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1.
Ann Med ; 56(1): 2398725, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-39221763

RESUMO

OBJECTIVES: Although systemic chemotherapy for pancreatic ductal adenocarcinoma (PDAC) has made progress, ensuring long-term survival remains difficult. There are several reports on the usefulness of neutrophil-to-lymphocyte ratio (NLR) in predicting the prognosis of PDAC, but few reports in systemic chemotherapy. We hereby investigated the usefulness of NLR in systemic chemotherapy for PDAC. MATERIALS AND METHODS: A retrospective study was conducted on patients with advanced PDAC treated with first-line systemic chemotherapy. Cox regression hazards models were performed to analyze the association between baseline patient characteristics and the initial treatment response, and overall survival (OS). RESULTS: A total of 60 patients with PDAC were enrolled. At baseline, there were significant differences in NLR and carbohydrate antigen 19-9 (CA19-9), as well as the selection rate of combination chemotherapy, between patients with partial response or stable disease and those with progressive disease. Univariate and multivariate analysis showed that NLR < 3.10, combination chemotherapy, and CA19-9 < 1011 U/mL were significant and independent predictive factors of the initial treatment response. Meanwhile, NLR < 3.10 and combination chemotherapy were independently associated with longer OS. Moreover, OS was significantly prolonged in patients with NLR < 3.10, regardless of whether combination chemotherapy or monotherapy. Patients with NLR < 3.10 at baseline had a significantly higher conversion rate to third-line chemotherapy and a longer duration of total chemotherapy. CONCLUSIONS: This study suggests that NLR may be a useful marker for predicting the initial treatment response to first-line chemotherapy and the prognosis for patients with advanced PDAC.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma Ductal Pancreático , Linfócitos , Neutrófilos , Neoplasias Pancreáticas , Humanos , Feminino , Masculino , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/sangue , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/patologia , Estudos Retrospectivos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/patologia , Pessoa de Meia-Idade , Idoso , Prognóstico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Adulto , Antígeno CA-19-9/sangue , Contagem de Linfócitos , Fluoruracila/uso terapêutico , Fluoruracila/administração & dosagem , Modelos de Riscos Proporcionais , Idoso de 80 Anos ou mais , Gencitabina , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Desoxicitidina/administração & dosagem , Resultado do Tratamento
2.
Surgery ; 176(4): 1314-1315, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39038999
3.
Ther Innov Regul Sci ; 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956005

RESUMO

BACKGROUND: Clinical trials have become larger and more complex. Thus, eSource should be used to enhance efficiency. This study aimed to evaluate the impact of the multisite implementation of eSource direct data capture (DDC), which we define as eCRFs for direct data entry in this study, on efficiency by analyzing data from a single investigator-initiated clinical trial in oncology. METHODS: Operational data associated with the targeted study conducted in Japan was used to analyze time from data occurrence to data entry and data finalization, and number of visits to the site and time spent at the site by clinical research associates (CRAs). Additionally, simulations were performed on the change in hours at the clinical sites during the implementation of eSource DDC. RESULTS: No difference in time from data occurrence to data entry was observed between the DDC and the transcribed data fields. However, the DDC fields could be finalized 4 days earlier than the non-DDC fields. Additionally, although no difference was observed in the number of visits for source data verification (SDV) by CRAs, a comparison among sites that introduced eSource DDC and those that did not showed that the time spent at the site for SDV was reduced. Furthermore, the simulation results indicated that even a small amount of data to be collected or a small percentage of DDC-capable items may lead to greater efficiency when the number of subjects per site is significant. CONCLUSIONS: The implementation of eSource DDC may enhance efficiency depending on the study framework and type and number of items to be collected.

4.
Surgery ; 176(2): 371-378, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38825398

RESUMO

BACKGROUND: The irrigation efficacy of a povidone-iodine solution to prevent surgical site infection is still controversial. We assessed the irrigation effect with a povidone-iodine solution on the incidence of surgical site infection after gastroenterological surgery. METHODS: This study is a single-center, prospective, randomized, blinded-end point superiority trial for surgical wound irrigation. Patients undergoing gastroenterological surgery were randomly assigned in a 1:1 replacement ratio using computer-generated randomization. Patients were grouped according to their surgical wound treatment into the control group using the normal sterile saline and the povidone-iodine group using 10% povidone-iodine solution after the NS solution. The main finding was 30-day surgical site infections assessed in the full analysis set. RESULTS: From November 2020 to December 2022, 697 of 894 patients were eligible for the study, among which 347 were in the povidone-iodine group and 350 in the control group. Thirty-day surgical site infections occurred in 100 (14%) patients-54 (16%) in the povidone-iodine group and 46 (13%) in the control group (odds ratio, 1.229; 95% CI, 0.800-1.889; P = .406). Superficial incisional surgical site infections occurred in 30 (9%) and 15 (4%) patients, respectively (odds ratio, 2.154; 95% CI, 1.134-4.090; P = .026). Only 3 patients (1%) in the control group developed adverse skin reactions. CONCLUSION: This study examined the irrigation efficacy of povidone-iodine for surgical site infection prevention compared to control in gastroenterological surgery. Povidone-iodine wound irrigation has shown no additional beneficial effect on the occurrence of surgical site infections.


Assuntos
Anti-Infecciosos Locais , Procedimentos Cirúrgicos do Sistema Digestório , Povidona-Iodo , Infecção da Ferida Cirúrgica , Irrigação Terapêutica , Humanos , Povidona-Iodo/administração & dosagem , Povidona-Iodo/uso terapêutico , Infecção da Ferida Cirúrgica/prevenção & controle , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/etiologia , Masculino , Feminino , Irrigação Terapêutica/métodos , Pessoa de Meia-Idade , Anti-Infecciosos Locais/administração & dosagem , Estudos Prospectivos , Idoso , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Adulto , Incidência , Resultado do Tratamento
5.
Methods Mol Biol ; 2808: 35-56, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38743361

RESUMO

Mononegaviruses are promising tools as oncolytic and transgene vectors for gene therapy and regenerative medicine. However, when mononegaviruses are used for therapeutic applications, the viral activity must be strictly controlled due to concerns about toxicity and severe side effects. With this technology, mononegavirus vectors can be grown where they are intended and can be easily removed when they are no longer needed. In particular, a photoswitch protein called Magnet (consisting of two magnet domains) is incorporated into the hinge region between the connector and methyltransferase domains of the mononegavirus polymerase protein (L protein) to disrupt the L protein functions. Blue light (470 ± 20 nm) irradiation causes the dimerization of the two magnet domains, and the L protein is restored to activity, allowing viral gene expression and virus replication. Since the magnet domains' dimerization is reversible, viral gene expression and replication cease when blue light irradiation is stopped.


Assuntos
Regulação Viral da Expressão Gênica , Replicação Viral , Replicação Viral/genética , Humanos , Proteínas Virais/genética , Proteínas Virais/metabolismo , Luz , Animais , Vetores Genéticos/genética
6.
Sci Rep ; 14(1): 11823, 2024 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-38783052

RESUMO

Our previous findings indicated that many respiratory syncytial virus (RSV) isolates are unstable at 4 °C compared to 20 °C. Some of the strains completely lose infectivity after 24 h at 4 °C. This study analyzed the inactivation process at 4 °C using a representative strain, RSV/Sendai/851/13. After 24 h of storage at 4 °C, the virus was completely inactivated but retained its ability to attach to and to be taken into host cells. It suggested a reduced fusion ability between the viral and cellular membranes. During storage at 4 °C, the RSV fusion (F) protein underwent a conformational change and was no longer recognized by pre-fusion form-specific antibodies. When the RSV/Sendai/851/13 strain was passaged at 4 °C, a variant with an amino acid substitution, I148T, in the F protein fusion peptide was selected. Also, an amino acid change in G protein demonstrating stability at low temperatures was obtained. These results show that the inactivation of RSV at 4 °C is due to the loss of membrane fusion activity in the F protein, which cannot maintain its pre-fusion state at 4 °C.


Assuntos
Temperatura Baixa , Vírus Sincicial Respiratório Humano , Proteínas Virais de Fusão , Inativação de Vírus , Proteínas Virais de Fusão/metabolismo , Proteínas Virais de Fusão/genética , Proteínas Virais de Fusão/química , Humanos , Vírus Sincicial Respiratório Humano/fisiologia , Animais , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sinciciais Respiratórios
7.
Surg Case Rep ; 10(1): 41, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38358535

RESUMO

BACKGROUND: Median arcuate ligament compression syndrome (MALS) causes upper abdominal pain and at times hemodynamic abnormalities in the pancreaticoduodenal region. Herein, we present a case of a 70 year-old man, initially diagnosed with splenic infarction and was successfully treated laparoscopically. CASE PRESENTATION: A 70-year-old man with abdominal pain admitted to our hospital. Abdominal-enhanced computed tomography revealed a poorly contrasted area in the spleen and stenosis at the root of the celiac artery. Arterial dilatation was observed around the pancreaticoduodenal arcade, however, no obvious aneurysm formation or arterial dissection was observed. Abdominal-enhanced magnetic resonance imaging indicated the disappearance of the flow void at the root of the celiac artery. The patient had no history of atrial fibrillation and was diagnosed with splenic infarction due to median arcuate ligament compression syndrome. We performed a laparoscopic median arcuate ligament section with five ports. Intraoperative ultrasonography showed a retrograde blood flow in the common hepatic artery and the celiac artery. After releasing the compression, the antegrade blood flow from the celiac artery to the splenic artery, and the common hepatic artery were visualized using intraoperative ultrasonography. The postoperative course of the patient was uneventful, and he was discharged on postoperative day 9. Postoperative computed tomography a month after surgery revealed no residual stenosis of the celiac artery or dilation of the pancreaticoduodenal arcade. Furthermore, the poorly contrasted area of the spleen improved. CONCLUSIONS: Reports indicate that hemodynamic changes in the abdominal visceral arteries due to median arcuate ligament compression are related to the formation of pancreaticoduodenal aneurysms. In this case, median arcuate ligament compression syndrome caused splenic infarction by reducing blood flow to the splenic artery.

8.
Am J Cancer Res ; 13(11): 5641-5655, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38058842

RESUMO

Tenascin C (TNC) is an extracellular matrix glycoprotein that is highly expressed in cancer stroma and is associated with tumor progression in pancreatic adenocarcinoma (PAAD). In this study, we aimed to investigate the potential involvement of TNC in the response to immune checkpoint inhibitors (ICI) among PAAD patients. Transcriptomic profiles were obtained from public databases and analyzed to compare TNC mRNA levels between tumor and normal tissues. Bioinformatic programs were used to predict paracrine communications between cancer cells and cancer-associated fibroblasts (CAFs), and the Tumor Immune Dysfunction and Exclusion (TIDE) score was calculated to predict response to ICI treatment in PAAD patients. An independent immunotherapeutic cohort was used to validate the clinical impact of the signatures. Results showed that TNC mRNA levels were significantly upregulated in tumors compared to normal tissues in PAAD, and patients with high TNC expression had significantly shorter overall survival than those with low TNC expression (P = 0.0125). TNC was predominantly expressed in CAFs of PAAD patients and was found to potentially enhance the epithelial-mesenchymal transition (EMT) of cancer cells via integrin receptors, contributing to resistance to ICI treatment. Patients with high TNC expression and high ITGαV or ITGB3 expression were associated with poor response to ICI therapy. In conclusion, these findings suggest that TNC-high CAFs play a crucial role in tumor progression and resistance to ICI therapy in PAAD patients, and targeting TNC and its interactions with cancer cells may provide a potential strategy for improving the efficacy of ICI therapy in PAAD.

9.
BMC Surg ; 23(1): 344, 2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-37964345

RESUMO

BACKGROUND: Pseudoaneurysm (PA) rupture after pancreaticoduodenectomy (PD) is a life-threatening complication. Most PA cases originate from postoperative pancreatic fistulas (POPFs). Although several risk factors for POPF have been identified, specific risk factors for PA formation remain unclear. Therefore, we retrospectively analyzed PD cases with soft pancreas and proposed a novel strategy for early detection of PA formation. METHODS: Overall, 120 patients underwent PD between 2010 and 2020 at our institution; of these, 65 patients with soft pancreas were enrolled. We evaluated the clinicopathological factors influencing PA formation and developed a risk score to predict PA formation. RESULTS: In total, 11 of the 65 patients developed PAs (PA formation group: PAG), and 8 of these 11 PAs ruptured. The median time to PA formation was 15 days, with a minimum of 5 days. The PAG was significantly older than the non-PA formation group, were predominantly men, and had comorbid diabetes mellitus. Pre- and intra-operative findings were similar between the two groups. Importantly, no significant differences were found in postoperative drain amylase levels and total drain amylase content. Cholinesterase and C-reactive protein (CRP) levels on postoperative day (POD) 3 were significantly different between the two groups. Multivariate analysis showed that cholinesterase ≤ 112 U/L and CRP ≥ 16.0 mg/dl on POD 3 were independent predictors of PA formation. CONCLUSIONS: Decreased cholinesterase and elevated CRP on POD 3 (Cho-C score) are useful predictors of PA formation in cases with soft pancreas. In such cases, periodic computed tomography evaluations and strict drain management are necessary to prevent life-threatening hemorrhage.


Assuntos
Falso Aneurisma , Pancreaticoduodenectomia , Masculino , Humanos , Feminino , Pancreaticoduodenectomia/efeitos adversos , Proteína C-Reativa/metabolismo , Estudos Retrospectivos , Colinesterases , Falso Aneurisma/diagnóstico , Falso Aneurisma/etiologia , Pâncreas/patologia , Fístula Pancreática/diagnóstico , Fístula Pancreática/etiologia , Fístula Pancreática/prevenção & controle , Fatores de Risco , Drenagem/efeitos adversos , Amilases/metabolismo , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia
10.
BMC Surg ; 23(1): 343, 2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-37957615

RESUMO

BACKGROUND: The usefulness of static monitoring using central venous pressure has been reported for anesthetic management in hepatectomy. It is unclear whether intra-hepatectomy dynamic monitoring can predict the postoperative course. We aimed to investigate the association between intraoperative dynamic monitoring and post-hepatectomy complications. Furthermore, we propose a novel anesthetic management strategy to reduce postoperative complication. METHODS: From 2018 to 2021, 93 patients underwent hepatectomy at our hospital. Fifty-three patients who underwent dynamic monitoring during hepatectomy were enrolled. Flo Trac system was used for dynamic monitoring. The baseline central venous oxygen saturation (ScvO2) was defined as the average ScvO2 for 30 min after anesthesia induction. ScvO2 fluctuation (ΔScvO2) was defined as the difference between the baseline and minimum ScvO2. Postoperative complications were evaluated using the comprehensive complication index (CCI). RESULTS: Patients with ΔScvO2 ≥ 10% had significantly higher CCI scores (0 vs. 20.9: p = 0.043). In univariate analysis, patients with higher CCI scores demonstrated significantly higher preoperative C-reactive protein-to-lymphocyte ratio (7.51 vs. 24.49: p = 0.039), intraoperative bleeding (105 vs. 581 ml: p = 0.008), number of patients with major hepatectomy (4/45 vs. 3/8: p = 0.028), and number of patients with ΔScvO2 ≥ 10% (11/45 vs. 6/8; p = 0.010). Multivariate logistic regression analysis revealed that ΔScvO2 ≥ 10% (odds ratio: 9.53, p = 0.016) was the only independent predictor of elevated CCI. CONCLUSIONS: Central venous oxygen saturation fluctuation during hepatectomy is a predictor of postoperative complications. Anesthetic management based on intraoperative dynamic monitoring and minimizing the change in ScvO2 is a potential strategy for decreasing the risk of post-hepatectomy complications.


Assuntos
Anestésicos , Hepatectomia , Humanos , Hepatectomia/efeitos adversos , Saturação de Oxigênio , Oxigênio , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle
11.
Virus Res ; 333: 199142, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37270034

RESUMO

Few evolutionary studies of the human respiratory virus (HRV) have been conducted, but most of them have focused on HRV3. In this study, the full-length fusion (F) genes in HRV1 strains collected from various countries were subjected to time-scaled phylogenetic, genome population size, and selective pressure analyses. Antigenicity analysis was performed on the F protein. The time-scaled phylogenetic tree using the Bayesian Markov Chain Monte Carlo method estimated that the common ancestor of the HRV1 F gene diverged in 1957 and eventually formed three lineages. Phylodynamic analyses showed that the genome population size of the F gene has doubled over approximately 80 years. Phylogenetic distances between the strains were short (< 0.02). No positive selection sites were detected for the F protein, whereas many negative selection sites were identified. Almost all conformational epitopes of the F protein, except one in each monomer, did not correspond to the neutralising antibody (NT-Ab) binding sites. These results suggest that the HRV1 F gene has constantly evolved over many years, infecting humans, while the gene may be relatively conserved. Mismatches between computationally predicted epitopes and NT-Ab binding sites may be partially responsible for HRV1 reinfection and other viruses such as HRV3 and respiratory syncytial virus.


Assuntos
Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Humanos , Filogenia , Teorema de Bayes , Vírus Sincicial Respiratório Humano/genética , Epitopos , Respirovirus , Infecções por Vírus Respiratório Sincicial/epidemiologia , Proteínas Virais de Fusão/genética
12.
Cancer Med ; 12(12): 13007-13018, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37096775

RESUMO

BACKGROUND: Owing to the lack of definite diagnostic modalities, it is challenging to distinguish malignant cases of cholangiocarcinoma (CCA), which often causes biliary tract obstruction, from benign ones. Here, we investigated a novel lipid biomarker of CCA in bile-derived small extracellular vesicles (sEVs) and developed a simple detection method for clinical application. METHODS: Bile samples from seven patients with malignant diseases (hilar CCA = 4, distal CCA = 3) and eight patients with benign diseases (gallstones = 6, primary sclerosing cholangitis = 1, autoimmune pancreatitis = 1) were collected through a nasal biliary drainage tube. sEVs were isolated via serial ultracentrifugation and characterized using nanoparticle tracking analysis, transmission electron microscopy, and immunoblotting (with CD9, CD63, CD81, and TSG101). Comprehensive lipidomic analysis was performed using liquid chromatography-tandem mass spectrometry. Using a measurement kit, we further confirmed whether lipid concentrations could be used as a potential CCA marker. RESULTS: Lipidomic analysis of bile sEVs in the two groups identified 209 significantly increased lipid species in the malignant group. When focusing on lipid class, phosphatidylcholine (PC) level was 4.98-fold higher in the malignant group than in the benign group (P = 0.037). The receiver operating characteristic (ROC) curve showed a sensitivity of 71.4%, a specificity of 100%, and an area under the curve (AUC) of 0.857 (95% confidence interval [CI]:0.643-1.000). Using a PC assay kit, the ROC curve showed a cutoff value of 16.1 µg/mL, a sensitivity of 71.4%, a specificity of 100%, and an AUC of 0.839 (95% CI: 0.620-1.000). CONCLUSION: PC level in sEVs from human bile is a potential diagnostic marker for CCA and can be assessed by a commercially available assay kit.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , Vesículas Extracelulares , Humanos , Bile/química , Fosfatidilcolinas/análise , Colangiocarcinoma/diagnóstico , Biomarcadores/análise , Neoplasias dos Ductos Biliares/diagnóstico , Ductos Biliares Intra-Hepáticos , Vesículas Extracelulares/química , Biomarcadores Tumorais/análise
13.
PLoS Pathog ; 18(12): e1010949, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36480520

RESUMO

Mumps virus (MuV) is the etiological agent of mumps, a disease characterized by painful swelling of the parotid glands and often accompanied by severe complications. To understand the molecular mechanism of MuV infection, a functional analysis of the involved host factors is required. However, little is known about the host factors involved in MuV infection, especially those involved in the late stage of infection. Here, we identified 638 host proteins that have close proximity to MuV glycoproteins, which are a major component of the viral particles, by proximity labeling and examined comprehensive protein-protein interaction networks of the host proteins. From siRNA screening and immunoprecipitation results, we found that a SNARE subfamily protein, USE1, bound specifically to the MuV fusion (F) protein and was important for MuV propagation. In addition, USE1 plays a role in complete N-linked glycosylation and expression of the MuV F protein.


Assuntos
Proteínas SNARE , Proteínas Virais de Fusão , Proteínas Virais de Fusão/genética
14.
mBio ; 13(6): e0169822, 2022 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-36346228

RESUMO

The lipid composition of the host cell membrane is one of the key determinants of the entry of enveloped viruses into cells. To elucidate the detailed mechanisms behind the cell entry of rubella virus (RuV), one of the enveloped viruses, we searched for host factors involved in such entry by using CRISPR/Cas9 genome-wide knockout screening, and we found sphingomyelin synthase 1 (SMS1), encoded by the SGMS1 gene, as a candidate. RuV growth was strictly suppressed in SGMS1-knockout cells and was completely recovered by the overexpression of enzymatically active SMS1 and partially recovered by that of SMS2, another member of the SMS family, but not by that of enzymatically inactive SMS1. An entry assay using pseudotyped vesicular stomatitis virus possessing RuV envelope proteins revealed that sphingomyelin generated by SMSs is crucial for at least RuV entry. In SGMS1-knockout cells, lipid mixing between the RuV envelope membrane and the membrane of host cells occurred, but entry of the RuV genome from the viral particles into the cytoplasm was strongly inhibited. This indicates that sphingomyelin produced by SMSs is essential for the formation of membrane pores after hemifusion occurs during RuV entry. IMPORTANCE Infection with rubella virus during pregnancy causes congenital rubella syndrome in infants. Despite its importance in public health, the detailed mechanisms of rubella virus cell entry have only recently become somewhat clearer. The E1 protein of rubella virus is classified as a class II fusion protein based on its structural similarity, but it has the unique feature that its activity is dependent on calcium ion binding in the fusion loops. In this study, we found another unique feature, as cellular sphingomyelin plays a critical role in the penetration of the nucleocapsid into the cytoplasm after hemifusion by rubella virus. This provides important insight into the entry mechanism of rubella virus. This study also presents a model of hemifusion arrest during cell entry by an intact virus, providing a useful tool for analyzing membrane fusion, a biologically important phenomenon.


Assuntos
Vírus da Rubéola , Rubéola (Sarampo Alemão) , Gravidez , Feminino , Humanos , Vírus da Rubéola/metabolismo , Esfingomielinas , Internalização do Vírus , Membrana Celular/metabolismo , Proteínas do Envelope Viral/genética , Citoplasma/metabolismo , Vírion/metabolismo , Nucleocapsídeo/metabolismo
15.
Viruses ; 14(11)2022 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-36366480

RESUMO

Molecular interactions between respiratory syncytial virus (RSV) fusion protein (F protein) and the cellular receptor Toll-like receptor 4 (TLR4) and myeloid differentiation factor-2 (MD-2) protein complex are unknown. Thus, to reveal the detailed molecular interactions between them, in silico analyses were performed using various bioinformatics techniques. The present simulation data showed that the neutralizing antibody (NT-Ab) binding sites in both prefusion and postfusion proteins at sites II and IV were involved in the interactions between them and the TLR4 molecule. Moreover, the binding affinity between postfusion proteins and the TLR4/MD-2 complex was higher than that between prefusion proteins and the TLR4/MD-2 complex. This increased binding affinity due to conformational changes in the F protein may be able to form syncytium in RSV-infected cells. These results may contribute to better understand the infectivity and pathogenicity (syncytium formation) of RSV.


Assuntos
Infecções por Vírus Respiratório Sincicial , Vírus Sincicial Respiratório Humano , Humanos , Anticorpos Neutralizantes , Anticorpos Antivirais , Sítios de Ligação de Anticorpos , Receptor 4 Toll-Like/metabolismo , Proteínas Virais de Fusão , Subfamília B de Transportador de Cassetes de Ligação de ATP , Ligação Proteica
16.
Clin J Gastroenterol ; 15(6): 1198-1203, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36208389

RESUMO

Bleeding is a fatal complication after pancreatectomy. Although coil embolization is a widely accepted treatment option, ischemia of the remaining organs should be prevented. This study reports the successful treatment of intra-abdominal hemorrhage following distal pancreatectomy with en bloc celiac axis resection (DP-CAR) using balloon-assisted coil embolization (BACE). A 59-year-old man was diagnosed with locally advanced pancreatic cancer. The tumor involves the common hepatic artery, splenic artery, and celiac artery. After four cycles of treatment with gemcitabine/nab-paclitaxel, the soft-density masses, surrounding the artery, shrunk. DP-CAR and R0 resections were performed. A minor postoperative pancreatic fistula occurred. Six months postoperatively, the computed tomography showed delayed asymptomatic bleeding from an anterior superior pancreaticoduodenal artery (ASPDA) pseudoaneurysm located near the gastroduodenal artery confluence. BACE was performed by placing a microballoon catheter in the region of confluence of the ASPDA and posterior superior pancreaticoduodenal artery (PSPDA) to prevent coil migration. After inserting the microballoon catheter, coil embolization was performed in the ASPDA. Hepatic blood flow was maintained from the PSPDA. BACE is a useful technique to preserve blood flow to the remnant organs when performing coil embolization for bleeding following a distal pancreatectomy, especially following a DP-CAR.


Assuntos
Falso Aneurisma , Neoplasias Pancreáticas , Masculino , Humanos , Pessoa de Meia-Idade , Pancreatectomia/efeitos adversos , Pancreatectomia/métodos , Artéria Celíaca/diagnóstico por imagem , Artéria Celíaca/cirurgia , Artéria Celíaca/patologia , Falso Aneurisma/diagnóstico por imagem , Falso Aneurisma/etiologia , Falso Aneurisma/cirurgia , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Artéria Hepática/cirurgia , Artéria Hepática/patologia , Complicações Pós-Operatórias/cirurgia
17.
Anticancer Res ; 42(7): 3313-3324, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35790250

RESUMO

BACKGROUND/AIM: Resistance to chemotherapy is a major obstacle for patients with unresectable colorectal cancer (CRC); however, the factors that induce chemoresistance have not been elucidated. Lipid composition influences neoplastic behaviour. Therefore, this study examined whether lipid composition affects sensitivity to chemotherapeutic agents in CRC. MATERIALS AND METHODS: We performed a lipidomic analysis of a CRC xenograft-derived spheroid model to identify potential relationships between the lipid profile and chemoresistance to 5-fluorouracil (5-FU). Genetic and pharmacological modulation of lipid synthesis were also used in the HCT-116 and DLD-1 CRC cell lines to further characterize resistance to 5-FU. RESULTS: Our lipidomic profiling revealed that phospholipids with saturated fatty acids (SFAs) were more abundant in 5-FU-resistant spheroids. The importance of phospholipids containing SFA in chemoresistance was confirmed by showing that in HCT-116 and DLD-1 cells, genetic or pharmacological inactivation of stearoyl-CoA desaturase-1, a key enzyme that converts SFAs to monounsaturated fatty acids, increased the proportion of SFAs in membranous phospholipids and reduced cell membrane fluidity, and this ultimately resulted in resistance to 5-FU. CONCLUSION: These data suggest that the saturated to monounsaturated fatty acid ratio in cellular membranous phospholipids affects sensitivity to chemotherapeutic agents.


Assuntos
Neoplasias Colorretais , Fluoruracila , Neoplasias Colorretais/genética , Ácidos Graxos , Ácidos Graxos Monoinsaturados , Fluoruracila/farmacologia , Fluoruracila/uso terapêutico , Humanos , Lipídeos de Membrana/uso terapêutico
18.
Surg Case Rep ; 8(1): 126, 2022 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-35764761

RESUMO

BACKGROUND: Staphylococcus hominis (S. hominis) is an opportunistic pathogen that is often highly resistant to antibiotics and is difficult to treat. In patients diagnosed with an adrenocorticotropic hormone (ACTH)-producing tumor that compromises the immune system due to hypercortisolemia, cancer treatment and infection control should be considered simultaneously. This report presents a case of refractory postoperative S. hominis bacteremia requiring the prolonged administration of several antibiotics in a patient with an ACTH-producing pancreatic neuroendocrine neoplasm (pNEN). CASE PRESENTATION: A 35-year-old man visited a neighboring hospital for a thorough examination after experiencing weight gain and lower limb weakness for several months. Enhanced computed tomography revealed a pancreatic tail tumor and bilateral adrenal enlargement. Elevated plasma ACTH and serum cortisol were noted. Biopsy under endoscopic ultrasonography revealed the tumor as an ACTH-producing pNEN. The patient was transferred to our hospital for further treatment. Pneumocystis pneumonia was noted and treated with sulfamethoxazole and adjunctive glucocorticoids. Hypercortisolism was controlled with metyrapone and trilostane. Somatostatin receptor scintigraphy and ethoxybenzyl magnetic resonance imaging detected other lesions in the pancreatic head. A total pancreatectomy was performed given that the lesions were found in both the pancreatic head and tail. Plasma ACTH and serum cortisol levels decreased immediately after the resection. Pathological examination revealed that the pancreatic tail tumor was NEN G2 and T3N1aM0 Stage IIB and the pancreatic head lesions were SSTR-positive hyperplasia of the islet of Langerhans cells. On postoperative day 11, catheter-associated bacteremia occurred. Initially, meropenem hydrate and vancomycin hydrochloride were administered empirically. S. hominis was identified and appeared sensitive to these antibiotics according to susceptibility testing. However, S. hominis was repeatedly positive in blood cultures for more than one month, despite treatment with several antibiotics. Eventually, with the combined use of three antibiotics (meropenem hydrate, vancomycin hydrochloride, and clindamycin phosphate) for more than 3 weeks, the S. hominis-associated bacteremia improved. He was discharged 79 days after surgery. CONCLUSIONS: Our patient with an ACTH-producing pNEN was immunocompromised and needed meticulous attention for infectious complications even after successful tumor removal. Specifically, S. hominis bacteremia in such patients demands intensive treatments, such as with combinational antibiotics.

19.
Influenza Other Respir Viruses ; 16(5): 837-841, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35488324

RESUMO

The impact of strengthening preventive measures against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on the prevalence of respiratory viruses in children was examined. After the SARS-CoV-2 pandemic, the rate of multiple virus detection among hospitalized children decreased. Immediately after the SARS-CoV-2 pandemic, respiratory syncytial and parainfluenza viruses were rarely detected and subsequently reemerged. Human metapneumovirus and influenza virus were not consistently detected. Non-enveloped viruses (bocavirus, rhinovirus, and adenovirus) were detected to some extent even after the pandemic. Epidemic-suppressed infectious diseases may reemerge as susceptibility accumulates in the population and should continue to be monitored.


Assuntos
COVID-19 , Infecções Respiratórias , COVID-19/diagnóstico , COVID-19/epidemiologia , Criança , Criança Hospitalizada , Humanos , Lactente , Pandemias/prevenção & controle , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/epidemiologia , Rhinovirus , SARS-CoV-2
20.
BMC Gastroenterol ; 22(1): 154, 2022 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-35351001

RESUMO

BACKGROUND: Various hemostatic devices have been utilized to reduce blood loss during hepatectomy. Nonetheless, a comparison between monopolar and bipolar coagulation, particularly their usefulness or inferiority, has been poorly documented. The aim of this study is to reveal the characteristics of these hemostatic devices. METHODS: A total of 264 patients who underwent open hepatectomy at our institution from January 2009 to December 2018 were included. Monopolar and bipolar hemostatic devices were used in 160 (monopolar group) and 104 (bipolar group) cases, respectively. Operative outcomes and thermal damage to the resected specimens were compared between these groups using propensity score matching according to background factors. Multivariate logistic regression analysis was performed to identify predictive factors for postoperative complications. RESULTS: After propensity score matching, 73 patients per group were enrolled. The monopolar group had significantly lower total operative time (239 vs. 275 min; P = 0.013) and intraoperative blood loss (487 vs. 790 mL; P < 0.001). However, the incidence rates of ascites (27.4% vs. 8.2%; P = 0.002) and grade ≥ 3 intra-abdominal infection (12.3% vs. 2.7%; P = 0.028) were significantly higher in the monopolar group. Thermal damage to the resected specimens was significantly longer in the monopolar group (4.6 vs. 1.2 mm; P < 0.001). Use of monopolar hemostatic device was an independent risk factor for ascites (odds ratio, 5.626, 95% confidence interval 1.881-16.827; P = 0.002) and severe intra-abdominal infection (odds ratio, 5.905, 95% confidence interval 1.096-31.825; P = 0.039). CONCLUSIONS: Although monopolar devices have an excellent hemostatic ability, they might damage the remnant liver. The use of monopolar devices can be one of the factors that increase the frequency of complications.


Assuntos
Perda Sanguínea Cirúrgica , Hepatectomia , Hepatectomia/efeitos adversos , Humanos , Duração da Cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Pontuação de Propensão
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