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Introduction: Enfortumab vedotin (EV) is an antibody-drug conjugate combining a monoclonal antibody targeting nectin-4 with a highly potent microtubule disrupting agent. EV is expected to be a candidate for the third-line treatment for urothelial carcinoma previously treated with platinum-based chemotherapy and PD-1/PD-L1 inhibitors. Very few cases of patients experienced hyperglycemia of unknown cause. Case Presentation: We describe a 72-year-old Asian man with mild obesity, type 2 diabetes, hyperlipidemia, hypertension, and chemo-resistant metastatic urothelial carcinoma. He developed hyperglycemia and febrile neutropenia after 3 doses of EV. He had hyperglycemia of 489 mg/dL and was started on continuous intravenous insulin infusion (CVII). The patient's intravenous insulin requirements peaked at 316 units per day. He also developed febrile neutropenia and consequent sepsis caused acute kidney injury. Continuous hemodialysis filtration (CHDF) together with antibiotics were started to treat the septic condition. The blood glucose level gradually decreased after CHDF treatment and CHDF was continued for 14 days. The timing of liberation from CHDF correlated with the elimination half-life of EV of 3.4 days. CVII was treated for 26 days and the patient was finally released from the intensive care unit. Conclusion: This case indicates that the uncontrollable hyperglycemia induced by EV during metastatic urothelial carcinoma treatment is effectively managed with CVII and CHDF until the elimination of the adverse effect of EV.
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Aims: The purpose of this study is to establish a novel diagnosis system in early acute coronary syndrome (ACS) using probe electrospray ionization-mass spectrometry (PESI-MS) and machine learning (ML) and to validate the diagnostic accuracy. Methods: A total of 32 serum samples derived from 16 ACS patients and 16 control patients were analyzed by PESI-MS. The acquired mass spectrum dataset was subsequently analyzed by partial least squares (PLS) regression to find the relationship between the two groups. A support vector machine, an ML method, was applied to the dataset to construct the diagnostic algorithm. Results: Control and ACS groups were separated into the two clusters in the PLS plot, indicating ACS patients differed from the control in the profile of serum composition obtained by PESI-MS. The sensitivity, specificity, and accuracy of our diagnostic system were all 93.8%, and the area under the receiver operating characteristic curve showed 0.965 (95% CI: 0.84-1). Conclusion: The PESI-MS and ML-based diagnosis system are likely an optimal solution to assist physicians in ACS diagnosis with its remarkably predictive accuracy.
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RATIONALE: Pyogenic spondylodiscitis is an infectious spinal disease that causes significant motor dysfunctions. Its diagnosis can be challenging owing to its rapid onset and nonspecific symptoms. PATIENT CONCERNS: A 79-year-old Japanese man with a history of type 2 diabetes mellitus and polymyalgia rheumatica presented to our department with tongue pain. Following partial glossectomy and wisdom tooth extraction under general anesthesia, on 10 postoperative day (POD) the patient developed right-sided abdominal pain and difficulty in walking. On 12 POD, the patient was admitted to a municipal hospital due to respiratory distress and paraplegia. DIAGNOSES: The patient was diagnosed with pyogenic spondylodiscitis and empyema. Blood tests revealed elevated C-reactive protein levels (36.5), white blood cell count (19,570), and neutrophil count (17,867). INTERVENTIONS: The patient received meropenem hydrate 3 g/2 days as empiric antibiotic treatment for acute infection. Upon admission to the emergency department on 16 POD, the lung abscess was drained, hemilaminectomy was performed. OUTCOMES: Blood cultures, sputum tests, and cultures from the thoracic and spinal abscesses drained during surgery revealed methicillin-sensitive Staphylococcus aureus. The infection was successfully managed, and the respiratory disturbance and inflammatory response improved. However, the lower half of the patient body remained paralyzed. Subsequently, the patient was transferred to a rehabilitation facility on 45 POD. The patient continued to undergo functional restoration training, gradually regained function, and eventually achieved the ability to walk with grasping gait. LESSONS: This is the first case report of S aureus causing pyogenic spondylodiscitis and empyema due to blood stream infection from a post-oral surgical wound. Pyogenic spondylodiscitis arising from a secondary hematogenous infection is difficult to diagnose and can lead to severe functional impairment. Prompt and appropriate diagnosis and treatment based on detailed patient interviews, additional blood tests, and computed tomography are essential.
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Discite , Neoplasias da Língua , Extração Dentária , Humanos , Masculino , Idoso , Extração Dentária/efeitos adversos , Discite/diagnóstico , Discite/microbiologia , Discite/etiologia , Neoplasias da Língua/cirurgia , Dente Serotino/cirurgia , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/complicações , Infecções Estafilocócicas/etiologia , Empiema/etiologia , Empiema/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/microbiologia , Antibacterianos/uso terapêuticoRESUMO
Background: Stratify new lung cancer patients based on the risk of in-hospital mortality rate after diagnosis. Methods: 522,941 lung cancer cases with available data on the Surveillance, Epidemiology, and End Results (SEER) were analyzed for the predicted probability based on six fundamental variables including age, gender, tumor size, T, N, and AJCC stages. The patients were randomly assigned to the training (n = 115,145) and validation datasets (n = 13,017). The remaining cohort with missing values (n = 394,779) was then combined with the primary lung tumour datasets (n = 1018) from The Cancer Genome Atlas, Lung Adenocarcinoma and Lung Squamous Cell Carcinoma projects (TCGA-LUAD & TCGA-LUSC) for external validation and sensitivity analysis. Results: Receiver Operating Characteristic (ROC) analyses showed high discriminatory power in the training and internal validation cohorts (Area under the curve [AUC] of 0.78 (95%CI = 0.78-0.79) and 0.78 (95%CI = 0.77-0.79), respectively), whereas that of the model on external validation data was 0.759 (95%CI = 0.757-0.761). We developed a static nomogram, a web app, and a risk table based on a logistic regression model using algorithm-selected variables. Conclusions: Our model can stratify lung cancer patients into high- and low-risk of in-hospital mortality to assist clinical further planning.
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Adenocarcinoma de Pulmão , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Mortalidade Hospitalar , Aprendizado de MáquinaRESUMO
RATIONALE: Infections that spread to the pterygomandibular muscle can be misdiagnosed as temporomandibular disorder (TMD) because of the resulting difficulty in opening the mouth. Importantly, infection of the pterygomandibular space can extend to the skull base in the early stages, and a delay in therapeutic intervention can lead to severe complications. PATIENT CONCERNS: A 77-year-old Japanese man with trismus after pulpectomy was referred to our department. This case report describes a rare instance of meningitis with septic shock caused by an odontogenic infection, initially misdiagnosed as TMD due to similar symptoms, leading to life-threatening complications. DIAGNOSIS: The patient was diagnosed with sepsis and meningitis resulting from cellulitis in the pterygomandibular space caused by iatrogenic infection after pulpectomy of the right upper second molar. INTERVENTIONS: After emergency hospitalization, the patient developed septic shock and required blood purification. Subsequently, abscess drainage and extraction of the causative tooth were performed. However, the patient developed hydrocephalus secondary to meningitis and underwent ventriculoperitoneal shunting to alleviate the condition. OUTCOMES: The infection was controlled and the patient level of consciousness improved following treatment for hydrocephalus. The patient was transferred to a hospital for rehabilitation on the 106th day of hospitalization. LESSONS: Infections of the pterygomandibular space may be misdiagnosed as TMD, owing to the main symptoms of restricted mouth opening and pain on mouth opening. A prompt and appropriate diagnosis is crucial because these infections can lead to life-threatening complications. A detailed interview, along with additional blood tests and computed tomography (CT) scans, can aid in making an accurate diagnosis.
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Diagnóstico Diferencial , Erros de Diagnóstico , Meningite , Transtornos da Articulação Temporomandibular , Humanos , Masculino , Idoso , Choque Séptico/etiologia , Meningite/complicações , Meningite/diagnóstico , Transtornos da Articulação Temporomandibular/diagnósticoRESUMO
BACKGROUND: Patients with severe acute kidney injury (AKI) who require continuous venovenous hemodiafiltration (CVVHDF) in intensive care unit (ICU) are at high mortality risk. Little is known about clinical biomarkers for risk prediction, optimal initiation, and optimal discontinuation of CVVHDF. METHODS: This prospective observational study was conducted in seven university-affiliated ICUs. For urinary neutrophil gelatinase-associated lipocalin (NGAL) and plasma IL-6 measurements, samples were collected at initiation, 24 h, 48 h after, and CVVHDF discontinuation in adult patients with severe AKI. The outcomes were deaths during CVVHDF and CVVHDF dependence. RESULTS: A total number of 133 patients were included. Twenty-eight patients died without CVVHDF discontinuation (CVVHDF nonsurvivors). Urinary NGAL and plasma IL-6 at the CVVHDF initiation were significantly higher in CVVHDF nonsurvivors than in survivors. Among 105 CVVHDF survivors, 70 patients were free from renal replacement therapy (RRT) or death in the next 7 days after discontinuation (success group), whereas 35 patients died or needed RRT again (failure group). Urinary NGAL at CVVHDF discontinuation was significantly lower in the success group (93.8 ng/ml vs. 999 ng/ml, p < 0.01), whereas no significant difference was observed in plasma IL-6 between the groups. Temporal elevations of urinary NGAL levels during the first 48 h since CVVHDF initiation were observed in CVVHDF nonsurvivors and those who failed in CVVHDF discontinuation. CONCLUSIONS: Urinary NGAL at CVVHDF initiation and discontinuation was associated with mortality and RRT dependence, respectively. The serial changes of urinary NGAL might also help predict the prognosis of patients with AKI on CVVHDF.
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Background: The Japan Society for Blood Purification in Critical Care (JSBPCC) has reported survey results on blood purification therapy (BPT) for critically ill patients in 2005, 2009, and 2013. To clarify the current clinical status, including details of the modes used, treated diseases, and survival rate, we conducted this cohort study using data from the nationwide JSBPCC registry in 2018. Methods: We analyzed data of 2371 patients who underwent BPT in the intensive care units of 43 facilities to investigate patient characteristics, disease severity, modes of BPTs, including the dose of continuous renal replacement therapy (CRRT) and hemofilters, treated diseases, and the survival rate for each disease. Disease severity was assessed using Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment (SOFA) scores. Results: BPT was performed 2867 times in the 2371 patients. Mean APACHE II and SOFA scores were 23.5 ± 9.4 and 10.0 ± 4.4, respectively. The most frequently used mode of BPT was CRRT (67.4%), followed by intermittent renal replacement therapy (19.1%) and direct hemoperfusion with the polymyxin B-immobilized fiber column (7.3%). The most commonly used anticoagulant was nafamostat mesilate (78.6%). Among all patients, the 28-day survival rate was 61.7%. CRRT was the most commonly used mode for many diseases, including acute kidney injury (AKI), multiple organ failure (MOF), and sepsis. The survival rate decreased according to the severity of AKI (P = 0.001). The survival rate was significantly lower in patients with multiple organ failure (MOF) (34.6%) compared with acute lung injury (ALI) (48.0%) and sepsis (58.0%). Multivariate logistic regression analysis revealed that sepsis, ALI, acute liver failure, cardiovascular hypotension, central nervous system disorders, and higher APACHE II scores were significant predictors of higher 28-day mortality. Conclusion: This large-scale cohort study revealed the current status of BPT in Japan. It was found that CRRT was the most frequently used mode for critically ill patients in Japan and that 28-day survival was lower in those with MOF or sepsis. Further investigations are required to clarify the efficacy of BPT for critically ill patients.Trial Registration : UMIN000027678. Supplementary Information: The online version contains supplementary material available at 10.1186/s41100-022-00445-0.
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Most of the diseases for which apheresis therapy is indicated are intractable and rare, and each patient has a different background and treatment course prior to apheresis therapy initiation. Therefore, it is difficult to conduct large-scale randomized controlled trials to secure high-quality evidence. Under such circumstances, the American Society for Apheresis (ASFA) issued its guidelines in 2007, which were repeatedly revised until the latest edition in 2019. The ASFA guidelines are comprehensive. However, in the United States, a centrifugal separation method is mainly used for apheresis, whereas the mainstream procedure in Japan is the membrane separation method. The target diseases and their backgrounds are different from those in Japan. Due to these differences, the direct adoption of the ASFA guidelines in Japanese practice creates various problems. One of the features of apheresis in Japan is the development of treatment methods using hollow-fiber devices such as double filtration plasmapheresis (DFPP) and selective plasma exchange and adsorption-type devices such as polymyxin B-immobilized endotoxin adsorption columns. Specialists in emergency medicine, hematology, collagen diseases/rheumatology, respiratory medicine, cardiovascular medicine, gastroenterology, neurology, nephrology, and dermatology who are familiar with apheresis therapy gathered for this guideline, which covers 86 diseases. In addition, since apheresis therapy involves not only physicians but also clinical engineers, nurses, dieticians, and many other medical professionals, this guideline was prepared in the form of a worksheet so that it can be easily understood at the bedside. Moreover, to the clinical purposes, this guideline is designed to summarize apheresis therapy in Japan and to disseminate and further develop Japanese apheresis technology to the world. As diagnostic and therapeutic techniques are constantly advancing, the guidelines need to be revised every few years. In order to ensure the high quality of apheresis therapy in Japan, both the Japanese Society for Apheresis Registry and the guidelines will be inseparable.
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Remoção de Componentes Sanguíneos/métodos , Remoção de Componentes Sanguíneos/normas , Humanos , Japão , Sociedades MédicasRESUMO
BACKGROUND: Shock and organ damage occur in critically ill patients in the emergency department because of biological responses to invasion, and cytokines play an important role in their development. It is important to predict early multiple organ dysfunction (MOD) because it is useful in predicting patient outcomes and selecting treatment strategies. This study examined the accuracy of biomarkers, including interleukin (IL)-6, in predicting early MOD in critically ill patients compared with that of quick sequential organ failure assessment (qSOFA). METHODS: This was a multicenter observational sub-study. Five universities from 2016 to 2018. Data of adult patients with systemic inflammatory response syndrome who presented to the emergency department or were admitted to the intensive care unit were prospectively evaluated. qSOFA score and each biomarker (IL-6, IL-8, IL-10, tumor necrosis factor-α, C-reactive protein, and procalcitonin [PCT]) level were assessed on Days 0, 1, and 2. The primary outcome was set as MOD on Day 2, and the area under the curve (AUC) was analyzed to evaluate qSOFA scores and biomarker levels. RESULTS: Of 199 patients, 38 were excluded and 161 were included. Patients with MOD on Day 2 had significantly higher qSOFA, SOFA, and Acute Physiology and Chronic Health Evaluation II scores and a trend toward worse prognosis, including mortality. The AUC for qSOFA score (Day 0) that predicted MOD (Day 2) was 0.728 (95% confidence interval [CI]: 0.651-0.794). IL-6 (Day 1) showed the highest AUC among all biomarkers (0.790 [95% CI: 0.711-852]). The combination of qSOFA (Day 0) and IL-6 (Day 1) showed improved prediction accuracy (0.842 [95% CI: 0.771-0.893]). The combination model using qSOFA (Day 1) and IL-6 (Day 1) also showed a higher AUC (0.868 [95% CI: 0.799-0.915]). The combination model of IL-8 and PCT also showed a significant improvement in AUC. CONCLUSIONS: The addition of IL-6, IL-8 and PCT to qSOFA scores improved the accuracy of early MOD prediction.
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Estado Terminal , Sepse , Adulto , Biomarcadores , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Insuficiência de Múltiplos Órgãos/diagnóstico , Escores de Disfunção Orgânica , Prognóstico , Curva ROC , Estudos Retrospectivos , Sepse/diagnósticoRESUMO
OBJECTIVES: Several inflammation markers have been reported to be associated with unfavorable clinical outcomes in critically ill patients. We aimed to elucidate whether serum interleukin-6 concentration considered with Sequential Organ Failure Assessment score can better predict mortality in critically ill patients. DESIGN: A prospective observational study. SETTING: Five university hospitals in 2016-2018. PATIENTS: Critically ill adult patients who met greater than or equal to two systemic inflammatory response syndrome criteria at admission were included, and those who died or were discharged within 48 hours were excluded. INTERVENTIONS: Inflammatory biomarkers including interleukin (interleukin)-6, -8, and -10; tumor necrosis factor-α; C-reactive protein; and procalcitonin were blindly measured daily for 3 days. Area under the receiver operating characteristic curve for Sequential Organ Failure Assessment score at day 2 according to 28-day mortality was calculated as baseline. Combination models of Sequential Organ Failure Assessment score and additional biomarkers were developed using logistic regression, and area under the receiver operating characteristic curve calculated in each model was compared with the baseline. MEASUREMENTS AND MAIN RESULTS: Among 161 patients included in the study, 18 (11.2%) did not survive at day 28. Univariate analysis for each biomarker identified that the interleukin-6 (days 1-3), interleukin-8 (days 0-3), and interleukin-10 (days 1-3) were higher in nonsurvivors than in survivors. Analyses of 28-day mortality prediction by a single biomarker showed interleukin-6, -8, and -10 at days 1-3 had a significant discrimination power, and the interleukin-6 at day 3 had the highest area under the receiver operating characteristic curve (0.766 [0.656-0.876]). The baseline area under the receiver operating characteristic curve for Sequential Organ Failure Assessment score predicting 28-day mortality was 0.776 (0.672-0.880). The combination model using additional interleukin-6 at day 3 had higher area under the receiver operating characteristic curve than baseline (area under the receiver operating characteristic curve = 0.844, area under the receiver operating characteristic curve improvement = 0.068 [0.002-0.133]), whereas other biomarkers did not improve accuracy in predicting 28-day mortality. CONCLUSIONS: Accuracy for 28-day mortality prediction was improved by adding serum interleukin-6 concentration to Sequential Organ Failure Assessment score.
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Background: Most pancreatic cancers are found at progressive stages when they cannot be surgically removed. Therefore, a highly accurate early detection method is urgently needed. Methods: This study analyzed serum from Japanese patients who suffered from pancreatic ductal adenocarcinoma (PDAC) and aimed to establish a PDAC-diagnostic system with metabolites in serum. Two groups of metabolites, primary metabolites (PM) and phospholipids (PL), were analyzed using liquid chromatography/electrospray ionization mass spectrometry. A support vector machine was employed to establish a machine learning-based diagnostic algorithm. Results: Integrating PM and PL databases improved cancer diagnostic accuracy and the area under the receiver operating characteristic curve. It was more effective than the algorithm based on either PM or PL database, or single metabolites as a biomarker. Subsequently, 36 statistically significant metabolites were fed into the algorithm as a collective biomarker, which improved results by accomplishing 97.4% and was further validated by additional serum. Interestingly, specific clusters of metabolites from patients with preoperative neoadjuvant chemotherapy (NAC) showed different patterns from those without NAC and were somewhat comparable to those of the control. Conclusion: We propose an efficient screening system for PDAC with high accuracy by liquid biopsy and potential biomarkers useful for assessing NAC performance.
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BACKGROUND: Predicting multiple organ dysfunction (MOD) in the late phase of critical illnesses is essential. Cytokines are considered biomarkers that can predict clinical outcomes; however, their predictive value for late-phase MOD is unknown. This study aimed to identify the biomarker with the highest predictive value for late-phase MOD. METHODS: This observational study prospectively evaluated data on adult patients with systemic inflammatory response syndrome, those who presented to the emergency department or were admitted to intensive care units in five tertiary hospitals (nâ=â174). Seven blood biomarkers levels (interleukin-6 [IL-6], IL-8, IL-10, tumor-necrosis factor-α, white blood cells, C-reactive protein, and procalcitonin) were measured at three timepoints (days 0, 1, and 2). The area under the receiver operating characteristic curve (AUC) was analyzed to evaluate predictive values for MOD (primary outcome, MOD on day 7 [late-phase]; secondary outcome, MOD on day 3 [early-phase]). RESULTS: Of the measured 7 biomarkers, blood IL-6 levels on day 2 had the highest predictive value for MOD on day 7 using single timepoint data (AUC 0.825, 95% confidence interval [CI] 0.754-0.879). Using three timepoint biomarkers, blood IL-6 levels had the highest predictive value of MOD on day 7 (AUC 0.838, 95% CI 0.768-0.890). Blood IL-6 levels using three timepoint biomarkers had also the highest predictive value for MOD on day 3 (AUC 0.836, 95% CI 0.766-0.888). CONCLUSION: Of the measured biomarkers, blood IL-6 levels had the highest predictive value for MOD on days 3 and 7. Blood IL-6 levels predict early- and late-phase MOD in critically ill patients.
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Interleucina-6/sangue , Insuficiência de Múltiplos Órgãos/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estado Terminal , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos ProspectivosRESUMO
The 2019 novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has caused a global outbreak of infection. In general, children with coronavirus disease-2019 have been reported to show milder respiratory symptoms than adult patients. Here, we have described a case of a SARS-CoV-2-infected infant who presented to our hospital with a severe episode of an apparent life-threatening event (ALTE). An 8-month-old, otherwise healthy female infant presented to our hospital because of a sudden cardiopulmonary arrest. Approximately 1 h before this episode, the patient showed no symptoms, except a worse humor than usual. On arrival at our hospital, the patient had severe acidosis, but there were no clear signs of inflammatory response. Chest computed tomography showed weak consolidations in the upper right lung and atelectasis in the lower left lung. No signs of congenital heart disease or cardiomyopathy were observed on echocardiography, and no significant arrhythmia was observed during the clinical course. However, SARS-CoV-2 RNA was detected by real-time reverse transcription polymerase chain reaction in tracheal aspirate and urine samples. Although the assessment of further similar cases is indispensable, this case suggests that SARS-CoV-2 infection may be an underlying factor in the pathophysiology of ALTE.
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Evento Inexplicável Breve Resolvido/etiologia , COVID-19/etiologia , Evento Inexplicável Breve Resolvido/diagnóstico por imagem , COVID-19/diagnóstico , Teste de Ácido Nucleico para COVID-19 , Eletrocardiografia , Feminino , Parada Cardíaca/etiologia , Testes Hematológicos , Humanos , Lactente , Tomografia Computadorizada por Raios XRESUMO
Novel coronavirus (SARS-Coronavirus-2:SARS-CoV-2) which emerged in Wuhan, China, has spread to multiple countries rapidly. We report the first case of meningitis associated with SARS-CoV-2 who was brought in by ambulance due to a convulsion accompanied by unconsciousness. He had never been to any foreign countries. He felt generalized fatigue and fever (day 1). He saw doctors nearby twice (day 2 and 5) and was prescribed Laninamivir and antipyretic agents, His family visited his home and found that he was unconsciousness and lying on the floor in his vomit. He was immediately transported to this hospital by ambulance (day 9). Under emergency transport, he had transient generalized seizures that lasted about a minute. He had obvious neck stiffness. The specific SARS-CoV-2 RNA was not detected in the nasopharyngeal swab but was detected in a CSF. Anti- HSV 1 and varicella-zoster IgM antibodies were not detected in serum samples. A brain MRI showed hyperintensity along the wall of right lateral ventricle and hyperintense signal changes in the right mesial temporal lobe and hippocampus, suggesting the possibility of SARS-CoV-2 meningitis. This case warns the physicians of patients who have CNS symptoms.
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Betacoronavirus , Infecções por Coronavirus/complicações , Encefalite/virologia , Meningite Viral/virologia , Pneumonia Viral/complicações , COVID-19 , China , Encefalite/diagnóstico por imagem , Fadiga , Febre , Humanos , Imageamento por Ressonância Magnética , Masculino , Meningite Viral/diagnóstico por imagem , Pandemias , SARS-CoV-2 , Adulto JovemRESUMO
RATIONALE: Ferulic acid (FA) is a standard matrix used for analyzing proteins. In this study, the ability of a halogenated FA to serve as an effective MALDI matrix was investigated. Various halogenated FAs were synthesized, and the characteristics and performance of each were compared with those of the standard matrices α-cyano-4-hydroxycinnamic acid (CHCA) and 2,5-dihydrobenzoic acid (DHBA). METHODS: The abilities of 6-bromoferulic acid (6-BFA), ferulic acid (FA), and eight other halogenated FA derivatives to ionize eight synthetic peptides were examined. Absorption measurements, MM2 structure optimizations, and proton affinity (PA) calculations were also performed for 6-BFA and FA. The suitabilities of these compounds as matrices for matrix-assisted laser desorption/ionization (MALDI) for lipids, sugar chains, polymers, cyanocobalamin, synthetic peptides, and tryptic peptides originating from two types of serum proteins were also tested. RESULTS: The 6-position of FA was found to be the best site for introducing a bromine because the generated compound allowed facile detection of cyanocobalamin and several peptides. 6-BFA exhibited good sensitivity for large peptides (3-5 kDa) and peptides containing acidic amino acids or proline. 6-BFA was also shown to be a suitable matrix for tandem mass spectrometry (MS/MS) analysis when using MALDI time-of-flight (TOF) mass spectrometry (MS) with a quadrupole ion trap (QIT) system. CONCLUSIONS: The properties of 6-BFA as a MALDI matrix differed from those of DHBA and CHCA. 6-BFA appears to be a useful matrix for de novo sequencing using MALDI-QIT-TOF-MS.
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Ácidos Cumáricos/química , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Animais , Proteínas Sanguíneas/análise , Halogenação , Humanos , Lipídeos/análise , Peptídeos/análise , Espectrometria de Massas em Tandem/métodos , Vitamina B 12/análiseRESUMO
In Kawasaki disease (KD), the effect of plasma exchange (PE) on immune cells has not been fully elucidated. Therefore, we examined the changes in the number of CD14+ CD16+ activated monocytes, regulatory T (Treg ), and T-helper type 17 (Th17) cells in KD patients treated with PE. The percentage of total monocytes and subclasses of lymphocytes, including CD4+ and CD8+ T cells, and CD19+ B cells, showed no significant difference before and after PE. However, the percentage of CD14+ CD16+ monocytes in total leukocytes decreased significantly after PE (1.1% ± 1.5% vs. 2.1% ± 2.3%, P < 0.05). Furthermore, while the percentage of Th17 cells in CD4+ T cells did not change, the percentage of Treg cells in CD4+ T cells increased significantly after PE (11.1% ± 5.1% vs. 8.0% ± 4.4%, P < 0.05). Therefore, PE downregulates activated monocytes and upregulates Treg cells toward normal levels and thus attenuates inflammation in KD.
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Monócitos/imunologia , Síndrome de Linfonodos Mucocutâneos , Troca Plasmática/métodos , Linfócitos T Reguladores/imunologia , Células Th17/imunologia , Antígenos de Diferenciação de Linfócitos T/análise , Pré-Escolar , Feminino , Humanos , Japão , Subpopulações de Linfócitos , Masculino , Síndrome de Linfonodos Mucocutâneos/diagnóstico , Síndrome de Linfonodos Mucocutâneos/imunologia , Síndrome de Linfonodos Mucocutâneos/terapia , Resultado do TratamentoRESUMO
In original publication of the article, some of the co-author's names were not included. The correct author group is published in this article.
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Autoantibodies against cardiac proteins play an important role in the development of dilated cardiomyopathy (DCM). The efficacy and safety of apheresis such as immunoadsorption (IA) or plasma exchange (PE) to remove such antibodies have been reported in adult DCM patients. However, apheresis for pediatric DCM has not been performed because of technical difficulty due to relatively low blood volume and instability of hemodynamics. As we have experiences of preforming apheresis on hemodynamically unstable children, we have preformed ten courses of PE on seven child DCM patients including both patients in chronic and acute phase to assess the safety and efficacy to PE. Under general anesthesia, the patients were administered PE three times during 3 days as 1 course. Simultaneously, continuous hemodiafiltration (CHDF) was performed in series with the PE circuit to stabilize hemodynamic status and to minimize the adverse effects of PE. The changes in LVEF, CTR, mBP, the dosage of furosemide and NYHA were assessed before and after the procedure of PE. There were no severe adverse effects such as systemic bleeding or refractory hypotension due to apheresis. Echocardiography showed that mean baseline LVEF was 24.3 ± 7.8%. Mean LVEF significantly increased 1 week after PE to 30.5 ± 12.5%. CTR significantly decreased after PE. Mean BP significantly increased 1 month after PE (54.5 ± 10.7 to 60.7 ± 9.8 mmHg). NYHA improved after PE significantly (NYHA; 3.4 ± 1.1 to 2.5 ± 1.1). PE is safe and effective in improving both cardiac function and daily activities.
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Atividades Cotidianas , Cardiomiopatia Dilatada/terapia , Hemodinâmica/fisiologia , Troca Plasmática/métodos , Adolescente , Cardiomiopatia Dilatada/fisiopatologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Resultado do Tratamento , Adulto JovemRESUMO
African trypanosomes are tsetse fly transmitted protozoan parasites responsible for human African trypanosomiasis, a disease characterized by a plethora of neurological symptoms and death. How the parasites under microvascular shear stress (SS) flow conditions in the brain cross the blood-brain barrier (BBB) is not known. In vitro studies using static models comprised of human brain microvascular endothelial cells (BMEC) show that BBB activation and crossing by trypanosomes requires the orchestration of parasite cysteine proteases and host calcium-mediated cell signaling. Here, we examine BMEC barrier function and the activation of extracellular signal-regulated kinase (ERK)1/2 and ERK5, mitogen-activated protein kinase family regulators of microvascular permeability, under static and laminar SS flow and in the context of trypanosome infection. Confluent human BMEC were cultured in electric cell-substrate impedance sensing (ECIS) and parallel-plate glass slide chambers. The human BMEC were exposed to 2 or 14 dyn/cm(2) SS in the presence or absence of trypanosomes. Real-time changes in transendothelial electrical resistance (TEER) were monitored and phosphorylation of ERK1/2 and ERK5 analyzed by immunoblot assay. After reaching confluence under static conditions human BMEC TEER was found to rapidly increase when exposed to 2 dyn/cm(2) SS, a condition that mimics SS in brain postcapillary venules. Addition of African trypanosomes caused a rapid drop in human BMEC TEER. Increasing SS to 14 dyn/cm(2), a condition mimicking SS in brain capillaries, led to a transient increase in TEER in both control and infected human BMEC. However, no differences in ERK1/2 and ERK5 activation were found under any condition tested. African trypanosomiasis alters BBB permeability under low shear conditions through an ERK1/2 and ERK5 independent pathway.
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Healthy bowel function is an important factor when judging the advisability of early enteral nutrition in critically ill patients, but long-term observation and objective evaluation of gastrointestinal motility are difficult. In the study, real-time continuous measurement of gastrointestinal motility was performed in patients with severe sepsis using a developed bowel sound analysis system, and the correlation between bowel sounds and changes over time in blood concentrations of interleukin (IL)-6, which is associated with sepsis severity, was evaluated. The subjects were five adult patients in the acute phase of severe sepsis on a mechanical ventilator, with IL-6 blood concentrations ≥100 pg/mL, who had consented to participate in the study. Gastrointestinal motility was measured for a total of 62,399 min: 31,544 min in 3 subjects in the no-steroids group and 30,855 min in 2 subjects in the steroid treatment group. In the no-steroids group, the bowel sound counts were negatively correlated with IL-6 blood concentration, suggesting that gastrointestinal motility was suppressed as IL-6 blood concentration increased. However, in the steroid treatment group, gastrointestinal motility showed no correlation with IL-6 blood concentration (r = -0.25, p = 0.27). The IL-6 blood concentration appears to have decreased with steroid treatment irrespective of changes in the state of sepsis, whereas bowel sound counts with the monitoring system reflected the changes in the state of sepsis, resulting in no correlation. This monitoring system provides a useful method of continuously, quantitatively, and non-invasively evaluating gastrointestinal motility in patients with severe sepsis. Gastrointestinal motility might be useful as a parameter reflecting disease severity, particularly in patients treated with steroids.