Intravitreal aflibercept 8 mg in neovascular age-related macular degeneration (PULSAR): 48-week results from a randomised, double-masked, non-inferiority, phase 3 trial.

BACKGROUND: Intravitreal aflibercept 8 mg could improve treatment outcomes and provide sustained disease control in patients with neovascular age-related macular degeneration (nAMD), with extended dosing compared with aflibercept 2 mg. METHODS: PULSAR is a phase 3, randomised, three-group, double-masked, non-inferiority, 96-week trial conducted across 223 sites worldwide. Adults with nAMD were randomised 1:1:1 to aflibercept 8 mg every 12 weeks (8q12), aflibercept 8 mg every 16 weeks (8q16), or aflibercept 2 mg every 8 weeks (2q8), following three initial monthly doses in all groups. From week 16, patients in the aflibercept 8 mg groups had their dosing interval shortened if pre-specified dose regimen modification criteria denoting disease activity were met. The primary endpoint was change from baseline in best-corrected visual acuity (BCVA) at week 48. All patients with at least one dose of study treatment were included in the efficacy and safety analyses. This trial is registered with ClinicalTrials.gov (NCT04423718) and is ongoing. FINDINGS: Of 1011 patients randomised to aflibercept 8q12 (n=336), 8q16 (n=338), or 2q8 (n=337) between Aug 11, 2020, and July 30, 2021, 1009 patients received study treatment (aflibercept 8q12 n=335; aflibercept 8q16 n=338; and aflibercept 2q8 n=336). Aflibercept 8q12 and 8q16 showed non-inferior BCVA gains versus aflibercept 2q8 (mean BCVA change from baseline +6·7 [SD 12·6] and +6·2 [11·7] vs +7·6 [12·2] letters). The least squares mean differences between aflibercept 8q12 versus 2q8 and 8q16 versus 2q8, respectively, were -0·97 (95% CI -2·87 to 0·92) and -1·14 (-2·97 to 0·69) letters (non-inferiority margin at 4 letters). The incidence of ocular adverse events in the study eye was similar across groups (aflibercept 8q12 n=129 [39%]; aflibercept 8q16 n=127 [38%]; and aflibercept 2q8 n=130 [39%]). INTERPRETATION: Aflibercept 8 mg showed efficacy and safety with extended dosing intervals, which has the potential to improve the management of patients with nAMD. FUNDING: Bayer AG and Regeneron Pharmaceuticals.

Diagnostic performance of CareStart™ malaria HRP2/pLDH (Pf/pan) combo test versus standard microscopy on falciparum and vivax malaria between China-Myanmar endemic borders.

BACKGROUND: Rapid diagnostic test (RDT) is becoming an alternative way of establishing quickly the diagnosis of malaria infections, by detecting specific malaria antigens in suspected patients' blood between the China-Myanmar endemic borders areas, towards achieving the National Malaria Elimination programme by 2020. The objective of this study is to evaluate the performance of CareStart™ Malaria Pf/Pan RDT kit for the diagnosis of malaria infections in suspected patients. Blood examination by microscopy was taken as gold standard to evaluate CareStart™ kit's sensitivity, specificity and predictive value and corrected with PCR assay. RESULTS: Overall 126 of 241 (52.28%) malaria cases were detected by microscopy compared to 115 of 241(47.72%) CareStart™ kit and 128 of 241 (53.11%) PCR corrected assay. CareStart™ kit's sensitivity and specificity for the diagnosis of malaria were 89.68% and 98.26% respectively, compared to standard microscopy, whereas the sensitivity and specificity for falciparum malaria were 88.52% and 98.26%, and for vivax malaria: 90.77% and 100%. The CareStart™ positive predictive values were 98.26% (93.88-99.52%, 95% CI) compared to 100% (96.77-100%, 95% CI) for PCR-corrected, and the negative predictive values of 89.68% (83.15-93.87%, 95% CI) were the same in microscopy as PCR-corrected. The diagnostic accuracy of CareStart™ kit versus microscopy and PCR were 93.78% (89.99-96.19%, 95% CI) and 94.61% (90.99-96.82%, 95% CI) respectively. The likelihood of diagnostic of malaria positive was almost similar between microscopy and CareStart™ kit, with an entropy reduction of 60.0% compared to a weak likelihood of misdiagnosis of 0.10 (0.09-0.12, 95% CI), with an entropy reduction of 36.01%. CONCLUSION: The accuracy of CareStart™ kit is comparable to gold standard microscopy in these areas, it is easy to perform and suitable for cross-border diagnosis and monitoring of local or imported malaria patterns by any local health staff in endemic remotes.

Public health preparedness for the world's largest mass gathering: 2010 World Exposition in Shanghai, China.

The 2010 World Exposition in Shanghai China (Expo) was the largest mass gathering in world history, attracting a record 72 million visitors. More than 190 countries participated in the Expo, along with more than 50 international organizations. The 2010 Expo was six months in duration (May 1 through October 30, 2010), and the size of the venue site comprised 5.28 square kilometers. Great challenges were imposed on the public health system in Shanghai due to the high number and density of visitors, long duration of the event, and other risk factors such as high temperatures, typhoon, etc. As the major metropolitan public health agency in Shanghai, the Shanghai Municipal Center for Disease Control and Prevention (SCDC) implemented a series of actions in preparing for, and responding to, the potential health impact of the world's largest mass gathering to date, which included partnerships for capacity building, enhancement of internal organizational structure, risk assessment, strengthened surveillance, disaster planning and exercises, laboratory management, vaccination campaign, health education, health intervention, risk communication and mass media surveillance, and technical support for health inspection. The clear-cut organizational structures and job responsibilities, as well as comprehensive operational and scientific preparations, were key elements to ensure the success of the 2010 World Exposition.

Novel umami peptides from tilapia lower jaw and molecular docking to the taste receptor T1R1/T1R3.

This study aimed to isolate and identify peptides with intense umami taste from tilapia lower jaw. The aqueous extract was separated using ultrafiltration and Sephadex G-15 gel filtration chromatography. The peptide fraction with an intense umami taste was selected by sensory evaluation. The five novel peptides with strong umami taste were VADLMR, STELFK, FVGLQER, DALKKK, and VVLNPVARVE. Electronic tongue analysis and sensory evaluation showed that five peptides had obvious umami taste characteristics, and the recognition thresholds of umami peptides were in the range 0.125-0.250 mg/mL. Molecular docking was used to study the interaction of the peptides and umami taste receptor T1R1/T1R3. The five peptides could perfectly be inserted into the binding pocket of the Venus flytrap domain in the T1R3 subunit. Hydrogen bonding and hydrophobic interaction were the important interaction forces. The five peptides may bind with Asp219, Glu217, and Glu148 in T1R1/T1R3 receptor and produce the umami taste.

Can Combined Therapy Benefit Immune Checkpoint Blockade Response in Hepatocellular Carcinoma?

BACKGROUND: Hepatocellular Carcinoma (HCC) is one of the most common cancers with high mortality rate. The effects of most therapies are limited. The Immune Checkpoint Blockade (ICB) improves the prognosis in multiple malignancies. The application of immune checkpoint blockade to hepatocellular carcinoma patients has recently started. Early phase clinical trials have shown some benefits to cancer patients. METHODS/RESULTS: This review focuses on the immune system of liver and clinical trials of ICB. In particular, we analyze the mechanisms by which immune checkpoint blockade therapies can be used for the treatment of hepatocellular carcinoma patients, then examine the factors in cancer resistance to the therapies and finally suggest possible combination therapies for the treatment of hepatocellular carcinoma patients. CONCLUSION: ICB is a promising therapy for advanced HCC patients. Combined therapy exhibits a great potential to enhance ICB response in these patients. The better understanding of the factors influencing the sensitivity of ICB and more clinical trials will consolidate the efficiency and minimize the adverse effects of ICB.