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Fulltext Asia-Pacific Perspectives on the Role of Continuous Glucose Monitoring in Optimizing Diabetes Management

Twigg S, Lim S, Yoo SH, Chen L, Bao Y, Kong A, et al.

J Diabetes Sci Technol, 2023 May 26.
PMID: 37232515 DOI: 10.1177/19322968231176533

Diabetes is prevalent, and it imposes a substantial public health burden globally and in the Asia-Pacific (APAC) region. The cornerstone for optimizing diabetes management and treatment outcomes is glucose monitoring, the techniques of which have evolved from self-monitoring of blood glucose (SMBG) to glycated hemoglobin (HbA1c), and to continuous glucose monitoring (CGM). Contextual differences with Western populations and limited regionally generated clinical evidence warrant regional standards of diabetes care, including glucose monitoring in APAC. Hence, the APAC Diabetes Care Advisory Board convened to gather insights into clinician-reported CGM utilization for optimized glucose monitoring and diabetes management in the region. We discuss the findings from a pre-meeting survey and an expert panel meeting regarding glucose monitoring patterns and influencing factors, patient profiles for CGM initiation and continuation, CGM benefits, and CGM optimization challenges and potential solutions in APAC. While CGM is becoming the new standard of care and a useful adjunct to HbA1c and SMBG globally, glucose monitoring type, timing, and frequency should be individualized according to local and patient-specific contexts. The results of this APAC survey guide methods for the formulation of future APAC-specific consensus guidelines for the application of CGM in people living with diabetes.
Neratinib could be effective as monotherapy or in combination with trastuzumab in HER2-low breast cancer cells and organoid models

Arshad M, Azad A, Chan PYK, Vigneswara V, Feldinger K, Nafi SNM, et al.

Br J Cancer, 2024 Apr 10.
PMID: 38600326 DOI: 10.1038/s41416-024-02665-z

BACKGROUND: Previous studies have suggested that patients with HER2-low breast cancers do not benefit from trastuzumab treatment although the reasons remain unclear.
METHODS: We investigated the effect of trastuzumab monotherapy and its combination with different HER2 targeting treatments in a panel of breast cancer cell lines and patient-derived organoids (PDOs) using biochemical methods and cell viability assays.
RESULTS: Compared to sensitive HER2 over-expressing (IHC3 + ) breast cancer cells, increasing doses of trastuzumab could not achieve IC50 in MDA-MB-361 (IHC 2 + FISH + ) and MDA-MB-453 (IHC 2 + FISH-) cells which showed an intermediate response to trastuzumab. Trastuzumab treatment induced upregulation of HER ligand release, resulting in the activation of HER receptors in these cells, which could account for their trastuzumab insensitivity. Adding a dual ADAM10/17 inhibitor to inhibit the shedding of HER ligands in combination with trastuzumab only showed a modest decrease in the cell viability of HER2-low breast cancer cells and PDOs. However, the panHER inhibitor neratinib was an effective monotherapy in HER2-low breast cancer cells and PDOs, and showed additive effects when combined with trastuzumab.
CONCLUSION: This study demonstrates that neratinib in combination with trastuzumab may be effective in a subset of HER2-low breast cancers although further validation is required in a larger panel of PDOs and in future clinical studies.
Fulltext The clinical impact of using complex molecular profiling strategies in routine oncology practice

Laes JF, Aftimos P, Barthelemy P, Bellmunt J, Berchem G, Camps C, et al.

Oncotarget, 2018 Apr 17;9(29):20282-20293.
PMID: 29755651 DOI: 10.18632/oncotarget.24757

Molecular profiling and functional assessment of signalling pathways of advanced solid tumours are becoming increasingly available. However, their clinical utility in guiding patients' treatment remains unknown. Here, we assessed whether molecular profiling helps physicians in therapeutic decision making by analysing the molecular profiles of 1057 advanced cancer patient samples after failing at least one standard of care treatment using a combination of next-generation sequencing (NGS), immunohistochemistry (IHC) and other specific tests. The resulting information was interpreted and personalized treatments for each patient were suggested. Our data showed that NGS alone provided the oncologist with useful information in 10-50% of cases (depending on cancer type), whereas the addition of IHC/other tests increased extensively the usefulness of the information provided. Using internet surveys, we investigated how therapy recommendations influenced treatment choice of the oncologist. For patients who were still alive after the provision of the molecular information (76.8%), 60.4% of their oncologists followed report recommendations. Most treatment decisions (93.4%) were made based on the combination of NGS and IHC/other tests, and an approved drug- rather than clinical trial enrolment- was the main treatment choice. Most common reasons given by physicians to explain the non-adherence to recommendations were drug availability and cost, which remain barriers to personalised precision medicine. Finally, we observed that 27% of patients treated with the suggested therapies had an overall survival > 12 months. Our study demonstrates that the combination of NGS and IHC/other tests provides the most useful information in aiding treatment decisions by oncologists in routine clinical practice.
Fulltext Genome-wide association study in a Chinese population identifies a susceptibility locus for type 2 diabetes at 7q32 near PAX4

Ma RC, Hu C, Tam CH, Zhang R, Kwan P, Leung TF, et al.

Diabetologia, 2013 Jun;56(6):1291-305.
PMID: 23532257 DOI: 10.1007/s00125-013-2874-4

AIMS/HYPOTHESIS: Most genetic variants identified for type 2 diabetes have been discovered in European populations. We performed genome-wide association studies (GWAS) in a Chinese population with the aim of identifying novel variants for type 2 diabetes in Asians.
METHODS: We performed a meta-analysis of three GWAS comprising 684 patients with type 2 diabetes and 955 controls of Southern Han Chinese descent. We followed up the top signals in two independent Southern Han Chinese cohorts (totalling 10,383 cases and 6,974 controls), and performed in silico replication in multiple populations.
RESULTS: We identified CDKN2A/B and four novel type 2 diabetes association signals with p
Global burden of disease attributable to metabolic risk factors in adolescents and young adults aged 15-39, 1990-2021

Zhou XD, Chen QF, Targher G, Byrne CD, Mantzoros CS, Zhang H, et al.

Clin Nutr, 2024 Nov 14;43(12):391-404.
PMID: 39579593 DOI: 10.1016/j.clnu.2024.11.016

BACKGROUND: Metabolic risk factors are a significant cause of global burden among adolescents and young adults, but there is a lack of attention to the burden attributable to these metabolic risk factors globally.
AIMS: This study aims to provide comprehensive estimates of five important metabolic risk factors and the attributable disease burden in people aged 15-39 years from 1990 to 2021, based on the Global Burden of Disease Study (GBD) database.
METHODS: Global total deaths and disability-adjusted life years (DALYs) were used to describe the burden attributable to five common metabolic risk factors, including high fasting plasma glucose (FPG), high low-density lipoprotein cholesterol (LDL-C), high systolic blood pressure (SBP), high body mass index (BMI), and kidney dysfunction, in adolescents and young adults. The estimated annual percentage changes (EAPC) of DALYs were utilized to depict the trends from 1990 to 2021.
RESULTS: From 1990 to 2021, the DALY rates attributable to all metabolic risk factors showed a globally significant upward trend, with EAPC reaching 33.0 % (27.4-38.7). Compared to females, males had a heavier burden and a more significant increase in deaths and DALYs attributable to metabolic risk factors. High BMI and high FPG have become the top two metabolic risk factors in 2021, with summary exposure variables (SEV) rising by 84.2 % and 53.6 %, respectively. Low-middle socio-demographic index (SDI), middle SDI, and high SDI regions experienced upward regional trends in DALY rates, while low SDI regions remained stable. Among 204 countries and territories, 101 (49.5 %) showed a significant increase in DALY rates, as indicated by the EAPC.
CONCLUSIONS: There is a substantial global burden attributable to metabolic risk factors in adolescents and young adults in 2021, especially high BMI and high FPG. This calls for further investigation and intervention to address this emerging trend.
Evidence for the Higgs Boson Decay to a Z Boson and a Photon at the LHC

Aad G, Abbott B, Abeling K, Abicht NJ, Abidi SH, Aboulhorma A, et al.

Phys Rev Lett, 2024 Jan 12;132(2):021803.
PMID: 38277607 DOI: 10.1103/PhysRevLett.132.021803

The first evidence for the Higgs boson decay to a Z boson and a photon is presented, with a statistical significance of 3.4 standard deviations. The result is derived from a combined analysis of the searches performed by the ATLAS and CMS Collaborations with proton-proton collision datasets collected at the CERN Large Hadron Collider (LHC) from 2015 to 2018. These correspond to integrated luminosities of around 140 fb^{-1} for each experiment, at a center-of-mass energy of 13 TeV. The measured signal yield is 2.2±0.7 times the standard model prediction, and agrees with the theoretical expectation within 1.9 standard deviations.
Combination of Measurements of the Top Quark Mass from Data Collected by the ATLAS and CMS Experiments at sqrt[s]=7 and 8 TeV

Hayrapetyan A, Tumasyan A, Adam W, Andrejkovic JW, Bergauer T, Chatterjee S, et al.

Phys Rev Lett, 2024 Jun 28;132(26):261902.
PMID: 38996325 DOI: 10.1103/PhysRevLett.132.261902

A combination of fifteen top quark mass measurements performed by the ATLAS and CMS experiments at the LHC is presented. The datasets used correspond to an integrated luminosity of up to 5 and 20 fb^{-1} of proton-proton collisions at center-of-mass energies of 7 and 8 TeV, respectively. The combination includes measurements in top quark pair events that exploit both the semileptonic and hadronic decays of the top quark, and a measurement using events enriched in single top quark production via the electroweak t channel. The combination accounts for the correlations between measurements and achieves an improvement in the total uncertainty of 31% relative to the most precise input measurement. The result is m_{t}=172.52±0.14(stat)±0.30(syst) GeV, with a total uncertainty of 0.33 GeV.