We identified seasonal human coronaviruses, influenza viruses and rhinoviruses in exhaled breath and coughs of children and adults with acute respiratory illness. Surgical face masks significantly ...reduced detection of influenza virus RNA in respiratory droplets and coronavirus RNA in aerosols, with a trend toward reduced detection of coronavirus RNA in respiratory droplets. Our results indicate that surgical face masks could prevent transmission of human coronaviruses and influenza viruses from symptomatic individuals.
Background
Although transarterial chemoembolization is recommended as the standard treatment for Barcelona Clinic Liver Cancer stage B hepatocellular carcinoma (BCLC‐B HCC), other treatments ...including liver resection have been used. This study aimed to determine the survival benefit of treatment strategies including resection for BCLC‐B HCC compared with non‐surgical treatments.
Methods
The nationwide multicentre database of the Korean Liver Cancer Association was reviewed. Patients with BCLC‐B HCC who underwent liver resection as a first or second treatment within 2 years of diagnosis and patients who received non‐surgical treatment were selected randomly. Survival outcomes of propensity score‐matched groups were compared.
Results
Among 887 randomly selected patients with BCLC‐B HCC, 83 underwent liver resection as first or second treatment and 597 had non‐surgical treatment. After propensity score matching, the two groups were well balanced (80 patients in each group). Overall median survival in the resection group was better than that for patients receiving non‐surgical treatment (50·9 versus 22·1 months respectively; P < 0·001). The 1‐, 2‐, 3‐ and 5‐year overall survival rates in the resection group were 90, 88, 75 and 63 per cent, compared with 79, 48, 35 and 22 per cent in the no‐surgery group (P < 0·001). In multivariable analysis, non‐surgical treatment only (hazard ratio (HR) 3·35, 95 per cent c.i. 2·16 to 5·19; P < 0·001), albumin level below 3·5 g/dl (HR 1·96, 1·22 to 3·15; P = 0·005) and largest tumour size greater than 5·0 cm (HR 1·81, 1·20 to 2·75; P = 0·005) were independent predictors of worse overall survival.
Conclusion
Treatment strategies that include liver resection offer a survival benefit compared with non‐surgical treatments for potentially resectable BCLC‐B HCC.
Selected patients benefit
There currently are no internationally recognised treatment guidelines for patients with advanced gastric cancer/gastro-oesophageal junction cancer (GC/GEJC) in whom two prior lines of therapy have ...failed. The randomised, phase III JAVELIN Gastric 300 trial compared avelumab versus physician’s choice of chemotherapy as third-line therapy in patients with advanced GC/GEJC.
Patients with unresectable, recurrent, locally advanced, or metastatic GC/GEJC were recruited at 147 sites globally. All patients were randomised to receive either avelumab 10mg/kg by intravenous infusion every 2weeks or physician’s choice of chemotherapy (paclitaxel 80mg/m2 on days 1, 8, and 15 or irinotecan 150mg/m2 on days 1 and 15, each of a 4-week treatment cycle); patients ineligible for chemotherapy received best supportive care. The primary end point was overall survival (OS). Secondary end points included progression-free survival (PFS), objective response rate (ORR), and safety.
A total of 371 patients were randomised. The trial did not meet its primary end point of improving OS {median, 4.6 versus 5.0months; hazard ratio (HR)=1.1 95% confidence interval (CI) 0.9–1.4; P=0.81} or the secondary end points of PFS median, 1.4 versus 2.7months; HR=1.73 (95% CI 1.4–2.2); P>0.99 or ORR (2.2% versus 4.3%) in the avelumab versus chemotherapy arms, respectively. Treatment-related adverse events (TRAEs) of any grade occurred in 90 patients (48.9%) and 131 patients (74.0%) in the avelumab and chemotherapy arms, respectively. Grade ≥3 TRAEs occurred in 17 patients (9.2%) in the avelumab arm and in 56 patients (31.6%) in the chemotherapy arm.
Treatment of patients with GC/GEJC with single-agent avelumab in the third-line setting did not result in an improvement in OS or PFS compared with chemotherapy. Avelumab showed a more manageable safety profile than chemotherapy.
ClinicalTrials.gov: NCT02625623.
Background. Infections caused by the pandemic H1N1 2009 influenza virus range from mild upper respiratory tract syndromes to fatal diseases. However, studies comparing virological and immunological ...profile of different clinical severity are lacking. Methods. We conducted a retrospective cohort study of 74 patients with pandemic H1N1 infection, including 23 patients who either developed acute respiratory distress syndrome (ARDS) or died (ARDS-death group), 14 patients with desaturation requiring oxygen supplementation and who survived without ARDS (survived-without-ARDS group), and 37 patients with mild disease without desaturation (mild-disease group). We compared their pattern of clinical disease, viral load, and immunological profile. Results. Patients with severe disease were older, more likely to be obese or having underlying diseases, and had lower respiratory tract symptoms, especially dyspnea at presentation. The ARDS-death group had a slower decline in nasopharyngeal viral loads, had higher plasma levels of proinflammatory cytokines and chemokines, and were more likely to have bacterial coinfections (30.4%), myocarditis (21.7%), or viremia (13.0%) than patients in the survived-without-ARDS or the mild-disease groups. Reactive hemophagocytosis, thrombotic phenomena, lymphoid atrophy, diffuse alveolar damage, and multiorgan dysfunction similar to fatal avian influenza A H5N1 infection were found at postmortem examinations. Conclusions. The slower control of viral load and immunodysregulation in severe cases mandate the search for more effective antiviral and immunomodulatory regimens to stop the excessive cytokine activation resulting in ARDS and death.
COVID toe in an adolescent boy: a case report Wong, J S C; Wong, T S; Chua, G T ...
Hong Kong medical journal = Xianggang yi xue za zhi,
04/2022, Letnik:
28, Številka:
2
Journal Article
Recenzirano
Odprti dostop
The appearance of chilblain-like lesions was not thought to be associated with a poor disease outcome.2 3 A major limitation of these reports is that only 11% of cases hospitalised tested positive ...for SARS-CoV-2 by polymerase chain reaction (PCR), with the remainder untested or testing negative. Another systematic review also concluded that some, but not all paediatric cases, who developed chilblain-like lesions during the COVID-19 pandemic had positive SARS-CoV-2 PCR, serology or viral particles confirmed in electron microscopy.5 Larger-scale epidemiological study is needed to confirm an association between these chilblain-like lesions and COVID-19 infection. Joshua SC Wong 1 †; TS Wong 1 †; Gilbert T Chua 2 †; Christy Wan 1; SH Lau 1; Samuel CS Ho 1; Jaime S Rosa Duque 2; Ian CK Wong 3,4; Kelvin KW To 5; Winnie WY Tso 2; Christine S Wong 6; Marco HK Ho 2; Janette Kwok 7; CB Chow 1; Paul KH Tam 8,9; Godfrey CF Chan; 2; WH Leung 2; YL Lau 2; Patrick Ip 2; Mike YW Kwan; CUHK 1 1 Department of Paediatrics and Adolescent Medicine, Princess Margaret Hospital, Hong Kong 2 Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 3 Centre for Safe Medication Practice and Research, Department of Pharmacology and Pharmacy, The University of Hong Kong, Hong Kong 4 Research Department of Practice and Policy, UCL School of Pharmacy, University College London, United Kingdom 5 Department of Microbiology, Carol Yu Centre for Infection, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong 6 Dermatology Division, Department of Medicine, Queen Mary Hospital, Hong Kong 7 Division of Transplantation and Immunogenetics, Department of Pathology, Queen Mary Hospital, Hong Kong 8 Division of Paediatric Surgery, Department of Surgery, The University of Hong Kong, Hong Kong 9 Dr Li Dak-Sum Research Centre, The University of Hong Kong–Karolinska Institutet Collaboration in Regenerative Medicine, The University of Hong Kong, Hong Kong † Co-first authors
Four-dimensional (4D) printing of shape memory polymer (SMP) imparts time responsive properties to 3D structures. Here, we explore 4D printing of a SMP in the submicron length scale, extending its ...applications to nanophononics. We report a new SMP photoresist based on Vero Clear achieving print features at a resolution of ~300 nm half pitch using two-photon polymerization lithography (TPL). Prints consisting of grids with size-tunable multi-colours enabled the study of shape memory effects to achieve large visual shifts through nanoscale structure deformation. As the nanostructures are flattened, the colours and printed information become invisible. Remarkably, the shape memory effect recovers the original surface morphology of the nanostructures along with its structural colour within seconds of heating above its glass transition temperature. The high-resolution printing and excellent reversibility in both microtopography and optical properties promises a platform for temperature-sensitive labels, information hiding for anti-counterfeiting, and tunable photonic devices.
Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome that elevates the risk of hepatocellular carcinoma (HCC). Although alteration of lipid metabolism has ...been increasingly recognized as a hallmark of cancer cells, the deregulated metabolic modulation of HCC cells in the NAFLD progression remains obscure. Here, we discovers an endoplasmic reticulum-residential protein, Nogo-B, as a highly expressed metabolic modulator in both murine and human NAFLD-associated HCCs, which accelerates high-fat, high-carbohydrate diet-induced metabolic dysfunction and tumorigenicity. Mechanistically, CD36-mediated oxLDL uptake triggers CEBPβ expression to directly upregulate Nogo-B, which interacts with ATG5 to promote lipophagy leading to lysophosphatidic acid-enhanced YAP oncogenic activity. This CD36-Nogo-B-YAP pathway consequently reprograms oxLDL metabolism and induces carcinogenetic signaling for NAFLD-associated HCCs. Targeting the Nogo-B pathway may represent a therapeutic strategy for HCC arising from the metabolic syndrome.
Strong field enhancement and confinement in plasmonic nanostructures provide suitable conditions for nonlinear optics in ultracompact dimensions. Despite these enhancements, second-harmonic ...generation (SHG) is still inefficient due to the centrosymmetric crystal structure of the bulk metals used, e.g., Au and Ag. Taking advantage of symmetry breaking at the metal surface, one could greatly enhance SHG by engineering these metal surfaces in regions where the strong electric fields are localized. Here, we combine top-down lithography and bottom-up self-assembly to lodge single rows of 8 nm diameter Au nanoparticles into trenches in a Au film. The resultant “double gap” structures increase the surface-to-volume ratio of Au colocated with the strong fields in ∼2 nm gaps to fully exploit the surface SHG of Au. Compared to a densely packed arrangement of AuNPs on a smooth Au film, the double gaps enhance SHG emission by 4200-fold to achieve an effective second-order susceptibility χ(2) of 6.1 pm/V, making it comparable with typical nonlinear crystals. This patterning approach also allows for the scalable fabrication of smooth gold surfaces with sub-5 nm gaps and presents opportunities for optical frequency up-conversion in applications that require extreme miniaturization.
Knee osteoarthritis is one of the most common degenerative diseases causing disability in elderly patients. Osteoarthritis is an increasing problem for ageing populations, such as that in Hong Kong. ...It is important for guidelines to be kept up to date with the best evidence-based osteoarthritis management practices available. The aim of this study was to review the current literature and international guidelines on non-surgical treatments for knee osteoarthritis and compared these with the current guidelines in Hong Kong, which were proposed in 2005. Internationally, exercise programmes for non-surgical management of osteoarthritis have been proven effective, and a pilot programme in Hong Kong for comprehensive non-surgical knee osteoarthritis management has been successful. Long-term studies on the effectiveness of such exercise programmes are required, to inform future changes to guidelines on osteoarthritis management.
Epidermal growth factor receptor (EGFR)-mutated lung cancer constitutes a major subgroup of non-small cell lung cancer (NSCLC) and osimertinib is administrated as first-line treatment. However, most ...patients with osimertinib treatment eventually relapse within one year. The underlying mechanisms of osimertinib resistance remain largely unexplored.
Exosomes isolation was performed by differential centrifugation. Co-culture assays were conducted to explore the alteration of drug sensitivity by cell viability and apoptosis assays. Immunofluorescence and flow cytometry were performed to visualize the formation or absorption of exosomes. Exosomes secretion was measured by Nanoparticle Tracking Analysis or ELISA. The xenograft tumor model in mice was established to evaluate the effect of exosomes on osimertinib sensitivity in vivo.
Intercellular transfer of exosomal wild type EGFR protein confers osimertinib resistance to EGFR-mutated sensitive cancer cells in vitro and in vivo. Co-culture of EGFR-mutated sensitive cells and EGFR-nonmutated resistant cells promoted osimertinib resistance phenotype in EGFR-mutated cancer cells, while depletion of exosomes from conditioned medium or blockade of exosomal EGFR by neutralizing antibody alleviated this phenotype. Mechanistically, osimertinib promoted the release of exosomes by upregulated a Rab GTPase (RAB17). Knockdown of RAB17 resulted in the decrease of exosomes secretion. Moreover, exosomes could be internalized by EGFR-mutated cancer cells via Clathrin-dependent endocytosis and then the encapsulated exosomal wild type EGFR protein activated downstream PI3K/AKT and MAPK signaling pathways and triggered osimertinib resistance.
Intercellular transfer of exosomal wild type EGFR promotes osimertinib resistance in NSCLC, which may represent a novel resistant mechanism of osimertinib and provide a proof of concept for targeting exosomes to prevent and reverse the osimertinib resistance.
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