ABSTRACT
Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a chronic inflammatory disease of the gastrointestinal tract. The introduction of biologics, particularly anti-interleukin (IL) agents, has revolutionized IBD treatment. This review summarizes the role of ILs in IBD pathophysiology and describes the efficacy and positioning of anti-IL therapies. We discuss the functions of key ILs in IBD and their potential as therapeutic targets. The review then discusses anti-IL therapies, focusing primarily on ustekinumab (anti-IL-12/23), risankizumab (anti-IL-23), and mirikizumab (anti-IL-23). Clinical trial data demonstrate their efficacy in inducing and maintaining remission in Crohn's disease and ulcerative colitis. The safety profiles of these agents are generally favorable. However, long-term safety data for newer agents are still limited. The review also briefly discusses emerging therapies such as guselkumab and brazikumab. Network meta-analyses suggest that anti-IL therapies perform well compared to other biological agents. These agents may be considered first- or second-line therapies for many patients, especially those with comorbidities or safety concerns. Anti-IL therapies represent a significant advancement in IBD treatment, offering effective and relatively safe options for patients with moderate to severe disease.
Subject(s)
Antibodies, Monoclonal , Inflammatory Bowel Diseases , Ustekinumab , Humans , Inflammatory Bowel Diseases/drug therapy , Ustekinumab/therapeutic use , Antibodies, Monoclonal/therapeutic use , Interleukins/metabolism , Interleukins/antagonists & inhibitors , Biological Products/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Interleukin-23/antagonists & inhibitors , Interleukin-23/metabolism , Crohn Disease/drug therapyABSTRACT
Diagnosing inflammatory bowel disease (IBD) can often be challenging, and differentiating between Crohn's disease and ulcerative colitis can be particularly difficult. Diagnostic procedures for IBD include laboratory tests, endoscopy, pathological tests, and imaging tests. Serological and stool tests can be easily performed in an outpatient setting and provide critical diagnostic clues. Although endoscopy is an invasive procedure, it offers essential diagnostic information and allows for tissue biopsy and therapeutic procedures. Video capsule endoscopy and device-assisted enteroscopy are endoscopic procedures used to evaluate the small bowel. In addition to endoscopy, magnetic resonance imaging, computed tomography, and ultrasound (US) are valuable tools for small bowel assessment. Among these, US is noninvasive and easily utilized, making its use highly practical in daily clinical practice. Endoscopic biopsy aids in the diagnosis of IBD and is crucial for assessing the histological activity of the disease, facilitating a thorough evaluation of disease remission, and aiding in the development of treatment strategies. Recent advances in artificial intelligence hold promise for enhancing various aspects of IBD management, including diagnosis, monitoring, and precision medicine. This review compiles current procedures and promising future tools for the diagnosis of IBD, providing comprehensive insights.
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Background/Objectives: Endoscopic papillectomy (EP) is the preferred treatment for ampullary tumors because it has fewer side effects than surgical removal. This study retrospectively compared a new anchoring EP method (A-EP) with the conventional (C-EP) approach. Methods: Ninety-nine patients who underwent EP at a single medical institution between 2009 and 2021 were retrospectively reviewed. In all patients, the indications for EP were pathological adenoma with <10 mm of biliary invasion and a tumor diameter <30 mm on endoscopic ultrasonography. The exclusion criteria were antiplatelet/anticoagulant use, previous upper GI surgery, or prior biliary/pancreatic endoscopic therapy. One expert endoscopist performed the two types of EPs, A-EP and C-EP. Results: Sixty-two patients underwent A-EP, and 37 underwent C-EP. There were no significant differences in baseline characteristics, such as sex, age, tumor size, and ductal invasion on endoscopic ultrasound. The A-EP group had higher en bloc resection rates (95.2% vs. 78.4%, p = 0.010). Although the difference was not statistically significant, it tended towards fewer incidences of pancreatitis (p = 0.081) and duct stricture (p = 0.081). The recurrence rate was lower in the A-EP group (8.1% vs. 37.8%, p = 0.000). There were no significant differences between the two groups regarding the follow-up period (A-EP vs. C-EP, 725 vs. 1045 days, p = 0.109) or the days of recurrence (A-EP vs. C-EP, 341 vs. 562 days, p = 0.551). Conclusions: A-EP showed better outcomes than C-EP in terms of en bloc resection and recurrence rates, providing evidence for the efficacy of this novel EP method.
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This case report presents the successful endoscopic submucosal dissection (ESD) of a well-differentiated esophageal liposarcoma in a 51-year-old male with persistent dysphagia. The cause was initially diagnosed as a 10 cm pedunculated lesion extending from the upper esophageal sphincter to the mid-esophagus. An ESD was chosen over traditional surgery because it is less invasive. The procedure involved a precise submucosal injection and excision with special techniques to manage bleeding from a central vessel. Despite the extraction challenges owing to the size of the lesion, it was successfully removed orally. A histopathological examination of the 8.3×4.2×2.3 cm specimen revealed the characteristic features of a well-differentiated liposarcoma, including MDM2 and CDK4 positivity. The follow-up revealed no recurrence, and active surveillance has been performed since. This report highlights the versatility of ESD in treating significant esophageal tumors and provides evidence for its efficacy as a minimally invasive alternative.
Subject(s)
Endoscopic Mucosal Resection , Esophageal Neoplasms , Liposarcoma , Humans , Male , Esophageal Neoplasms/surgery , Esophageal Neoplasms/pathology , Esophageal Neoplasms/diagnosis , Middle Aged , Liposarcoma/surgery , Liposarcoma/pathology , Liposarcoma/diagnosis , Tomography, X-Ray Computed , Cyclin-Dependent Kinase 4/metabolism , Proto-Oncogene Proteins c-mdm2/metabolism , EsophagoscopyABSTRACT
Viral load and the duration of viral shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are important determinants of the transmission of coronavirus disease 2019. In this study, we examined the effects of viral doses on the lung and spleen of K18-hACE2 transgenic mice by temporal histological and transcriptional analyses. Approximately, 1×105 plaque-forming units (PFU) of SARS-CoV-2 induced strong host responses in the lungs from 2 days post inoculation (dpi) which did not recover until the mice died, whereas responses to the virus were obvious at 5 days, recovering to the basal state by 14 dpi at 1×102 PFU. Further, flow cytometry showed that number of CD8+ T cells continuously increased in 1×102 PFU-virus-infected lungs from 2 dpi, but not in 1×105 PFU-virus-infected lungs. In spleens, responses to the virus were prominent from 2 dpi, and number of B cells was significantly decreased at 1×105 PFU; however, 1×102 PFU of virus induced very weak responses from 2 dpi which recovered by 10 dpi. Although the defense responses returned to normal and the mice survived, lung histology showed evidence of fibrosis, suggesting sequelae of SARS-CoV-2 infection. Our findings indicate that specific effectors of the immune response in the lung and spleen were either increased or depleted in response to doses of SARS-CoV-2. This study demonstrated that the response of local and systemic immune effectors to a viral infection varies with viral dose, which either exacerbates the severity of the infection or accelerates its elimination.
ABSTRACT
Avian pathogenic Escherichia coli (APEC) causes enormous economic losses and is a primary contributor to the emergence of multidrug resistance (MDR)-related problems in the poultry industry. Bacteriophage (phage) therapy has been successful in controlling MDR, but phage-resistant variants have rapidly emerged through the horizontal transmission of diverse phage defense systems carried on mobile genetic elements. Consequently, while multiple phage cocktails are recommended for phage therapy, there is a growing need to explore simpler and more cost-effective phage treatment alternatives. In this study, we characterized two novel O78-specific APEC phages, φWAO78-1 and φHAO78-1, in terms of their morphology, genome, physicochemical stability and growth kinetics. Additionally, we assessed the susceptibility of thirty-two O78 APEC strains to these phages. We analyzed the roles of highly susceptible cells in intestinal settlement and fecal shedding (susceptible cell-assisted intestinal settlement and shedding, SAIS) of phages in chickens via coinoculation with phages. Furthermore, we evaluated a new strategy, susceptible cell-assisted resistant cell killing (SARK), by comparing phage susceptibility between resistant cells alone and a mixture of resistant and highly susceptible cells in vitro. As expected, high proportions of O78 APEC strains had already acquired multiple phage defense systems, exhibiting considerable resistance to φWAO78-1 and φHAO78-1. Coinoculation of highly susceptible cells with phages prolonged phage shedding in feces, and the coexistence of susceptible cells markedly increased the phage susceptibility of resistant cells. Therefore, the SAIS and SARK strategies were demonstrated to be promising both in vivo and in vitro.
Subject(s)
Bacteriophages , Escherichia coli Infections , Poultry Diseases , Animals , Bacteriophages/genetics , Chickens , Escherichia coli/genetics , Coliphages , Cell Death , Poultry Diseases/therapyABSTRACT
Four mutants varying the length of the G and SH genes, including a G-truncated mutant (ΔG) and three G/SH-truncated mutants (ΔSH/G-1, ΔSH/G-2, and ΔSH/G-3), were generated via serially passaging the avian metapneumovirus strain SNU21004 into the cell lines Vero E6 and DF-1 and into embryonated chicken eggs. The mutant ΔG particles resembled parental virus particles except for the variance in the density of their surface projections. G and G/SH truncation significantly affected the viral replication in chickens' tracheal ring culture and in infected chickens but not in the Vero E6 cells. In experimentally infected chickens, mutant ΔG resulted in the restriction of viral replication and the attenuation of the virulence. The mutants ΔG and ΔSH/G-1 upregulated three interleukins (IL-6, IL-12, and IL-18) and three interferons (IFNα, IFNß, and IFNγ) in infected chickens. In addition, the expression levels of innate immunity-related genes such as Mda5, Rig-I, and Lgp2, in BALB/c mice were also upregulated when compared to the parental virus. Immunologically, the mutant ΔG induced a strong, delayed humoral immune response, while the mutant ΔSH/G-1 induced no humoral immune response. Our findings indicate the potential of the mutant ΔG but not the mutant ΔSH/G-1 as a live attenuated vaccine candidate.
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BACKGROUND: The global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has led to approximately 500 million cases and 6 million deaths worldwide. Previous investigations into the pathophysiology of SARS-CoV-2 primarily focused on peripheral blood mononuclear cells from patients, lacking detailed mechanistic insights into the virus's impact on inflamed tissue. Existing animal models, such as hamster and ferret, do not faithfully replicate the severe SARS-CoV-2 infection seen in patients, underscoring the need for more relevant animal system-based research. METHODS: In this study, we employed single-cell RNA sequencing (scRNA-seq) with lung tissues from K18-hACE2 transgenic (TG) mice during SARS-CoV-2 infection. This approach allowed for a comprehensive examination of the molecular and cellular responses to the virus in lung tissue. FINDINGS: Upon SARS-CoV-2 infection, K18-hACE2 TG mice exhibited severe lung pathologies, including acute pneumonia, alveolar collapse, and immune cell infiltration. Through scRNA-seq, we identified 36 different types of cells dynamically orchestrating SARS-CoV-2-induced pathologies. Notably, SPP1+ macrophages in the myeloid compartment emerged as key drivers of severe lung inflammation and fibrosis in K18-hACE2 TG mice. Dynamic receptor-ligand interactions, involving various cell types such as immunological and bronchial cells, defined an enhanced TGFß signaling pathway linked to delayed tissue regeneration, severe lung injury, and fibrotic processes. INTERPRETATION: Our study provides a comprehensive understanding of SARS-CoV-2 pathogenesis in lung tissue, surpassing previous limitations in investigating inflamed tissues. The identified SPP1+ macrophages and the dysregulated TGFß signaling pathway offer potential targets for therapeutic intervention. Insights from this research may contribute to the development of innovative diagnostics and therapies for COVID-19. FUNDING: This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (2020M3A9I2109027, 2021R1A2C2004501).
Subject(s)
COVID-19 , Melphalan , gamma-Globulins , Animals , Cricetinae , Mice , Humans , SARS-CoV-2 , Leukocytes, Mononuclear , Ferrets , Bronchi , Transforming Growth Factor beta , Mice, Transgenic , Disease Models, Animal , LungABSTRACT
Avian pathogenic E. coli (APEC) causes severe economic losses in the poultry industry, and O78 serogroup APEC strains are prevalent in chickens. In this study, we aimed to understand the evolutionary pathways and relationships between O78 APEC and other E. coli strains. To trace these evolutionary pathways, we classified 3101 E. coli strains into 306 subgenotypes according to the numbers and types of single nucleotide polymorphisms (RST0 to RST63-1) relative to the consensus sequence (RST0) of the RNA polymerase beta subunit gene and performed network analysis. The E. coli strains showed four apparently different evolutionary pathways (I-1, I-2, I-3, and II). The thirty-two Korean O78 APEC strains tested in this study were classified into RST4-4 (45.2%), RST3-1 (32.3%), RST21-1 (12.9%), RST4-5 (3.2%), RST5-1 (3.2%), and RST12-6 (3.2%), and all RSTs except RST21-1 (I-2) may have evolved through the same evolutionary pathway (I-1). A comparative genomic study revealed the highest relatedness between O78 strains of the same RST in terms of genome sequence coverage/identity and the spacer sequences of CRISPRs. The early-appearing RST3-1 and RST4-4 prevalence among O78 APEC strains may reflect the early settlement of O78 E. coli in chickens, after which these bacteria accumulated virulence and antibiotic resistance genes to become APEC strains. The zoonotic risk of the conventional O78 APEC strains is low at present, but the appearance of genetically distinct and multiple virulence gene-bearing RST21-1 O78 APEC strains may alert us to a need to evaluate their virulence in chickens as well as their zoonotic risk.
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Translational regulation in tissue environments during in vivo viral pathogenesis has rarely been studied due to the lack of translatomes from virus-infected tissues, although a series of translatome studies using in vitro cultured cells with viral infection have been reported. In this study, we exploited tissue-optimized ribosome profiling (Ribo-seq) and severe-COVID-19 model mice to establish the first temporal translation profiles of virus and host genes in the lungs during SARS-CoV-2 pathogenesis. Our datasets revealed not only previously unknown targets of translation regulation in infected tissues but also hitherto unreported molecular signatures that contribute to tissue pathology after SARS-CoV-2 infection. Specifically, we observed gradual increases in pseudoribosomal ribonucleoprotein (RNP) interactions that partially overlapped the trails of ribosomes, being likely involved in impeding translation elongation. Contemporaneously developed ribosome heterogeneity with predominantly dysregulated 5 S rRNP association supported the malfunction of elongating ribosomes. Analyses of canonical Ribo-seq reads (ribosome footprints) highlighted two obstructive characteristics to host gene expression: ribosome stalling on codons within transmembrane domain-coding regions and compromised translation of immunity- and metabolism-related genes with upregulated transcription. Our findings collectively demonstrate that the abrogation of translation integrity may be one of the most critical factors contributing to pathogenesis after SARS-CoV-2 infection of tissues.
Subject(s)
COVID-19 , Animals , Mice , RNA, Messenger/genetics , COVID-19/genetics , SARS-CoV-2/genetics , Protein Biosynthesis , Lung/metabolismABSTRACT
Foreign body ingestion is commonly seen in children. However, occasionally it may also be seen among adults and is often associated with intellectual disability, psychiatric disorders, and alcoholism. Ingestion of a magnetic foreign body may cause complications such as gastrointestinal tract perforation, wherein emergency endoscopic removal of the foreign body is generally required. Here, we report a rare case of a 59-year-old male with an intellectual disability and psychiatric disorder in whom metallic objects in the stomach cavity were accidentally discovered during abdominal CT. Esophagogastroduodenoscopy revealed several metallic objects attached to two magnets, which had been ingested several years before and had remained in the stomach cavity. The magnets and metallic objects were safely removed endoscopically using rat-tooth forceps without complications.
Subject(s)
Foreign Bodies , Intellectual Disability , Male , Child , Adult , Humans , Middle Aged , Intellectual Disability/complications , Stomach , Foreign Bodies/complications , Foreign Bodies/diagnosis , Eating , Magnetic PhenomenaABSTRACT
BACKGROUND: To date, various genotypes of infectious bronchitis virus (IBV) have co-circulated and in Korea, GI-15 and GI-19 lineages were prevailing. The spike protein, particularly S1 subunit, is responsible for receptor binding, contains hypervariable regions and is also responsible for the emerging of novel variants. OBJECTIVE: This study aims to investigate the putative major amino acid substitutions for the variants in GI-19. METHODS: The S1 sequence data of IBV isolated from 1986 to 2021 in Korea (n = 188) were analyzed. Sequence alignments were carried out using Multiple alignment using Fast Fourier Transform of Geneious prime. The phylogenetic tree was generated using MEGA-11 (ver. 11.0.10) and Bayesian analysis was performed by BEAST v1.10.4. Selective pressure was analyzed via online server Datamonkey. Highlights and visualization of putative critical amino acid were conducted by using PyMol software (version 2.3). RESULTS: Most (93.5%) belonged to the GI-19 lineage in Korea, and the GI-19 lineage was further divided into seven subgroups: KM91-like (Clade A and B), K40/09-like, QX-like (I-IV). Positive selection was identified at nine and six residues in S1 for KM91-like and QX-like IBVs, respectively. In addition, several positive selection sites of S1-NTD were indicated to have mutations at common locations even when new clades were generated. They were all located on the lateral surface of the quaternary structure of the S1 subunits in close proximity to the receptor-binding motif (RBM), putative RBM motif and neutralizing antigenic sites in S1. CONCLUSIONS: Our results suggest RBM surrounding sites in the S1 subunit of IBV are highly susceptible to mutation by selective pressure during evolution.
Subject(s)
Coronavirus Infections , Infectious bronchitis virus , Poultry Diseases , Animals , Chickens/metabolism , Infectious bronchitis virus/genetics , Phylogeny , Bayes Theorem , Coronavirus Infections/veterinary , Recombination, Genetic , Mutation , Spike Glycoprotein, Coronavirus/geneticsABSTRACT
PURPOSE: The aim of this study was to conduct a nationwide population-based study to estimate the incidence of primary sclerosing cholangitis in patients with ulcerative colitis (UC-PSC) and investigate healthcare use, medication use, surgery, cancer, and death as adverse clinical events of UC-PSC. METHODS: We identified incident cases of UC with (UC-PSC) or without PSC (UC-alone) between 2008 and 2018 using health insurance claims data in Korea. Univariate (crude hazard ratio (HR)) and multivariate analyses were performed to compare the risk of adverse clinical events between groups. RESULTS: A total of 14,406 patients with UC using population-based claims data were detected in the cohort. Overall, 3.38% (487/14,406) of patients developed UC-PSC. During a mean follow-up duration of approximately 5.92 years, the incidence of PSC in patients with UC was 185 per 100,000 person-years. The UC-PSC group showed statistically more frequent healthcare use (hospitalization and emergency department visits: HRs, 5.986 and 9.302, respectively; P < .001), higher immunomodulator and biologic use (azathioprine, infliximab, and adalimumab: HRs, 2.061, 3.457, and 3.170, respectively; P < .001), and higher surgery rate (operation for intestinal obstruction, and colectomy: HRs, 9.728 and 2.940, respectively; P < .001) than did the UC-alone group. The UC-PSC group also showed significantly higher colorectal cancer and biliary tract cancer (HRs, 2.799 and 36.343, respectively; P < .001) and mortality (HR, 4.257) rates than did the UC-alone group. CONCLUSION: Patients with UC-PSC have higher risks of colorectal cancer, biliary tract cancer, and death than do patients with UC-alone. Although considered a rare disease, managing this complex and costly disease requires recognition of the impact of increased burden on healthcare services.
Subject(s)
Cholangitis, Sclerosing , Colitis, Ulcerative , Humans , Colitis, Ulcerative/complications , Colitis, Ulcerative/epidemiology , Colitis, Ulcerative/surgery , Incidence , Cholangitis, Sclerosing/complications , Cholangitis, Sclerosing/epidemiology , Colectomy/adverse effects , AzathioprineABSTRACT
BACKGROUND: Owing to the rising number of screening endoscopies and instrumental advances in endoscopic ultrasound (EUS), colorectal subepithelial tumors (SETs) are being increasingly detected. We aimed to determine the feasibility of endoscopic resection (ER) and the impact of EUS-based surveillance on colorectal SETs. METHODS: The medical records of 984 patients with incidentally detected colorectal SETs between 2010 and 2019 were retrospectively reviewed. Overall, 577 colorectal SETs underwent ER, and 71 colorectal SETs underwent serial colonoscopy for > 12 months. RESULTS: The mean tumor size (± standard deviation) of 577 colorectal SETs for which ER was performed was 7.0 ± 5.7 (median, 55; range, 1-50) mm; 475 tumors were located in the rectum and 102, in the colon. En bloc resection was achieved in 560/577 treated lesions (97.1%), and complete resection was achieved in 516/577 (89.4%). ER-related adverse events occurred in 15/577 (2.6%) patients. SETs originating from the muscularis propria showed a higher risk of ER-related adverse events and perforation than SETs arising from the mucosal or submucosal layer (odds ratio [OR] 19.786, 95% confidence interval [CI] 4.556-85.919; P = 0.002 and OR 141.250, 95% CI 11.596-1720.492; P = 0.046, respectively). Seventy-one patients were followed up after EUS without any treatment for > 12 months, during which three showed progression; eight, regression; and sixty, no changes. CONCLUSIONS: ER for colorectal SETs showed excellent efficacy and safety. Additionally, colorectal SETs without high-risk features in surveillance with colonoscopy showed an excellent prognosis.
Subject(s)
Colorectal Neoplasms , Endoscopic Mucosal Resection , Stomach Neoplasms , Humans , Stomach Neoplasms/surgery , Retrospective Studies , Feasibility Studies , Treatment Outcome , Colorectal Neoplasms/diagnostic imaging , Colorectal Neoplasms/surgeryABSTRACT
BACKGROUND: The Omicron variant has become the most prevalent SARS-CoV-2 variant. Omicron is known to induce milder lesions compared to the original Wuhan strain. Fatal infection of the Wuhan strain into the brain has been well documented in COVID-19 mouse models and human COVID-19 cases, but apparent infections into the brain by Omicron have not been reported in human adult cases or animal models. In this study, we investigated whether Omicron could spread to the brain using K18-hACE2 mice susceptible to SARS-CoV-2 infection. RESULTS: K18-hACE2 mice were intranasally infected with 1 × 105 PFU of the original Wuhan strain and the Omicron variant of SARS-CoV-2. A follow-up was conducted 7 days post infection. All Wuhan-infected mice showed > 20% body weight loss, defined as the lethal condition, whereas two out of five Omicron-infected mice (40%) lost > 20% body weight. Histopathological analysis based on H&E staining revealed inflammatory responses in the brains of these two Omicron-infected mice. Immunostaining analysis of viral nucleocapsid protein revealed severe infection of neuron cells in the brains of these two Omicron-infected mice. Lymphoid depletion and apoptosis were observed in the spleen of Omicron-infected mice with brain infection. CONCLUSION: Lethal conditions, such as severe body weight loss and encephalopathy, can occur in Omicron-infected K18-hACE2 mice. Our study reports, for the first time, that Omicron can induce brain infection with lymphoid depletion in the mouse COVID-19 model.
ABSTRACT
H9N2 avian influenza A viruses (AIVs) cause economic losses in the poultry industry and provide internal genomic segments for the evolution of H5N1 and H7N9 AIVs into more detrimental strains for poultry and humans. In addition to the endemic Y439/Korea-lineage H9N2 viruses, the Y280-lineage spread to Korea since 2020. Conventional recombinant H9N2 vaccine strains, which bear mammalian pathogenic internal genomes of the PR8 strain, are pathogenic in BALB/c mice. To reduce the mammalian pathogenicity of the vaccine strains, the PR8 PB2 was replaced with the non-pathogenic and highly productive PB2 of the H9N2 vaccine strain 01310CE20. However, the 01310CE20 PB2 did not coordinate well with the hemagglutinin (HA) and neuraminidase (NA) of the Korean Y280-lineage strain, resulting in a 10-fold lower virus titer compared to the PR8 PB2. To increase the virus titer, the 01310CE20 PB2 was mutated (I66M-I109V-I133V) to enhance the polymerase trimer integrity with PB1 and PA, which restored the decreased virus titer without causing mouse pathogenicity. The reverse mutation (L226Q) of HA, which was believed to decrease mammalian pathogenicity by reducing mammalian receptor affinity, was verified to increase mouse pathogenicity and change antigenicity. The monovalent Y280-lineage oil emulsion vaccine produced high antibody titers for homologous antigens but undetectable titers for heterologous (Y439/Korea-lineage) antigens. However, this defect was corrected by the bivalent vaccine. Therefore, the balance of polymerase and HA/NA activities can be achieved by fine-tuning PB2 activity, and a bivalent vaccine may be more effective in controlling concurrent H9N2 viruses with different antigenicities.
Subject(s)
Influenza A Virus, H5N1 Subtype , Influenza A Virus, H7N9 Subtype , Influenza A Virus, H9N2 Subtype , Influenza in Birds , Humans , Animals , Mice , Influenza A Virus, H9N2 Subtype/genetics , Influenza A Virus, H5N1 Subtype/genetics , Vaccines, Synthetic , Vaccines, Combined , Chickens , MammalsABSTRACT
Since the development of the fiberoptic colonoscope in the late 1960s, colonoscopy has been a useful tool to diagnose and treat various intestinal diseases. This article reviews the clinical use of colonoscopy for various intestinal diseases based on present and future perspectives. Intestinal diseases include infectious diseases, inflammatory bowel disease (IBD), neoplasms, functional bowel disorders, and others. In cases of infectious diseases, colonoscopy is helpful in making the differential diagnosis, revealing endoscopic gross findings, and obtaining the specimens for pathology. Additionally, colonoscopy provides clues for distinguishing between infectious disease and IBD, and aids in the post-treatment monitoring of IBD. Colonoscopy is essential for the diagnosis of neoplasms that are diagnosed through only pathological confirmation. At present, malignant tumors are commonly being treated using endoscopy because of the advancement of endoscopic resection procedures. Moreover, the characteristics of tumors can be described in more detail by image-enhanced endoscopy and magnifying endoscopy. Colonoscopy can be helpful for the endoscopic decompression of colonic volvulus in large bowel obstruction, balloon dilatation as a treatment for benign stricture, and colon stenting as a treatment for malignant obstruction. In the diagnosis of functional bowel disorder, colonoscopy is used to investigate other organic causes of the symptom.
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BACKGROUND/AIMS: The optimal treatment for acute malignant obstruction of the proximal colon (MOPC, proximal to the splenic flexure) remains challenging. Emergency resection, the traditional modality for MOPC, has shown significantly high mortality and morbidity rates, according to recent studies. This study aimed to investigate the clinical outcomes of stent vs stoma as a bridge to curative surgery for MOPC. METHODS: This retrospective cohort study included 72 patients who underwent endoscopic placement of a self-expanding metallic stent (SEMS) or loop ileostomy for MOPC at six referral centers between January 2011 and July 2021. Clinical and pathological characteristics, procedure-related complications, and long-term mortality rates after curative surgery were analyzed. RESULTS: During a mean follow-up period of 32 months, 30 patients (41.7%) underwent ileostomy preferentially for more proximal cancer, complete obstruction, and advanced tumor stage compared to the SEMS group. No difference was found in procedure-related complications, but five deaths were observed after ileostomy. Survival analysis for 5-year mortality after curative surgery showed no significant difference between the bridge modalities (log-rank p = 0.253). CONCLUSION: In this study, SEMS as a bridge to surgery showed relatively safe results in terms of post-procedural mortality. However, these results should be considered when performing ileostomy in patients with more advanced malignant obstruction.