This study aims to determine the outcomes of stereotactic body radiotherapy (SBRT) for liver metastases in patients not eligible for surgery.
This study included 31 consecutive patients with ...unresectable liver metastases who received SBRT between January 2012 and December 2017; 22 patients had primary colorectal cancer and nine patients had primary non-colorectal cancer. Treatments ranged from 24 Gy to 48 Gy in 3 to 6 fractions over 1 to 2 weeks. Survival, response rates, toxicities, clinical characteristics, and dosimetric parameters were evaluated. Multivariate analysis was performed to identify significant prognostic factors for survival.
Among these 31 patients, 65% had received at least one prior regimen of systemic therapy for metastatic disease, whereas 29% had received chemotherapy for disease progression or immediately after SBRT. The median follow-up interval was 18.9 months; actuarial in-field local control rates at 1, 2, and 3 years after SBRT were 94%, 55%, and 42%, respectively. The median survival duration was 32.9 months; 1-year, 2-year, and 3-year actuarial survival rates were 89.6%, 57.1%, and 46.2%, respectively. The median time to progression was 10.9 months. Stereotactic body radiotherapy was well-tolerated, with grade 1 toxicities of fatigue (19%) and nausea (10%). Patients who received post-SBRT chemotherapy had significant longer overall survival (P=0.039 for all patients and P=0.001 for patients with primary colorectal cancer).
Stereotactic body radiotherapy can be safely administered to patients with unresectable liver metastases, and it may delay the need for chemotherapy. This treatment should be considered for selected patients with unresectable liver metastases.
Multiple lung pathogens such as chemical agents, H5N1 avian flu, or SARS cause high lethality due to acute respiratory distress syndrome. Here we report that Toll-like receptor 4 (TLR4) mutant mice ...display natural resistance to acid-induced acute lung injury (ALI). We show that TLR4-TRIF-TRAF6 signaling is a key disease pathway that controls the severity of ALI. The oxidized phospholipid (OxPL) OxPAPC was identified to induce lung injury and cytokine production by lung macrophages via TLR4-TRIF. We observed OxPL production in the lungs of humans and animals infected with SARS, Anthrax, or H5N1. Pulmonary challenge with an inactivated H5N1 avian influenza virus rapidly induces ALI and OxPL formation in mice. Loss of TLR4 or TRIF expression protects mice from H5N1-induced ALI. Moreover, deletion of
ncf1, which controls ROS production, improves the severity of H5N1-mediated ALI. Our data identify oxidative stress and innate immunity as key lung injury pathways that control the severity of ALI.
Live poultry markets (LPMs) are a recognized source of influenza viruses. Since 2001 and 2003, respectively, a first and second monthly "rest-day" has been implemented in Hong Kong's LPMs, when ...stalls are cleared of unsold poultry and disinfected. We assessed the incremental effectiveness of each rest-day and the banning of live quail sales in 2002 in reducing (H9N2) subtype isolation rates for chickens and minor poultry, by using a multivariable Poisson generalized linear model. There was a 58% reduction (p = 0.001) in virus isolation after 1 monthly rest-day in minor poultry compared with 27% (p = 0.22) in chickens. Combining 1 rest-day with the removal of quails further reduced virus isolation in chickens but not in minor poultry. However, an additional rest-day each month did not appear to affect isolation rates for either species.
Abstract
Background
Human spillovers of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to dogs and the emergence of a highly contagious avian-origin H3N2 canine influenza virus have ...raised concerns on the role of dogs in the spread of SARS-CoV-2 and their susceptibility to existing human and avian influenza viruses, which might result in further reassortment.
Methods
We systematically studied the replication kinetics of SARS-CoV-2, SARS-CoV, influenza A viruses of H1, H3, H5, H7, and H9 subtypes, and influenza B viruses of Yamagata-like and Victoria-like lineages in ex vivo canine nasal cavity, soft palate, trachea, and lung tissue explant cultures and examined ACE2 and sialic acid (SA) receptor distribution in these tissues.
Results
There was limited productive replication of SARS-CoV-2 in canine nasal cavity and SARS-CoV in canine nasal cavity, soft palate, and lung, with unexpectedly high ACE2 levels in canine nasal cavity and soft palate. Canine tissues were susceptible to a wide range of human and avian influenza viruses, which matched with the abundance of both human and avian SA receptors.
Conclusions
Existence of suitable receptors and tropism for the same tissue foster virus adaptation and reassortment. Continuous surveillance in dog populations should be conducted given the many chances for spillover during outbreaks.
Ex vivo canine respiratory and soft palate explants supported limited productive replication of SARS-CoV-2 and SARS-CoV and efficient replication of a wide range of human and avian influenza viruses, especially H5 and H7 highly pathogenic avian influenza viruses and H9N2 virus.
Samples of drinking water from poultry cages, which can be collected conveniently and noninvasively, provide higher rates of influenza (H9N2) virus isolation than do samples of fecal droppings. ...Studies to confirm the usefulness of poultry drinking water for detecting influenza (H5N1) should be conducted in disease-endemic areas.
Abstract Background Avian influenza virus (AIV) surveillance in birds is important for public health. Faecal droppings from wild-birds are more readily available for such studies, but the inability ...to identify the species-origin of faecal samples limits their value. Objectives To develop, optimise, and field-test a method to simultaneously detect AIV and identify the species-origin from faecal samples. Study design Analytical sensitivity of the species-identification RT-PCR was assessed on serial dilutions of faecal droppings. Overall sensitivity of the methods for species-identification and AIV detection was assessed on 92 faecal and cloacal samples collected from wildlife, poultry markets, and experimentally H5N1-infected birds. Results All 92 samples were correctly identified to 24 different species, with a detection limit of 2.8 μg of faecal material. All 20 specimens previously shown by virus culture to be positive for influenza virus were correctly identified by RT-PCR for influenza A using the same nucleic-acid extracts used for species-identification. Conclusion We have optimised and evaluated a method for identifying the species of origin and detecting AIV from bird faecal droppings that can be applied to routine surveillance of influenza viruses in wild-birds.
The potential for a global influenza pandemic remains significant with epidemiologic and ecologic indicators revealing the entrenchment of the highly pathogenic avian influenza A H5N1 in both wild ...bird populations and domestic poultry flocks in Asia and in many African and European countries. Indisputably, the single most effective public health intervention in mitigating the devastation such a pandemic could unleash is the availability of a safe and effective vaccine that can be rapidly deployed for pre-exposure vaccination of millions of people. We have developed two vaccinia-based influenza vaccines that are molecularly adjuvanted with the immune stimulatory cytokine IL-15. The pentavalent Wyeth/IL-15/5Flu vaccine expresses the hemagglutinin, neuraminidase, and nucleoprotein derived from the H5N1 influenza virus A/Vietnam/1203/2004 and the matrix proteins M1 and M2 from the H5N1 A/CK/Indonesia/PA/2003 virus on the backbone of a currently licensed smallpox vaccine. The bivalent MVA/IL-15/HA/NA vaccine expresses only the H5 hemagglutinin and N1 neuraminidase on the modified vaccinia virus Ankara (MVA) backbone. Both vaccines induced cross-neutralizing Abs and robust cellular immune responses in vaccinated mice and conferred sterile cross-clade protection when challenged with the H5N1 virus of a different clade. In addition to having potential as a universal influenza vaccine, in the event of an impending pandemic the Wyeth/IL-15/5Flu is also readily amenable to bulk production to cover the global population. For those individuals for whom the use of the Wyeth vaccine is contraindicated, our MVA/IL-15/HA/NA offers a substitute or a prevaccine to be used in a mass vaccination campaign similar to the smallpox eradication campaigns of few decades ago.
Pulmonary artery sarcoma is a rare disease with poor prognosis that has not been reported in Hong Kong. Its clinical and radiological presentation frequently mimics pulmonary embolism. Diagnosis is ...usually delayed until surgery, which is the treatment option that provides the best survival. Endobronchial ultrasound-guided transbronchial needle aspiration is an effective non-surgical technique for lymph node staging of lung cancer and diagnosis of mediastinal lesions via bronchoscopy. Here we discuss a case of pulmonary artery sarcoma diagnosed by this method, the second one in the literature, which serves to illustrate its potential use for early and minimally invasive diagnosis of the condition. Although such aspiration is a safe procedure, tissue sampling of extravascular extensions is advisable wherever possible.
Realizable one-step RT-PCR assays specific for influenza PB2, PB1 and PA segments are described in this report. The designs of the consensus primers were based on more than five thousands polymerase ...genes derived from avian or mammalian viral strains. All the viral RNA tested in this study could be consistently amplified by the assays. The reaction products were specific and could be used for direct DNA sequencing. These assays might be useful tools to study the sequences of these genes.
PDF
