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1.
Sci Rep ; 14(1): 13983, 2024 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886410

RESUMO

The relationship between blood group and rebleeding in acute lower gastrointestinal bleeding (ALGIB) remains unclear. This study aimed to investigate the association between blood group O and clinical outcomes in patients with ALGIB. The study included 2336 patients with ALGIB whose bleeding source was identified during initial endoscopy (from the CODE BLUE-J Study). The assessed outcomes encompassed rebleeding and other clinical parameters. The rebleeding rates within 30 days in patients with blood group O and those without blood group O were 17.9% and 14.9%, respectively. Similarly, the rates within 1 year were 21.9% for patients with blood group O and 18.2% for those without blood group O. In a multivariate analysis using age, sex, vital signs at presentation, blood test findings, comorbidities, antithrombotic medication, active bleeding, and type of endoscopic treatment as covariates, patients with blood group O exhibited significantly higher risks for rebleeding within 30 days (odds ratio [OR] 1.31; 95% confidence interval [CI] 1.04-1.65; P = 0.024) and 1 year (OR 1.29; 95% CI 1.04-1.61; P = 0.020) compared to those without blood group O. However, the thrombosis and mortality rates did not differ significantly between blood group O and non-O patients. In patients with ALGIB, blood group O has been identified as an independent risk factor for both short- and long-term rebleeding.


Assuntos
Sistema ABO de Grupos Sanguíneos , Hemorragia Gastrointestinal , Recidiva , Humanos , Hemorragia Gastrointestinal/etiologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Fatores de Risco , Estudos de Coortes , Doença Aguda
2.
J Gastroenterol ; 2024 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-38811423

RESUMO

BACKGROUND: Symptom scales for achalasia after per-oral endoscopic myotomy (POEM) are lacking. This study aimed to propose a new scale based on the conventional Eckardt score (c-ES) and evaluate persistent symptoms that impair patients' quality of life (QOL) post-POEM. METHODS: Dysphagia, regurgitation, and chest pain frequencies were assessed using a 6-point scale modified-ES (m-ES) after POEM, with "occasional" symptoms on the c-ES further subdivided into three-period categories on m-ES. Symptom severity was further evaluated using a 5-point scale ranging from 1 to 5 points, with a score ≥ 3 points defined as persistent symptoms impairing QOL. We analyzed the correlation between the m-ES and severity score, diagnostic performance of the m-ES for persistent symptoms, and overlaps between each residual symptom. RESULTS: Overall, 536 patients (median follow-up period, 2.9 years) post-POEM were included in this multicenter study. Significant correlations were observed between the m-ES and severity scores for dysphagia (r = 0.67, p < 0.01), regurgitation (r = 0.73, p < 0.01), and chest pain (r = 0.85, p < 0.01). Twenty-six patients (4.9%) had persistent symptoms post-POEM, and 23 of them had m-ES-specific symptom frequency ≥ once a month, which was determined as the optimal frequency threshold for screening persistent symptoms. The total m-ES predicted persistent symptoms more accurately than the total c-ES (area under the curve: 0.95 vs. 0.79, p < 0.01). Furthermore, dysphagia and chest pain were the major residual symptoms post-POEM covering 91.4% of regurgitation. CONCLUSIONS: The new post-POEM scale successfully evaluated the QOL-based patient symptom severities. Our study implied the possibility of a simpler scale using residual dysphagia and chest pain.

3.
Sci Rep ; 14(1): 11246, 2024 05 16.
Artigo em Inglês | MEDLINE | ID: mdl-38755175

RESUMO

This study investigates the impact of the COVID-19 pandemic on pediatric out-of-hospital cardiac arrest (OHCA) outcomes in Japan, aiming to address a critical research gap. Analyzing data from the All-Japan Utstein registry covering pediatric OHCA cases from 2018 to 2021, the study observed no significant changes in one-month survival, neurological outcomes, or overall performance when comparing the pre-pandemic (2018-2019) and pandemic (2020-2021) periods among 6765 cases. However, a notable reduction in pre-hospital return of spontaneous circulation (ROSC) during the pandemic (15.1-13.1%, p = .020) was identified. Bystander-initiated chest compressions and rescue breaths declined (71.1-65.8%, 22.3-13.0%, respectively; both p < .001), while bystander-initiated automated external defibrillator (AED) use increased (3.7-4.9%, p = .029). Multivariate logistic regression analyses identified factors associated with reduced pre-hospital ROSC during the pandemic. Post-pandemic, there was no noticeable change in the one-month survival rate. The lack of significant change in survival may be attributed to the negative effects of reduced chest compressions and ventilation being offset by the positive impact of widespread AED availability in Japan. These findings underscore the importance of innovative tools and systems for safe bystander cardiopulmonary resuscitation during a pandemic, providing insights to optimize pediatric OHCA care.


Assuntos
COVID-19 , Reanimação Cardiopulmonar , Parada Cardíaca Extra-Hospitalar , Sistema de Registros , Humanos , Parada Cardíaca Extra-Hospitalar/epidemiologia , Parada Cardíaca Extra-Hospitalar/terapia , Parada Cardíaca Extra-Hospitalar/mortalidade , Japão/epidemiologia , COVID-19/epidemiologia , Feminino , Criança , Masculino , Reanimação Cardiopulmonar/métodos , Pré-Escolar , Lactente , Adolescente , Pandemias , Desfibriladores , SARS-CoV-2/isolamento & purificação , Serviços Médicos de Emergência , Recém-Nascido , Retorno da Circulação Espontânea , Taxa de Sobrevida
4.
J Gastrointest Surg ; 28(5): 672-678, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38704205

RESUMO

BACKGROUND: The common hepatic artery lymph node (CHALN) represents a second-echelon node for tumors in the head of the pancreas. Although early studies suggested survival was comparable between the CHALN and remote metastasis in pancreatic ductal adenocarcinoma (PDAC), whether the lymph node is associated with adverse survival remains equivocal. Here, we examined a prospective cohort of patients calculating actual survival to better understand implications of this specific lymph node metastasis. METHODS: We studied 215 patients with pancreatic head PDAC, who underwent pancreaticoduodenectomies at a single institution between 2010 and 2017, wherein the CHALNs were excised. We performed actual and actuarial overall survival and disease-free survival (DFS) analyses, with subsequent univariate and multivariate analyses in node-positive patients. RESULTS: Of this cohort, 7.3% of patients had involvement of the CHALN, and all of them had metastatic spread to first-echelon nodes. Actual median survival of patients with no lymph node involvement was 49 months. In patients with any nodal involvement, the survival was no different when comparing the lymph node positive and negative (13 and 20 months, respectively). Univariate and multivariate analyses likewise attached no significance to the lymph node metastasis, while demonstrating worse survival with positive margin status and poorly differentiated histology. Our DFS analyses yielded similar results. CONCLUSION: We found no difference in actual survival in node-positive patients regardless of the CHALN involvement and recommended against its assessment in prognosticating survival or guiding surgical treatment.


Assuntos
Carcinoma Ductal Pancreático , Artéria Hepática , Linfonodos , Metástase Linfática , Neoplasias Pancreáticas , Pancreaticoduodenectomia , Humanos , Carcinoma Ductal Pancreático/mortalidade , Carcinoma Ductal Pancreático/cirurgia , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/secundário , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/cirurgia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Linfonodos/patologia , Linfonodos/cirurgia , Intervalo Livre de Doença , Taxa de Sobrevida , Excisão de Linfonodo , Idoso de 80 Anos ou mais , Adulto , Estudos Prospectivos
5.
Mol Ther Oncol ; 32(2): 200806, 2024 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-38745748

RESUMO

Intraperitoneal tumor-associated macrophages (TAMs) are involved in evading anti-tumor immunity and promoting the peritoneal metastasis (PM) of gastric cancer (GC). Oncolytic viruses are known to induce the activation of host anti-tumor immunity in addition to tumor lysis. This study investigated whether a wild-type p53-loading telomerase-specific oncolytic adenovirus (OBP-702) could elicit the remodeling of intraperitoneal macrophages and enhance the efficacy of immune therapy. Increased numbers of CD163 TAMs and few CD8+ lymphocytes were immunohistochemically observed in clinical samples with PM, which suggested that TAMs were associated with the suppression of anti-tumor immunity. OBP-702 induced immunogenic cell death and upregulated PD-L1 expression in human and murine GC cell lines. Intraperitoneal administration of OBP-702 increased recruitment of CD8+ lymphocytes into the PM via the functional remodeling of intraperitoneal macrophages from TAM toward a pro-inflammatory phenotype, resulting in significantly suppressed tumor growth for the in vivo model. Furthermore, the combination of intraperitoneal OBP-702 with anti-programmed cell death-1 antibody enhanced anti-tumor immunity and prolonged the survival of mice bearing PM. Intraperitoneal immunotherapy using OBP-702 restores anti-tumor immunity via the remodeling of intraperitoneal macrophages in addition to direct tumor lysis and cooperates with immune checkpoint inhibitors to suppress PM in GC.

6.
Surg Neurol Int ; 15: 119, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38742002

RESUMO

Background: Cupping therapy is an alternative treatment that uses a small glass cup to suck the skin with a needle and has been used to manage skin problems and pain. However, serious complications have been reported. Herein, we describe a case of intracranial mycotic aneurysm rupture after cupping therapy. Case Description: A 25-year-old male patient presented with a headache and fever after cupping therapy for atopic dermatitis. He was diagnosed with infective endocarditis, and antibiotic therapy was initiated. After that, he suddenly lost consciousness, and head imaging revealed a cerebral hemorrhage due to a ruptured intracranial mycotic aneurysm. He underwent craniotomy, which was successful, and he was transferred to a rehabilitation center with a modified Rankin scale score of 2 at three months post-stroke. Conclusion: This case serves as a reminder of life-threatening infectious complication risks after cupping therapy. A patient who has a compromised skin barrier may experience serious adverse effects, especially when cupping is performed without implementing suitable infection prevention measures.

7.
Artigo em Inglês | MEDLINE | ID: mdl-38750825

RESUMO

BACKGROUND: The Index of Severity for Eosinophilic Esophagitis (I-SEE) is a new expert-defined clinical tool that classifies disease severity of eosinophilic esophagitis (EoE). OBJECTIVE: We aimed to determine whether I-SEE is associated with patient characteristics, molecular features of EoE, or both. METHODS: We analyzed a prospective cohort of patients with EoE from the Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR). Associations between I-SEE and clinical and molecular features (assessed by an EoE diagnostic panel [EDP]) were assessed. RESULTS: In 318 patients with chronic EoE (209 adults, 109 children), median total I-SEE score was 7.0, with a higher symptoms and complications score in children than adults (4.0 vs 1.0; P < .001) and higher inflammatory and fibrostenotic features scores in adults than children (3.0 vs 1.0 and 3.0 vs 0, respectively; both P < .001). Total I-SEE score had a bimodal distribution with the inactive to moderate categories and severe category. EDP score correlated with total I-SEE score (r = -0.352, P < .001) and both inflammatory and fibrostenotic features scores (r = -0.665, P < .001; r = -0.446, P < .001, respectively), but not with symptoms and complications scores (r = 0.047, P = .408). Molecular severity increased from inactive to mild and moderate, but not severe, categories. Longitudinal changes of modified I-SEE scores and inflammatory and fibrostenotic features scores reflected histologic and molecular activity. CONCLUSIONS: I-SEE score is associated with select clinical features across severity categories and with EoE molecular features for nonsevere categories, warranting further validation.

8.
Cancer Rep (Hoboken) ; 7(4): e2034, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38577721

RESUMO

BACKGROUND: Adhesion of cancer cells to extracellular matrix laminin through the integrin superfamily reportedly induces drug resistance. Heterodimers of integrin α6 (CD49f) with integrin ß1 (CD29) or ß4 (CD104) are major functional receptors for laminin. Higher CD49f expression is reportedly associated with a poorer response to induction therapy in childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL). Moreover, a xenograft mouse model transplanted with primary BCP-ALL cells revealed that neutralized antibody against CD49f improved survival after chemotherapy. AIMS: Considering the poor outcomes in Philadelphia chromosome (Ph)-positive ALL treated with conventional chemotherapy without tyrosine kinase inhibitors, we sought to investigate an involvement of the laminin adhesion. METHODS AND RESULTS: Ph-positive ALL cell lines expressed the highest levels of CD49f among the BCP-ALL cell lines with representative translocations, while CD29 and CD104 were ubiquitously expressed in BCP-ALL cell lines. The association of Ph-positive ALL with high levels of CD49f gene expression was also confirmed in two databases of childhood ALL cohorts. Ph-positive ALL cell lines attached to laminin and their laminin-binding properties were disrupted by blocking antibodies against CD49f and CD29 but not CD104. The cell surface expression of CD49f, but not CD29 and CD104, was downregulated by imatinib treatment in Ph-positive ALL cell lines, but not in their T315I-acquired sublines. Consistently, the laminin-binding properties were disrupted by the imatinib pre-treatment in the Ph-positive ALL cell line, but not in its T315I-acquired subline. CONCLUSION: BCR::ABL1 plays an essential role in the laminin adhesion of Ph-positive ALL cells through upregulation of CD49f.


Assuntos
Integrina alfa6 , Laminina , Leucemia-Linfoma Linfoblástico de Células Precursoras , Regulação para Cima , Animais , Humanos , Camundongos , Mesilato de Imatinib/farmacologia , Mesilato de Imatinib/uso terapêutico , Integrina alfa6/genética , Laminina/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética
9.
Surg Neurol Int ; 15: 80, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38628507

RESUMO

Background: Surgery is effective for extracranial internal carotid artery (EICA) aneurysms. However, the risk of cranial nerve injury associated with surgical repair, such as graft-assisted resection and extracranial-intracranial bypass techniques, is relatively high. Here, we report two cases of surgical treatment for EICA aneurysms and describe the surgical techniques and strategies to avoid cranial nerve injury. Methods: Two patients presented to our facility with an increasing cervical pulsatile mass and no neurological symptoms. Angiography showed a large aneurysm in the cervical internal carotid artery. Surgical treatment was performed to prevent rupture of the aneurysm. In both patients, the aneurysm was strongly attached to the vagus nerve. The aneurysm and vagus nerve were carefully dissected using a low-power bipolar (20 Malis; 3 watts), leaving connective tissue on the vagus nerve side. Results: The aneurysm was detached from the vagus nerve without injury. Based on intraoperative findings, one patient underwent clipping, and the other underwent aneurysmectomy and primary closure for aneurysm obliteration and angioplasty. Both patients were discharged without any cranial nerve dysfunction. Conclusion: The selection of a strategy based on intraoperative findings and low-power bipolar cutting is important for the treatment of extracranial carotid artery aneurysms to preserve cranial nerves.

10.
BMC Cancer ; 24(1): 489, 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38632507

RESUMO

BACKGROUND: Next-generation sequencing (NGS) is essential for lung cancer treatment. It is important to collect sufficient tissue specimens, but sometimes we cannot obtain large enough samples for NGS analysis. We investigated the yield of NGS analysis by frozen cytology pellets using an Oncomine Comprehensive Assay or Oncomine Precision Assay. METHODS: We retrospectively enrolled patients with lung cancer who underwent bronchoscopy at Kobe University Hospital and were enrolled in the Lung Cancer Genomic Screening Project for Individualized Medicine. We investigated the amount of extracted DNA and RNA and determined the NGS success rates. We also compared the amount of DNA and RNA by bronchoscopy methods. To create the frozen cytology pellets, we first effectively collected the cells and then quickly centrifuged and cryopreserved them. RESULTS: A total of 132 patients were enrolled in this study between May 2016 and December 2022; of them, 75 were subjected to frozen cytology pellet examinations and 57 were subjected to frozen tissue examinations. The amount of DNA and RNA obtained by frozen cytology pellets was nearly equivalent to frozen tissues. Frozen cytology pellets collected by endobronchial ultrasound-guided transbronchial needle aspiration yielded significantly more DNA than those collected by transbronchial biopsy methods. (P < 0.01) In RNA content, cytology pellets were not inferior to frozen tissue. The success rate of NGS analysis with frozen cytology pellet specimens was comparable to the success rate of NGS analysis with frozen tissue specimens. CONCLUSIONS: Our study showed that frozen cytology pellets may have equivalent diagnostic value to frozen tissue for NGS analyses. Bronchial cytology specimens are usually used only for cytology, but NGS analysis is possible if enough cells are collected to create pellet specimens. In particular, the frozen cytology pellets obtained by endobronchial ultrasound-guided transbronchial needle aspiration yielded sufficient amounts of DNA. TRIAL REGISTRATION: This was registered with the University Medical Hospital Information Network in Japan (UMINCTR registration no. UMIN000052050).


Assuntos
Neoplasias Pulmonares , Humanos , Estudos Retrospectivos , Neoplasias Pulmonares/patologia , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico/métodos , Broncoscopia/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , DNA , RNA , Linfonodos/patologia
11.
Cureus ; 16(3): e55629, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38586743

RESUMO

An 85-year-old female with situs inversus totalis presented with right hemiplegia, right facial nerve palsy, eye deviation to the left, and aphasia. Magnetic resonance imaging revealed acute ischemic lesions in the left insular cortex and the frontal lobe. Magnetic resonance angiography revealed an occlusion of the left internal carotid artery. Reversed-image mechanical thrombectomy achieved complete reperfusion in three passes within 54 minutes. Six months post-intervention, the patient could walk indoors independently. Our technique, which replicates the normal arterial anatomy by inversion and angulation, was adapted to situs inversus totalis.

12.
Surg Endosc ; 38(4): 2297-2304, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38499782

RESUMO

BACKGROUND: Visualization of the pancreatobiliary junction is one of the challenges faced by endoscopic ultrasonography (EUS). The water-filling technique, which allows for the observation of the ampulla at a suitable distance by injecting water into the lumen of the duodenum, was used for this purpose. However, a new gel immersion technique has recently been introduced for visualizing the gastrointestinal tract. This study investigated the effectiveness of visualizing the pancreatobiliary junction in EUS by comparing both water filling and the new gel immersion technique in identical cases. METHODS: The study ran from June to December 2021. Ten images from each technique were retrospectively compared by three independent researchers. The primary result of the study was the number of images depicting the "Pancreatic and Biliary Ducts Penetrating the Duodenal Muscularis Propria" (defined as Excellent observation) in each technique. The secondary outcome was defined as gel immersion technique's safety and impact on duodenal lumen distension. RESULTS: Ten patients used the gel immersion technique. All patients underwent the water-filling technique first, followed by gel injection after the water was completely aspirated. The average number of pictures rated as "Excellent observation," which is the primary outcome, was significantly higher with the gel immersion technique than with water filling, and no adverse events were observed. The subanalysis revealed that both convex and radial echoendoscopes are equally effective at depicting the ampulla with the gel immersion technique. CONCLUSIONS: The ability to depict the pancreatobiliary junction using the gel immersion technique is superior to that of the water-filling method, which may allow for a more detailed assessment of the ampullary region with both radial and convex echoendoscopes. This can be a useful EUS technique for diagnosing pancreaticobiliary maljunction or periampullary tumors.


Assuntos
Ampola Hepatopancreática , Neoplasias do Ducto Colédoco , Humanos , Ampola Hepatopancreática/diagnóstico por imagem , Ampola Hepatopancreática/patologia , Neoplasias do Ducto Colédoco/patologia , Endossonografia , Estudos Retrospectivos , Água
13.
Sci Rep ; 14(1): 5367, 2024 03 04.
Artigo em Inglês | MEDLINE | ID: mdl-38438534

RESUMO

The study aimed to identify prognostic factors for patients with acute lower gastrointestinal bleeding and to develop a high-accuracy prediction tool. The analysis included 8254 cases of acute hematochezia patients who were admitted urgently based on the judgment of emergency physicians or gastroenterology consultants (from the CODE BLUE J-study). Patients were randomly assigned to a derivation cohort and a validation cohort in a 2:1 ratio using a random number table. Assuming that factors present at the time of admission are involved in mortality within 30 days of admission, and adding management factors during hospitalization to the factors at the time of admission for mortality within 1 year, prognostic factors were established. Multivariate analysis was conducted, and scores were assigned to each factor using regression coefficients, summing these to measure the score. The newly created score (CACHEXIA score) became a tool capable of measuring both mortality within 30 days (ROC-AUC 0.93) and within 1 year (C-index, 0.88). The 1-year mortality rates for patients classified as low, medium, and high risk by the CACHEXIA score were 1.0%, 13.4%, and 54.3% respectively (all P < 0.001). After discharge, patients identified as high risk using our unique predictive score require ongoing observation.


Assuntos
Líquidos Corporais , Caquexia , Humanos , Hemorragia Gastrointestinal/terapia , Hospitalização , Alta do Paciente , Estudos Retrospectivos
14.
Hum Genome Var ; 11(1): 13, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38548799

RESUMO

A young patient diagnosed with advanced colon cancer and liver metastasis was found to have familial adenomatous polyposis (FAP) through comprehensive genomic analysis. Whole-genome array comparative genomic hybridization (aCGH) revealed germline deletions at chromosome 5q22.1-22.2 encompassing the entire APC gene. The patient and her son exhibited mild intellectual disability without developmental delay. This case highlights the need for further exploration of the characteristics associated with whole APC deletions. aCGH is a valuable tool for studying FAP and provides a detailed analysis of large deletions.

15.
J Neurol Surg B Skull Base ; 85(2): 119-122, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38449577

RESUMO

Objectives The bacteriological features of the frontal sinus mucosa may impose significant complications in neurosurgery, when breached unintentionally. This study aimed to investigate the bacterial flora in patients undergoing frontal craniotomy for cerebrovascular substrate surgery. Design This is a single-center prospective study. Setting When mucosal laceration occurred, the patients underwent frontal sinus reconstruction with mucosa reconstruction, preserving the nasofrontal duct. Participants We enrolled eight consecutive patients who underwent bifrontal craniotomy associated with frontal sinus mucosa laceration. Main Outcome Measures A portion of the mucosa was extracted during the reconstructive procedure and was sent for microbiological analysis. Results None of the patients presented with the bacterial flora in the mucosal cultures. No patient experienced postoperative cerebrospinal fluid leakage or meningitis. One patient with a clinical history of chronic maxillary sinusitis presented with a subcutaneous abscess around the forehead at 9 months postoperatively. The patient rapidly recovered after receiving oral administration of antibiotics. Conclusions Our findings demonstrated that the frontal sinuses were maintained in an aseptic environment in all cases. The results may encourage the development and wider use of transfrontal sinus approaches.

16.
Intern Med ; 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38432990

RESUMO

A woman in her 60s presented with a small pancreatic head tumor. Imaging studies revealed a 13-mm well-defined pancreatic head tumor. A neuroendocrine neoplasm was suspected, and the patient opted for observation at that time. After 8 months, the patient began experiencing sweating while fasting, and blood tests during regular follow-up visits showed hypoglycemia. Hypoglycemia was induced during fasting test. The tumor exhibited clear features of an insulinoma during follow-up observation. While small neuroendocrine neoplasms are often managed through observation, caution should be exercised regarding their transformation into functional neuroendocrine tumors.

17.
Pancreas ; 53(5): e395-e404, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38416857

RESUMO

OBJECTIVES: The role of long noncoding RNAs (lncRNAs) in pancreatic ductal adenocarcinoma (PDAC) remain unclear. Extracellular vesicle (EV)-encapsulated RNAs could be effective targets for liquid biopsy. We aimed to identify previously unknown EV-encapsulated lncRNAs in PDAC and establish highly accurate methods for isolating EVs. MATERIALS AND METHODS: Extracellular vesicles were isolated using existing and newly developed methods, namely, PEViA-UC and PEViA-IP, from serum samples of 20 patients with PDAC, 22 patients with intraductal papillary mucinous neoplasms, and 21 healthy individuals. Extracellular vesicle lncRNA expression was analyzed using digital PCR. RESULTS: Gene expression analysis using cDNA microarray revealed a highly expressed lncRNA, HEVEPA , in serum EVs from patients with PDAC. We established PEViA-UC and PEViA-IP using PEViA reagent, ultracentrifugation, and immunoprecipitation. Although detection of EV-encapsulated HEVEPA using existing methods is challenging, PEViA-UC and PEViA-IP detected EV HEVEPA , which was highly expressed in patients with PDAC compared with non-PDAC patients. The detection sensitivity for discriminating PDAC from non-PDAC using the combination of HEVEPA and HULC , which are highly expressed lncRNAs in PDAC, and carbohydrate antigen 19-9 (CA19-9), was higher than that of HEVEPA , HULC , or CA19-9 alone. CONCLUSIONS: Extracellular vesicle lncRNAs isolated using PEViA-IP and CA19-9 together could be effective targets in liquid biopsy for PDAC diagnosis.


Assuntos
Biomarcadores Tumorais , Carcinoma Ductal Pancreático , Vesículas Extracelulares , Neoplasias Pancreáticas , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/sangue , RNA Longo não Codificante/genética , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patologia , Biópsia Líquida/métodos , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/sangue , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Estudos de Casos e Controles
18.
Oncogene ; 43(15): 1087-1097, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38383726

RESUMO

BRCA1-associated protein 1 (BAP1) has emerged as a major tumor suppressor gene in diverse cancer types, notably in malignant pleural mesothelioma (DPM), and has also been identified as a germline cancer predisposition gene for DPM and other select cancers. However, its role in the response to DNA damage has remained unclear. Here, we show that BAP1 inactivation is associated with increased DNA damage both in Met-5A human mesothelial cells and human DPM cell lines. Through proteomic analyses, we identified PRKDC as an interaction partner of BAP1 protein complexes in DPM cells and 293 T human embryonic kidney cells. PRKDC encodes the catalytic subunit of DNA protein kinase (DNA-PKcs) which functions in the nonhomologous end-joining (NHEJ) pathway of DNA repair. Double-stranded DNA damage resulted in prominent nuclear expression of BAP1 in DPM cells and phosphorylation of BAP1 at serine 395. A plasmid-based NHEJ assay confirmed a significant effect of BAP1 knockdown on cellular NHEJ activity. Combination treatment with X-ray irradiation and gemcitabine (as a radiosensitizer) strongly suppressed the growth of BAP1-deficient cells. Our results suggest reciprocal positive interactions between BAP1 and DNA-PKcs, based on phosphorylation of BAP1 by the latter and deubiquitination of DNA-PKcs by BAP1. Thus, functional interaction of BAP1 with DNA-PKcs supports a role for BAP1 in NHEJ DNA repair and may provide the basis for new therapeutic strategies and new insights into its role as a tumor suppressor.


Assuntos
Neoplasias , Proteômica , Humanos , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Quebras de DNA de Cadeia Dupla , Reparo do DNA/genética , Proteína Quinase Ativada por DNA/genética , Proteína Quinase Ativada por DNA/metabolismo , DNA/genética , Reparo do DNA por Junção de Extremidades/genética , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo , Ubiquitina Tiolesterase/genética , Ubiquitina Tiolesterase/metabolismo
19.
Endoscopy ; 56(4): 291-301, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38354743

RESUMO

BACKGROUND: The rebleeding risks and outcomes of endoscopic treatment for acute lower gastrointestinal bleeding (ALGIB) may differ depending on the bleeding location, type, and etiology of stigmata of recent hemorrhage (SRH) but have yet to be fully investigated. We aimed to identify high risk endoscopic SRH and to propose an optimal endoscopic treatment strategy. METHODS: We retrospectively analyzed 2699 ALGIB patients with SRH at 49 hospitals (CODE BLUE-J Study), of whom 88.6 % received endoscopic treatment. RESULTS: 30-day rebleeding rates of untreated SRH significantly differed among locations (left colon 15.5 % vs. right colon 28.6 %) and etiologies (diverticular bleeding 27.5 % vs. others [e. g. ulcerative lesions or angioectasia] 8.9 %), but not among bleeding types. Endoscopic treatment reduced the overall rebleeding rate (adjusted odds ratio [AOR] 0.69; 95 %CI 0.49-0.98), and the treatment effect was significant in right-colon SRH (AOR 0.46; 95 %CI 0.29-0.72) but not in left-colon SRH. The effect was observed in both active and nonactive types, but was not statistically significant. Moreover, the effect was significant for diverticular bleeding (AOR 0.60; 95 %CI 0.41-0.88) but not for other diseases. When focusing on treatment type, the effectiveness was not significantly different between clipping and other modalities for most SRH, whereas ligation was significantly more effective than clipping in right-colon diverticular bleeding. CONCLUSIONS: A population-level endoscopy dataset allowed us to identify high risk endoscopic SRH and propose a simple endoscopic treatment strategy for ALGIB. Unlike upper gastrointestinal bleeding, the rebleeding risks for ALGIB depend on colonic location, bleeding etiology, and treatment modality.


Assuntos
Divertículo do Colo , Hemostase Endoscópica , Humanos , Estudos Retrospectivos , Japão/epidemiologia , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/terapia , Endoscopia Gastrointestinal/efeitos adversos , Hemostase Endoscópica/efeitos adversos , Divertículo do Colo/complicações , Colonoscopia/efeitos adversos
20.
Cureus ; 16(1): e51905, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38333491

RESUMO

Background During the early phase of the coronavirus disease 2019 (COVID-19) pandemic, a global reduction in hospitalizations for acute myocardial infarction (AMI) was observed. Generally, patients experienced increased severity of AMI with delays in time from symptom onset to treatment during the pandemic. However, the impact of the COVID-19 pandemic on in-hospital mortality among patients with AMI remains unclear. This study aimed to compare the long-term prognosis of patients with AMI during the COVID-19 pandemic to that observed in the pre-pandemic period and to evaluate the influence of the COVID-19 pandemic on the prognosis of patients with AMI. Methods We reviewed the data of patients admitted to our hospital for AMI treatment between April 1, 2018, and March 31, 2021. The time from admission to major adverse cardiac events (MACE), as well as the time from admission to all-cause death, were examined between the pandemic period (April 1, 2020, to March 31, 2021) and the pre-pandemic period (April 1, 2018, to March 31, 2020). Results Eighty patients were included in the study, and those admitted during the pandemic exhibited a higher likelihood of advanced age, lower levels of LDL-cholesterol, and a reduced prevalence of hypertension. The 2.5-year MACE-free survival and overall survival rates between the patients during the pre-pandemic and pandemic periods were not significantly different. Conclusion The long-term prognosis of patients with AMI during the COVID-19 pandemic remains unclear. In this study, we reported that the 2.5-year MACE-free survival and overall survival rates of the patients with AMI admitted during the COVID-19 pandemic were not significantly different from those during the pre-pandemic period. The impact of the COVID-19 pandemic on the prognosis of patients with AMI appears to vary according to the study population.

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