-PD-L1, durvalumab, in combination with cisplatin and pemetrexed for the first-line treatment of unresectable malignant pleural mesothelioma (PrE0505)] combining the programmed death ligand-1 (PD-L1) inhibitor durvalumab with standard first-line chemotherapy exceeded prespecified safety and activity criteria to proceed to a phase 3 confirmatory trial to assess this combination. We present the protocol of the DREAM3R trial.

This multicentre open-label randomised trial will recruit 480 treatment-naïve adults with advanced pleural mesothelioma, randomised (21) to either 3-weekly durvalumab 1500 mg plus 3-weekly doublet chemotherapy (cisplatin 75 mg/m

or carboplatin, Area Under the Curve,AUC 5 anded in the DuRvalumab with chEmotherapy as first-line treAtment in advanced pleural Mesothelioma (DREAM) and PrE0505 studies, PD-L1 expression, tumour mutational burden, genomic characteristics and human leukocyte antigen subtypes) in tissue and serial blood samples. An imaging databank will be assembled for validation of radiological measures of response, and studies of possible radiomic biomarkers in mesothelioma.

The protocol was approved by human research ethics review committees for all participating sites. Results will be disseminated in peer-reviewed journals and at scientific conferences.

AstraZeneca.

CTC 0231 / TOGA 18/001 / PrE0506 3.0, 29 July 2021.

ClinicalTrials.gov Identifier NCT04334759 ACTRN 12620001199909.

ClinicalTrials.gov Identifier NCT04334759 ACTRN 12620001199909.

The Pan African Clinical Trials Registry (PACTR) is a WHO International Clinical Trials Registry Platform primary register, which caters for clinical trials conducted in Africa. PACTR is the first and, at present, the only member of the Network of WHO Primary Registers in Africa. LJI308 chemical structure The aim is to describe and report on the trends of trial records registered in PACTR.

PACTR was established in 2007 as the AIDS, Tuberculosis, and Malaria Clinical Trials Registry. The scope of the registry was then expanded in 2009 to include all diseases. This is a cross-sectional study of trials registered in PACTR from inception to 18 August 2021. A descriptive analysis of the use and trends of the following data fields study intervention, disease condition, sex of the participants, sample size, ethics, funding and availability of results was conducted using Microsoft Excel.

The number of trials registered has increased year on year, reaching 606 trials registered in 2020. The total number of trials registered at the time of the analysis was 2998.