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1.
Clin Drug Investig ; 44(5): 357-366, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38684605

RESUMEN

BACKGROUND: Chemotherapy-induced thrombocytopenia is often a use-limiting adverse reaction to gemcitabine and cisplatin (GC) combination chemotherapy, reducing therapeutic intensity, and, in some cases, requiring platelet transfusion. OBJECTIVE: A retrospective cohort study was conducted on patients with urothelial cancer at the initiation of GC combination therapy and the objective was to develop a prediction model for the incidence of severe thrombocytopenia using machine learning. METHODS: We performed receiver operating characteristic analysis to determine the cut-off values of the associated factors. Multivariate analyses were conducted to identify risk factors associated with the occurrence of severe thrombocytopenia. The prediction model was constructed from an ensemble model and gradient-boosted decision trees to estimate the risk of an outcome using the risk factors associated with the occurrence of severe thrombocytopenia. RESULTS: Of 186 patients included in this study, 46 (25%) experienced severe thrombocytopenia induced by GC therapy. Multivariate analyses revealed that platelet count ≤ 21.4 (×104/µL) [odds ratio 7.19, p < 0.01], hemoglobin ≤ 12.1 (g/dL) [odds ratio 2.41, p = 0.03], lymphocyte count ≤ 1.458 (×103/µL) [odds ratio 2.47, p = 0.02], and dose of gemcitabine ≥ 775.245 (mg/m2) [odds ratio 4.00, p < 0.01] were risk factors of severe thrombocytopenia. The performance of the prediction model using these associated factors was high (area under the curve 0.76, accuracy 0.82, precision 0.68, recall 0.50, and F-measure 0.58). CONCLUSIONS: Platelet count, hemoglobin level, lymphocyte count, and gemcitabine dose contributed to the development of a novel prediction model to identify the incidence of GC-induced severe thrombocytopenia.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica , Cisplatino , Desoxicitidina , Gemcitabina , Trombocitopenia , Humanos , Desoxicitidina/análogos & derivados , Desoxicitidina/efectos adversos , Desoxicitidina/administración & dosificación , Trombocitopenia/inducido químicamente , Trombocitopenia/epidemiología , Trombocitopenia/diagnóstico , Cisplatino/efectos adversos , Cisplatino/administración & dosificación , Masculino , Femenino , Estudios Retrospectivos , Anciano , Persona de Mediana Edad , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Neoplasias Urológicas/tratamiento farmacológico , Recuento de Plaquetas , Factores de Riesgo , Aprendizaje Automático
2.
Cancer Med ; 13(4): e6839, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38457231

RESUMEN

BACKGROUND: Mannitol is exclusively recommended in the National Comprehensive Cancer Network guidelines for diuresis in cisplatin (CDDP)-based chemotherapy. The utility of furosemide, a widely used and convenient diuretic, thus requires clarification. METHODS: This is a prospective, single-centered, open-label, noninferiority phase II study. Patients with thoracic malignancies who planned to receive CDDP-based chemotherapy were randomly assigned to receive either mannitol (arm A) or furosemide (arm B). The primary end point was set as the proportion of patients who experienced any grade of "creatinine (Cr) increased" based on the upper limit of the normal range (ULN) during the first cycle as assessed by Common Terminology Criteria for Adverse Events Version 4.0. Secondary end points were Cr increased based on the baseline value during the first cycle, Cr increased after the completion of CDDP, and the proportion of patients with phlebitis. RESULTS: Between April 2018 and March 2022, 115 patients were enrolled and 106 were analyzed. Any grade of Cr increased based on the ULN during the first cycle was 17.3% (arm A) and 24.1% (arm B), respectively (p = 0.34). Therefore, the primary end point was not met. After completion of chemotherapy, any grade of Cr increased was observed in 23.1% (arm A) and 31.5% (arm B), respectively. However, the actual serum Cr level and Cr clearance during the courses were not different between the arms. Phlebitis occurred more frequently in arm A (28.8%) than arm B (16.7%). CONCLUSIONS: Mannitol should remain the standard diuresis in CDDP-based chemotherapy assessed by conventional CTCAE grading, but furosemide can be room for consideration when assessed by actual serum Cr level and Cr clearance.


Asunto(s)
Flebitis , Neoplasias Torácicas , Humanos , Cisplatino/efectos adversos , Furosemida/efectos adversos , Manitol/efectos adversos , Flebitis/inducido químicamente , Flebitis/tratamiento farmacológico , Estudios Prospectivos
3.
J Pain Symptom Manage ; 67(3): 204-211.e1, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37992848

RESUMEN

CONTEXT: The efficacy and tolerability of high-flow nasal cannula (HFNC) for relieving dyspnea in advanced cancer patients with limited prognosis requires elucidation. OBJECTIVES: The primary aim of this trial was to assess the efficacy and tolerability of HFNC regarding dyspnea including severe as well as moderate for longer durations in patients under palliative care. METHODS: In this prospective study, hospitalized patients with advanced cancer who had dyspnea at rest (numeric rating scale, NRS≥3) and hypoxemia were enrolled. They were treated with HFNC for five days in the respiratory unit. Primary endpoint was mean change of modified Borg scale at 24 hours. Key secondary endpoints consisted of mean changes in modified Borg scale during the study period and feasibility (Trial Identifier, UMIN000035738). RESULTS: Between February 2019 and February 2022, 25 patients were enrolled and 21 were analyzed. Twenty patients used inspired oxygen and the mean fraction of inspired oxygen (FiO2) was 0.34 (range, 0.21-1.0). At baseline, mean NRS (dyspnea) was 5.9 (range, 3-10). Median survival time was 19 days (range, 3-657). The mean change of modified Borg scale was 1.4 (80% confidence interval [CI]: 0.8-1.9) at 24 hours, 12 patients (57%) showed 1.0 points improvement of modified Borg scale. Within two hours, 15 patients showed 1.0 points improvement of modified Borg scale and such early responders were likely to maintain dyspnea improvement for 24 hours. Nineteen patients could continue HFNC for 24 hours and 11 patients completed five days of HFNC. CONCLUSION: To our knowledge, this trial is the first prospective study to assess the five-day efficacy and tolerability of HFNC for dyspnea in patients under palliative care. Although this did not reach the prespecified endpoint, about half of the patients showed 1.0 point improvement, a minimally clinically important difference (MCID) in the chronic lung disease. HFNC can be a palliative treatment option in advanced cancer patients with dyspnea.


Asunto(s)
Neoplasias , Insuficiencia Respiratoria , Humanos , Cánula , Estudios Prospectivos , Disnea/etiología , Disnea/terapia , Oxígeno , Neoplasias/complicaciones , Neoplasias/terapia , Terapia por Inhalación de Oxígeno , Insuficiencia Respiratoria/terapia
4.
J Thorac Dis ; 15(11): 6019-6028, 2023 Nov 30.
Artículo en Inglés | MEDLINE | ID: mdl-38090301

RESUMEN

Background: An association exists among the diagnostic yield of transbronchial biopsy using endobronchial ultrasonography with a guide sheath (EBUS-GS-TBB) and several factors, such as simple within or adjacent endobronchial ultrasonography (EBUS) findings. Here, we aimed to investigate whether more detailed EBUS findings affect the diagnostic yield of lung cancer in EBUS-GS-TBB. Methods: We conducted this retrospective single-center cohort study, enrolling consecutive patients with lung cancer who underwent EBUS-GS-TBB. The primary outcome was examination of predictive factors affecting the diagnostic yield of lung cancer using EBUS-GS-TBB. The secondary outcome was a subgroup analysis of within and adjacent lesions. The adjacent angle was defined as the angle formed by the midpoint of the probe and the two points where the edge of the probe and shadow of the tumor intersected. Results: Of the 179 lesions investigated, 140 (78.2%) were diagnosed using EBUS-GS-TBB. The diagnostic yields of within and adjacent lesions were 91.6% and 51.7%, respectively. In the multivariable analysis, within lesions had significantly higher diagnostic yields than did the adjacent lesions (P<0.001). The adjacent angle was larger in lesions diagnosed using EBUS-GS-TBB than in undiagnosed lesions (P=0.003). In adjacent lesions, the diagnostic yields were 75.0% and 36.1% for lesions ≥180° and <180°, respectively. Conclusions: In adjacent lesions, the diagnostic yields differed significantly depending on the adjacent angle. Even if EBUS findings are adjacent, the operator should identify the branch of the bronchus with a greater adjacent angle. Future studies should investigate improvements in diagnostic yields via additional procedures for lesions with small adjacent angles.

5.
In Vivo ; 37(3): 1236-1245, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37103081

RESUMEN

BACKGROUND/AIM: Sepsis is a life-threatening biological condition that induces systemic tissue and organ dysfunction and confers a high mortality risk. Although the use of hydrocortisone in combination with ascorbic acid and thiamine (HAT therapy) significantly reduced mortality from sepsis or septic shock in a previous study, it did not improve mortality in subsequent randomized controlled trials (RCTs). Therefore, no definitive conclusion has been established on the benefits of HAT therapy for sepsis or septic shock. We performed a meta-analysis to assess the treatment outcomes of HAT therapy in patients with sepsis or septic shock. PATIENTS AND METHODS: We searched databases (PubMed/MEDLINE, Embase, Scopus and Cochrane Library) for RCTs using the terms "ascorbic acid", "thiamine", "sepsis", "septic shock", and "RCT". The primary outcome of this meta-analysis was the mortality rate, and the secondary outcomes were the incidence of new-onset acute renal injury (AKI), intensive care unit (ICU) length of stay (ICU-LOS), change in the Sequential Organ Failure Assessment (SOFA) score within 72 hours, and duration of vasopressor use. RESULTS: Nine RCTs were identified and included in the outcome evaluation. HAT therapy did not improve the 28-day and ICU mortality, new-onset AKI, ICU-LOS, or SOFA scores. However, HAT therapy significantly shortened the duration of vasopressor use. CONCLUSION: HAT therapy did not improve mortality, the SOFA score, renal injury, or ICU-LOS. Further studies are needed to confirm whether it shortens the duration of vasopressor use.


Asunto(s)
Lesión Renal Aguda , Sepsis , Choque Séptico , Humanos , Hidrocortisona/uso terapéutico , Tiamina/uso terapéutico , Ácido Ascórbico/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Choque Séptico/tratamiento farmacológico
6.
Pediatr Nephrol ; 38(10): 3285-3296, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37052692

RESUMEN

BACKGROUND: Glucocorticoids affect bone turnover. Little is known about how bone turnover changes when glucocorticoids are discontinued following long-term administration. METHODS: This retrospective observational study was conducted on the relationship between discontinuation of long-term administration of glucocorticoid and bone turnover markers (BTMs) in patients with childhood-onset idiopathic nephrotic syndrome. Serum bone alkaline phosphatase (BAP), intact procollagen type 1 N-terminal propeptide (P1NP), and tartrate-resistant acid phosphatase-5b (TRACP-5b) were evaluated as BTMs. RESULTS: Thirty-eight pairs of BTMs at glucocorticoid administration and after discontinuation were analyzed in 29 patients. The median age at baseline was 12.4 (interquartile range, 9.0-14.5) years, and the median time from the onset of nephrotic syndrome was 5.9 (3.3-9.7) years. The mean period from prednisolone discontinuation to the measurement of BTMs after glucocorticoid discontinuation was 3.5 ± 1.0 months. Changes in BTMs after glucocorticoid discontinuation were modest when the daily prednisolone dose was < 0.25 mg/kg/day (ln BAP standard deviation [SD] score, p = 0.19; log intact P1NP SD score, p = 0.70; TRACP-5b, p = 0.95). When the daily prednisolone dose was ≥ 0.25 mg/kg/day, all BTMs increased significantly after glucocorticoid discontinuation (ln BAP SD score, p < 0.01; log intact P1NP SD score, p < 0.01; TRACP-5b, p < 0.01). CONCLUSIONS: Decreased BTMs can rise within a few months of discontinuing long-term glucocorticoid administration. When the administered glucocorticoid dose is low, changes in BTMs may be small. A higher resolution version of the Graphical abstract is available as Supplementary information.


Asunto(s)
Glucocorticoides , Síndrome Nefrótico , Humanos , Niño , Glucocorticoides/efectos adversos , Síndrome Nefrótico/tratamiento farmacológico , Fosfatasa Ácida Tartratorresistente , Biomarcadores , Prednisolona/efectos adversos , Fosfatasa Alcalina , Remodelación Ósea , Densidad Ósea
7.
Cancer Med ; 11(20): 3743-3750, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35434933

RESUMEN

BACKGROUND: First-generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) sometimes causes lung injury, thereby affecting survival. Although pre-existing interstitial lung abnormal shadow (pre-ILS) increases the risk of lung injury by EGFR-TKIs, its impact on osimertinib, a third-generation EGFR-TKI, remains unknown. PATIENTS AND METHODS: This retrospective cohort study consecutively enrolled patients of EGFR-mutated non-small cell lung cancer treated with osimertinib. Computed tomography images were obtained and evaluated independently by three pulmonologists in a blinded manner. Factors associated with lung injury were assessed using a logistic regression model. Survival curves were calculated by the Kaplan-Meier method and compared using a log-rank test. RESULTS: Of the 195 patients, 40 had pre-ILS, and 21 (8 with and 13 without pre-ILS) developed lung injury during the observation period. Multivariate analysis revealed that pre-ILS was independently associated with lung injury (odds ratio, 3.1; 95% confidence interval [CI], 1.1-8.2; p = 0.025). Severe (≥Grade 3) lung injury was observed in eight (4.1%) patients, of whom, two (5%) and six (3.9%) had and did not have pre-ILS (p = 0.67), respectively. Grade 5 lung injury was not observed, and survival curves were similar between the patients who developed lung injury and those who did not (median 11 vs. 12 months; hazard ratio, 1.2; 95% CI, 0.56-2.7; p = 0.60). CONCLUSIONS: Pre-ILS increased the risk of lung injury in patients of non-small cell lung cancer treated with osimertinib, while the severity of lung injury was not clearly affected by the presence of pre-ILS.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Humanos , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Estudios Retrospectivos , Receptores ErbB/genética , Mutación , Inhibidores de Proteínas Quinasas/efectos adversos , Pulmón
8.
Cancer Immunol Immunother ; 71(9): 2109-2116, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35037070

RESUMEN

While PD-1/L1 inhibitors are characterized by durable tumor control, they also prolong survival without prolongation of progression-free survival (PFS) in part of patients. However, little is known about the factors and mechanisms involved in this. Between December 2015 and September 2018, 106 patients with advanced non-small cell lung cancer treated with ICI monotherapy were enrolled in a prospective-observational study. Sixty-nine of whom progressed or died within 6 months after ICI initiation were defined as patients without durable clinical benefit (NDBs). Clinical factors and 39 serum proteins before ICI initiation and at the time of progressive disease (PD) were explored for an association with overall survival (OS) and OS after PD (OS-PD). As a result, median PFS, OS, and OS-PD were 44 days [95% confidence interval (CI): 39-56), 211 days (95% CI: 158-425), and 193 days (95% CI: 118-349), respectively. By multivariate analysis for OS, CRP (> 1.44 mg/dl) [HR 2.59 (95% CI:1.33-5.04), P = 0.005] and follistatin (> 685 pg/ml) [HR 2.29 (95% CI:1.12-4.69), P = 0.023] before ICI initiation were significantly predictive. Notably, no serum protein at the time of PD was predictive for OS-PD. There were also no serum predictive factors of OS in the 33 patients with durable clinical benefit. In conclusion, serum levels of CRP and follistatin before ICI initiation, not at the time of PD, are predictive for OS in NDBs, suggesting long-term survivor in NDBs are predetermined by the immune status before ICI initiation.


Asunto(s)
Antineoplásicos Inmunológicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Antineoplásicos Inmunológicos/uso terapéutico , Antígeno B7-H1/uso terapéutico , Biomarcadores de Tumor/análisis , Carcinoma de Pulmón de Células no Pequeñas/patología , Folistatina/uso terapéutico , Humanos , Neoplasias Pulmonares/patología , Receptor de Muerte Celular Programada 1/uso terapéutico , Estudios Prospectivos
9.
Pediatr Int ; 64(1): e14725, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33826766

RESUMEN

BACKGROUND: Rituximab (RTX) is an effective treatment for maintaining remission in patients with nephrotic syndrome (NS), but there are few reports on the effect of RTX treatment on quality of life (QOL). The purpose of this study was to examine the effect of periodically repeated RTX treatment from the perspective of QOL. METHODS: We systematically assessed the QOL of pediatric patients with refractory NS and parents' perceptions of their children's QOL through a 2 year RTX treatment protocol. Pediatric patients from Hokkaido University Hospital with refractory NS who met our specific criteria were enrolled between January 2015 and December 2015. The RTX infusion was performed 4 times at 6-month intervals, followed by mizoribine administration with early discontinuation of calcineurin inhibitors. Quality of life scores were measured by the Pediatric Quality of Life Inventory version 4.0 (PedsQL) at each RTX administration and evaluated 2 years later. RESULTS: Twenty-two patients were analyzed. The patients' QOL and their parents' perceptions of their QOL improved over our 2 year treatment protocol. Nevertheless, the parents' scores were lower than the patients' scores on all scales, with slower improvement. CONCLUSIONS: Our treatment protocol showed a significant improvement of QOL in patients with refractory NS. Although the risk of the RTX treatment should be considered, the treatment is useful for patients with refractory NS.


Asunto(s)
Síndrome Nefrótico , Calidad de Vida , Inhibidores de la Calcineurina , Niño , Humanos , Síndrome Nefrótico/tratamiento farmacológico , Rituximab/uso terapéutico , Resultado del Tratamiento
10.
J Med Microbiol ; 70(6)2021 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-34165424

RESUMEN

We characterized 515 Mycoplasma pneumoniae specimens in Hokkaido. In 2013 and 2014, the p1 gene type 1 strain, mostly macrolide-resistant, was dominant and the prevalence of macrolide resistance was over 50 %. After 2017, the p1 gene type 2 lineage, mostly macrolide-sensitive, increased and the prevalence of macrolide resistance became 31.0 % in 2017, 5.3 % in 2018 and 16.3 % in 2019.


Asunto(s)
Macrólidos/farmacología , Mycoplasma pneumoniae/genética , Neumonía por Mycoplasma/epidemiología , Niño , Farmacorresistencia Bacteriana/genética , Técnicas de Genotipaje/métodos , Humanos , Japón/epidemiología , Mutación , Mycoplasma pneumoniae/clasificación , Mycoplasma pneumoniae/efectos de los fármacos , Nasofaringe/microbiología , Neumonía por Mycoplasma/tratamiento farmacológico , Neumonía por Mycoplasma/microbiología , ARN Ribosómico 23S/genética
11.
Cancers (Basel) ; 13(10)2021 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-34064720

RESUMEN

Although programmed death-ligand 1 (PD-L1) expression on tumor tissue is a validated predictive biomarker for a PD-1 pathway blockade in non-small cell lung cancer (NSCLC), longitudinal changes in its expression during treatment remains elusive. Circulating tumor cells (CTCs) are assumed to reflect the transition of characteristics of the primary tumor undergoing anticancer treatment. Here, we sequentially evaluated the PD-L1 expression on CTCs in NSCLC patients treated with nivolumab. Forty-five patients were enrolled, and CTCs were enriched from 3 mL of peripheral blood using a microcavity array system at baseline and weeks 4, 8, 12, and 24 or until progressive disease. The effective responses to therapy were compared between patients without progressive disease (PD) at week 8 (i.e., non-PD patients) and in those with PD between weeks 4 and 8 (PD patients) in terms of increased vs. decreased or equal CTC status at week 8 (for non-PD patients) or at the point of PD (for PD patients) compared to the baseline. Significantly more non-PD patients were classified as decreased or equal in number and proportion to PD-L1-positive CTCs among the detected CTCs (PD-L1 positivity rates) (p < 0.05). Moreover, progression-free survival was significantly longer in patients with ≥7.7% PD-L1 positivity rates (n = 8) than in those with <7.7% rates (n = 8; p < 0.01) at week 8. These results suggest the predictive significance of the early evaluation of PD-L1 expression on CTCs for maintaining the benefits from nivolumab treatment.

12.
Acute Med Surg ; 8(1): e654, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33968417

RESUMEN

AIM: The emergency department requires simple and useful clinical indicators to identify bacteremia. This retrospective study explored the Systemic Inflammatory Response Syndrome (SIRS) and quick Sequential Organ Failure Assessment (qSOFA) scores for predicting bacteremia. METHODS: Between April and September 2017, we assessed blood cultures of 307 patients in our emergency department. We calculated the SIRS and qSOFA scores for these patients and evaluated their correlation with bacteremia. RESULTS: Of 307 patients, 66 (21.5%) had bacteremia, 237 (77.2%) were SIRS-positive, and 123 (40.0%) were qSOFA-positive. The sensitivity and specificity of the SIRS score for predicting bacteremia were 87.9% and 25.7%, respectively. The sensitivity and specificity of the qSOFA score were 47.0% and 61.8%, respectively. Multivariate analysis revealed that body temperature (odds ratio, 2.16; 95% confidence interval, 1.22-3.84; P = 0.009) and blood pressure (odds ratio, 2.72; 95% confidence interval, 1.39-5.35; P = 0.004) significantly associated with bacteremia. CONCLUSIONS: The SIRS score was a more sensitive indicator than the qSOFA score for predicting bacteremia.

13.
Clin Lung Cancer ; 22(6): e833-e841, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34049821

RESUMEN

BACKGROUND: Programmed cell death ligand 1 is a biomarker of immune checkpoint inhibitors (ICIs) for treating advanced non-small-cell lung cancer (NSCLC). Here, we evaluated serum proteins from patients with advanced NSCLC treated with ICIs to determine their potential as noninvasive predictive biomarkers for efficacy and immune-related adverse events (irAEs). PATIENTS AND METHODS: Patients with advanced NSCLC who received nivolumab or pembrolizumab monotherapy until disease progression or unacceptable toxicity were integrated with previously reported nivolumab-treated patients. Blood samples were collected serially from baseline until the disease progressed. Serum protein levels were quantified using the Luminex assay. Associations of clinical benefit (CB) and onset of irAEs with serum protein levels were evaluated. RESULTS: Sixty-three patients with advanced NSCLC were studied, and we used 63 and 47 paired serum samples at baseline and the second sampling point, respectively, for efficacy analysis. Baseline growth-regulated oncogene 1 (GRO-1) levels were significantly lower in durable CB (DCB) patients than in non-DCB patients (P < .05). Changes in monocyte chemoattractant protein 1 (MCP-1) levels significantly decreased between baseline and the second sampling point (P < .05). Patients with the low GRO-1/decreased MCP-1 subtype showed significantly longer progression-free survival (PFS) and overall survival (OS) than the high GRO-1/increased MCP-1 subgroup did (median PFS, not reached vs. 47 days, P < .0001; median OS, 985 days vs. 148 days, P = .0002, respectively). Elevated GRO-1 levels were associated with immune-related adverse event onset. CONCLUSIONS: Serum GRO-1 and MCP-1 levels can identify patients with advanced NSCLC who are likely to benefit from ICI treatment. Time-course tracing of these protein levels might be valuable in ICI treatment.


Asunto(s)
Biomarcadores , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Citocinas/sangre , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Inhibidores de Puntos de Control Inmunológico/inmunología , Neoplasias Pulmonares/tratamiento farmacológico , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/sangre , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Masculino , Persona de Mediana Edad , Resultado del Tratamiento
14.
Cancer Sci ; 112(1): 72-80, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33084148

RESUMEN

CD24, a heavily glycosylated glycosylphosphatidylinositol-anchored surface protein, inhibits phagocytosis as potently as CD47. The relationship between such anti-phagocytic factors and the immune response with immune-checkpoint inhibitors (ICI) remains unexplored. We evaluated CD24 and CD47 tumor proportion scores (TPS) in 68 of the 106 patients with advanced non-small-cell lung cancer who participated in a prospective observational study of ICI treatment. We also explored the impact of CD24 TPS and CD47 TPS on ICI efficacy and serum cytokine changes. CD24 positivity (TPS ≥ 1) was negatively associated with progression-free survival (PFS) of ICI when PD-L1 TPS was < 50 (median PFS; 37 vs 127 d, P = .033), but there was no association when PD-L1 TPS was ≥ 50 (median PFS; 494 vs 144 d, P = .168). CD24 positivity was also related to significantly higher increase of CCL2 from baseline to 4-6 wk later, and such increase was notably observed only when PD-L1 TPS < 50 (P = .0004). CCL2 increase after ICI initiation was negatively predictive for survival after initiation of ICI (median survival time; not reached vs 233 d; P = .028). CD47 TPS high (≥60) significantly suppressed the increase in vascular endothelial growth factor (VEGF)-A, D and PDGF-AB/BB after ICI initiation. There was no association, however, between CD47 tumor expression and the efficacy of ICI. In conclusion, CD24, not CD47, is a candidate negative predictive marker of ICI in advanced, non-small-cell lung cancer with PD-L1 TPS < 50. Tumor expression of both CD24 and CD47 was associated with changes in factors related to monocytes and angiogenesis after ICI initiation (UMIN000024414).


Asunto(s)
Antígeno B7-H1/metabolismo , Antígeno CD24/metabolismo , Antígeno CD47/metabolismo , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Neoplasias Pulmonares/metabolismo , Receptor de Muerte Celular Programada 1/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Supervivencia sin Progresión , Puntaje de Propensión , Estudios Prospectivos , Factor A de Crecimiento Endotelial Vascular/metabolismo
15.
Respir Investig ; 59(2): 204-211, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33339738

RESUMEN

BACKGROUND: Legionella spp. can cause severe pneumonia and most Legionella pneumonia (LP) cases are diagnosed using the urine antigen test (UAT). However, diagnosis of LP with negative UAT results (LPNUAT) is challenging. We investigated the clinical and radiological features of LPNUAT. METHODS: We retrospectively collected LP cases with positive UAT (LPPUAT) and cases of suspected LP with negative UAT that were examined by Legionella culture between July 2014 and March 2020. We investigated the clinical and CT findings for LP that showed negative UAT results and was diagnosed by culture and compared these findings with those for other pneumonias suspicious for LP with negative results in UAT and Legionella culture (OPSLP). RESULTS: Eight LPNUAT, 20 LPPUAT, and 19 OPSLP cases were included in this study. There were no significant differences in the clinical and CT findings between LPPUAT and LPNUAT when examined by UAT. In LPNUAT, dyspnea, renal dysfunction, liver dysfunction, and bilateral lesions were more commonly observed and inflammatory changes and the number of affected lobes were significantly higher when examined by culture than when examined by UAT. Comparison to OPSLP, LPNUAT did not show such differences, but rather showed disturbances in consciousness, hyponatremia and rhabdomyolysis. Furthermore, lobar consolidation was observed more frequently and bronchial wall thickening and centrilobular nodules were observed less frequently in LPNUAT. CONCLUSIONS: LP characteristics such as disturbance of consciousness, hyponatremia, rhabdomyolysis, lobar consolidation, and less bronchial wall thickening and centrilobular nodule contribute to the diagnosis of LP in patients with negative UAT results.


Asunto(s)
Antígenos Bacterianos/orina , Pruebas Inmunológicas/métodos , Enfermedad de los Legionarios/diagnóstico por imagen , Resultados Negativos , Tomografía Computarizada por Rayos X , Adulto , Anciano , Biomarcadores/orina , Femenino , Humanos , Legionella pneumophila/inmunología , Legionella pneumophila/aislamiento & purificación , Enfermedad de los Legionarios/diagnóstico , Enfermedad de los Legionarios/microbiología , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
16.
J Clin Pharm Ther ; 46(1): 114-120, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32949161

RESUMEN

WHAT IS KNOWN AND OBJECTIVE: Hypertension (HTN) and chronic kidney disease (CKD) are recognized as silent killers because they are asymptomatic conditions that contribute to the burden of multiple comorbidities. The achievement of a blood pressure (BP) goal can dramatically reduce the risks of CKD. In this study, we aimed to assess the effectiveness of pharmacist intervention on BP control in patients with CKD and evaluate the usefulness of home-based BP telemonitoring. METHODS: The terms "chronic kidney disease," "pharmacist," "BP" and "randomized controlled trial (RCT)" were used five databases to search for information regarding pharmacist intervention on BP control in patients with CKD. The inclusion criteria were as follows: (a) studies for adult patients with uncontrolled HTN and (b) studies with adequate data for meta-analysis. The primary outcome was an evaluation of achievement of BP goal in patients with CKD. The secondary outcome was usefulness of home-based BP telemonitoring by pharmacists in patients with CKD. RESULTS AND DISCUSSION: Six RCTs were identified and included in the meta-analysis with a total of 2573 patients (mean age 66.0 years and 63.9% male). Pharmacist interventions resulted in significantly better BP control vs usual care (OR = 1.53, 95% CI = 1.15-2.04, P < .01). Pharmacist interventions using home-based BP telemonitoring were significantly superior to control/usual care (OR = 2.03, 95% CI = 1.49-2.77, P < .01), whereas pharmacist interventions without home-based BP telemonitoring did not significantly improve BP control compared to that with control/usual care (OR = 1.30, 95% CI = 0.97-1.75, P = .08). Home-based BP telemonitoring supported team-based care for HTN in these studies. In addition, patient self-monitoring with telemedicine devices might enhance patients' abilities to manage their condition by pharmacist instruction. WHAT IS NEW AND CONCLUSION: The findings of this meta-analysis showed that pharmacist interventions with home-based BP telemonitoring improve BP control among adult patients with CKD.


Asunto(s)
Antihipertensivos/uso terapéutico , Hipertensión/tratamiento farmacológico , Servicios Farmacéuticos , Insuficiencia Renal Crónica , Telemedicina , Antihipertensivos/administración & dosificación , Humanos , Ensayos Clínicos Controlados Aleatorios como Asunto
17.
Respir Investig ; 58(3): 169-176, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32146120

RESUMEN

BACKGROUND: No study has investigated the capability of high-resolution computed tomography (HRCT) to detect a lateral bronchus abnormality, degree of air bronchogram, and distribution of affected lesions in the diagnosis of Mycoplasma pneumoniae pneumonia (MPP). METHODS: We prospectively enrolled patients with serologically-confirmed MPP or culture-confirmed other bacterial pneumonia (OBP). The distribution of affected areas, abnormalities in lateral bronchial lesions, the degree of air bronchogram, and previously reported findings on HRCT were evaluated for MPP and OBP. Predictive HRCT findings for MPP were determined by logistic regression analysis. We provisionally designed our HRCT criteria (negative, probable, or highly suspected) for diagnosing MPP and investigated the diagnostic yield of the HRCT criteria. RESULTS: Sixty-three MPP and 126 OBP patients were included in this study. Logistic regression analysis showed that the absence of peripheral predominance, bronchial wall thickening, lateral bronchial wall thickening, intralobular or lobular ground-glass opacities, intralobular ground-glass opacities connected to a lateral bronchus, and less air bronchogram in infiltrates were significant predictors of MPP. Our HRCT criteria showed that the sensitivity and specificity in negative, probable, and highly suspected MPP were 0.0 and 0.33, 1.0 and 0.69, and 0.5 and 0.98, respectively. CONCLUSIONS: HRCT had considerable ability to detect a lateral bronchial abnormality and to diagnose or rule out MPP based on the distribution of affected areas, abnormalities in lateral bronchial lesions, and the degree of air bronchogram in the infiltrates.


Asunto(s)
Bronquios/diagnóstico por imagen , Neumonía por Mycoplasma/diagnóstico por imagen , Intensificación de Imagen Radiográfica/métodos , Tomografía Computarizada por Rayos X/métodos , Broncografía , Diagnóstico Diferencial , Humanos , Neumonía Bacteriana/diagnóstico por imagen
18.
Cancer Med ; 9(6): 2122-2133, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-31999390

RESUMEN

Noninvasive diagnostics using circulating tumor cells (CTCs) are expected to be useful for decision making in precision cancer therapy. AXL, a receptor tyrosine kinase is associated with tumor progression, epithelial-to-mesenchymal transition (EMT), and drug resistance, and is a potential therapeutic target. However, the epithelial markers generally used for CTC detection may be not enough to detect AXL-expressing CTCs due to EMT. Here, we evaluated the detection of AXL-expressing CTCs using the mesenchymal marker vimentin with a microcavity array system. To evaluate the recovery of cancer cells, spike-in experiments were performed using cell lines with varying cytokeratin (CK) or vimentin (VM) expression levels. With high CK and low VM-expressing cell lines, PC-9 and HCC827, the recovery rate of AXL-expressing cancer cells was 1%-17% using either CK or VM as markers. Whereas, with low CK and high VM-expressing cell lines, MDA-MB231 and H1299, it was 52%-75% using CK and 72%-88% using VM as a marker. For clinical evaluation, peripheral blood was collected from 20 non-small cell lung cancer patients and CTCs were detected using CK or VM as markers in parallel. Significantly more AXL-expressing single CTCs were detected in VM-positive than CK-positive CTCs (P < .001). Furthermore, CTC clusters were identified only among VM-positive CTCs in 20% of patients. Patients with one or more prior treatments harbored significantly more VM-positive AXL-expressing CTCs, suggesting the involvement of these CTCs in drug resistance. These results indicate the necessity of integrating mesenchymal markers with CTC detection and this should be further evaluated clinically.


Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Separación Celular/instrumentación , Neoplasias Pulmonares/diagnóstico , Células Neoplásicas Circulantes/metabolismo , Proteínas Proto-Oncogénicas/análisis , Proteínas Tirosina Quinasas Receptoras/análisis , Anciano , Anciano de 80 o más Años , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/sangre , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Línea Celular Tumoral , Resistencia a Antineoplásicos , Estudios de Factibilidad , Femenino , Humanos , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/tratamiento farmacológico , Masculino , Persona de Mediana Edad , Proteínas Proto-Oncogénicas/metabolismo , Proteínas Tirosina Quinasas Receptoras/metabolismo , Vimentina/análisis , Vimentina/metabolismo , Tirosina Quinasa del Receptor Axl
19.
Arch Virol ; 165(2): 433-438, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31828510

RESUMEN

A regional epidemic of aseptic meningitis caused by echovirus 30 (E30) occurred in Hokkaido, Japan, during the period of August-December 2017. To investigate their phylogenetic relationship to other human enteroviruses, we determined the complete genomic nucleotide sequences of isolates from this outbreak. Phylogenetic analysis of the viral capsid protein 1 gene showed that the strains were most closely related to E30 strains detected in Germany, France, and Russia in 2013. In contrast, the region encoding the viral protease and the RNA-dependent RNA polymerase had a close phylogenetic relationship to non-E30 enteroviruses detected in the United Kingdom and Switzerland in 2015-2017, suggesting that a recombination event had occurred.


Asunto(s)
Infecciones por Echovirus/virología , Enterovirus Humano B/genética , Meningitis Aséptica/virología , Proteínas de la Cápside/genética , Brotes de Enfermedades , Infecciones por Enterovirus/virología , Epidemias , Francia , Genotipo , Alemania , Humanos , Japón , Epidemiología Molecular/métodos , Filogenia , ARN Viral/genética , Federación de Rusia , Análisis de Secuencia de ADN/métodos , Suiza , Reino Unido
20.
Int J Chron Obstruct Pulmon Dis ; 14: 1967-1977, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-31564845

RESUMEN

Purpose: The improvement of physical activity in patients with COPD is an important issue. However, no standard for the recommended number of steps for patients with COPD has been determined. We conducted a retrospective observational study to create a simple standard equation for the daily step count, which makes it easier to determine whether each subject is attaining his/her predicted value or not. Patients and methods: Stable outpatients diagnosed with COPD whose physical activities had been measured using a triaxial accelerometer for more than 2 weeks were recruited from 5 institutes in Japan. Factors associated with the step count were detected by multivariate regression analysis. After the data were transformed to a normalized distribution, a multivariate linear regression equation was created using stepwise regression. Results: One hundred sixty-two patients aged 72.3 (7.2) years and of FEV1 %pred 59.2 (22.8) % were recruited. Among the parameters, age, mMRC dyspnea scale and inspiratory capacity (IC) were detected by the stepwise method. The created standard equation was "Step count = (-0.079×[age]-1.595×[mMRC]+2.078×[IC]+18.149)3". The correlations between the calculated values and the measured values were observed, and fixed, and proportional biases between them were also observed. When patients with <6500 steps/day were selected, no systematic bias between them could be detected. Conclusion: A simple standard equation for Japanese patients with COPD was created using age, mMRC and IC, and could provide an individual-predicted value, especially for patients with <6500 steps/day.


Asunto(s)
Tolerancia al Ejercicio/fisiología , Pulmón/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Caminata/fisiología , Acelerometría , Anciano , Ejercicio Físico/fisiología , Femenino , Estudios de Seguimiento , Humanos , Incidencia , Capacidad Inspiratoria , Japón/epidemiología , Masculino , Enfermedad Pulmonar Obstructiva Crónica/diagnóstico , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Estudios Retrospectivos , Índice de Severidad de la Enfermedad
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