RESUMEN
BACKGROUND/OBJECTIVES: Obesity, defined by body mass index (BMI), is a well-known risk factor for the severity of coronavirus disease 2019 (COVID-19). Adipose tissue distribution has also been implicated as an important factor in the body's response to infection, and excess visceral fat (VF), which is prevalent in Japanese, may contribute significantly to the severity. Therefore, this study aimed to evaluate the association of obesity and VF with COVID-19 severe illness in Japan. SUBJECTS/METHODS: This retrospective cohort study involved 550 COVID-19 patients admitted to a tertiary care hospital with BMI and body composition data, including VF. The primary endpoint was severe illness, including death, due to COVID-19 during hospitalization. Logistic regression analysis was applied to examine the quartiles of BMI and VF on severe illness after adjusting for covariates such as age, sex, subcutaneous fat, paraspinal muscle radiodensity, and comorbidities affecting VF (COPD, cancer within 5 years, immunosuppressive agent use). RESULTS: The median age was 56.0 years; 71.8% were males. During hospitalization, 82 (14.9%) experienced COVID-19 severe illness. In the multivariate logistic regression analysis, Q4 of BMI was not significantly associated with severe illness compared to Q1 of BMI (OR 1.03; 95% CI 0.37-2.86; p = 0.95). Conversely, Q3 and Q4 of VF showed a higher risk for severe illness compared to Q1 of VF (OR 2.68; 95% CI 1.01-7.11; p = 0.04, OR 3.66; 95% CI 1.30-10.26; p = 0.01, respectively). Stratified analysis by BMI and adjusted for covariates showed the positive association of VF with severe illness only in the BMI < 25 kg/m2 group. CONCLUSIONS: High BMI was not an independent risk factor for COVID-19 severe illness in hospitalized patients in Japan, whereas excess VF significantly influenced severe illness, especially in patients with a BMI < 25 kg/m2.
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Índice de Masa Corporal , COVID-19 , Hospitalización , Grasa Intraabdominal , SARS-CoV-2 , Humanos , Masculino , COVID-19/epidemiología , COVID-19/complicaciones , Femenino , Persona de Mediana Edad , Japón/epidemiología , Estudios Retrospectivos , Grasa Intraabdominal/diagnóstico por imagen , Hospitalización/estadística & datos numéricos , Anciano , Factores de Riesgo , Índice de Severidad de la Enfermedad , Adulto , Pandemias , Comorbilidad , Obesidad/epidemiología , Obesidad/complicacionesRESUMEN
Although it is known that BK polyomavirus (BKPyV) causes hemorrhagic cystitis (HC) after allogeneic hematopoietic stem cell transplantation (HSCT), the clinical significance of BKPyV viremia has not been fully evaluated. We retrospectively analyzed the results of quantitative polymerase chain reaction (PCR) evaluations for detecting BKPyV in the whole blood samples of patients undergoing allogeneic HSCT during the period from January 2010 to June 2020 at a single institute, Tokyo Medical and Dental University. BKPyV was detected in the blood of 28 of the 107 evaluated patients, and the cumulative incidence of was 27.9% (95%CI: 20.2-37.9%). HC due to BKPyV developed in four of the 28 patients with BKPyV viremia (14.3%) and in two of the 79 patients without it (2.5%; P < 0.05). BKPyV viremia itself did not affect the patients' post-transplant estimated glomerular filtration rate (eGFR), but BKPyV viremia with a high viral load was significantly associated with decreased eGFR values (P < 0.05). BKPyV viremia was also associated with significantly lower progression-free survival at 3 years (35.1% [95%CI: 17.8-53.1%] vs. 60.4% [95%CI: 48.4-70.5], P < 0.05). Our findings demonstrated that BKPyV viremia was associated with onset of HC, an early decline of renal function, and poorer survival after allogeneic HSCT. Further studies are needed to test these results and elucidate the mechanisms of renal dysfunction associated with BKPyV viremia.
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Virus BK , Cistitis Hemorrágica , Cistitis , Trasplante de Células Madre Hematopoyéticas , Infecciones por Polyomavirus , Infecciones Tumorales por Virus , Humanos , Estudios Retrospectivos , Viremia/complicaciones , Infecciones por Polyomavirus/complicaciones , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Infecciones Tumorales por Virus/epidemiologíaRESUMEN
Methotrexate (MTX)-associated lymphoproliferative disorder (MTX-LPD) is a troublesome problem in patients receiving MTX for rheumatoid arthritis (RA). However, its incidence, prognosis, and risk factors remain unclear. In this retrospective study, we evaluated the actual incidence, prognostic impact, and risk factors of MTX-LPD. Of the 986 patients with RA treated with MTX, 90 patients experienced 95 new malignancies (NMs), with LPD as the most frequent in 26 patients. The cumulative LPD incidences were 1.3% and 4.7% at 5 and 10 years after MTX initiation, respectively. Among the 24 patients who discontinued MTX after developing LPD, 15 showed sustained regression, without difference in overall survival between patients with LPD and without NM. Inflammatory markers and absolute lymphocyte counts were not useful for early LPD development detection, but most of the patients with LPD had persistently elevated erythrocyte sedimentation ratios. Regarding concomitant drugs, tacrolimus increased the risk only if patients were not receiving biological disease-modifying antirheumatic drugs (bDMARDs). bDMARDs did not increase the risk for any of the drugs or the number of classes used. The number of LPD cases was lower in patients with IL-6A even after a long period after MTX, although with no statistically significant difference. Thus, approximately 1 in 20 patients with RA developed MTX-LPD over the 10 years of MTX treatment, but it did not affect the survival of patients with RA. Tacrolimus increased the risk of developing LPD for certain patients and should be used with caution.
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Antirreumáticos , Artritis Reumatoide , Trastornos Linfoproliferativos , Humanos , Metotrexato/efectos adversos , Estudios Retrospectivos , Tacrolimus/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/inducido químicamente , Artritis Reumatoide/complicaciones , Antirreumáticos/efectos adversos , Trastornos Linfoproliferativos/inducido químicamente , Trastornos Linfoproliferativos/epidemiologíaRESUMEN
The effectiveness of remdesivir on survival in coronavirus disease 2019 (COVID-19), especially in cases treated in the intensive care unit (ICU), is controversial. We investigated the effectiveness of remdesivir with corticosteroids on the survival of COVID-19 patients in a real ICU clinical practice. For laboratory-confirmed COVID-19 patients admitted to the ICU of a tertiary hospital in Tokyo (April 2020-November 2021) and who received corticosteroids, the effectiveness of remdesivir for survival, stratified by interval length (within 9 or 10+ days), was retrospectively analyzed using Cox regression model. A total of 168 patients were included: 35 with no remdesivir use (control), 96 with remdesivir use within 9 days, and 37 with remdesivir use with an interval of 10+ days. In-hospital mortality was 45.7%, 10.4%, and 16.2%, respectively. After adjusting for possible covariates including comorbidities, laboratory data, oxygen demand, or level of pneumonia, remdesivir use within 9 days from symptom onset reduced mortality risk (hazard ratio [HR]: 0.10; 95% confidence interval (CI): 0.025-0.428) compared to the control group. However, remdesivir use with an interval of 10+ days showed no significant association with mortality (HR: 0.42; 95% CI: 0.117-1.524). Among COVID-19 patients who received corticosteroids in ICU, remdesivir use within 9 days from symptom onset was associated with reduced in-hospital mortality risk.
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COVID-19 , Humanos , SARS-CoV-2 , Estudios Retrospectivos , Tratamiento Farmacológico de COVID-19 , Unidades de Cuidados Intensivos , Hospitales , Alanina/uso terapéutico , Corticoesteroides/uso terapéuticoRESUMEN
Endothelial cell (EC) migration is essential for healing vascular injuries. Previous studies suggest that high-density lipoprotein (HDL) and apolipoprotein A-I (apoA-I), the major protein constituent of HDL, have endothelial healing functions. In cardiovascular disease, HDL is modified by myeloperoxidase (MPO) and N-homocysteine, resulting in apoA-I/apoA-II heterodimer and N-homocysteinylated (N-Hcy) apoA-I formation. This study investigated whether these modifications attenuate HDL-mediated endothelial healing. Wound healing assays were performed to analyze the effect of MPO-oxidized HDL and N-Hcy HDL in vitro. HDL obtained from patients with varying troponin I levels were also examined. MPO-oxidized HDL reduces EC migration compared to normal HDL in vitro, and N-Hcy HDL showed a decreasing trend toward EC migration. EC migration after treatment with HDL from patients was decreased compared to HDL isolated from healthy controls. Increased apoA-I/apoA-II heterodimer and N-Hcy apoA-I levels were also detected in HDL from patients. Wound healing cell migration was significantly negatively correlated with the ratio of apoA-I/apoA-II heterodimer to total apoA-II and N-Hcy apoA-I to total apoA-I. MPO-oxidized HDL containing apoA-I/apoA-II heterodimers had a weaker endothelial healing function than did normal HDL. These results indicate that MPO-oxidized HDL and N-Hcy HDL play a key role in the pathogenesis of cardiovascular disease.
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Enfermedades Cardiovasculares , Lipoproteínas HDL , Apolipoproteína A-I/metabolismo , Apolipoproteína A-II , Enfermedades Cardiovasculares/metabolismo , Humanos , Lipoproteínas HDL/metabolismo , Peroxidasa/metabolismoRESUMEN
The rapid spread of the Delta variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became a serious concern worldwide in summer 2021. We examined the copy number and variant types of all SARS-CoV-2-positive patients who visited our hospital from February to August 2021 using polymerase chain reaction (PCR) tests. Whole genome sequencing was performed for some samples. The R.1 variant (B.1.1.316) was responsible for most infections in March, replacing the previous variant (B.1.1.214); the Alpha (B.1.1.7) variant caused most infections in April and May; and the Delta variant (B.1.617.2) was the most prevalent in July and August. There was no significant difference in the copy numbers among the previous variant cases (n = 29, median 3.0 × 104 copies/µl), R.1 variant cases (n = 28, 2.1 × 105 copies/µl), Alpha variant cases (n = 125, 4.1 × 105 copies/µl), and Delta variant cases (n = 106, 2.4 × 105 copies/µl). Patients with Delta variant infection were significantly younger than those infected with R.1 and the previous variants, possibly because many elderly individuals in Tokyo were vaccinated between May and August. There was no significant difference in mortality among the four groups. Our results suggest that the increased infectivity of Delta variant may be caused by factors other than the higher viral loads. Clarifying these factors is important to control the spread of Delta variant infection.
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COVID-19/epidemiología , COVID-19/virología , SARS-CoV-2/fisiología , Carga Viral , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Mutación , Reacción en Cadena de la Polimerasa , ARN Viral/genética , SARS-CoV-2/clasificación , SARS-CoV-2/genética , Tokio/epidemiología , Secuenciación Completa del GenomaRESUMEN
Patients infected with the Omicron variant of severe acute respiratory syndrome coronavirus 2 has increased worldwide since the beginning of 2022 and the variant has spread more rapidly than the Delta variant, which spread in the summer of 2021. It is important to clarify the cause of the strong transmissibility of the Omicron variant to control its spread. In 694 patients with coronavirus disease 2019, the copy numbers of virus in nasopharyngeal swab-soaked samples and the viral genotypes were examined using quantitative polymerase chain reaction (PCR) and PCR-based melting curve analysis, respectively. Whole-genome sequencing was also performed to verify the viral genotyping data. There was no significant difference (p = 0.052) in the copy numbers between the Delta variant cases (median 1.5 × 105 copies/µl, n = 174) and Omicron variant cases (median 1.2 × 105 copies/µl, n = 328). During this study, Omicron BA.1 cases (median 1.1 ×105 copies/µl, n = 275) began to be replaced by BA.2 cases (median 2.3 × 105 copies/µl, n = 53), and there was no significant difference between the two groups (p = 0.33). Our results suggest that increased infectivity of the Omicron variant and its derivative BA.2 is not caused by higher viral loads but by other factors, such as increased affinity to cell receptors or immune escape.
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COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Carga ViralRESUMEN
Although many wearable single-lead electrocardiogram (ECG) monitoring devices have been developed, information regarding their ECG quality is limited. This study aimed to evaluate the quality of single-lead ECG in healthy subjects under various conditions (body positions and motions) and in patients with arrhythmias, to estimate requirements for automatic analysis, and to identify a way to improve ECG quality by changing the type and placement of electrodes. A single-lead ECG transmitter was placed on the sternum with a pair of electrodes, and ECG was simultaneously recorded with a conventional Holter ECG in 12 healthy subjects under various conditions and 35 patients with arrhythmias. Subjects with arrhythmias were divided into sinus rhythm (SR) and atrial fibrillation (AF) groups. ECG quality was assessed by calculating the sensitivity and positive predictive value (PPV) of the visual detection of QRS complexes (vQRS), automatic detection of QRS complexes (aQRS), and visual detection of P waves (vP). Accuracy was defined as a 100% sensitivity and PPV. We also measured the amplitude of the baseline, P wave, and QRS complex, and calculated the signal-to-noise ratio (SNR). We then focused on aQRS and estimated thresholds to obtain an accurate aQRS in more than 95% of the data. Finally, we sought to improve ECG quality by changing electrode placement using offset-type electrodes in 10 healthy subjects. The single-lead ECG provided 100% accuracy for vQRS, 87% for aQRS, and 74% for vP in healthy subjects under various conditions. Failure for accurate detection occurred in several motions in which the baseline amplitude was increased or in subjects with low QRS or P amplitude, resulting in low SNR. The single-lead ECG provided 97% accuracy for vQRS, 80% for aQRS in patients with arrhythmias, and 95% accuracy for vP in the SR group. The AF group showed higher baseline amplitude than the SR group (0.08 mV vs. 0.02 mV, P < 0.01) but no significant difference in accuracy for aQRS (79% vs. 81%, P = 1.00). The thresholds to obtain an accurate aQRS were a QRS amplitude > 0.42 mV and a baseline amplitude < 0.20 mV. The QRS amplitude was significantly influenced by electrode placement and body position (P < 0.01 for both, two-way analysis of variance), and the maximum reduction by changing body position was estimated as 30% compared to the sitting posture. The QRS amplitude significantly increased when the inter-electrode distance was extended vertically (1.51 mV for vertical extension vs. 0.93 mV for control, P < 0.01). The single-lead ECG provided at least 97% accuracy for vQRS, 80% for aQRS, and 74% for vP. To obtain stable aQRS in any body positions, a QRS amplitude > 0.60 mV and a baseline amplitude < 0.20 mV were required in the sitting posture considering the reduction induced by changing body position. Vertical extension of the inter-electrode distance increased the QRS amplitude.
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Fibrilación Atrial , Dispositivos Electrónicos Vestibles , Fibrilación Atrial/diagnóstico , Electrocardiografía , Electrodos , Humanos , Relación Señal-RuidoRESUMEN
Paroxysmal nocturnal hemoglobinuria (PNH) is characterized by hemolysis, thrombosis, and bone marrow failure. Infection, pregnancy, and surgical operation have the potential to evoke severe episodes of hemolysis and thrombosis. Therefore, the use of an antibody agent against complement component 5 (C5), eculizumab, one day before the operation is recommended. Ravulizumab is a newly approved long-acting antibody agent against C5. Thus, little is known about perioperative management with ravulizumab. We experienced a 43-year-old female patient who safely underwent laparoscopic cholecystectomy under ravulizumab treatment for PNH. Ravulizumab was administered one day before the operation. Laparoscopic cholecystectomy for cholelithiasis was performed under intravenous anesthesia, intermittent air compression of the lower extremities, and low pneumoperitoneum pressure. Additionally, heparin was administered, and the patient left the sickbed early without significant postoperative complications. Like eculizumab, complement inhibition by ravulizumab is also considered effective in the perioperative management of patients with PNH. However, close cooperation with surgeons and anesthesiologists and careful management based on clinical symptoms and laboratory data such as LDH, CH50, and D-dimer are essential.
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Colecistectomía Laparoscópica , Hemoglobinuria Paroxística , Trombosis , Adulto , Anticuerpos Monoclonales Humanizados , Colecistectomía Laparoscópica/efectos adversos , Femenino , Hemoglobinuria Paroxística/complicaciones , Hemoglobinuria Paroxística/tratamiento farmacológico , Hemólisis , Humanos , Embarazo , Trombosis/etiologíaRESUMEN
Triglyceride hydrolysis by lipoprotein lipase (LPL), regulated by apolipoproteins C-II (apoC-II) and C-III (apoC-III), is essential for maintaining normal lipid homeostasis. During triglyceride lipolysis, the apoCs are known to be transferred from very low-density lipoprotein (VLDL) to high-density lipoprotein (HDL), but the detailed mechanisms of this transfer remain unclear. In this study, we investigated the extent of the apoC transfers and their distribution in HDL subfractions, HDL2 and HDL3. Each HDL subfraction was incubated with VLDL or biotin-labeled VLDL, and apolipoproteins and lipids in the re-isolated HDL were quantified using western blotting and high-performance liquid chromatography (HPLC). In consequence, incubation with VLDL showed the increase of net amount of apoC-II and apoC-III in the HDL. HPLC analysis revealed that the biotin-labeled apolipoproteins, including apoCs and apolipoprotein E, were preferably transferred to the larger HDL3. No effect of cholesteryl ester transfer protein inhibitor on the apoC transfers was observed. Quantification of apoCs levels in HDL2 and HDL3 from healthy subjects (n = 8) showed large individual differences between apoC-II and apoC-III levels. These results suggest that both apoC-II and apoC-III transfer disproportionately from VLDL to HDL2 and the larger HDL3, and these transfers might be involved in individual triglyceride metabolism.
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Apolipoproteína C-III/metabolismo , Apolipoproteína C-II/metabolismo , Lipoproteínas HDL2/metabolismo , Lipoproteínas HDL3/metabolismo , Lipoproteínas LDL/metabolismo , Voluntarios Sanos , HumanosRESUMEN
The spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, such as B.1.1.7 and B.1.351, has become a crucial issue worldwide. Therefore, we began testing all patients with COVID-19 for the N501Y and E484K mutations by using polymerase chain reaction (PCR)-based methods. Nasopharyngeal swab samples from 108 patients who visited our hospital between February and April 2021 were analyzed. The samples were analyzed using reverse transcription-PCR with melting curve analysis to detect the N501Y and E484K mutations. A part of the samples was also subjected to whole-genome sequencing (WGS). Clinical parameters such as mortality and admission to the intensive care unit were analyzed to examine the association between increased disease severity and the E484K mutation. The ratio of cases showing the 501N + 484K mutation rapidly increased from 8% in February to 46% in March. WGS revealed that the viruses with 501N + 484K mutation are R.1 lineage variants. Evidence of increased disease severity related to the R.1 variants was not found. We found that the R.1 lineage variants rapidly prevailed in Tokyo in March 2021, which suggests the increased transmissibility of R.1 variants, while they showed no increased severity.
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COVID-19/epidemiología , COVID-19/virología , SARS-CoV-2/genética , Anciano , Femenino , Humanos , Masculino , Mutación/genética , Glicoproteína de la Espiga del Coronavirus/genética , Tokio/epidemiología , Secuenciación Completa del Genoma/métodosRESUMEN
BACKGROUND: There are few agents that have been proven effective for COVID-19. Predicting clinical improvement as well as mortality or severity is very important. OBJECTIVES: This study aimed to investigate the factors associated with the clinical improvement of COVID-19. METHODS: Overall, 74 patients receiving treatment for COVID-19 at Tokyo Medical and Dental University Hospital from April 6th to May 15th, 2020 were included in this study. Clinical improvement was evaluated, which defined as the decline of two levels on a six-point ordinal scale of clinical status or discharge alive from the hospital within 28 days after admission. The clinical courses were particularly investigated and the factors related to time to clinical improvement were analyzed with the log-rank test and the Cox proportional hazard model. RESULTS: Forty-nine patients required oxygen support during hospitalization, 22 patients required invasive mechanical ventilation, and 5 patients required extracorporeal membrane oxygenation. A total of 83% of cases reached clinical improvement. Longer period of time from onset to admission (≥10 days) (HR, 1.057; 95% CI, 1.002-1.114), no hypertension (HR, 2.077; 95% CI, 1.006-4.287), and low D-dimer levels (<1 µg/ml) (HR, 2.372; 95% CI, 1.229-4.576) were confirmed to be significant predictive factors for time to clinical improvement. Furthermore, a lower SARS-CoV-2 RNA copy number was also a predictive factor for clinical improvement. CONCLUSIONS: Several predictors for the clinical improvement of COVID-19 pneumonia were identified. These results may be important for the management of COVID-19 pneumonia.
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COVID-19/terapia , Adulto , Anciano , COVID-19/diagnóstico , Oxigenación por Membrana Extracorpórea , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Hospitalización , Humanos , Hipertensión , Masculino , Persona de Mediana Edad , ARN Viral/aislamiento & purificación , Respiración Artificial , TokioRESUMEN
Here, we assessed the utility of a polymerase chain reaction-based open reading frame typing assay for investigating the clonality of Clostridioides difficile isolates. This assay has a higher discriminatory power than multi-locus sequence typing for molecular epidemiological analysis of C. difficile isolates and can provide additional information about toxin genotypes.
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Clostridioides difficile/clasificación , Clostridioides difficile/genética , Infecciones por Clostridium/diagnóstico , Infecciones por Clostridium/microbiología , Tipificación de Secuencias Multilocus , Sistemas de Lectura Abierta , Reacción en Cadena de la Polimerasa , Clostridioides difficile/aislamiento & purificación , Humanos , Filogenia , Reacción en Cadena de la Polimerasa/métodos , Juego de Reactivos para Diagnóstico , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: Helicobacter cinaedi is an important pathogen that causes bloodstream infections. Owing to the challenges in its culture and identification, its clinical and bacterial characteristics remain unknown. Our study aimed to investigate the molecular epidemiology and antimicrobial susceptibility of H cinaedi. MATERIALS AND METHODS: From 2003 to 2016, we analyzed 16 non-repetitive H cinaedi strains, isolated from blood, at the medical hospital of Tokyo Medical and Dental University. Multilocus sequence typing was performed to analyze the genetic relationship across the different isolates. The minimum inhibitory concentrations (MIC) of antibiotics were determined by the agar dilution method. RESULTS: The median age of subjects in this study was 61 years (range, 18-84 years). The most common risk factors included the use of steroids (75.0%) and immunosuppressant drugs (37.5%). In addition, the most common symptoms of H cinaedi bacteremia included colitis (37.5%) and cellulitis (31.3%). The infection recurred in three of seven cases (42.8%) that underwent antibiotic therapy for <10 days. The strains were classified into five sequence types (ST), of which, ST 10 (43.8%) and ST 4 (31.3%) were predominant. The MIC90 values of amoxicillin, gentamycin, imipenem, ciprofloxacin, and clarithromycin were 4, 0.5, 0.25, 64, and 128 mg/L, respectively. CONCLUSIONS: Since there is no recommended guideline yet for the choice or duration of antibiotic therapy and antimicrobial break points, our results suggested, for the first time, that prolonged antibiotic therapy, except with ciprofloxacin and clarithromycin, would be required to ensure resolution of symptoms and prevention of recurrence.
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Bacteriemia/epidemiología , Infecciones por Helicobacter/microbiología , Helicobacter/aislamiento & purificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/uso terapéutico , Bacteriemia/microbiología , Femenino , Helicobacter/clasificación , Helicobacter/efectos de los fármacos , Helicobacter/genética , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/epidemiología , Humanos , Japón/epidemiología , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Epidemiología Molecular , Adulto JovenRESUMEN
A 45-year-old man initially diagnosed with aplastic anemia had been receiving treatment for >4 years when he visited our hospital for a detailed examination. On admission, bone marrow (BM) aspiration showed erythroid dysplasia and chromosomal abnormalities, including trisomy 3 in 1/20 cells. After 3 months of observation, BM aspiration showed the involvement of 5% abnormal lymphocytes, and flow cytometry revealed a monoclonal B-cell phenotype. After a further 5 months of observation, his blood test showed a sudden elevation in white blood cell (WBC) count and the presence of villous lymphocytes. Fluorodeoxyglucose-positron emission tomography (FDG-PET) only revealed strong uptake by systemic BM, and BM aspiration showed the involvement of 76.4% abnormal lymphocytes, which were positive for CD19 and dim CD11c; negative for CD25, CD103, cyclin D1, and BRAF-V600E; and exhibited light chain restriction. The patient was diagnosed with marginal zone lymphoma-like primary bone marrow (BM) lymphoma. Treatment with R-CHOP and R-cladribine failed. He then underwent an allogeneic peripheral blood stem cell transplantation from a human leucocyte antigen (HLA)-identical sibling, and he has since remained in good health and without relapse for 9 years. Further clinical and biological analyses are necessary to establish an optimal treatment strategy for this disease.
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Neoplasias Óseas , Linfoma de Células B de la Zona Marginal , Pancitopenia , Médula Ósea , Humanos , Linfoma de Células B de la Zona Marginal/complicaciones , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia , Pancitopenia/complicacionesRESUMEN
A 54-year-old female complained of oral erosion. A flaccid blister appeared on the trunk 2 months after the onset. The high titer of the anti-desmoglein 1 antibody in the absence of Nikolsky's sign led to the diagnosis of pemphigus vulgaris. The lymphadenopathy in the mesenteric and para-aortic regions indicated the possibility of paraneoplastic pemphigus. The steroid pulse therapy and therapeutic plasma exchange were ineffective. As CT-guided intraperitoneal lymph node biopsy revealed follicular lymphoma, R-CHOP therapy was performed. Although partial remission was attained accompanied by an improvement in the skin and mucosal findings after four courses of R-CHOP therapy, an occlusive ventilatory disturbance, possibly attributed to bronchiolitis obliterans, appeared 4 months after the treatment initiation. Although the treatment with tacrolimus was attempted, it was not feasible to be continued because of opportunistic infection, and the patient died 9 months after the onset of the skin lesion. Although specific anti-plakin antibodies were negative, this case was diagnosed as paraneoplastic pemphigus due to follicular lymphoma and complicated by obstructive bronchiolitis based on the clinical findings. The accumulation of similar cases is needed to establish effective treatment strategies.
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Bronquiolitis Obliterante/diagnóstico , Linfoma Folicular/diagnóstico , Síndromes Paraneoplásicos/diagnóstico , Pénfigo/diagnóstico , Anticuerpos Monoclonales de Origen Murino/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ciclofosfamida/uso terapéutico , Doxorrubicina/uso terapéutico , Femenino , Humanos , Persona de Mediana Edad , Prednisona/uso terapéutico , Rituximab , Vincristina/uso terapéuticoRESUMEN
The recently developed PCR-based open reading frame typing (POT) method is a useful molecular typing tool. Here, we evaluated the performance of POT for molecular typing of methicillin-resistant Staphylococcus aureus (MRSA) isolates and compared its performance to those of multilocus sequence typing (MLST) and Staphylococcus protein A gene typing (spa typing). Thirty-seven MRSA isolates were collected between July 2012 and May 2015. MLST, spa typing, and POT were performed, and their discriminatory powers were evaluated using Simpson's index analysis. The MRSA isolates were classified into 11, 18, and 33 types by MLST, spa typing, and POT, respectively. The predominant strains identified by MLST, spa typing, and POT were ST8 and ST764, t002, and 93-191-127, respectively. The discriminatory power of MLST, spa typing, and POT was 0.853, 0.875, and 0.992, respectively, indicating that POT had the highest discriminatory power. Moreover, the results of MLST and spa were available after 2 days, whereas that of POT was available in 5 h. Furthermore, POT is rapid and easy to perform and interpret. Therefore, POT is a superior molecular typing tool for monitoring nosocomial transmission of MRSA.
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Staphylococcus aureus Resistente a Meticilina/clasificación , Tipificación de Secuencias Multilocus/métodos , Sistemas de Lectura Abierta/genética , Reacción en Cadena de la Polimerasa/métodos , Proteína Estafilocócica A/genética , Genotipo , Humanos , Staphylococcus aureus Resistente a Meticilina/genética , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Infecciones Estafilocócicas/microbiologíaRESUMEN
Single nucleotide polymorphisms (SNPs) within or near interferon lambda 4 (IFNL4) gene located upstream of IFNL3 are associated with response to anti-HCV therapy both in interferon (IFN)-based and IFN-free regimens. IFNL4 encodes IFNλ4, a newly discovered type III IFN, and its expression is controlled by rs368234815-TT/ΔG, which is in strong linkage disequilibrium (LD) with other tag SNPs within or near IFNL4 such as rs12979860 and rs8099917. Intrahepatic expression levels of IFN-stimulated genes (ISGs) affect the responsiveness to IFNα and are also associated with IFNL4 genotype. However, IFNL4 expressions and its role in intrinsic antiviral innate immunity remain unclear. This study evaluated the effect of IFNL4 on intrahepatic ISG expression and investigated its relationship with treatment outcomes in liver samples obtained from 49 chronic hepatitis C patients treated with pegylated (PEG)-IFN/ribavirin therapy. IFNL4 mRNA was detected in 11 of 22 patients with IFNL4-unfavorable SNPs but not in patients with favorable genotypes. IFNL4 expression was associated with non-response to PEG-IFN/ribavirin therapy. Intrahepatic expression of antiviral ISGs (ISG15 and MX1) was significantly higher in IFNL4-unfavorable patients with detectable IFNL4 mRNA than in patients with undetectable IFNL4 mRNA, whereas the expression of suppressive ISGs (RNF125, SOCS1, SOCS3, and RNF11) was lower in patients with detectable IFNL4 mRNA. In summary, intrahepatic expression of IFNL4 was associated with increased antiviral ISG expression and decreased suppressive ISG expression at baseline, resulting in poor responsiveness to IFNα-based therapy in HCV infection.
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Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/inmunología , Interferones/uso terapéutico , Interleucinas/genética , Hígado/efectos de los fármacos , Adulto , Anciano , Citocinas/genética , Farmacorresistencia Viral , Femenino , Regulación de la Expresión Génica , Genotipo , Hepacivirus/genética , Hepatitis C Crónica/genética , Humanos , Interferón-alfa/uso terapéutico , Interleucinas/metabolismo , Hígado/inmunología , Hígado/virología , Masculino , Persona de Mediana Edad , Proteínas de Resistencia a Mixovirus/genética , Polimorfismo de Nucleótido Simple , ARN Mensajero , Ribavirina/efectos adversos , Ribavirina/uso terapéutico , Proteína 1 Supresora de la Señalización de Citocinas/genética , Ubiquitinas/genéticaRESUMEN
AIM: Sofosbuvir (SOF) and ribavirin (RBV) combination therapy produces a sustained response in many patients with genotype 2 chronic hepatitis C. However, RBV-induced anemia is a troublesome side-effect that may limit this treatment. Genetic variation leading to inosine triphosphatase (ITPA) deficiency is known to protect against RBV-induced hemolytic anemia. This study aimed to evaluate the relationships between the efficacy and safety of SOF/RBV treatment and ITPA gene variants. METHODS: Ninety patients with genotype 2 chronic hepatitis C treated with SOF/RBV were studied. The relationships among genetic polymorphisms of ITPA and the decline in hemoglobin levels from baseline, RBV dose reduction, and sustained virological response (SVR) rates were analyzed. RESULTS: Overall SVR at 12 weeks was 94.4% (85/90). Patients with the ITPA CA/AA genotypes had a lower degree of anemia throughout the therapy than those with the ITPA CC genotype. The percentage of patients requiring RBV dose reduction was significantly lower for those with the ITPA CA/AA variation, a difference even more apparent when the pretreatment hemoglobin level was <12 g/dL. The dose reduction of RBV and serum albumin level were significantly associated with SVR. CONCLUSIONS: Patients with the ITPA CA/AA genotype were less likely to develop anemia than those with the ITPA CC genotype and were more likely to complete SOF/RBV therapy. These results may provide a valuable pharmacogenetic diagnostic tool to predict drug-induced adverse events, particularly in patients with pre-existing anemia.
RESUMEN
Standardization based on clinical guidelines and personalization by molecular-targeted therapy have been introduced into the field of cancer treatment. To select patients appropriate for molecular-targeted drugs, various companion diagnostics have been developed. To catch up with revision of the clinical guidelines and progress of companion diagnostics, the effective utilization of "Guidelines for clinical examinations JSLM2015" is desirable. [Review].