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1.
Respir Investig ; 62(3): 365-368, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38428090

RESUMEN

The primary objective of this study was to identify the predominant organisms associated with ventilator-associated pneumonia (VAP) in Japan. Studies on VAP conducted in Japan were systematically reviewed, and seven studies with a total of 374 cases were included. The detection rate of each bacterium and multidrug-resistant (MDR) pathogen was analyzed using the inverse variance method. Pseudomonas aeruginosa was identified as the predominant pathogen in 29.2 % of cases, followed by methicillin-resistant Staphylococcus aureus (MRSA) (12.0 %), and Klebsiella spp. (9.5 %). An integrated analysis revealed a detection rate of 57.8 % (95 % confidence interval: 48.7%-66.8 %) for MDR pathogens. This review highlights P. aeruginosa and MRSA as the predominant VAP-associated organisms in Japan, with a significant prevalence of MDR pathogens. This analysis provides valuable insights based on the regional distribution of bacteria detected in VAP, which is critical for selecting appropriate empirical therapy.


Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Neumonía Asociada al Ventilador , Humanos , Neumonía Asociada al Ventilador/diagnóstico , Neumonía Asociada al Ventilador/epidemiología , Neumonía Asociada al Ventilador/microbiología , Antibacterianos/uso terapéutico , Japón/epidemiología , Bacterias , Pseudomonas aeruginosa
2.
Sci Rep ; 13(1): 19143, 2023 11 06.
Artículo en Inglés | MEDLINE | ID: mdl-37932342

RESUMEN

The close relationship between infectious diseases and iron metabolism is well known, but a more detailed understanding based on current knowledge may provide new insights into the diagnosis and treatment of infectious diseases, considering the growing threat of antibiotic-resistant bacteria. This study investigated adult patients with bloodstream infections, temporal changes, and relationships between blood levels of iron and related markers, including hepcidin and lipocalin-2 (LCN2). We included 144 samples from 48 patients (mean age 72 years, 50% male), with 30 diagnosed with sepsis. During the acute phase of infection, blood levels of hepcidin and LCN2 increased rapidly, whereas iron levels decreased, with values in 95.8% of cases below the normal range (40-188 µg/dL). Later, hepcidin and LCN2 decreased significantly during the recovery phase, and the decreased iron concentrations were restored. In the case of persistent inflammation, iron remained decreased. Acute LCN2 levels were significantly higher in patients with sepsis (p < 0.01). Hypoferremia induced by increased hepcidin would reduce iron in the environment of extracellular pathogens, and the increased LCN2 would inhibit siderophores, resulting in the prevention of the pathogen's iron acquisition in each manner during the acute phase of bloodstream infection.


Asunto(s)
Enfermedades Transmisibles , Sepsis , Humanos , Masculino , Anciano , Femenino , Hepcidinas/metabolismo , Lipocalina 2/metabolismo , Hierro/metabolismo , Sideróforos/metabolismo
3.
Parkinsonism Relat Disord ; 115: 105817, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37647745

RESUMEN

INTRODUCTION: A study is eagerly awaited that will reveal the unknown mechanisms of multiple system atrophy (MSA), in which the risk of sudden death is the greatest during sleep. The blunted pulse response to nocturnal respiratory events suggests an abnormal cardiac response to a sleep-related breathing disorder. Patients with MSA have a lower pulse event index (PEI), despite a greater hypoxic burden and a similar frequency of respiratory events. However, the evidence is speculative and not directly proven, and many limitations require further study. METHODS: We conducted a retrospective analysis of 26 patients with MSA who had undergone overnight oximetry between April 2016 and December 2022. RESULTS: The median 4% oxyhemoglobin desaturation index (ODI) was 11.6/h, the 6-bpm PEI was 8.9/h, and the PEI/ODI ratio was as low as 0.91. There were three patients with suspected sudden death; all had low PEI/ODI ratios. The PEI/ODI ratio was followed over time in seven patients, all of whom had a decrease in the ratio. However, the PEI was higher than the ODI in 12/26 (46%) of the patients. CONCLUSION: A low PEI/ODI ratio, reflecting a blunted pulse response to nocturnal respiratory events in patients with MSA, may indicate a worse prognosis. This finding and the significance of the longitudinal decrease in the PEI/ODI ratio will require a prospective study.

5.
Sleep Med ; 106: 106-115, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37087824

RESUMEN

BACKGROUND: Chronic intermittent hypoxia (IH) plays a significant role in the pathogenesis of obstructive sleep apnea (OSA) comorbidities. The prevalence of chronic kidney disease is higher in patients with OSA than the general population, and renal function decline is well correlated with renal tubular injury. However, little is known about the impact of OSA-induced chronic IH on the renal tubules. METHODS: We conducted a retrospective survey of clinical records performing multiple regression analysis and cluster analysis with particular attention to the 3% oxygen desaturation index (ODI) and urinary N-acetyl-ß-d-glucosaminidase (NAG). RESULTS: In patients with suspicion of OSA, urinary NAG creatinine ratio (UNCR) was elevated as their 3% ODI increased (n = 197, p < 0.001), and the elevated UNCR decreased following CPAP treatment in patients with OSA (n = 46, p = 0.014). Multiple regression analysis showed that 3% ODI was associated with UNCR. Cluster analysis identified three clusters of patients with OSA, including two younger age clusters, one of which was characterized by high BMI, high 3% ODI, and high prevalence of major comorbidities. In a comparative analysis of younger age cases (age ≤ 55, n = 82), the UNCR level was higher in patients with severe 3% ODI (3% ODI > 40 events/h, n = 24) (p = 0.014). CONCLUSIONS: Our results indicate that even at younger ages, OSA patients with severe chronic IH and major comorbidities are susceptible to renal tubular damage. Early treatment with CPAP may attenuate renal tubular injury and progression toward end-stage renal disease.


Asunto(s)
Presión de las Vías Aéreas Positiva Contínua , Apnea Obstructiva del Sueño , Humanos , Presión de las Vías Aéreas Positiva Contínua/métodos , Estudios Retrospectivos , Estudios de Cohortes , Hipoxia/complicaciones , Oxígeno , Creatinina
6.
PLoS One ; 18(3): e0283070, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36920951

RESUMEN

Nasal breathing disorders are associated with obstructive sleep apnea (OSA) syndrome and influence the availability of continuous positive airway pressure (CPAP) therapy. However, information is scarce about the impact of nasal resistance assessed by rhinomanometry on CPAP therapy. This study aimed to examine the relationship between CPAP adherence and nasal resistance evaluated by rhinomanometry, and to identify clinical findings that can affect adherence to CPAP therapy for patients with OSA. This study included 260 patients (199 men, 61 women; age 58 [interquartile ranges (IQR) 50-66] years) with a new diagnosis of OSA who underwent rhinomanometry (before, and 1 and 3 months after CPAP introduction) between January 2011 and December 2018. CPAP use was recorded, and the good and poor CPAP adherence groups at the time of patient registration were compared. Furthermore, those with improved and unimproved pre-CPAP high rhinomanometry values were also compared. Their apnea-hypopnea index (AHI) by polysomnography at diagnosis was 45.6 (IQR 33.7-61.6)/hour, but the residual respiratory event (estimated AHI) at enrollment was 2.5 (IQR 1.4-3.9)/hour and the usage time was 318 (IQR 226-397) minutes, indicating that CPAP was effective and adherence was good. CPAP adherence was negatively correlated with nasal resistance (r = -0.188, p = 0.002). The participants were divided into good (n = 153) and poor (n = 107) CPAP adherence groups. In the poor adherence group, rhinomanometry values before CPAP introduction were worse (inspiration, p = 0.003; expiration, p = 0.006). There was no significant difference in patient background when comparing those with improved (n = 16) and unimproved (n = 12) pre-CPAP high rhinomanometry values. However, CPAP usage time was significantly longer in the improved group 1 month (p = 0.002) and 3 months (p = 0.026) after CPAP introduction. The results suggest that nasal resistance evaluated by rhinomanometry is a useful predictor of CPAP adherence, and that improved rhinomanometry values may contribute to extending the duration of CPAP use.


Asunto(s)
Enfermedades Nasales , Apnea Obstructiva del Sueño , Masculino , Humanos , Femenino , Preescolar , Presión de las Vías Aéreas Positiva Contínua/métodos , Rinomanometría , Polisomnografía/métodos , Cooperación del Paciente
7.
J Infect Chemother ; 28(11): 1471-1477, 2022 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-35850402

RESUMEN

INTRODUCTION: This study aimed to examine the factors associated with cytomegalovirus (CMV) antigenemia and the time of onset of CMV antigenemia among patients with rheumatic diseases. METHODS: A single-center, retrospective, observational study was conducted in our institution from January 2009 to December 2017. This study included patients with rheumatic diseases who had at least one CMV antigen measurement. Multivariate analysis and receiver operating characteristic analysis was performed. RESULTS: A total of 249 patients underwent CMV antigenemia assay, and 84 (33.7%) patients tested positive. When the association between CMV antigenemia and possible associated factors was investigated, multivariate analysis showed that daily steroid dose increased the odds of having CMV [odds ratio 16.25, 95% confidence interval (CI), 5.360-49.253]. In this study, the cutoff value of daily steroid dose found in this study (0.45 mg/kg/day) was reasonable in clinical practice, and the area under the curve of the steroid dose was 0.838 [95% CI 0.781-0.882], which was the largest of the known indicators. Moreover, the median time from the start of immunosuppressive therapy to the onset of CMV antigenemia was 30 (interquartile range, 21-44) days, and most of the daily steroid users (85.7%) developed CMV antigenemia within 60 days. CONCLUSIONS: The daily steroid dose is the most important factor associated with CMV antigenemia. Therefore, monitoring and treatment strategies based on the steroid dose, especially in the initial 2 months, are important.


Asunto(s)
Infecciones por Citomegalovirus , Enfermedades Reumáticas , Antígenos Virales , Citomegalovirus , Infecciones por Citomegalovirus/complicaciones , Humanos , Estudios Retrospectivos , Enfermedades Reumáticas/complicaciones , Enfermedades Reumáticas/tratamiento farmacológico
8.
Transl Lung Cancer Res ; 11(1): 43-52, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35242626

RESUMEN

BACKGROUND: Procalcitonin (PCT) is a serological marker whose utility has been established in infectious disease areas. Although serum calcitonin is a prognostic predictor in patients with medullary thyroid carcinoma, the clinical usefulness of PCT remains unclear in lung cancer patients. METHODS: As a discovery cohort, we retrospectively analyzed consecutive patients with non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) who received first-line chemotherapy at our institution, and PCT blood levels were measured. As the validation cohort, PCT blood levels were prospectively evaluated in SCLC patients before first-line chemotherapy. The correlation between a PCT increase and prognosis was examined in the discovery and validation cohorts. RESULTS: Twenty-three SCLC patients and 26 NSCLC patients were enrolled as the discovery cohort, and 30 SCLC patients were enrolled as the validation cohort. The PCT level in SCLC patients was significantly higher than that in NSCLC patients. The PCT level was not associated with WBC count and weakly associated with the CRP level. In both the discovery and validation cohorts, the median survival time was significantly shorter in SCLC patients with PCT-high than in SCLC patients with PCT-normal (discovery; 11.7 vs. 89.7 months, P<0.005, validation; 9.6 vs. 22.6 months, P<0.005). CONCLUSIONS: It may be difficult to differentiate bacterial infections in SCLC patients by PCT, as PCT is elevated even in SCLC patients without infectious diseases. This is the first study to prospectively verify that pretreatment PCT levels have a significant negative correlation with prognosis in SCLC patients.

9.
Infect Control Hosp Epidemiol ; 43(12): 1934-1936, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-34325756

RESUMEN

An outbreak of serotype 19A Streptococcus pneumoniae occurred among the residents of a relief facility. Pneumonia developed in 5 of 99 residents (attack rate, 5.1%). We obtained pharyngeal specimens from non-onset residents, and S. pneumoniae was isolated from 6 individuals (6.4%), 5 of whom had serotype 19A.


Asunto(s)
Infecciones Neumocócicas , Neumonía Neumocócica , Humanos , Neumonía Neumocócica/epidemiología , Serogrupo , Japón/epidemiología , Streptococcus pneumoniae , Brotes de Enfermedades , Serotipificación
10.
Cancer Immunol Immunother ; 71(6): 1357-1369, 2022 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34657194

RESUMEN

Lymphodepleting cytotoxic regimens enhance the antitumor effects of adoptively transferred effector and naïve T cells. Although the mechanisms of antitumor immunity augmentation by lymphodepletion have been intensively investigated, the effects of lymphodepletion followed by T cell transfer on immune checkpoints in the tumor microenvironment remain unclear. The current study demonstrated that the expression of immune checkpoint molecules on transferred donor CD4+ and CD8+ T cells was significantly decreased in lymphodepleted tumor-bearing mice. In contrast, lymphodepletion did not reduce immune checkpoint molecule levels on recipient CD4+ and CD8+ T cells. Administration of anti-PD-1 antibodies after lymphodepletion and adoptive transfer of T cells significantly inhibited tumor progression. Further analysis revealed that transfer of both donor CD4+ and CD8+ T cells was responsible for the antitumor effects of a combination therapy consisting of lymphodepletion, T cell transfer and anti-PD-1 treatment. Our findings indicate that a possible mechanism underlying the antitumor effects of lymphodepletion followed by T cell transfer is the prevention of donor T cell exhaustion and dysfunction. PD-1 blockade may reinvigorate exhausted recipient T cells and augment the antitumor effects of lymphodepletion and adoptive T cell transfer.


Asunto(s)
Linfocitos T CD8-positivos , Neoplasias , Traslado Adoptivo , Animales , Humanos , Inmunoterapia Adoptiva , Ratones , Neoplasias/terapia , Receptor de Muerte Celular Programada 1 , Microambiente Tumoral
11.
Front Oncol ; 11: 704475, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34631533

RESUMEN

OBJECTIVES: Although immune checkpoint inhibitors (ICIs) have been shown to improve overall survival (OS) in advanced non-small-cell lung cancer (NSCLC) patients, ICIs sometimes cause various types of immune-related adverse events (irAEs), which lead to the interruption of ICI treatment. This study aims to evaluate the clinical significance of the continuation of ICIs in NSCLC patients with irAEs and to assess the safety and efficacy of the readministration of ICIs after their discontinuation due to irAEs. METHODS: We retrospectively identified patients with advanced NSCLC who were treated with first- to third-line anti-programmed cell death-1 (PD-1) therapy from January 2016 through October 2017 at multiple institutions belonging to the Niigata Lung Cancer Treatment Group. Progression-free survival (PFS) and OS from the initiation of ICI treatment were analyzed in patients with and without irAEs, with and without ICI interruption, and with and without ICI readministration. A 6-week landmark analysis of PFS and OS was performed to minimize the lead-time bias associated with time-dependent factors. RESULTS: Of 231 patients who received anti-PD-1 antibodies, 93 patients (40%) developed irAEs. Of 84 eligible patients with irAEs, 32 patients (14%) continued ICIs, and OS was significantly longer in patients who continued ICIs than that in patients who discontinued ICIs [not reached (95% CI: NE-NE) vs. not reached (95% CI: 22.4-NE); p = 0.025]. Of 52 patients who discontinued ICIs, 14 patients (6.1%) readministered ICIs, and OS in patients with ICI readministration was significantly longer than that in patients without ICI readministration [not reached (95% CI: NE-NE) vs. not reached (95% CI: 8.4-NE); p = 0.031]. CONCLUSION: The current study demonstrated that both the continuation and readministration of ICIs after irAE occurrence improved OS compared to the permanent interruption of ICIs in NSCLC patients with ICI-related irAEs.

12.
Transl Lung Cancer Res ; 10(7): 3132-3143, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34430353

RESUMEN

BACKGROUND: Although immune checkpoint inhibitors (ICIs) are effective for advanced non-small cell lung cancer (NSCLC), ICIs may cause interstitial lung disease (ILD), which results in treatment discontinuation and is sometimes fatal. Despite the high incidence of ICI-related ILD, there are few cancer treatment options for patients. This study aimed to evaluate the safety and efficacy of subsequent systemic cancer therapy in NSCLC patients with ICI-related ILD. METHODS: We retrospectively assessed NSCLC patients who received programmed cell death-1 (PD-1) inhibitors as first- to third-line therapy at participating institutions of the Niigata Lung Cancer Treatment Group from January 2016 to October 2017. RESULTS: This analysis included 231 patients, 32 (14%) of whom developed ICI-related ILD. Of these patients, 16 (7%) received subsequent systemic cancer treatments. The median overall survival (OS) tended to be longer in the systemic cancer therapy group than in the no systemic cancer therapy group [22.2 months (95% CI: 1-NE) vs. 4.5 months (95% CI: 1-NE); P=0.067]. ICI-related ILD recurred in half of the patients who received systemic cancer therapy, and the median OS tended to be shorter in patients with recurrent ICI-related ILD [22.0 months (95% CI: 1-NE) vs. 7.0 months (95% CI: 1-NE); P=0.3154]. CONCLUSIONS: According to the current study, systemic cancer treatment is effective in patients with ICI-related ILD; however, its safety is uncertain because of the high risk of ICI-related ILD recurrence and poor survival outcome following ILD recurrence.

13.
PLoS One ; 16(8): e0255172, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34437556

RESUMEN

BACKGROUND: Each of the currently available (1→3)-ß-D-glucan (BDG) measurement kits follows a different measurement method and cut-off value. Comparisons of diagnostic performance for invasive fungal infections (IFIs) are desirable. Additionally, ecological considerations are becoming increasingly important in the development of new measurement kits. METHODS: The plasma BDG levels in clinical samples were measured using the following currently available kits: the Fungitec G test MKII, the Fungitec G test ES, Fungitell, the ß-Glucan test Wako, and the newly developed Wako kit (Wako-Eu). Wako-Eu uses a pre-treatment solution that conforms to European regulations for the registration, evaluation, authorisation, and restriction of chemicals. The values obtained for the samples using each kit were studied and compared. RESULTS: Of the 165 patients evaluated, 12 had IFIs, including pneumocystis pneumonia, aspergillosis, and candidiasis. BDG values obtained using the kits were moderately correlated with each other. Clinical diagnoses of the evaluated cases indicated that 21 false positives were diagnosed by at least one kit. The sensitivity of the Fungitell kit was relatively low, but those of the other four were over 90%. The specificity was above 90% for all kits. For positive predictive value, the Wako and the Wako-Eu methods were superior to the others owing to fewer false positive results. CONCLUSIONS: The newly developed Wako-Eu method, which considers ecological concerns, shows diagnostic performance equivalent to that of its predecessor. To improve the diagnostic accuracy of IFIs, it is necessary to interpret the results carefully, giving due consideration to the characteristics of each measurement kit.


Asunto(s)
Infecciones Fúngicas Invasoras/diagnóstico , Juego de Reactivos para Diagnóstico , beta-Glucanos/análisis , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Curva ROC
14.
Respir Investig ; 59(3): 367-371, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33518470

RESUMEN

We herein report the case of a 20 year-old-man who developed bronchiolitis obliterans after living-donor renal transplantation. The patient presented with dyspnea on exertion and wheezing two years after renal transplantation, and spirometry showed an obstructive pattern. Surgical lung biopsy revealed subepithelial fibrosis that constricted and obstructed the intrabronchiolar space. Based on these findings, the patient was diagnosed with bronchiolitis obliterans. He was prescribed bronchodilators and azithromycin, and he achieved stable respiratory function for two years. The differential diagnosis of respiratory symptoms after renal transplantation includes opportunistic infection and drug-induced lung injury; however, bronchiolitis obliterans should also be considered.


Asunto(s)
Bronquiolitis Obliterante/diagnóstico , Bronquiolitis Obliterante/etiología , Trasplante de Riñón/efectos adversos , Trasplante de Riñón/métodos , Donadores Vivos , Complicaciones Posoperatorias/etiología , Adulto , Azitromicina/uso terapéutico , Bronquiolitis Obliterante/tratamiento farmacológico , Bronquiolitis Obliterante/patología , Broncodilatadores/uso terapéutico , Diagnóstico Diferencial , Fibrosis , Humanos , Pulmón/patología , Pulmón/fisiopatología , Masculino , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/patología , Espirometría , Adulto Joven
15.
Intern Med ; 60(12): 1921-1926, 2021 Jun 15.
Artículo en Inglés | MEDLINE | ID: mdl-33518558

RESUMEN

A 31-year-old woman who was clinically diagnosed with Silver-Russell syndrome (SRS) in childhood was admitted with complaints of dyspnea. She had hypercapnic respiratory failure accompanied by nocturnal hypoventilation. Computed tomography revealed systemic muscle atrophy and superior mesenteric artery syndrome; however, the bilateral lung fields were normal. She was treated with nocturnal noninvasive positive pressure ventilation and showed improvement of respiratory failure. In this case, loss of methylation on chromosome 11p15 and maternal uniparental disomy of chromosome 7, which are the common causes of SRS, were not detected. This is a rare case of adult SRS manifesting as chronic hypercapnic respiratory failure.


Asunto(s)
Insuficiencia Respiratoria , Síndrome de Silver-Russell , Adulto , Femenino , Humanos , Insuficiencia Respiratoria/etiología , Insuficiencia Respiratoria/genética , Síndrome de Silver-Russell/complicaciones , Síndrome de Silver-Russell/diagnóstico , Síndrome de Silver-Russell/genética , Disomía Uniparental
16.
Sci Rep ; 11(1): 750, 2021 01 12.
Artículo en Inglés | MEDLINE | ID: mdl-33437029

RESUMEN

Cisplatin, one of the most active anticancer agents, is widely used in standard chemotherapy for various cancers. Cisplatin is more poorly tolerated than other chemotherapeutic drugs, and the main dose-limiting toxicity of cisplatin is its nephrotoxicity, which is dose-dependent. Although less toxic methods of cisplatin administration have been established, cisplatin-induced nephrotoxicity remains an unsolved problem. Megalin is an endocytic receptor expressed at the apical membrane of proximal tubules. We previously demonstrated that nephrotoxic drugs, including cisplatin, are reabsorbed through megalin and cause proximal tubular cell injury. We further found that cilastatin blocked the binding of cisplatin to megalin in vitro. In this study, we investigated whether cilastatin could reduce cisplatin-induced nephrotoxicity without influencing the antitumor effects of cisplatin. Nephrotoxicity was decreased or absent in mice treated with cisplatin and cilastatin, as determined by kidney injury molecule-1 staining and the blood urea nitrogen content. Combined with cilastatin, a twofold dose of cisplatin was used to successfully treat the mice, which enhanced the antitumor effects of cisplatin but reduced its nephrotoxicity. These findings suggest that we can increase the dose of cisplatin when combined with cilastatin and improve the outcome of cancer patients.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Neoplasias del Colon/tratamiento farmacológico , Insuficiencia Renal/prevención & control , Animales , Apoptosis , Proliferación Celular , Cilastatina/administración & dosificación , Cisplatino/administración & dosificación , Neoplasias del Colon/metabolismo , Neoplasias del Colon/patología , Femenino , Tasa de Filtración Glomerular , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Endogámicos ICR , Ratones Endogámicos NOD , Ratones SCID , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
17.
Intern Med ; 60(7): 1077-1082, 2021 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-33162474

RESUMEN

Viral pneumonia caused by varicella-zoster virus (VZV) infection is a rare but important complication, especially regarding varicella infections. Although disseminated cutaneous herpes zoster (DCHZ) is often associated with visceral diseases, there have been few reports of DCHZ-related pneumonia. We herein report a rare case of a lethal disseminated VZV infection that caused severe pneumonia in a Japanese patient who had chronic interstitial pneumonia. Physicians should consider the possibility of VZV-related pneumonia, especially in patients with a medical history of hematopoietic stem cell transplantation and immunosuppressive therapy.


Asunto(s)
Varicela , Herpes Zóster , Enfermedades Pulmonares Intersticiales , Neumonía , Antivirales/uso terapéutico , Varicela/tratamiento farmacológico , Herpes Zóster/complicaciones , Herpes Zóster/diagnóstico , Herpes Zóster/tratamiento farmacológico , Herpesvirus Humano 3 , Humanos , Huésped Inmunocomprometido , Enfermedades Pulmonares Intersticiales/complicaciones , Enfermedades Pulmonares Intersticiales/diagnóstico , Neumonía/tratamiento farmacológico
18.
BMC Cancer ; 19(1): 1170, 2019 Dec 02.
Artículo en Inglés | MEDLINE | ID: mdl-31791266

RESUMEN

BACKGROUND: Cisplatin is a potent chemotherapeutic agent used to treat a variety of solid tumors. One of the major side effects of cisplatin is dose-limiting nephrotoxicity. We recently demonstrated that the renal uptake of cisplatin and resultant cisplatin-induced nephrotoxicity are mediated in part by megalin, an endocytic receptor in proximal tubule epithelial cells (PTECs). We also developed sandwich enzyme-linked immunosorbent assays to measure the megalin ectodomain (A-megalin) and full-length megalin (C-megalin) in urine using monoclonal antibodies against the amino- and carboxyl-termini of megalin, respectively. The present study examined the correlation of urinary megalin level with cisplatin-induced nephrotoxicity and its utility as a biomarker in patients with thoracic cancer. METHODS: This prospective observational study involved 45 chemotherapy-naïve patients scheduled to receive chemotherapy with ≥60 mg/m2 cisplatin for histologically diagnosed small cell lung cancer, non-small cell lung cancer, or malignant pleural mesothelioma. Before and after the first course of chemotherapy, we measured urinary A- and C-megalin and other markers of PTEC injury, such as N-acetyl-ß-D-glucosaminidase, α1-microglobulin, ß2-microglobulin, neutrophil gelatinase-associated lipocalin, and liver-type fatty acid-binding protein, and compared the values with the change in the estimated glomerular filtration rate (eGFR) and clinical risk factors for renal impairment. RESULTS: A negative correlation was found between baseline urinary A-megalin levels and change in eGFR (r = - 0.458, P = 0.002). According to Kaplan-Meier survival curves, eGFR decline was associated with the baseline urinary A-megalin quartile (P = 0.038). In addition, according to the hazard ratios (HRs) for eGFR decline > 10 mL/min/1.73 m2 calculated using a Cox proportional hazard model, the highest quartile had a significantly higher risk of eGFR decline compared with the lowest quartile (HR 7.243; 95% confidence interval 1.545-33.962). Other baseline urinary markers showed no correlation with eGFR decline. CONCLUSIONS: This is the first report demonstrating that prechemotherapy urinary A-megalin levels are correlated with the development of cisplatin-induced nephrotoxicity. This finding has clinical implications for the identification of patients at risk for cisplatin-induced nephrotoxicity and the development of possible prophylactic therapies.


Asunto(s)
Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/orina , Antineoplásicos/efectos adversos , Cisplatino/efectos adversos , Proteína 2 Relacionada con Receptor de Lipoproteína de Baja Densidad/metabolismo , Lesión Renal Aguda/patología , Lesión Renal Aguda/fisiopatología , Anciano , Biomarcadores/metabolismo , Biomarcadores/orina , Ensayo de Inmunoadsorción Enzimática , Femenino , Tasa de Filtración Glomerular , Humanos , Estimación de Kaplan-Meier , Túbulos Renales Proximales/metabolismo , Túbulos Renales Proximales/patología , Túbulos Renales Proximales/fisiopatología , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Neoplasias Torácicas/tratamiento farmacológico , Neoplasias Torácicas/patología , Neoplasias Torácicas/orina
19.
PLoS One ; 14(4): e0215292, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30978241

RESUMEN

Although the blockade of programmed cell death 1 (PD-1)/PD-ligand (L) 1 has demonstrated promising and durable clinical responses for non-small-cell lung cancers (NSCLCs), NSCLC patients with epidermal growth factor receptor (EGFR) mutations responded poorly to PD-1/PD-L1 inhibitors. Previous studies have identified several predictive biomarkers, including the expression of PD-L1 on tumor cells, for PD-1/PD-L1 blockade therapies in NSCLC patients; however, the usefulness of these biomarkers in NSCLCs with EGFR mutations has not been elucidated. The present study was conducted to evaluate the predictive biomarkers for PD-1/PD-L1 inhibitors in EGFR-mutated NSCLCs. We retrospectively analyzed 9 patients treated with nivolumab for EGFR-mutated NSCLCs. All but one patient received EGFR-tyrosine kinase inhibitors before nivolumab treatment. The overall response rate and median progression-free survival were 11% and 33 days (95% confidence interval (CI); 7 to 51), respectively. Univariate analysis revealed that patients with a good performance status (P = 0.11; hazard ratio (HR) 0.183, 95% CI 0.0217 to 1.549), a high density of CD4+ T cells (P = 0.136; HR 0.313, 95% CI 0.045 to 1.417) and a high density of Foxp3+ cells (P = 0.09; HR 0.264, 95% CI 0.0372 to 1.222) in the tumor microenvironment tended to have longer progression-free survival with nivolumab. Multivariate analysis revealed that a high density of CD4+ T cells (P = 0.005; HR<0.001, 95% CI <0.001 to 0.28) and a high density of Foxp3+ cells (P = 0.003; HR<0.001, 95% CI NA) in tumor tissues were strongly correlated with better progression-free survival. In contrast to previous studies in wild type EGFR NSCLCs, PD-L1 expression was not associated with the clinical benefit of anti-PD-1 treatment in EGFR-mutated NSCLCs. The current study indicated that immune status in the tumor microenvironment may be important for the effectiveness of nivolumab in NSCLC patients with EGFR mutations.


Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Nivolumab/uso terapéutico , Adulto , Anciano , Antígeno B7-H1/antagonistas & inhibidores , Biomarcadores de Tumor/inmunología , Recuento de Linfocito CD4 , Carcinoma de Pulmón de Células no Pequeñas/inmunología , Receptores ErbB/genética , Femenino , Factores de Transcripción Forkhead/metabolismo , Genes erbB-1 , Humanos , Neoplasias Pulmonares/inmunología , Masculino , Persona de Mediana Edad , Mutación , Pronóstico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Estudios Retrospectivos , Microambiente Tumoral/inmunología
20.
BMC Infect Dis ; 19(1): 263, 2019 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-30885152

RESUMEN

BACKGROUND: Mycobacterium avium complex lung disease (MAC-LD) can deteriorate rapidly to become fatal. Reported poor prognostic factors include radiographic findings, undernutrition, anemia and high inflammation test values. However, the association of these prognostic factors with the pathophysiology of the disease remains unknown. We aimed to clarify the pathophysiology of MAC-LD and develop a new biomarker that reflects the immune response to the disease. METHODS: We performed the cytokine panel analyses of serum from patients with MAC-LD and compared each cytokine level with clinically negative prognostic factors (radiographic disease type, body mass index, albumin, C-reactive protein and hemoglobin) and high-resolution CT scores. RESULTS: We analyzed 27 patients with MAC-LD, 6 with the fibrocavitary form and 21 with the nodular bronchiectatic form on high-resolution CT. Serum CXC motif ligand 10 (CXCL10) concentration was significantly elevated in patients with the fibrocavitary form (p = 0.008). CXCL10 levels correlated with body mass index (r = - 0.60, p = 0.0008), serum albumin concentration (r = - 0.45, p = 0.016) and high-resolution CT scores (r = 0.61, p = 0.0006). Among 14 patients initially untreated, antibiotic therapy was initiated for five during the study period. CXCL10 concentration was significantly higher in these patients (p = 0.046), and receiver operating characteristic analysis for CXCL10 concentration on treatment initiation produced an area under the curve of 0.844, with a sensitivity of 100%, specificity of 66.7%, and cut-off value of 366.5 pg/mL. CONCLUSION: We revealed cytokine profiles in patients with MAC-LD. Serum CXCL10 levels probably reflect the severity of MAC-LD. Our findings suggest that CXCL10 concentration may be a promising biomarker for managing treatment for patients with MAC disease of the lung.


Asunto(s)
Quimiocina CXCL10/sangre , Citocinas/sangre , Enfermedades Pulmonares/inmunología , Complejo Mycobacterium avium , Infección por Mycobacterium avium-intracellulare/inmunología , Anciano , Antibacterianos , Biomarcadores , Índice de Masa Corporal , Bronquiectasia/inmunología , Bronquiectasia/microbiología , Femenino , Humanos , Pulmón , Enfermedades Pulmonares/microbiología , Masculino , Persona de Mediana Edad , Pronóstico , Curva ROC , Sensibilidad y Especificidad
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