RESUMEN
Discrepancies in self-rated and observer-rated depression severity may underlie the basis for biological heterogeneity in depressive disorders and be an important predictor of outcomes and indicators to optimize intervention strategies. However, the neural mechanisms underlying this discrepancy have been understudied. This study aimed to examine the brain networks that represent the neural basis of the discrepancy between self-rated and observer-rated depression severity using resting-state functional MRI. To examine the discrepancy between self-rated and observer-rated depression severity, self- and observer-ratings discrepancy (SOD) was defined, and the higher and lower SOD groups were selected from depressed patients as participants showing extreme deviation. Resting-state functional MRI analysis was performed to examine regions with significant differences in functional connectivity in the two groups. The results showed that, in the higher SOD group compared to the lower SOD group, there was increased functional connectivity between the frontal pole and precuneus, both of which are subregions of the default mode network that have been reported to be associated with ruminative and self-referential thinking. These results provide insight into the association of brain circuitry with discrepancies between self- and observer-rated depression severity and may lead to more treatment-oriented diagnostic reclassification in the future.
Asunto(s)
Depresión , Lóbulo Frontal , Imagen por Resonancia Magnética , Lóbulo Parietal , Humanos , Imagen por Resonancia Magnética/métodos , Femenino , Masculino , Adulto , Lóbulo Parietal/diagnóstico por imagen , Lóbulo Parietal/fisiopatología , Lóbulo Frontal/diagnóstico por imagen , Lóbulo Frontal/fisiopatología , Depresión/diagnóstico por imagen , Depresión/fisiopatología , Depresión/psicología , Persona de Mediana Edad , Adulto Joven , Trastornos del Humor/diagnóstico por imagen , Trastornos del Humor/fisiopatología , Trastornos del Humor/psicología , Autoinforme , Vías Nerviosas/fisiopatología , Vías Nerviosas/diagnóstico por imagen , Descanso , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/fisiopatología , Índice de Severidad de la Enfermedad , Mapeo Encefálico/métodosRESUMEN
"Pigmentibacter ruber" was first reported in 2021, a novel bacterium of the family Silvanigrellaceae, isolated from human blood of the patient with aspiration pneumonia after the drowning accident in Republic of China. However, until now, there is only one report describing "P. ruber" infection, and no case of isolation from natural environment has been reported so far. Thus, the infectivity and pathogenicity of "Pigmentibacter" spp. has not been clearly understood. In this report, we described the fatal case of "Pigmentibacter" bacteremia subsequently occurred after aspiration pneumonia probably due to accidental ingestion of irrigation water in the elderly patient. Despite administration of broad-spectrum antibiotic, the patient dramatically deteriorated and eventually deceased. Whole-genome sequencing showed the strain isolated from the patient was identified as "Pigmentibacter" sp. (designated as strain Takaoka) and antimicrobial sensitivity testing showed it displayed high minimum inhibitory concentrations against various antibiotics including ß-lactam. Further studies are needed to clarify the clinical characteristics of "Pigmentibacter" and its relative's infections and their antimicrobial sensitivity; however, the present case supported the clinical characteristics of "Pigmentibacter" infection, which can lead to bacteremia following aspiration pneumonia caused by mis-swallowing contaminated water, and poor outcome potentially due to multidrug resistances.
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Antibacterianos , Bacteriemia , Neumonía por Aspiración , Humanos , Neumonía por Aspiración/microbiología , Bacteriemia/microbiología , Bacteriemia/tratamiento farmacológico , Bacteriemia/diagnóstico , Antibacterianos/uso terapéutico , Resultado Fatal , Pruebas de Sensibilidad Microbiana , Masculino , Anciano , Anciano de 80 o más Años , Secuenciación Completa del GenomaRESUMEN
OBJECTIVES: To identify factors associated with plasma D-dimer levels in outpatients with rheumatoid arthritis (RA). METHODS: We consecutively recruited 460 RA patients who visited our hospital for routine follow-ups between June and October 2021. Plasma D-dimer, RA-related characteristics, comorbidities, and cardiovascular and venous thromboembolism (VTE) risk factors were examined at enrolment. Patients with elevated D-dimer levels underwent whole-leg venous ultrasonography to diagnose deep vein thrombosis (DVT). RESULTS: Participants had no DVT signs or symptoms. Among them, 252 (54.8%) were positive for plasma D-dimer (≥0.5 µg/ml) and 40 (8.7%) had high D-dimer levels (≥3 µg/ml). The mean was 1.07 µg/ml. After adjustments, age [odds ratio (OR) 1.88 per additional 10 years, P = .003], high and moderate clinical disease activity index (OR 8.79, P < .001), and the presence of comorbidities or cardiovascular/VTE risk factors (OR 2.94, P = .017) were identified as the factors independently associated with high D-dimer levels. Among patients with D-dimer levels ≥3 µg/ml, 10 (25%) had DVT in their lower limbs, and D-dimer levels were significantly higher in patients with DVT compared with those without it (mean 6.0 vs. 4.1 µg/ml, P < .001). CONCLUSIONS: Clinical disease activity is a major contributor to plasma D-dimer elevation in RA outpatients.
Asunto(s)
Artritis Reumatoide , Productos de Degradación de Fibrina-Fibrinógeno , Tromboembolia Venosa , Trombosis de la Vena , Humanos , Niño , Tromboembolia Venosa/diagnóstico por imagen , Tromboembolia Venosa/etiología , Trombosis de la Vena/diagnóstico por imagen , Trombosis de la Vena/etiología , Pacientes Ambulatorios , Estudios Transversales , Artritis Reumatoide/complicaciones , Artritis Reumatoide/diagnósticoRESUMEN
OBJECTIVES: To evaluate the antibody response to 13-valent pneumococcal conjugate vaccine (PCV13) in patients with rheumatoid arthritis receiving Janus kinase inhibitors (JAKIs). METHODS: Fifty-three patients receiving methotrexate (MTX; n = 10), JAKI (n = 20), or MTX + JAKI (n = 23) were vaccinated with PCV13. Serum concentrations of immunoglobulin G (IgG) antibodies to 13 pneumococcal serotype capsular polysaccharides were quantified before and 4-6 weeks after vaccination. Positive antibody response was defined as a 2-fold or more increase in IgG concentrations from prevaccination levels. RESULTS: After vaccination, IgG concentrations significantly increased in all treatment groups (P <0.001), but fold increases (postvaccination to prevaccination ratios) were different among treatment groups (9.30 for MTX, 6.36 for JAKI, and 3.46 for combination therapy). Positive antibody response rates were comparable between the MTX group (90%) and the JAKI group (95%) but lower in the MTX + JAKI group (52.2%). In a multivariable logistic regression analysis, the combination therapy was the only factor associated with a reduced antibody response to PCV13. No severe adverse events were observed in any treatment group. CONCLUSION: Although JAKIs do not impair PCV13 immunogenicity in rheumatoid arthritis patients, the combination of MTX with JAKI can reduce the antibody response in this patient population.
Asunto(s)
Antirreumáticos , Artritis Reumatoide , Inhibidores de las Cinasas Janus , Humanos , Antirreumáticos/uso terapéutico , Vacunas Conjugadas/uso terapéutico , Inhibidores de las Cinasas Janus/efectos adversos , Formación de Anticuerpos , Artritis Reumatoide/tratamiento farmacológico , Metotrexato/uso terapéutico , Vacunas Neumococicas/uso terapéutico , Inmunoglobulina GRESUMEN
OBJECTIVES: The aim is to evaluate outcomes and risk factors for death in patients with rheumatoid arthritis (RA) who developed Pneumocystis pneumonia (PCP). METHODS: We included RA patients who were diagnosed with PCP at seven participating community hospitals between July 2005 and October 2020. Clinical features were compared between survivors and non-survivors. Disease-modifying antirheumatic drugs (DMARDs) before PCP onset and after PCP recovery were also examined. RESULTS: Seventy RA patients developed PCP, and among them, 60 (85.7%) received methotrexate (MTX) monotherapy (40%) or MTX combination therapy with other DMARDs (45.7%). PCP was more likely to occur after 12 months of MTX monotherapy and within 3 months of MTX combination therapy. Thirteen patients (18.6%) died despite PCP treatment. Multivariable logistic regression analysis revealed that coexisting RA-associated interstitial lung disease (odds ratio, 6.18; 95% confidence interval, 1.17-32.63) and delayed PCP treatment with anti-Pneumocystis drugs (odds ratio, 15.29; 95% confidence interval, 1.50-156.15) are significant risk factors for PCP mortality in RA patients. Most survivors successfully resumed DMARD therapy without PCP prophylaxis; one recurrent PCP case was observed during follow-up (median, 4.1 years). CONCLUSIONS: To avoid a treatment delay, RA patients should be followed up for signs and symptoms of PCP development, especially those with RA-associated interstitial lung disease.
Asunto(s)
Antirreumáticos , Artritis Reumatoide , Enfermedades Pulmonares Intersticiales , Neumonía por Pneumocystis , Humanos , Neumonía por Pneumocystis/complicaciones , Neumonía por Pneumocystis/tratamiento farmacológico , Estudios Retrospectivos , Artritis Reumatoide/complicaciones , Artritis Reumatoide/tratamiento farmacológico , Metotrexato , Antirreumáticos/efectos adversos , Factores de Riesgo , Enfermedades Pulmonares Intersticiales/complicaciones , Enfermedades Pulmonares Intersticiales/tratamiento farmacológicoRESUMEN
The adrenal glands are one of the most common sites of malignant tumor metastasis. However, metastatic adrenal carcinoma of unknown primary origin with localized adrenal gland involvement is an extremely rare condition. Herein, we reported two cases of carcinoma of unknown primary origin with isolated adrenal metastasis. In the first case, back pain was the trigger; while in the second case, the triggers were low fever and weight loss. Metabolic abnormalities such as hypertension and obesity were not detected in either case. Neither patient had relevant previous medical histories, including malignancy. However, both had a long-term history of smoking. Systemic imaging studies revealed only adrenal tumors and surrounding lesions. Primary adrenocortical carcinoma was initially suspected, and chemotherapy including mitotane was considered. However, due to difficulty in complete resection of the tumor, core needle tumor biopsies were performed. Histopathological examination of biopsy specimens led to the diagnosis of carcinoma of unknown primary origin with isolated adrenal metastasis. In both cases, additional laboratory testing showed high levels of serum squamous cell carcinoma-related antigen and serum cytokeratin fragment. Malignant lesions confined to the adrenal glands are rare. As in our cases, it could be occasionally difficult to differentiate non-functioning primary adrenocortical carcinoma from metastatic adrenal carcinoma of unknown primary origin localized to the adrenal gland. If the lesion is unresectable and there are elevated levels of several tumor markers with no apparent hormonal excess, core needle tumor biopsy should be considered to differentiate the primary tumor from the metastatic tumor.
Asunto(s)
Neoplasias de las Glándulas Suprarrenales/diagnóstico por imagen , Carcinoma Corticosuprarrenal/diagnóstico , Carcinoma/diagnóstico por imagen , Neoplasias Primarias Desconocidas/diagnóstico por imagen , Neoplasias de las Glándulas Suprarrenales/sangre , Neoplasias de las Glándulas Suprarrenales/patología , Neoplasias de las Glándulas Suprarrenales/secundario , Antígenos de Neoplasias/sangre , Biopsia con Aguja , Carcinoma/sangre , Carcinoma/patología , Carcinoma/secundario , Diagnóstico Diferencial , Humanos , Queratinas/sangre , Masculino , Persona de Mediana Edad , Neoplasias Primarias Desconocidas/sangre , Neoplasias Primarias Desconocidas/patología , Serpinas/sangreRESUMEN
In eukaryotes and archaea, tRNA genes frequently contain introns, which are removed during maturation. However, biological roles of tRNA introns remain elusive. Here, we constructed a complete set of Saccharomyces cerevisiae strains in which the introns were removed from all the synonymous genes encoding 10 different tRNA species. All the intronless strains were viable, but the tRNAPheGAA and tRNATyrGUA intronless strains displayed slow growth, cold sensitivity and defective growth under respiratory conditions, indicating physiological importance of certain tRNA introns. Northern analyses revealed that removal of the introns from genes encoding three tRNAs reduced the amounts of the corresponding mature tRNAs, while it did not affect aminoacylation. Unexpectedly, the tRNALeuCAA intronless strain showed reduced 5.8S rRNA levels and abnormal nucleolar morphology. Because pseudouridine (Ψ) occurs at position 34 of the tRNAIleUAU anticodon in an intron-dependent manner, tRNAIleUAU in the intronless strain lost Ψ34. However, in a portion of tRNAIleUAU population, position 34 was converted into 5-carbamoylmethyluridine (ncm5U), which could reduce decoding fidelity. In summary, our results demonstrate that, while introns are dispensable for cell viability, some introns have diverse roles, such as ensuring proper growth under various conditions and controlling the appropriate anticodon modifications for accurate pairing with the codon.
Asunto(s)
Intrones , ARN de Transferencia/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Anticodón , Northern Blotting , Codón , Genoma Fúngico , Leucina/química , Mutación , Conformación de Ácido Nucleico , Fenotipo , Plásmidos/metabolismo , Seudouridina , ARN/química , Procesamiento Postranscripcional del ARN , ARN de Hongos/metabolismo , ARN Ribosómico 5.8S/metabolismoRESUMEN
The fish fin is a breathtaking repository full of evolutionary diversity, novelty, and convergence. Over 500 million years, the adaptation to novel habitats has provided landscapes of fin diversity. Although comparative anatomy of evolutionarily divergent patterns over centuries has highlighted the fundamental architectures and evolutionary trends of fins, including convergent evolution, the developmental constraints on fin evolution, which bias the evolutionary trajectories of fin morphology, largely remain elusive. Here, we review the evolutionary history, developmental mechanisms, and evolutionary underpinnings of paired fins, illuminating possible developmental constraints on fin evolution. Our compilation of anatomical and genetic knowledge of fin development sheds light on the canalized and the unpredictable aspects of fin shape in evolution. Leveraged by an arsenal of genomic and genetic tools within the working arena of spectacular fin diversity, evolutionary developmental biology embarks on the establishment of conceptual framework for developmental constraints, previously enigmatic properties of evolution.
Asunto(s)
Adaptación Fisiológica/genética , Aletas de Animales , Regulación del Desarrollo de la Expresión Génica/genética , Aletas de Animales/metabolismo , Animales , Evolución BiológicaRESUMEN
Many biological disease-modifying antirheumatic drugs (bDMARDs) and targeted synthetic DMARDs (tsDMARDs) are currently available as treatment options for rheumatoid arthritis (RA), but a subset of RA patients shows inadequate responses to any of these DMARDs. This phenomenon, which we call super-resistance, is becoming a serious concern. In this study, I present two cases of super-resistant RA in which patients failed to respond to treatment with bDMARDs of any class as well as to tsDMARD therapy with tofacitinib. In these cases, leukocytapheresis (LCAP), a treatment that removes overabundant leukocytes from the body, rapidly induced low disease activity and made patients subsequently responsive to previously ineffective DMARDs. My experience with the present cases suggests that LCAP is worth considering as an alternative therapeutic option for the management of RA patients with super-resistance to DMARD therapies.
Asunto(s)
Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Leucaféresis/métodos , Piperidinas/uso terapéutico , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirimidinas/uso terapéutico , Anciano , Antirreumáticos/farmacología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Piperidinas/farmacología , Inhibidores de Proteínas Quinasas/farmacología , Pirimidinas/farmacologíaRESUMEN
BACKGROUND: Psoas muscle mass is a surrogate marker for sarcopenia: a depletion of skeletal muscle mass. This study was conducted to elucidate the prognostic significance of the psoas muscle index (PMI: cross-sectional area of the bilateral psoas muscle at the umbilical level on computed tomography/height2 [cm2/m2]) in patients undergoing surgery for lung squamous cell carcinoma (SCC) and lung adenocarcinoma (ADC). METHODS: One hundred and sixty-five patients with SCC and 556 patients with ADC who underwent R0 resection between 2007 and 2014 were reviewed for analysis. In SCC patients, the mean value (standard deviation) of the PMI was 6.15 (1.49) in men and 4.65 (1.36) in women. Among ADC patients, the PMI was 7.12 (1.60) in men and 5.29 (1.22) in women. Clinicopathological characteristics as well as the survival were evaluated. RESULTS: The PMI was associated with the age, body mass index (BMI), and serum albumin. In the multivariable Cox regression analysis, after adjusting for age, BMI, serum albumin, sex, pathological stage, and diffusing capacity for carbon monoxide, the PMI showed a significant association with the overall survival (OS) and disease-free survival (DFS) in SCC patients (hazard ratios 0.50 and 0.56, 95% confidence intervals 0.39-0.65 and 0.45-0.71, respectively). On the other hand, in ADC patients, the PMI had no impact on the OS or DFS. CONCLUSIONS: The PMI was significantly associated with the survival of lung SCC patients, but not of lung ADC patients, suggesting the presence of a previously unidentified relationship between skeletal muscle and lung SCC progression.
Asunto(s)
Adenocarcinoma del Pulmón/cirugía , Carcinoma de Células Escamosas/cirugía , Neoplasias Pulmonares/cirugía , Músculos Psoas , Sarcopenia/diagnóstico , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/mortalidad , Anciano , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/patología , Quimioterapia Adyuvante , Supervivencia sin Enfermedad , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Masculino , Recurrencia Local de Neoplasia/tratamiento farmacológico , Periodo Preoperatorio , Pronóstico , Modelos de Riesgos Proporcionales , Músculos Psoas/diagnóstico por imagen , Estudios Retrospectivos , Sarcopenia/etiología , Tomografía Computarizada por Rayos XRESUMEN
OBJECTIVES: To compare retention of tocilizumab (TCZ) as monotherapy vs combination therapy with MTX in RA patients achieving clinical improvements during the first year. METHODS: We performed a multicentre cohort study using a real-life registry containing RA patients who had begun TCZ with or without MTX between April 2008 and November 2016. Among patients with ≥50% improvement of clinical disease activity index (CDAI) during the first year (CDAI50 responders), we evaluated whether MTX use may have affected TCZ discontinuation during the second and subsequent years (maintenance therapy). RESULTS: Among 510 patients with high or moderate CDAI, 328 (64.3%) were CDAI50 responders. The rate of MTX use was 53.0% among responders and 54.4% among non-responders. During maintenance therapy (mean follow-up 30.7 months), 43.9% of CDAI50 responders discontinued TCZ. The most common cause was efficacy loss followed by adverse events. Kaplan-Meier estimates for TCZ retention were 48.3 months (95% CI 42.0, 54.5) for monotherapy and 50.0 months (95% CI 45.9, 54.0) for combination therapy. According to Gray's test, there was no significant impact of MTX use on cumulative incidence of efficacy loss or adverse events. In the Fine-Gray competing risk regression model, CDAI >10 at the start of maintenance therapy and age were predictive factors for TCZ discontinuation due to efficacy loss (hazard ratio 2.58, 95% CI 1.41, 4.72) and adverse events (hazard ratio 1.04, 95% CI 1.01, 1.08), respectively. CONCLUSION: There was no significant difference in TCZ retention between monotherapy and combination therapy with MTX.
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Anticuerpos Monoclonales Humanizados/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Reumatoide/tratamiento farmacológico , Metotrexato/uso terapéutico , Anciano , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Antirreumáticos/administración & dosificación , Antirreumáticos/efectos adversos , Estudios de Cohortes , Esquema de Medicación , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Humanos , Quimioterapia de Mantención/métodos , Masculino , Metotrexato/administración & dosificación , Persona de Mediana Edad , Sistema de Registros , Inducción de Remisión/métodos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Privación de Tratamiento/estadística & datos numéricosRESUMEN
BACKGROUND: For thymic epithelial tumors (TETs), the National Comprehensive Cancer Network guideline has suggested that complete excision of the tumor should be performed without a preoperative biopsy when resectable. However, little evidence has been provided to support this strategy. The purpose of this study was to review our diagnostic process and to evaluate the validity of radical resection of anterior mediastinal masses (AMMs) without pathological confirmation. METHODS: A total of 254 patients underwent surgical resection for AMMs between 2004 and 2015. This study included 181 patients with likely TETs according to clinical features, serum levels of tumor markers and autoimmune-antibodies, and radiological findings. In addition, AMMs likely TETs were classified into resectable or unresectable tumors. We retrospectively reviewed the diagnostic process of those patients and validated surgical resection of AMMs without a definitive diagnosis. RESULTS: Among 254 patients, 181 were suspected of having a TET based on the serum levels of tumor markers and autoimmune-antibodies and the radiological findings. Of them, 157 patients were deemed resectable and underwent surgical resection without histological confirmation, and 144 (92%) were diagnosed with TETs in the final pathological examinations. In 13 patients with non-TETs, the tumors were difficult to differentiate from TETs by imaging and clinical findings alone. CONCLUSIONS: A total of 92% of patients suspected of having a TET and who underwent complete resection without pathological confirmation were accurately diagnosed and properly treated. Surgical resection without a definitive diagnosis was feasible in patients suspected of having a TET when they were considered resectable.
Asunto(s)
Neoplasias del Mediastino/diagnóstico , Neoplasias Glandulares y Epiteliales/diagnóstico , Neoplasias del Timo/diagnóstico , Adolescente , Adulto , Anciano , Biomarcadores de Tumor/sangre , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Neoplasias del Mediastino/patología , Neoplasias del Mediastino/cirugía , Persona de Mediana Edad , Neoplasias Glandulares y Epiteliales/patología , Neoplasias Glandulares y Epiteliales/cirugía , Estudios Retrospectivos , Neoplasias del Timo/patología , Neoplasias del Timo/cirugía , Tomografía por Rayos XRESUMEN
PURPOSE: In the most recent (eighth) edition of the TNM classification, the clinical T descriptor has been adapted to measure the consolidation size of sub-solid lung cancer. Sub-centimeter non-small cell lung cancer (NSCLC) has thereby been subclassified into three groups: Tis, T1mi, and T1a; however, the revision has not been validated well. Thus, we investigated the clinicopathological characteristics and long-term oncological outcomes of sub-centimeter NSCLCs based on the solid size. METHODS: The subjects of this retrospective review were 99 patients who underwent complete resection for NSCLC with ≤ 1 cm in consolidation size on computed tomography (CT). Survival was reanalyzed after reclassification according to the new TNM classification. RESULTS: This cohort consisted of 14 patients with cTis tumors, 18 with cT1mi tumors, and 67 with cT1a tumors. Among the patients with tumors classified as cT1a, two had lymph node metastasis and two had vascular invasion. The cumulative incidences of recurrence at 5 and 10 years were 0% for cTis/cT1mi tumors, and 4.5% and 6.1% for cT1a tumors, respectively. CONCLUSIONS: There may be pathological and survival differences between cTis/cT1mi tumors and cT1a tumors, but not between cTis tumors and cT1mi tumors.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/patología , Estadificación de Neoplasias/métodos , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/clasificación , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Estudios de Cohortes , Femenino , Estudios de Seguimiento , Humanos , Neoplasias Pulmonares/clasificación , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/epidemiología , Pronóstico , Estudios Retrospectivos , Tasa de Supervivencia , Factores de TiempoRESUMEN
PURPOSE: We assessed the utility of the tumor doubling time (TDT) for predicting the histological type of thymic epithelial tumors. METHODS: We retrospectively reviewed 130 patients with thymic epithelial tumors who underwent computed tomography two or more times before surgery. The patients were divided into low-risk thymoma (types A, AB and B1), high-risk thymoma (types B2 and B3) and thymic carcinoma (thymic carcinoma and thymic neuroendocrine tumor) groups. In the 96 patients who showed tumor enlargement, the relationship between the histological type and the TDT of the tumor was investigated. RESULTS: The study population included 55 men and 41 women from 26 to 82 years of age. The TDT of the thymic carcinoma group (median 205 days) was significantly shorter in comparison to the low-risk thymoma (median 607 days) and high-risk thymoma (median 459 days) groups. No significant differences were observed between the low-risk thymoma and high-risk thymoma groups. When we set the cutoff time for differentiating thymic carcinoma group from thymoma at 313 days, the sensitivity and specificity were 83.8% and 82.1%, respectively. CONCLUSIONS: The TDT is a useful parameter for differentiating between thymoma and thymic carcinoma group.
Asunto(s)
Transformación Celular Neoplásica/patología , Neoplasias Glandulares y Epiteliales/patología , Neoplasias del Timo/patología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Neoplasias Glandulares y Epiteliales/diagnóstico por imagen , Estudios Retrospectivos , Timoma/diagnóstico por imagen , Timoma/patología , Neoplasias del Timo/diagnóstico por imagen , Factores de Tiempo , Tomografía Computarizada por Rayos XRESUMEN
In at risk populations, Pneumocystis pneumonia (PCP) may occur as a solitary event as well as in a cluster- or outbreak setting due to interpatient transmission of Pneumocystis jirovecii. Despite the data and insights obtained from studies of outbreaks of PCP, the development and implementation of comprehensive recommendations for the prevention of healthcare related transmission of P. jirovecii have been delayed. Both optimization of chemoprophylaxis strategies as well as combination with prudent use of isolation precautions are warranted to achieve this goal. The rationale of the available measures for the prevention of PCP should be viewed in the context of what is currently known about the complex biology and epidemiology of P. jirovecii. From there, phased but practical prevention strategies can be deducted to balance the efforts, costs and negative consequences of chemoprophylaxis and isolation precautions with the beneficial effect of preventing healthcare related transmission of P. jirovecii and development of PCP.
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Profilaxis Antibiótica/métodos , Infección Hospitalaria/transmisión , Brotes de Enfermedades/prevención & control , Pneumocystis carinii/patogenicidad , Neumonía por Pneumocystis/transmisión , Infección Hospitalaria/epidemiología , Infección Hospitalaria/microbiología , Infección Hospitalaria/prevención & control , Humanos , Huésped Inmunocomprometido , Neumonía por Pneumocystis/epidemiología , Neumonía por Pneumocystis/microbiología , Neumonía por Pneumocystis/prevención & control , Factores de RiesgoRESUMEN
OBJECTIVE: Recent studies have reported a high prevalence of primary aldosteronism (PA) among hypertensive patients. However, few data exist regarding the prevalence of PA in the general population. Therefore, we examined the prevalence of PA in the general population including normotensive subjects. METHODS: Plasma renin activity (ng/mL/hr), plasma aldosterone concentration (pg/mL) and aldosterone renin ratio (ARR) were determined in 309 subjects aged >40 years in Horimatsu and Higashi-Matsuho district, Shika-machi, Ishikawa, Japan. RESULTS: Among them, 195 subjects (78 males, mean age: 62 ± 11 years) did not take antihypertensive agents: 113 normotensive subjects and 82 hypertensive subjects. Under these conditions, 68 subjects (13 males, age 62 ± 10 years) had an ARR >200. In 14 subjects who underwent captopril suppression test, PA was documented in 5 subjects, yielding a minimum prevalence of 2.6% in total subjects (1.8% in normotensive subjects and 3.7% in hypertensive subjects). Interestingly, females subjects demonstrated significant differences in ARR between subjects with age <50 (172 ± 105) and those with age 51-60 (388 ± 531), although there were no differences in male subjects. CONCLUSIONS: These results demonstrate that PA including normotensive subjects exists more commonly than that expected in the general population. We suggest further investigation about the cause and progression of PA associated with sex and aging.
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Aldosterona/sangre , Hiperaldosteronismo/sangre , Hiperaldosteronismo/epidemiología , Renina/sangre , Adulto , Anciano , Presión Sanguínea , Progresión de la Enfermedad , Femenino , Humanos , Hipertensión/epidemiología , Japón/epidemiología , Masculino , Persona de Mediana Edad , PrevalenciaRESUMEN
Experimental models recently suggested an interaction between aldosterone and adipose tissue, but clinical investigation has been limited. We studied the effects of eplerenone compared to hydrochlorothiazide (HCTZ) on blood pressure (BP), glucose, and lipid levels in 50 patients with essential hypertension (EHT) and type 2 diabetes mellitus whose BP failed to reach target levels with 8 mg of candesartan alone. BP improved similarly in both groups over the 12-month study period, but BMI, waist circumference, and LDL-cholesterol were decreased in the eplerenone group, while glycohemoglobin was elevated in the HCTZ group.
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Bencimidazoles , Presión Sanguínea/efectos de los fármacos , Diabetes Mellitus Tipo 2 , Hidroclorotiazida , Espironolactona/análogos & derivados , Tetrazoles , Adulto , Anciano , Antagonistas de Receptores de Angiotensina/administración & dosificación , Antihipertensivos/administración & dosificación , Bencimidazoles/administración & dosificación , Bencimidazoles/efectos adversos , Compuestos de Bifenilo , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Monitoreo de Drogas/métodos , Quimioterapia Combinada/métodos , Eplerenona , Hipertensión Esencial , Femenino , Hemoglobina Glucada/análisis , Humanos , Hidroclorotiazida/administración & dosificación , Hidroclorotiazida/efectos adversos , Hipertensión/complicaciones , Hipertensión/diagnóstico , Hipertensión/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Antagonistas de Receptores de Mineralocorticoides/administración & dosificación , Espironolactona/administración & dosificación , Espironolactona/efectos adversos , Tetrazoles/administración & dosificación , Tetrazoles/efectos adversos , Resultado del TratamientoRESUMEN
Liquid biopsy is defined as a non-invasive blood test that detects features of tumor cells, which are shed into the blood stream from the primary tumor and/or metastatic sites. This method is developing based on research on circulating tumor cells (CTCs) and the circulating free/fragments of tumor DNA (cfDNA). CfDNA can be detected in the absence of detectable CTCs, and has been shown to increase with the disease condition. The detection of cfDNA can be used for tumor genotyping, monitoring of the tumor burden, and monitoring minimal residual diseases, and recent results showed that cfDNA is a highly specific biomarker with intermediate sensitivity. Liquid biopsy with cfDNA is promising, and is becoming an alternative to re- biopsy. However, there are some caveats: it has not been elucidated which patients and tumor types can be accessed with cfDNA. Further research is warranted.
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Neoplasias Pulmonares/diagnóstico , Biomarcadores de Tumor/sangre , Biomarcadores de Tumor/genética , Receptores ErbB/genética , Genotipo , Biopsia Líquida , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , MutaciónRESUMEN
The lysosomal adaptor protein p18 is an essential anchor of a scaffolding complex for the mTORC1 and MAPK pathways, which play crucial roles in controlling cell growth and energy homeostasis. To elucidate the in vivo function of the p18-mediated pathway, we conditionally ablated p18 in the mouse epidermis. Mutant mice were born with severe defects in formation of the stratum corneum and died within 12 h after birth due to dehydration caused by loss of skin barrier function. Mutant epidermal cells can grow and differentiate into granular cells, but exhibit functional defects in corneocyte maturation. Electron microscopy identified abnormal immature cells, overlying the mutant granular cells, which accumulated autophagosomes, glycogen granules and dead nuclei. Cell culture analysis showed that loss of p18 attenuated lysosome function, resulting in accumulation of immature lysosomes and autophagosomes. Analyses of lysosome behavior revealed that p18 is required for functional interaction between lysosomes and target organelles including autophagosomes. These findings suggest that p18-mediated pathways control lysosome-mediated catabolic processes, which are crucial for the development of mouse epidermis.
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Proteínas Adaptadoras Transductoras de Señales/metabolismo , Epidermis/crecimiento & desarrollo , Epidermis/metabolismo , Lisosomas/metabolismo , Nucleósido Difosfato Quinasas NM23/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Animales , Animales Recién Nacidos , Autofagia/fisiología , Células Epidérmicas , Homeostasis , Queratinocitos/citología , Queratinocitos/metabolismo , Sistema de Señalización de MAP Quinasas , Ratones , Ratones Transgénicos , Microscopía Electrónica de Transmisión , Nucleósido Difosfato Quinasas NM23/genética , Transducción de SeñalRESUMEN
Therapy for polymyalgia rheumatica (PMR) varies widely in clinical practice as international recommendations for PMR treatment are not currently available. In this paper, we report the 2015 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) recommendations for the management of PMR. We used the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) methodology as a framework for the project. Accordingly, the direction and strength of the recommendations are based on the quality of evidence, the balance between desirable and undesirable effects, patients' and clinicians' values and preferences, and resource use. Eight overarching principles and nine specific recommendations were developed covering several aspects of PMR, including basic and follow-up investigations of patients under treatment, risk factor assessment, medical access for patients and specialist referral, treatment strategies such as initial glucocorticoid (GC) doses and subsequent tapering regimens, use of intramuscular GCs and disease modifying anti-rheumatic drugs (DMARDs), as well as the roles of non-steroidal anti-rheumatic drugs and non-pharmacological interventions. These recommendations will inform primary, secondary and tertiary care physicians about an international consensus on the management of PMR. These recommendations should serve to inform clinicians about best practices in the care of patients with PMR.