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The Ophioglossaceae family, one of the oldest orders of extant ferns, exhibits diverse morphological and chromosomal characteristics. This study presents the first complete plastome sequence of thermal adder's-tongue fern (Ophioglossum thermale), a species renowned for its antioxidant properties in traditional Chinese medicine. Our analyses revealed 27 simple sequence repeats (SSRs) in the plastome, with variations in SSR frequencies compared to related genera. Our phylogenetic analyses placed O. thermale within the Ophioglossum s.s. clade, supporting previous studies and suggesting polyphyly within the genus Ophioglossum based on the sensu PPG I system. The enlarged noncoding regions in fern organelles (ENRFOs) resulting from foreign DNA insertions in O. thermale were identified in the ycf2-trnH and trnT-trnfM regions, similar to other Ophioglossum species. ENRFOs were found at the LSC and SSC, but not in IRs in Ophioglossaceae. Consequently, foreign DNA insertions and lineage-specific SSRs shed light on plastome evolution in the Ophioglossaceae family.
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Purpose: Proximal gastrectomy is an alternative to total gastrectomy (TG) for early gastric cancer (EGC) treatment in the upper stomach. However, its benefits in terms of perioperative and long-term outcomes remain controversial. The aim of this study was to compare the perioperative, body compositional, nutritional, and survival outcomes of patients undergoing proximal gastrectomy with double-tract reconstruction (PG-DTR) and TG for pathological stage I gastric cancer in upper stomach. Materials and Methods: The study included 506 patients who underwent gastrectomy for pathological stage I gastric cancer in the upper stomach between 2015 and 2019. Clinicopathological, perioperative, body compositional, nutritional, and survival outcomes were compared between the PG-DTR and TG groups. Results: The PG-DTR and TG groups included 197 (38.9%) and 309 (61.1%) patients, respectively. The PG-DTR group had a lower rate of early complications (p=0.041), lower diagnosis rate of anemia and vitamin B12 deficiency (all p<0.001), and lower replacement rate of iron and vitamin B12 compared to TG group (all p<0.001). The PG-DTR group showed reduced incidence of sarcopenia at 6-months postoperatively, preserved higher amount of visceral fat after surgery (p=0.032 and p=0.040, respectively), and showed a higher hemoglobin level (p=0.007). Oncologic outcomes were comparable between the groups. Conclusion: The PG-DTR for EGC located in the upper stomach offered advantages of fewer complications, lower incidence of anemia and vitamin B12 deficiency, less decrease in visceral fat volume, and similar survival compared to TG. Consequently, PG-DTR may be considered a superior alternative treatment option to TG.
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Background: Osteoporosis and fragility fractures are crucial musculoskeletal complications in long-term survivors of gastric cancer. However, the relationship between changes in body composition after gastrectomy and bone loss has not been investigated. Therefore, this study aimed to explore whether computed tomography (CT)-derived body composition parameters are associated with bone loss after gastrectomy in patients with gastric cancer. Methods: We retrospectively reviewed medical records and abdomen CT scans of patients who underwent gastrectomy at Yonsei University Severance Hospital between 2009 and 2018. Patients with non-metastatic gastric adenocarcinoma and preoperative and postoperative non-contrast CT scans were analyzed. Section area of skeletal muscle (SMA), visceral fat (VFA), and subcutaneous fat (SFA) were assessed using semi-automatic segmentation software. Changes in trabecular bone attenuation of L1 mid-vertebra level (L1 Hounsfield units [HU]) were measured. Results: Fifty-seven patients (mean age, 65.5±10.6; 70.2% males) were analyzed, and the median duration was 31 months. Fortyseven patients (82.5%) lost weight after gastrectomy. Baseline SMA and VFA did not differ between the bone loss and preserved groups; however, baseline SFA was significantly higher in the bone preserved group than in the bone loss group (P=0.020). In a multivariable linear regression model adjusted for confounding factors, one standard deviation higher VFA at baseline was associated with greater annualized L1 HU loss (%) (P=0.034). However, higher preoperative SFA was associated with protection against bone loss after gastrectomy (P=0.025). Conclusion: Higher preoperative SFA exhibited a protective effect against bone loss after gastrectomy in patients with non-metastatic gastric cancer, whereas VFA exhibited a negative effect.
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BACKGROUND: Determination of vessel resection in patients with pancreatectomy after neo-adjuvant chemotherapy remains controversial. The recently introduced computed tomography-based vascular burden index presents a potential solution to this challenge. This study aimed to evaluate the model performance for the prediction of vascular resection and pathological invasion. METHODS: Patients who underwent surgery after neo-adjuvant chemotherapy were included. Two independent reviewers measured the vascular tumour burden index around the adjacent artery (AVBI), and vein (VVBI). The area under the curve was compared to assess the predictive capacity of vascular burden index values and their changes for vascular resection and pathological vascular invasion. RESULTS: Among 252 patients, 179 and 73 had borderline resectable and locally advanced pancreatic cancer, respectively. Concurrent vessel resection and pathological vascular invasion were observed in 121 (48.0 %) and 42 (16.6 %) patients, respectively. In all patients, the VVBI (area under the curve: 0.872) and AVBI (0.911) after neo-adjuvant therapy significantly predicted vessel resection. In patients with vascular resection, the VVBI after neo-adjuvant chemotherapy (0.752) and delta value of the AVBI (0.706) demonstrated better performance for predicting pathological invasion of the resected vein. The regression of the AVBI and VVBI was an independent prognostic factor for survival (hazard ratio: 0.54, 95 % confidence interval: 0.34-0.85; P = 0.009) CONCLUSIONS: Regressed VVBI on serial computed tomography scans is useful for predicting vein resection and pathological venous invasion before surgery. The delta value of the AVBI may therefore be helpful for predicting pathological arterial invasion after neo-adjuvant chemotherapy.
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High-grade serous ovarian cancers (HGSOCs) with homologous recombination deficiency (HRD) are initially responsive to poly (ADP-ribose) polymerase inhibitors (PARPi), but resistance ultimately emerges. HGSOC with CCNE1 amplification (CCNE1 amp) are associated with resistance to PARPi and platinum treatments. High replication stress in HRD and CCNE1 amp HGSOC leads to increased reliance on checkpoint kinase 1 (CHK1), a key regulator of cell cycle progression and the replication stress response. Here, we investigated the anti-tumor activity of the potent, highly selective, orally bioavailable CHK1 inhibitor (CHK1i), SRA737, in both acquired PARPi-resistant BRCA1/2 mutant and CCNE1 amp HGSOC models. We demonstrated that SRA737 increased replication stress and induced subsequent cell death in vitro. SRA737 monotherapy in vivo prolonged survival in CCNE1 amp models, suggesting a potential biomarker for CHK1i therapy. Combination SRA737 and PARPi therapy increased tumor regression in both PARPi-resistant and CCNE1 amp patient-derived xenograft models, warranting further study in these HGSOC subgroups.
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OBJECTIVE: To develop and validate a preoperative risk score incorporating carbohydrate antigen (CA) 19-9, CT, and fluorine-18-fluorodeoxyglucose (18F-FDG) PET/CT variables to predict recurrence-free survival (RFS) after upfront surgery in patients with resectable pancreatic ductal adenocarcinoma (PDAC). MATERIALS AND METHODS: Patients with resectable PDAC who underwent upfront surgery between 2014 and 2017 (development set) or between 2018 and 2019 (test set) were retrospectively evaluated. In the development set, a risk-scoring system was developed using the multivariable Cox proportional hazards model, including variables associated with RFS. In the test set, the performance of the risk score was evaluated using the Harrell C-index and compared with that of the postoperative pathological tumor stage. RESULTS: A total of 529 patients, including 335 (198 male; mean age ± standard deviation, 64 ± 9 years) and 194 (103 male; mean age, 66 ± 9 years) patients in the development and test sets, respectively, were evaluated. The risk score included five variables predicting RFS: tumor size (hazard ratio [HR], 1.29 per 1 cm increment; P < 0.001), maximal standardized uptake values of tumor ≥ 5.2 (HR, 1.29; P = 0.06), suspicious regional lymph nodes (HR, 1.43; P = 0.02), possible distant metastasis on 18F-FDG PET/CT (HR, 2.32; P = 0.03), and CA 19-9 (HR, 1.02 per 100 U/mL increment; P = 0.002). In the test set, the risk score showed good performance in predicting RFS (C-index, 0.61), similar to that of the pathologic tumor stage (C-index, 0.64; P = 0.17). CONCLUSION: The proposed risk score based on preoperative CA 19-9, CT, and 18F-FDG PET/CT variables may have clinical utility in selecting high-risk patients with resectable PDAC.
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Antígeno CA-19-9 , Carcinoma Ductal Pancreático , Fluordesoxiglucose F18 , Neoplasias Pancreáticas , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Compostos Radiofarmacêuticos , Humanos , Masculino , Feminino , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Pessoa de Meia-Idade , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/cirurgia , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/mortalidade , Idoso , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/mortalidade , Estudos Retrospectivos , Antígeno CA-19-9/sangue , Tomografia Computadorizada por Raios X/métodos , Recidiva Local de Neoplasia/diagnóstico por imagem , Medição de Risco , Intervalo Livre de Doença , Valor Preditivo dos TestesRESUMO
Arrhythmogenic cardiomyopathy (ACM) is a cardiomyopathy that is predominantly inherited and characterized by cardiac arrhythmias and structural abnormalities. TMEM43 (transmembrane protein 43) is one of the well-known genetic culprits behind ACM. In this study, we successfully generated an induced pluripotent stem cell (iPSC) line, YCMi010-A, derived from a male patient diagnosed with ACM. Although these iPSCs harbored a heterozygous intronic splice variant, TMEM43 c.443-2A > G, they still displayed normal cellular morphology and were confirmed to express pluripotency markers. YCMi010-A iPSC line is a promising model for investigating the pathomechanisms associated with ACM and exploring potential therapeutic strategies.
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Displasia Arritmogênica Ventricular Direita , Células-Tronco Pluripotentes Induzidas , Proteínas de Membrana , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Displasia Arritmogênica Ventricular Direita/genética , Displasia Arritmogênica Ventricular Direita/patologia , Displasia Arritmogênica Ventricular Direita/metabolismo , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Linhagem Celular , Adulto , Sítios de Splice de RNA/genética , Diferenciação CelularRESUMO
OBJECTIVES: The purpose of this study was to compare the different versions of the National Comprehensive Cancer Network (NCCN) guidelines for defining resectability of pancreatic ductal adenocarcinoma (PDAC) in predicting margin-negative (R0) resection, and to assess inter-reader agreement. METHODS: This retrospective study included 283 patients (mean age, 65.1 years ± 9.4 [SD]; 155 men) who underwent upfront pancreatectomy for PDAC between 2017 and 2019. Two radiologists independently determined the resectability on preoperative CT according to the 2017, 2019, and 2020 NCCN guidelines. The sensitivity and specificity for R0 resection were analyzed using a multivariable logistic regression analysis with generalized estimating equations. Inter-reader agreement was assessed using kappa statistics. RESULTS: R0 resection was accomplished in 239 patients (84.5%). The sensitivity and specificity averaged across two readers were, respectively, 76.6% and 29.5% for the 2020 guidelines, 74.1% and 32.9% for the 2019 guidelines, and 72.6% and 34.1% for the 2017 guidelines. Compared with the 2020 guidelines, both 2019 and 2017 guidelines showed significantly lower sensitivity for R0 resection (p ≤ .009). Specificity was significantly higher with the 2017 guidelines (p = .043) than with the 2020 guidelines. Inter-reader agreements for determining the resectability of PDCA were strong (k ≥ 0.83) with all guidelines, being highest with the 2020 guidelines (k = 0.91). CONCLUSION: The 2020 NCCN guidelines showed significantly higher sensitivity for prediction of R0 resection than the 2017 and 2019 guidelines.
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Carcinoma Ductal Pancreático , Margens de Excisão , Pancreatectomia , Neoplasias Pancreáticas , Guias de Prática Clínica como Assunto , Sensibilidade e Especificidade , Tomografia Computadorizada por Raios X , Humanos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Masculino , Feminino , Idoso , Estudos Retrospectivos , Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/cirurgia , Carcinoma Ductal Pancreático/patologia , Pancreatectomia/métodos , Tomografia Computadorizada por Raios X/métodos , Pessoa de Meia-IdadeRESUMO
BACKGROUND AND OBJECTIVES: Pancreatic neuroendocrine tumor (PanNET), although rare in incidence, is increasing in recent years. Several clinicopathologic and molecular factors have been suggested for patient stratification due to the extensive heterogeneity of PanNETs. We aimed to discover the prognostic role of assessing the tumor border of PanNETs with pre-operative computed tomography (CT) images and correlate them with other clinicopathologic factors. METHODS: The radiologic, macroscopic, and microscopic tumor border of 183 surgically resected PanNET cases was evaluated using preoperative CT images (well defined vs. poorly defined), gross images (expansile vs. infiltrative), and hematoxylin and eosin-stained slides (pushing vs. infiltrative). The clinicopathologic and prognostic significance of the tumor border status was compared with other clinicopathologic factors. RESULTS: A poorly defined radiologic tumor border was observed in 65 PanNET cases (35.5 %), and were more frequent in male patients (P = 0.031), and tumor with larger size, infiltrative macroscopic growth pattern, infiltrative microscopic tumor border, higher tumor grade, higher pT category, lymph node metastasis, lymphovascular and perineural invasions (all, P < 0.001). Patients with PanNET with a poorly defined radiologic tumor border had significantly worse overall survival (OS) and recurrence-free survival (RFS; both, P < 0.001). Multivariable analysis revealed that PanNET with a poorly defined radiologic border is an independent poor prognostic factor for both OS (P = 0.049) and RFS (P = 0.027). CONCLUSION: Pre-operative CT-based tumor border evaluation can provide additional information regarding survival and recurrence in patients with PanNET.
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Tumores Neuroendócrinos , Neoplasias Pancreáticas , Tomografia Computadorizada por Raios X , Humanos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/patologia , Prognóstico , Idoso , Adulto , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Adulto JovemRESUMO
Background: Distinct bacterial strains may affect the prognosis of patients with chronic respiratory diseases. However, little is known about the clinical significance of respiratory bacteria in patients with chronic pulmonary aspergillosis (CPA), a progressive and debilitating disease caused by Aspergillus spp. Objectives: This study aimed to analyze data obtained from CPA patients and their sputum or bronchial washing samples and investigate the prevalence and composition of respiratory bacteria and clinical implications. Patients and Methods. We retrospectively reviewed the data of patients diagnosed with CPA between March 2019 and February 2023 in a tertiary referral hospital. We assessed the clinical characteristics and overall and pneumonia-specific survival rates of patients with CPA based on the presence of bacteria. Results and Conclusions. We included 142 patients with CPA. The most commonly identified bacteria were Klebsiella pneumoniae (22.5%), followed by Pseudomonas aeruginosa (21.8%) and Escherichia coli (4.2%). Patients with isolated bacteria had a higher prevalence of older age, female sex, diabetes, and a history of extrathoracic malignancy than those without isolated bacteria (P = 0.024, 0.013, 0.021, and 0.034, respectively). Furthermore, over a median follow-up of 11 (4-21) months, the pneumonia-specific mortality rate was 13.4% (19/142), which was higher in patients with isolated bacteria than in those without (P = 0.045, log-rank test). Particularly, patients with the presence of P. aeruginosa had a significantly higher mortality rate from pneumonia than those without the presence of P. aeruginosa (adjusted hazard ratio, 3.34; P = 0.015). In conclusion, CPA patients with isolated bacteria, especially P. aeruginosa, showed higher mortality rates due to pneumonia. Performing tests to identify bacteria in the lower respiratory tract of patients with CPA may be helpful in predicting future prognosis. Further studies are required to validate these findings in diverse ethnic groups.
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The dermal-epidermal junction (DEJ) is essential for maintaining skin structural integrity and regulating cell survival and proliferation. Thus, DEJ rejuvenation is key for skin revitalization, particularly in age-related DEJ deterioration. Radiofrequency (RF) treatment, known for its ability to enhance collagen fiber production through thermal mechanisms and increase heat shock protein (HSP) expression, has emerged as a promising method for skin rejuvenation. Additionally, RF activates Piezo1, an ion channel implicated in macrophage polarization toward an M2 phenotype and enhanced TGF-ß production. This study investigated the impact of RF treatment on HSP47 and HSP90 expression, known stimulators of DEJ protein expression. Furthermore, using in vitro and aged animal skin models, we assessed whether RF-induced Piezo1 activation and the subsequent M2 polarization could counter age-related DEJ changes. The RF treatment of H2O2-induced senescent keratinocytes upregulated the expression of HSP47, HSP90, TGF-ß, and DEJ proteins, including collagen XVII. Similarly, the RF treatment of senescent macrophages increased Piezo1 and CD206 (M2 marker) expression. Conditioned media from RF-treated senescent macrophages enhanced the expression of TGF-ß and DEJ proteins, such as nidogen and collagen IV, in senescent fibroblasts. In aged animal skin, RF treatment increased the expression of HSP47, HSP90, Piezo1, markers associated with M2 polarization, IL-10, and TGF-ß. Additionally, RF treatment enhanced DEJ protein expression. Moreover, RF reduced lamina densa replication, disrupted lesions, promoted hemidesmosome formation, and increased epidermal thickness. Overall, RF treatment effectively enhanced DEJ protein expression and mitigated age-related DEJ structural changes by increasing HSP levels and activating Piezo1.
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Epiderme , Animais , Epiderme/metabolismo , Epiderme/efeitos da radiação , Camundongos , Derme/metabolismo , Queratinócitos/metabolismo , Macrófagos/metabolismo , Envelhecimento da Pele/efeitos da radiação , Pele/metabolismo , Pele/efeitos da radiação , Pele/patologia , Humanos , Envelhecimento/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo , Proteínas de Choque Térmico HSP47/metabolismo , Proteínas de Choque Térmico HSP47/genéticaRESUMO
BACKGROUND: Peritoneal recurrence is a significant cause of treatment failure after radical gastrectomy for gastric cancer. The prediction of metachronous peritoneal recurrence would have a significantly impact risk stratification and tailored treatment planning. This study aimed to externally validate the previously established PERI-Gastric 1 and 2 models to assess their generalizability in an independent population. METHODS: Retrospective external validation was conducted on a cohort of 8564 patients who underwent elective gastrectomy for stage Ib-IIIc gastric cancer between 1998 and 2018 at the Yonsei Cancer Center. Discrimination was tested using the area under the receiver operating characteristic curves (AUROC). Accuracy was tested by plotting observations against the predicted risk of peritoneal recurrence and analyzing the resulting calibration plots. Clinical usefulness was tested with a decision curve analysis. RESULTS: In the validation cohort, PERI-Gastric 1 and PERI-Gastric 2 exhibited an AUROC of 0.766 (95 % C.I. 0.752-0.778) and 0.767 (95 % C.I. 0.755-0.780), a calibration-in-the-large of 0.935 and 0.700, a calibration belt with a 95 % C.I. over the bisector in the risk range of 24%-33 % and 35%-47 %. The decision curve analysis revealed a positive net benefit in the risk range of 10%-42 % and 15%-45 %, respectively. CONCLUSIONS: This study presents the external validation of the PERI-Gastric 1 and 2 scores in an Eastern population. The models demonstrated fair discrimination and satisfactory calibration for predicting the risk of peritoneal recurrence after radical gastrectomy, even in Eastern patients. PERI-Gastric 1 and 2 scores could also be applied to predict the risk of metachronous peritoneal recurrence in Eastern populations.
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Gastrectomia , Neoplasias Peritoneais , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Feminino , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias Peritoneais/secundário , Neoplasias Peritoneais/cirurgia , República da Coreia/epidemiologia , Medição de Risco , Idoso , Curva ROC , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Bases de Dados Factuais , Área Sob a CurvaRESUMO
Mutations resulting in decreased activity of p53 tumor suppressor protein promote tumorigenesis. P53 protein levels are tightly regulated through the Ubiquitin Proteasome System (UPS). Several E3 ligases were shown to regulate p53 stability, including MDM2. Here we report that the ubiquitin E3 ligase XIAP (X-linked Inhibitors of Apoptosis) is a direct ligase for p53 and describe a novel approach for modulating the levels of p53 by targeting the XIAP pathway. Using in vivo (live-cell) and in vitro (cell-free reconstituted system) ubiquitylation assays, we show that the XIAP-antagonist ARTS regulates the levels of p53 by promoting the degradation of XIAP. XIAP directly binds and ubiquitylates p53. In apoptotic cells, ARTS inhibits the ubiquitylation of p53 by antagonizing XIAP. XIAP knockout MEFs express higher p53 protein levels compared to wild-type MEFs. Computational screen for small molecules with high affinity to the ARTS-binding site within XIAP identified a small-molecule ARTS-mimetic, B3. This compound stimulates apoptosis in a wide range of cancer cells but not normal PBMC (Peripheral Blood Mononuclear Cells). Like ARTS, the B3 compound binds to XIAP and promotes its degradation via the UPS. B3 binding to XIAP stabilizes p53 by disrupting its interaction with XIAP. These results reveal a novel mechanism by which ARTS and p53 regulate each other through an amplification loop to promote apoptosis. Finally, these data suggest that targeting the ARTS binding pocket in XIAP can be used to increase p53 levels as a new strategy for developing anti-cancer therapeutics.
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Apoptose , Proteólise , Proteína Supressora de Tumor p53 , Ubiquitinação , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismo , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/genética , Humanos , Proteína Supressora de Tumor p53/metabolismo , Proteína Supressora de Tumor p53/genética , Apoptose/efeitos dos fármacos , Ubiquitinação/efeitos dos fármacos , Proteólise/efeitos dos fármacos , Animais , Camundongos , Linhagem Celular Tumoral , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitina-Proteína Ligases/genética , Regulação para Cima/efeitos dos fármacos , Ligação ProteicaRESUMO
PURPOSE: The clinical significance of negative toxin enzyme immunoassays (EIA) for Clostridioides difficile infections (CDIs) is unclear. Our study aimed to investigate the significance of toxin EIA-negative in the diagnosis and prognosis of CDI. METHODS: All stool specimens submitted for C. difficile toxin EIA testing were cultured to isolate C. difficile. In-house PCR for tcdA, tcdB, cdtA, and cdtB genes were performed using C. difficile isolates. Stool specimens were tested with C. difficile toxins A and B using EIA kit (RIDASCREEN Clostridium difficile toxin A/B, R-Biopharm AG, Darmstadt, Germany). Characteristics and subsequent CDI episodes of toxin EIA-negative and -positive patients were compared. RESULTS: Among 190 C. difficile PCR-positive patients, 83 (43.7%) were toxin EIA-negative. Multivariate analysis revealed independent associations toxin EIA-negative results and shorter hospital stays (OR = 0.98, 95% CI 0.96-0.99, p = 0.013) and less high-risk antibiotic exposure in the preceding month (OR = 0.38, 95% CI 0.16-0.94, p = 0.035). Toxin EIA-negative patients displayed a significantly lower white blood cell count rate (11.0 vs. 35.4%, p < 0.001). Among the 54 patients who were toxin EIA-negative and did not receive CDI treatment, three (5.6%) were diagnosed with CDI after 7-21 days without complication. CONCLUSION: Our study demonstrates that toxin EIA-negative patients had milder laboratory findings and no complications, despite not receiving treatment. Prolonged hospitalisation and exposure to high-risk antibiotics could potentially serve as markers for the development of toxin EIA-positive CDI.
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Proteínas de Bactérias , Toxinas Bacterianas , Clostridioides difficile , Infecções por Clostridium , Fezes , Humanos , Clostridioides difficile/genética , Fezes/microbiologia , Masculino , Feminino , Toxinas Bacterianas/análise , Infecções por Clostridium/diagnóstico , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/microbiologia , Idoso , Pessoa de Meia-Idade , Proteínas de Bactérias/genética , Proteínas de Bactérias/análise , Enterotoxinas/análise , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Técnicas Imunoenzimáticas , Adulto , Resultado do Tratamento , Reação em Cadeia da Polimerase , PrognósticoRESUMO
PURPOSE: Commercial double J stents (DJS) have a uniform shape regardless of the specific nature of various ureteral diseases. We tested renovated DJS and compared them with conventional DJS using ureter models. METHODS: One straight ureter model included stenosis at the distal ureter near the ureterovesical junction and the other did not. We used conventional DJS and renovated 5- and 6-Fr soft DJS for ureter stones and 6-, 7-, and 8.5-Fr hard DJS for tumors. The DJS comprised holes in the upper, middle, or lower one-third of the shaft (length, 24 cm; 2-cm-diameter coils at both ends). More holes were created along the shaft based on the ureteral disease location. Conventional DJS had holes spaced 1 cm apart along the shaft. Renovated DJS had holes spaced 1 cm apart along the shaft with 0.5-cm intervals on the upper, middle, or lower one-third of the shaft. Urine flow was evaluated. RESULTS: As the DJS diameter increased, the flow rate decreased. The flow rates of DJS with holes in the lower shaft were relatively lower than those of conventional DJS and DJS with holes in the upper and middle shafts. In the ureter model without stenosis, 6-, 7-, and 8.5-Fr renovated stents exhibited significantly higher flow rates than conventional stents. In the ureter model with stenosis, 5-, 6-, 7-, and 8.5-Fr renovated stents did not exhibit significantly higher flow rates than conventional stents. CONCLUSION: Renovated stents and conventional stents did not exhibit significant differences in urine flow with stenosis.
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Ureter , Ureterolitíase , Humanos , Ureter/cirurgia , Constrição Patológica , StentsRESUMO
BACKGROUND AND AIM: The benefits of entecavir (ETV) versus tenofovir disoproxil fumarate (TDF) in reducing the development of chronic hepatitis B (CHB)-related hepatocellular carcinoma remain controversial. Whether mortality rates differ between patients with CHB treated with ETV and those treated with TDF is unclear. METHODS: A total of 2542 patients with CHB treated with either ETV or TDF were recruited from a multinational cohort. A 1:1 propensity score matching was performed to balance the differences in baseline characteristics between the two patient groups. We aimed to compare the all-cause, liver-related, and non-liver-related mortality between patients receiving ETV and those receiving TDF. RESULTS: The annual incidence of all-cause mortality in the entire cohort was 1.0/100 person-years (follow-up, 15 757.5 person-years). Patients who received TDF were younger and had a higher body mass index, platelet count, hepatitis B virus deoxyribonucleic acid levels, and proportion of hepatitis B e-antigen seropositivity than those who received ETV. The factors associated with all-cause mortality were fibrosis-4 index > 6.5 (hazard ratio [HR]/confidence interval [CI]: 3.13/2.15-4.54, P < 0.001), age per year increase (HR/CI: 1.05/1.04-1.07, P < 0.001), alanine aminotransferase level per U/L increase (HR/CI: 0.997/0.996-0.999, P = 0.003), and γ-glutamyl transferase level per U/L increase (HR/CI: 1.002/1.001-1.003, P < 0.001). No significant difference in all-cause mortality was observed between the ETV and TDF groups (log-rank test, P = 0.69). After propensity score matching, no significant differences in all-cause, liver-related, or non-liver-related mortality were observed between the two groups. CONCLUSIONS: Long-term outcomes of all-cause mortality and liver-related and non-liver-related mortality did not differ between patients treated with ETV and those receiving TDF.
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Antivirais , Guanina , Hepatite B Crônica , Tenofovir , Humanos , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/mortalidade , Tenofovir/uso terapêutico , Guanina/análogos & derivados , Guanina/uso terapêutico , Masculino , Feminino , Pessoa de Meia-Idade , Antivirais/uso terapêutico , Adulto , Estudos de Coortes , Carcinoma Hepatocelular/mortalidade , Neoplasias Hepáticas/mortalidade , Pontuação de PropensãoRESUMO
Background: Ultraviolet B (UVB) from sunlight represents a major environmental factor that causes toxic effects resulting in structural and functional cutaneous abnormalities in most living organisms. Although numerous studies have indicated the biological mechanisms linking UVB exposure and cutaneous manifestations, they have typically originated from a single study performed under limited conditions. Methods: We accessed all publicly accessible expression data of various skin cell types exposed to UVB, including skin biopsies, keratinocytes, and fibroblasts. We performed biological network analysis to identify the molecular mechanisms and identify genetic biomarkers. Results: We interpreted the inflammatory response and carcinogenesis as major UVB-induced signaling alternations and identified three candidate biomarkers (IL1B, CCL2, and LIF). Moreover, we confirmed that these three biomarkers contribute to the survival probability of patients with cutaneous melanoma, the most aggressive and lethal form of skin cancer. Conclusion: Our findings will aid the understanding of UVB-induced cutaneous toxicity and the accompanying molecular mechanisms. In addition, the three candidate biomarkers that change molecular signals due to UVB exposure of skin might be related to the survival rate of patients with cutaneous melanoma.
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Melanoma , Neoplasias Cutâneas , Humanos , Melanoma/genética , Neoplasias Cutâneas/genética , Sequência de Bases , Biomarcadores , RNARESUMO
BACKGROUND: Fluorescent lymphography (FL) using indocyanine green (ICG) allows for the visualization of all draining lymph nodes (LNs), thereby increasing LN retrieval. However, no studies have assessed the efficacy of FL in high body mass index (BMI) gastric cancer patients, even as LN yield decreases with increasing BMI in gastrectomy. This study aimed to investigate the influence of FL on LN retrieval in high BMI gastric cancer patients. METHODS: Gastric cancer patients who underwent laparoscopic or robotic gastrectomies from 2013 to 2021 were included. Patients were classified into two groups, with FL (FL group) or without FL (non-FL group). The effect of FL on LN retrieval was assessed by BMI. Inverse probability of treatment weighting (IPTW) was used to ensure comparability between groups. RESULTS: Retrieved LN number decreased as BMI increased regardless of FL application (P < 0.001). According to the IPTW analysis, the mean retrieved LN number was significantly higher in the FL group (48.4 ± 18.5) than in the non-FL group (39.8 ± 16.3, P < 0.001), irrespective of BMI. The FL group exhibited a significantly higher proportion of patients with 16 or more LNs (99.5%) than the non-FL group (98.1%, P < 0.001). The FL group also had a significantly higher proportion of patients with 30 or more LNs (86.6%) than the non-FL group (72.2%, P < 0.001). In both the normal and high-BMI patients, the FL group had a significantly larger percentage of patients with a higher nodal classification than the non-FL group. CONCLUSION: FL resulted in more LN retrieval, even in high BMI patients. FL ensures accurate staging by maintaining the appropriate retrieved LN number in high BMI gastric cancer patients.
Assuntos
Linfografia , Neoplasias Gástricas , Humanos , Linfografia/métodos , Excisão de Linfonodo/métodos , Índice de Massa Corporal , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Linfonodos/diagnóstico por imagem , Linfonodos/cirurgia , Linfonodos/patologia , Corantes , Gastrectomia/métodos , Estudos RetrospectivosRESUMO
Postoperative pancreatic fistula is a life-threatening complication with an unmet need for accurate prediction. This study was aimed to develop preoperative artificial intelligence-based prediction models. Patients who underwent pancreaticoduodenectomy were enrolled and stratified into model development and validation sets by surgery between 2016 and 2017 or in 2018, respectively. Machine learning models based on clinical and body composition data, and deep learning models based on computed tomographic data, were developed, combined by ensemble voting, and final models were selected comparison with earlier model. Among the 1333 participants (training, n = 881; test, n = 452), postoperative pancreatic fistula occurred in 421 (47.8%) and 134 (31.8%) and clinically relevant postoperative pancreatic fistula occurred in 59 (6.7%) and 27 (6.0%) participants in the training and test datasets, respectively. In the test dataset, the area under the receiver operating curve [AUC (95% confidence interval)] of the selected preoperative model for predicting all and clinically relevant postoperative pancreatic fistula was 0.75 (0.71-0.80) and 0.68 (0.58-0.78). The ensemble model showed better predictive performance than the individual ML and DL models.
Assuntos
Aprendizado Profundo , Fístula Pancreática , Humanos , Fístula Pancreática/diagnóstico , Fístula Pancreática/etiologia , Pancreaticoduodenectomia/efeitos adversos , Inteligência Artificial , Fatores de Risco , Curva ROC , Complicações Pós-Operatórias/etiologiaRESUMO
Background: Extracorporeal membrane oxygenation (ECMO) is an intervention for severe heart and lung failure; however, it poses the risk of complications, including gastrointestinal bleeding (GIB). Comprehensive analyses of GIB in patients undergoing ECMO are limited, and its impact on clinical outcomes remains unclear. Methods: This retrospective study included 484 patients who received venovenous and venoarterial ECMO between January 2015 and December 2022. Data collected included patient characteristics, laboratory results, GIB details, and interventions. Statistical analyses were performed to identify risk factors and assess the outcomes. Results: GIB occurred in 44 of 484 patients (9.1%) who received ECMO. Multivariable analysis revealed that older age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.01-1.06; p=0.0130) and need to change the ECMO mode (OR, 3.74; 95% CI, 1.75-7.96; p=0.0006) were significant risk factors for GIB, whereas no association was found with antiplatelet or systemic anticoagulation therapies during ECMO management. Half of the patients with GIB (22/44, 50%) underwent intervention, with endoscopy as the primary modality (19/22, 86.4%). Patients who underwent ECMO and developed GIB had higher rates of mortality (40/44 [90.9%] vs. 262/440 [59.5%]) and ECMO weaning failure (38/44 [86.4%] vs. 208/440 [47.3%]). Conclusion: GIB in patients undergoing ECMO is associated with adverse outcomes, including increased risks of mortality and weaning failure. Even in seemingly uncomplicated cases, it is crucial to avoid underestimating the significance of GIB.