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BACKGROUND: The global impact of the coronavirus disease 2019 (COVID-19) pandemic has resulted in significant morbidity and mortality. Immunocompromised patients, particularly those treated for B-cell lymphoma, have shown an increased risk of persistent infection with SARS-CoV-2 and severe outcomes and mortality. Multi-mutational SARS-CoV-2 variants can arise during the course of such persistent cases of COVID-19. No optimal, decisive strategy is currently available for patients with persistent infection that allows clinicians to sustain viral clearance, determine optimal timing to stop treatment, and prevent virus reactivation. We introduced a novel treatment combining antivirals, neutralizing antibodies, and genomic analysis with frequent monitoring of spike-specific antibody and viral load for immunocompromised patients with persistent COVID-19 infection. The aim of this retrospective study was to report and evaluate the efficacy of our novel treatment for immunocompromised B-cell lymphoma patients with persistent COVID-19 infection. METHODS: This retrospective descriptive analysis had no controls. Patients with B-cell lymphoma previously receiving immunotherapy including anti-CD20 antibodies, diagnosed as having COVID-19 infection, and treated in our hospital after January 2022 were included. We selected anti-SARS-CoV-2 monoclonal antibodies according to subvariants. Every 5 days, viral load was tested by RT-PCR, with antivirals continued until viral shedding was confirmed. Primary outcome was virus elimination. Independent predictors of prolonged viral shedding time were determined by multivariate Cox regression. RESULTS: Forty-four patients were included in this study. Thirty-five patients received rituximab, 19 obinutuzumab, and 26 bendamustine. Median treatment duration was 10 (IQR, 10-20) days; 22 patients received combination antiviral therapy. COVID-19 was severe in 16 patients, and critical in 2. All patients survived, with viral shedding confirmed at median 28 (IQR, 19-38) days. Bendamustine use or within 1 year of last treatment for B-cell lymphoma, and multiple treatment lines for B-cell lymphoma significantly prolonged time to viral shedding. CONCLUSIONS: Among 44 consecutive patients treated, anti-SARS-CoV-2 monoclonal antibodies and long-term administration of antiviral drugs, switching, and combination therapy resulted in virus elimination and 100% survival. Bendamustine use, within 1 year of last treatment for B-cell lymphoma, and multiple treatment lines for B-cell lymphoma were the significant independent predictors of prolonged viral shedding time.
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Antivirais , COVID-19 , Linfoma de Células B , SARS-CoV-2 , Carga Viral , Eliminação de Partículas Virais , Humanos , Estudos Retrospectivos , Masculino , Feminino , Pessoa de Meia-Idade , Eliminação de Partículas Virais/efeitos dos fármacos , SARS-CoV-2/imunologia , SARS-CoV-2/efeitos dos fármacos , COVID-19/virologia , COVID-19/imunologia , Antivirais/uso terapêutico , Antivirais/administração & dosagem , Idoso , Linfoma de Células B/tratamento farmacológico , Linfoma de Células B/virologia , Linfoma de Células B/imunologia , Fatores de Risco , Carga Viral/efeitos dos fármacos , Tratamento Farmacológico da COVID-19 , Hospedeiro Imunocomprometido , Adulto , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais/administração & dosagem , Anticorpos Antivirais/sangue , Anticorpos Antivirais/imunologia , Rituximab/uso terapêutico , Rituximab/administração & dosagem , Anticorpos Neutralizantes/imunologia , Idoso de 80 Anos ou maisRESUMO
BACKGROUND: Serum Krebs von den Lungen 6 (KL-6), which reflects alveolar epithelial injury, was reported to be useful to predict the progression of pneumonitis induced by COVID-19 in the early phase. This study aimed to evaluate the peak value of serum KL-6 during hospitalization for COVID-19 to discover a more useful biomarker for predicting prognosis in COVID-19 patients. METHODS: In this retrospective, single-center, observational study, we analyzed the data of 147 hospitalized patients who required supplemental oxygen, high-flow oxygen therapy, or invasive mechanical ventilation for respiratory failure due to COVID-19 from March 2020 to February 2021. We extracted data on patient sex, age, comorbidities, treatment, and biomarkers including the initial and peak values of KL-6. Inclusion criteria were examination of the studied biomarkers at least once within 3 days of admission, then at least once a week, and at a minimum, at least twice during the entire hospitalization. Area under the receiver operating curve (AUC) was analyzed to determine the accuracy of several biomarkers including KL-6 and LDH for predicting poor prognosis defined as survivors requiring invasive mechanical ventilation for over 28 days or non-survivors of COVID-19. Univariable and multivariate logistic regression analyses were performed to investigate the prognostic value of the baseline characteristics and biomarkers. RESULTS: Among the 147 patients, 108 (73.5%) had a good prognosis and 39 (26.5%) had a poor prognosis. The AUC analysis indicated that peak KL-6 showed precise accuracy in the discrimination of patients with poor prognosis (AUC 0.89, p < 0.001). The best cut-off value for KL-6 concentration was 966 U/mL (sensitivity 81.6%, specificity84.3%). After adjustment, increasing peak values of KL-6 or LDH were associated with a high risk of poor prognosis, with an adjusted odds ratio of 1.35 for peak value of KL-6, per 100 U/mL increase (95% CI 1.17-1.57, p < 0.001) and 2.16 for peak value of LDH, per 100 U/L increase (95% CI 1.46-3.20, p < 0.001). CONCLUSIONS: Peak values of KL-6 and LDH measured during hospitalization might help to identify COVID-19 patients with respiratory failure who are at higher risk for a poor prognosis.
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COVID-19 , Insuficiência Respiratória , Biomarcadores , Humanos , Oxigênio , Prognóstico , Estudos RetrospectivosRESUMO
BACKGROUND: Dabigatran is one of the four drugs currently used as a direct oral anticoagulant in Japan. Idarucizumab, which specifically targets dabigatran, was recently approved in Japan. We present a case of intracranial hemorrhage in a traumatic brain injury patient taking dabigatran who was treated by administering idarucizumab. CASE PRESENTATION: A 72-year-old man was injured in a traffic accident and was transferred to our emergency room. On arrival, his Glasgow Coma Scale score was 14 (eye, 3; verbal, 5; motor, 6), and his other vital signs were stable. Computed tomography (CT) imaging on arrival showed a small intracranial hematoma. A second CT 3 h later revealed expansion of the hematoma. We received information that he was taking dabigatran only after the second CT. Idarucizumab was then promptly administered, and emergency craniotomy for hematoma removal was performed. There was no tendency for bleeding during the operation, and blood transfusion was not required during the perioperative period. Although the patient underwent additional surgery for subdural effusion and hydrocephalus, his postoperative course was uneventful. He was transferred to a rehabilitation hospital on postoperative day 102. CONCLUSION: We managed a patient taking dabigatran who suffered traumatic intracranial hemorrhage by administering idarucizumab preoperatively without the need for blood transfusion perioperatively. We suggest that idarucizumab could be a potent therapeutic bridge to definitive surgical management in such patients with traumatic brain injury who are taking dabigatran.
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Computed tomography (CT) embedded in the emergency room has gained importance in the early diagnostic phase of trauma care. In 2011, we implemented a new trauma workflow concept with a sliding CT scanner system with interventional radiology features (IVR-CT) that allows CT examination and emergency therapeutic intervention without relocating the patient, which we call the Hybrid emergency room (Hybrid ER). In the Hybrid ER, all life-saving procedures, CT examination, damage control surgery, and transcatheter arterial embolisation can be performed on the same table. Although the trauma workflow realized in the Hybrid ER may improve mortality in severe trauma, the Hybrid ER can potentially affect the efficacy of other in/outpatient diagnostic workflow because one room is occupied by one severely injured patient undergoing both emergency trauma care and CT scanning for long periods. In July 2017, we implemented a new trauma workflow concept with a dual-room sliding CT scanner system with interventional radiology features (dual-room IVR-CT) to increase patient throughput. When we perform emergency surgery or interventional radiology for a severely injured or ill patient in the Hybrid ER, the sliding CT scanner moves to the adjacent CT suite, and we can perform CT scanning of another in/outpatient. We believe that dual-room IVR-CT can contribute to the improvement of both the survival of severely injured or ill patients and patient throughput.
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Eficiência Organizacional , Serviço Hospitalar de Emergência , Tomografia Computadorizada Multidetectores , Radiografia Intervencionista , Fluxo de Trabalho , Catéteres , Embolização Terapêutica , Estudo Historicamente Controlado , Humanos , Japão , Imagem Multimodal , Estudos Retrospectivos , Imagem Corporal TotalRESUMO
BACKGROUND: Blunt thoracic aortic injury (BTAI) is associated with a high mortality rate and the paradigm of treating patients with BTAI currently favours thoracic endovascular aneurysm repair (TEVAR) if possible. In BTAI, lethal malperfusion caused by a pseudoaneurysm has rarely been reported. We present the first report of a successful case in which a pseudoaneurysm causing the infrequent occurrence of lethal malperfusion and subsequent acute severe ischaemia in the distal portion of the thoracic descending aorta was overcome by veno-arterial extracorporeal membrane oxygenation (VA ECMO) as a bridging therapy until the initiation of TEVAR. CASE PRESENTATION: An adult woman was transferred to our emergency room after injuries sustained by falling from height. Her vital signs were unstable on admission. CT examination revealed the multiple injuries: traumatic subarachnoid haemorrhage, severe unstable pelvic fracture, and a grade III injury of the thoracic aorta. We made the decision to perform TEVAR after external fixation and transcatheter arterial embolization (TAE) for the pelvic injury. During preparations for TEVAR, her lower limbs rapidly felt cold, and her blood lactate level and serum potassium rapidly increased. By the clinical data and ultrasonography and lower extremity Doppler, we diagnosed severe ischaemia in distal portion of the descending aorta caused by a pseudoaneurysm proximal to the descending thoracic aorta. Because we still had not prepared for TEVAR, we immediately started VA ECMO until TEVAR could begin. After the initiation of VA ECMO, her lactate and potassium levels could be controlled. Under VA ECMO support, she underwent TEVAR. After inpatient rehabilitation, she was discharged home without neurologic sequelae. CONCLUSIONS: VA ECMO could be an important, less-invasive treatment as a bridging therapy for acute severe malperfusion syndrome until TEVAR is initiated for BTAI.
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Falso Aneurisma/terapia , Aorta Torácica/lesões , Oxigenação por Membrana Extracorpórea , Traumatismos Torácicos/terapia , Lesões do Sistema Vascular/terapia , Ferimentos não Penetrantes/terapia , Adulto , Falso Aneurisma/etiologia , Aneurisma Aórtico/etiologia , Aneurisma Aórtico/terapia , Procedimentos Endovasculares , Feminino , HumanosRESUMO
We report four cases of peritoneal serous papillary adenocarcinoma (PSPC), a rare disease; all patients had ascites and high levels of serum CA125. Clinical and radiological examinations could not differentiate the disease from peritoneal metastatic tumors and mesothelioma, and histopathological analysis including immunochemistry on the specimen obtained at laparotomy or laparoscopy was necessary for the diagnosis. One patient lived for 58 months with cytoreductive surgery and chemotherapy, and another is still living after 20 months by chemotherapy alone. In patients with peritoneal tumors of unknown origin and a high level of serum CA125, taking PSPC into consideration in the differential diagnosis, histopathological examination should be performed.
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Cistadenocarcinoma Papilar/diagnóstico , Neoplasias Peritoneais/diagnóstico , Adulto , Idoso , Biomarcadores Tumorais/metabolismo , Antígeno Ca-125/metabolismo , Cistadenocarcinoma Papilar/metabolismo , Cistadenocarcinoma Papilar/patologia , Diagnóstico Diferencial , Feminino , Humanos , Imuno-Histoquímica , Mesotelioma/diagnóstico , Pessoa de Meia-Idade , Neoplasias Peritoneais/metabolismo , Neoplasias Peritoneais/patologia , PrognósticoRESUMO
A 41-year-old asymptomatic man was, by chance, diagnosed as having a mass in the left upper quadrant of the abdomen by ultrasound. Computed tomography and magnetic resonance imaging showed a slightly enhanced heterogeneous mass, measuring about 5 cm in diameter, adjacent to the pancreas tail and spleen. On abdominal angiography the tumor was found to be fed by the splenic artery, and no encasement was observed. At operation the tumor was connected to the pancreas tail and attached to the spleen, and no metastasis was evident. As a result of these observations, a curative resection was performed. On histological examination the tumor cells had no ductal or architectural organization and were continuous to the normal pancreatic tissues. The cells were negative for Grimelius argylphile and the periodic acid schiff stain. Immunohistochemistry indicated that the tumor cells were positive for keratin and epithelial membrane antigen, but negative for chromogranin A, vimentin, alpha1-antitrypsin and alpha1-antichymotrypsin. The tumor was diagnosed as a small cell carcinoma of the pancreas, which is a rare disease. In previously reported cases curative resection of the tumor had not been possible because of its rapid progression and metastasis, and the prognosis is generally very poor. In our case, however, curative resection of the tumor was done, and the patient is healthy with no signs of recurrence for 56 months after the operation and with no additional therapy.
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Carcinoma de Células Pequenas/cirurgia , Neoplasias Pancreáticas/cirurgia , Adulto , Carcinoma de Células Pequenas/diagnóstico , Carcinoma de Células Pequenas/patologia , Diagnóstico Diferencial , Diagnóstico por Imagem , Humanos , Imuno-Histoquímica , Masculino , Pancreatectomia , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/patologiaRESUMO
BACKGROUND AND AIM: The severe inflammation, increased cell proliferation and marked acid inhibition observed in subjects with Helicobacter pylori-associated enlarged-fold gastritis suggest that enlarged-fold gastritis may be a risk factor for gastric carcinoma. The purpose of the present study was to determine whether a relationship exists between enlarged-fold gastritis and gastric carcinoma. METHODS: One hundred and thirty-five H. pylori-positive patients with early gastric carcinoma and 141 age- and sex-matched H. pylori-positive controls without gastric carcinoma were involved in the study. The widths of gastric body folds were measured by double-contrast radiographs. The mutagenicity of gastric juice was assayed using the Ames test and Salmonella typhimurium TA-98 or TA-100 with S9-mix. Levels of 8-hydroxydeoxyguanosine (8-OHdG) in gastric mucosa were examined using high-performance liquid chromatographic-electrochemical detection. RESULTS: An upward shift in the distribution of gastric fold widths in H. pylori-positive patients with early gastric carcinoma was found. Enlarged-fold gastritis (fold width >/=5 mm) was observed in 81% of the patients with gastric carcinoma, compared with 46% of H. pylori-positive controls. The odds ratio for gastric carcinoma increased with increasing fold width to a maximum of 35.5 in persons with fold width >/=7 mm. The prevalence of diffuse-type early gastric carcinoma in the body region increased with increasing fold width. The mutagenicity of gastric juice from the patients with enlarged-fold gastritis was significantly higher than that in H. pylori-negative controls and H. pylori-positive patients without enlarged folds. Mucosal 8-OHdG levels in the body region of patients with enlarged-fold gastritis were significantly higher than in H. pylori-negative controls and H. pylori-positive patients without enlarged-fold gastritis. Eradication of H. pylori significantly decreased the mutagenicity of gastric juice and 8-OHdG levels in the gastric mucosa from patients with enlarged-fold gastritis. CONCLUSION: A significant association is suggested between enlarged-fold gastritis and gastric carcinoma.
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Dano ao DNA/fisiologia , Suco Gástrico/fisiologia , Gastrite Hipertrófica/microbiologia , Gastrite Hipertrófica/patologia , Infecções por Helicobacter/patologia , Estresse Oxidativo/fisiologia , Neoplasias Gástricas/microbiologia , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Gastrite Hipertrófica/metabolismo , Infecções por Helicobacter/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Testes de Mutagenicidade , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologiaRESUMO
Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is a member of the EGF family. Juxtacrine activity of proHB-EGF (the membrane-anchored form of HB-EGF) has been shown to be significantly potentiated when it is coexpressed with CD9 in vitro. The purpose of our study was to investigate the issue of whether proHB-EGF and CD9 are coexpressed in gastric cancer. HB-EGF gene expression and protein production in human gastric cancers was investigated, and EGF receptor and CD9 expressions were also evaluated. HB-EGF mRNA levels in gastric cancers were elevated, compared with normal gastric tissues, especially in the intestinal type. ProHB-EGF immunoreactivity was detected primarily in the cytoplasm and plasma membrane of gastric cancer cells. Of 66 patients, 40 (60.6%) exhibited proHB-EGF immunoreactivity and the level of its expression was significantly associated with tumor status (p < 0.01) and histological differentiation (p < 0.001). In addition, proHB-EGF mRNA was detected at high levels in the intestinal type by in situ hybridization. CD9 immunoreactivity was found to be preserved in 26 of 36 patients (72.2%) and CD9 protein expression was inversely associated with lymph node status (p < 0.05). A significant correlation between its expression and histological differentiation (p < 0.01) was found, and the association of CD9 with proHB-EGF was increased in the intestinal type, as evidenced by an immunoprecipitation method. These results indicate that the coexpression of proHB-EGF and CD9 may be involved in the tumorigenesis and/or proliferation of gastric cancers in a juxtacrine manner.