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1.
Medicine (Baltimore) ; 99(6): e18984, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32028408

RESUMO

RATIONALE: Autoimmune hemolytic AQ5 anemia (AIHA) is an immune disorder caused by antibodies directed against unmodified autologous red blood cells. In rare cases, AIHA is comorbid with other immunological disorders; for instance, when AIHA is complicated with immunologic thrombocytopenic purpura (ITP) it is called Evans Syndrome (ES). These multiple autoimmune mechanisms are referred to as "immunological tolerance loss," which is known as a characteristic autoimmunity specific for AIHA. And there are no estimation of the risk for thromboembolism in the "immunological tolerance loss" case. PATIENT CONCERNS: A 66-year-old man was diagnosed with ES after autologous stem cell transplantation for malignant lymphoma. His background immunological status was complicated because AIHA was mixed-type (warm and cold antibody type). The direct/indirect Coombs tests were positive. The anticomplement antibody was positive and his cold hemagglutinin level had increased. Anticardiolipin antibodies were negative: anticardiolipin ß2GPI antibody ≤1.2 U/mL (<3.5), anticardiolipin immunoglobulin G antibody ≤8 U/mL (<10), and anticardiolipin immunoglobulin M antibody ≤5 U/mL (<8). DIAGNOSES: ITP and mixed-type AIHA. INTERVENTIONS: The patient achieved complete response by initial prednisolone therapy; however, he did not respond to corticosteroid therapy after AIHA recurrence. He required the red blood cell transfusion due to the progression of hemolytic anemia. OUTCOMES: On the fourth day of refractory treatment following AIHA recurrence, the patient had acute respiratory failure with severe hypoxia and died. The cause of death was identified as pulmonary embolism (PE) based on the laboratory data and echocardiography findings, and a literature search suggested rapidly progressive hemolysis-induced PE. LESSONS: Although infrequent, comorbid thromboembolism to AIHA is well documented; however, a mixed-type AIHA case complicated with thromboembolism has not been previously reported. The combined pathophysiology of AIHA and thromboembolism should be considered in the clinical course of hemolysis. Our case suggested multiple immunological background, ITP, and mixed type AIHA, could be associated to a risk for thromboembolism (TE).


Assuntos
Anemia Hemolítica Autoimune/complicações , Embolia Pulmonar/etiologia , Idoso , Anemia Hemolítica Autoimune/diagnóstico , Evolução Fatal , Humanos , Masculino , Embolia Pulmonar/diagnóstico , Púrpura Trombocitopênica Idiopática/complicações , Púrpura Trombocitopênica Idiopática/diagnóstico , Trombocitopenia/complicações , Trombocitopenia/diagnóstico
2.
Oxf Med Case Reports ; 2019(8): omz082, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31772749

RESUMO

A 65-year-old man was referred to our hospital to undergo orthopedic surgery due to severe cervical ossification of the posterior longitudinal ligament. Computed tomography scanning showed a massive osteolytic lesion in his pelvis. Other screening examinations including detection of bone mineral density and osteoporosis biomarkers, bone scintigram and 18F-fluorodeoxyglucose-positron emission tomography were all normal. Bone marrow aspiration revealed slightly increased plasmacytes at 3.8%. These findings led to a diagnosis of monoclonal gammopathy with undetermined significance (MGUS). Architectural osteolytic bone associated with MGUS without apparent abnormality in bone mineral metabolism could be a common occurrence prior to onset or occurrence of multiple myeloma.

3.
Mol Cytogenet ; 12: 46, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31754375

RESUMO

Background: Clonal chromosomal alterations (CCAs) reflect recurrent genetic changes derived from a single evolving clone, whereas nonclonal chromosomal alterations (NCCAs) comprise a single or nonrecurrent chromosomal abnormality. CCAs and NCCAs in hematopoietic cells have been partially investigated in cytopenic patients without hematological malignancies. Methods: This single-center retrospective study included 253 consecutive patients who underwent bone marrow aspiration to determine the cause of cytopenia between 2012 and 2015. Patients with hematological malignancies were excluded. CCA was defined as a chromosomal aberration detected in more than two cells, and NCCA was defined as a chromosomal aberration detected in a single cell. Results: The median age of the patients was 66 years. There were 135 patients without hematological malignancies (median age, 64 years; 69 females); of these, 27 patients (median age, 69 years; 8 females) harbored chromosomal abnormalities. CCAs were detected in 14 patients; the most common CCA was -Y in eight patients, followed by inv.(9) in three patients and mar1+, inv. (12), and t (19;21) in one patient each. NCCAs were detected in 13 patients; the most frequent NCCA was +Y in four patients, followed by del (20), + 8, inv. (2), - 8, and add (6) in one patient each. Moreover, nonclonal translocation abnormalities, including t (9;14), t (14;16), and t (13;21), were observed in three patients. One patient had a complex karyotype in a single cell. The remaining 106 patients with normal karyotypes comprised the control group (median age, 65 years; range, 1-92 years; 56 females). Further, follow-up analysis revealed that the overall survival of the NCCA group was worse than that of the CCA and the normal karyotype groups (P < 0.0001; log-rank test).The survival of the NCCA-harboring cytopenic patients was worse than that of the CCA-harboring cytopenic patients without hematological malignancies, suggesting that follow-up should be considered for both CCA- and NCCA-harboring cytopenic patients.

4.
Transplantation ; 103(10): e323-e324, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31568232
5.
BMC Infect Dis ; 19(1): 885, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31651242

RESUMO

BACKGROUND: Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infection that has recently emerged. This infectious disease is due to the transfer of SFTS virus (SFTSV) from the infected blood of animals to humans. Approximately 30% of patients who are infected with SFTS die from multiorgan failure associated with severe infection, systemic inflammatory response syndrome, or disseminated intravascular coagulation. We treated an elderly Japanese couple (husband and wife) who had genetically identical SFTSV infections and who both developed severe rhabdomyolysis. CASE PRESENTATION: An 80-year-old man presented to the clinic with a fever; his 74-year-old wife presented with a fever 9 days later. Their laboratory results at diagnosis showed severe rhabdomyolysis with significantly elevated creatinine kinase (detected levels: husband, 9546 U/L; wife, 15,933 U/L). The creatinine kinase isozyme was 100% MM type in both patients. In both the husband and wife, SFTSV was identified with real-time polymerase chain reaction analysis. The detected SFTSVs in both the husband and wife were identical according to the genome sequence analysis. The husband's bone marrow indicated macrophage activation syndrome, but he responded to supportive therapy. He was discharged after being hospitalized for 32 days. The wife was admitted to our hospital in critical condition 2 days after SFTS symptom onset. She died of multiorgan failure 8 days after onset, despite being cared for in an intensive care unit. Both of the patients presented with rhabdomyolysis following SFTS symptom onset. The patients' clinical outcomes were different from each other; i.e., the husband survived, and the wife died. CONCLUSIONS: SFTSV infection-associated rhabdomyolysis has been reported in one patient, and simultaneous onset in two related patients has not been described previously. Our findings suggest that similar biological responses occurred, but they resulted in different clinical outcomes in the patients infected by the identical SFTSV isolates. Notably, a patient's clinical outcome depends on their own immune response. We suggest that one component of viral rhabdomyolysis involves immune-mediated responses. Severe immunological responses may adversely affect the treatment outcome, as demonstrated by the wife's clinical course. Our findings demonstrate that a patient's immune response contributes to their prognosis following SFTSV infection.


Assuntos
Infecções por Bunyaviridae/etiologia , Phlebovirus/genética , Rabdomiólise/etiologia , Idoso , Idoso de 80 Anos ou mais , Medula Óssea/patologia , Medula Óssea/virologia , Infecções por Bunyaviridae/imunologia , Infecções por Bunyaviridae/terapia , China , Feminino , Humanos , Masculino , Insuficiência de Múltiplos Órgãos , Phlebovirus/patogenicidade , Reação em Cadeia da Polimerase em Tempo Real , Rabdomiólise/terapia , Rabdomiólise/virologia , Cônjuges
6.
BMC Infect Dis ; 19(1): 857, 2019 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-31619174

RESUMO

BACKGROUND: Central venous catheters (CVCs) are necessary for critically ill patients, including those with hematological malignancies. However, CVC insertion is associated with inevitable risks for various adverse events. Whether ultrasound guidance decreases the risk of catheter-related infection remains unclear. METHODS: We observed 395 consecutive CVC insertions between April 2009 and January 2013 in our hematological oncology unit. Because the routine use of ultrasound guidance upon CVC insertion was adopted based on our hospital guidelines implemented after 2012, the research period was divided into before December 2011 (early term) and after January 2012 (late term). RESULTS: Underlying diseases included hematological malignancies and immunological disorders. In total, 235 and 160 cases were included in the early- and late term groups, respectively. The median insertion duration was 26 days (range, 2-126 days) and 18 days (range, 2-104 days) in the early- and late term groups, respectively. The internal jugular, subclavian, and femoral veins were the sites of 22.6, 40.2, and 25.7% of the insertions in the early term group and 32.3, 16.9, and 25.4% of the insertions in the late term group, respectively. The frequency of catheter-related bloodstream infection (CRBSI) was 1.98/1000 catheter days and 2.17/1000 catheter days in the early- and late term groups, respectively. In the subgroup analysis, the detected causative pathogens of CRBSI did not differ between the two term groups; gram-positive cocci, gram-positive bacilli, and gram-negative bacilli were the causative pathogens in 68.9, 11.5, and 14.8% of the cases in the early term group and in 68.2, 11.4, and 18.2% of the cases in the late term group, respectively. In the multivariate analysis to determine the risk of CRBSI, only age was detected as an independent contributing factor; the indwelling catheter duration was detected as a marginal factor. A significant reduction in mechanical complications was associated with the use of ultrasound guidance. CONCLUSIONS: Ultrasound-guided CVC insertion did not decrease the incidence of CRBSI. The only identified risk factor for CRBSI was age in our cohort. However, we found that the introduction of ultrasound-guided insertion triggered an overall change in safety management with or without the physicians' intent.


Assuntos
Bacteriemia/epidemiologia , Infecções Relacionadas a Cateter/epidemiologia , Cateterismo Venoso Central , Cateteres Venosos Centrais/efeitos adversos , Ultrassonografia de Intervenção , Cateterismo Venoso Central/efeitos adversos , Cateterismo Venoso Central/métodos , Cateterismo Venoso Central/estatística & dados numéricos , Humanos , Incidência , Ultrassonografia de Intervenção/métodos , Ultrassonografia de Intervenção/estatística & dados numéricos
7.
Med Sci Monit Basic Res ; 25: 187-198, 2019 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-31503241

RESUMO

BACKGROUND: This retrospective, historically controlled investigative study examined the benefit of a nutritional support pathway that included nutritional education before the start of conditioning and emphasized oral nutrition in response to nutrition-related adverse events in patients undergoing hematopoietic stem cell transplantation (HSCT). MATERIAL AND METHODS: Participants were patients undergoing allogeneic HSCT; 46 were in the control group (i.e., did not follow our nutritional pathway) and 36 were in the group that underwent nutritional intervention (enhanced nutrition group). We compared the following parameters between groups from the day before the start of conditioning to the day after completion of parenteral nutrition (PN): percent loss of body weight (%LBW), percent loss of skeletal muscle mass (%LSMM), and estimated basal energy expenditure (EBEE) sufficiency rate. The relationship between each parameter and %LBW was also examined. We also compared nutritional indices, gastrointestinal graft versus host disease (GvHD) grade, oral energy intake, and %LBW between groups. RESULTS: There was a relationship between %LBW, %LSMM, and EBEE sufficiency rate in both groups. Compared with the control group, the enhanced nutrition group had significantly improved energy intake amount, EBEE sufficiency rate, PN duration, and oral energy intake over time. The enhanced nutrition group also had increased oral energy intake, no difference in gastrointestinal GvHD grade, and improved %LBW compared with the control group. CONCLUSIONS: Use of our nutritional support pathway in patients undergoing HSCT may be beneficial for %LBW and gastrointestinal GvHD grade, enabling early enhanced nutritional intervention after HSCT.

10.
Acta Haematol ; : 1-6, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31330512

RESUMO

BACKGROUND: Myelodysplastic syndromes (MDS) and idiopathic cytopenia of undetermined significance (ICUS) are heterogeneous hematological disorders characterized by hematopoietic dysplasia and/or chromosomal aberrancy. OBJECTIVES: This study aimed to evaluate the diagnostic value of flow cytometry standardized using the European LeukemiaNet (ELN) for MDS and ICUS by analyzing samples obtained from patients with cytopenia based on morphological examination, cytogenetic analysis, and flow cytometry. METHODS: We retrospectively analyzed bone marrow samples aspirated from 253 consecutive patients (median age: 66 years [range: 1-92]) to identify the cause of cytopenia. RESULTS: Sixty patients presented with MDS, and 16 with ICUS. MDS subtypes were distributed as follows: MDS with single-lineage dysplasia (n = 10); MDS with multi-lineage dysplasia (n = 10); MDS with ringed sideroblasts (n = 4); MDS with excess blasts-1 (n = 9); MDS with excess blasts-2 (n = 13), MDS unclassified (n = 5); 5q-syndrome (n = 6); and MDS/myeloproliferative neoplasms (n = 3). Four representative ELN indexes were used. Two or more ELN MDS indexes were in the abnormal range in 35 MDS cases (58.3%) and 4 ICUS cases (25.0%). CONCLUSIONS: Morphological examination remains the standard for MDS diagnosis. Considering the low incidence of genetically proven ICUS (20.2-27.5%), the low sensitivity of ELN MDS indexes for ICUS is considered a valuable alternative.

11.
Pediatr Hematol Oncol ; 36(1): 46-51, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30912988

RESUMO

Congenital sideroblastic anemia (CSA) is a rare hereditary disease causing disorders of hemoglobin synthesis. Severe, progressive congenital sideroblastic anemia becomes transfusion dependent and results in iron overload. In such cases, patients must undergo stem cell transplantation (SCT) before critical organ dysfunction occurs. However, there has been no consensus on the criteria for SCT for congenital sideroblastic anemia. A 17-year-old Japanese boy was newly diagnosed with congenital sideroblastic anemia manifesting dyspnea on effort. His gene analysis revealed ALAS2 R170L. He gradually become dependent on RBC transfusion. Vitamin B6 (pyridoxal, 30 mg/day) therapy and high-dose alpha-linoleic acid supplementation (150 mg/day) had not been effective. We treated the patient with reduced-intensity SCT from a human leukocyte antigen (HLA) alle 8/8-identical unrelated female donor. The preparation regimen applied consisted of cyclophosphamide, fludarabine, total body irradiation (2 Gy), and anti-thymocyte globulin. We experienced secondary graft failure, nevertheless we used enough immunosuppression. Here we discuss the optimal transplantation regimen for an adult-onset congenital sideroblastic anemia patient with transfusion dependency and mild hemosiderosis. We consider a positive indication for SCT in younger (< 20-year-old) patients with congenital sideroblastic anemia with transfusion dependency. Each case should be individually considered for their suitability for SCT depending on the feasibility and the clinical condition of the patient.


Assuntos
5-Aminolevulinato Sintetase/genética , Anemia Sideroblástica/congênito , Anemia Sideroblástica/terapia , Rejeição de Enxerto/genética , Mutação de Sentido Incorreto , Transplante de Células-Tronco , Adolescente , Aloenxertos , Substituição de Aminoácidos , Humanos , Masculino
13.
Int J Clin Oncol ; 24(5): 590-595, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30604157

RESUMO

BACKGROUND: D-index is a recently established clinical tool for assessing neutropenia severity. This study examined whether the D-index can predict the onset of various infections in patients with febrile neutropenia (FN). METHODS: We retrospectively investigated FN events in consecutive patients aged < 65 years who were treated for newly diagnosed acute myeloid leukemia at our institution. We collected data on all FN events during chemotherapy and evaluated the association of FN severity with infectious events. RESULTS: This study included 35 patients (18 women and 17 men; median age, 51 years [range 18-65 years]) with 122 FN events. The response rate to induction chemotherapy was 60% (21/35), and all but one patient survived the treatment. The D-index did not predict FN onset. However, in multivariate analysis, high-dose cytarabine and total D-index were statistically significant explanatory factors for microbiological-proven infections. In addition, multivariate analysis showed that diabetes mellitus is the only risk factor for FN onset. Furthermore, older age, consolidation therapy, and cumulative D-index (c-D-index) were risk factors for prolonged FN. The FN period was the longest in patients with respiratory infections. CONCLUSION: The D-index did not predict the onset of infection. However, FN duration might be prolonged during consolidation therapy in elderly patients with diabetes mellitus, and it is important to manage respiratory infections. These findings indicate the c-D-index is a useful tool to predict prolonged FN.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neutropenia Febril/induzido quimicamente , Quimioterapia de Indução/efeitos adversos , Leucemia Mieloide Aguda/tratamento farmacológico , Adolescente , Adulto , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Neutropenia Febril/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neutrófilos/patologia , Infecções Respiratórias/complicações , Estudos Retrospectivos , Fatores de Risco
14.
Clin Nucl Med ; 44(2): e85-e86, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30516664

RESUMO

Here we report on the treatment of a 38-year-old woman with primary cutaneous γδT-cell lymphoma, which is a rare subset of cutaneous T-cell lymphoma. She presented with multiple subtle subcutaneous nodules, which were not clearly observed on computed tomography scans or after biopsy. However, F-fluorodeoxyglucose positron emission tomography (F-FDG-PET) accurately detected small cutaneous lesions. She achieved a second complete remission, as demonstrated by F-FDG-PET performed after pralatrexate infusion.


Assuntos
Aminopterina/análogos & derivados , Linfoma Cutâneo de Células T/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Aminopterina/uso terapêutico , Feminino , Fluordesoxiglucose F18 , Humanos , Linfoma Cutâneo de Células T/diagnóstico por imagem , Tomografia por Emissão de Pósitrons , Neoplasias Cutâneas/diagnóstico por imagem , Resultado do Tratamento
16.
Oxf Med Case Reports ; 2018(10): omy048, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30250742

RESUMO

A 39-year-old male diagnosed as chronic myeloid leukemia, had no abdominal symptoms. However, his physical examination revealed apparent abdominal fullness. His liver and spleen were palpable. His abdominal CT revealed that a narrow space to pass intestinal digestive contents. Asymptomatic hepatosplenomegaly is somewhat typical in these chronic type hematological diseases.

17.
BMC Clin Pathol ; 18: 5, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29796007

RESUMO

Background: Chronic lymphocytic leukemia (CLL) is a mature lymphoid neoplasm currently categorized as an indolent type of malignant lymphoma. CLL progresses slowly over years, but it eventually transforms to a more aggressive lymphoma such as the diffuse large B-cell (DLBCL) type, also known as Richter's syndrome. Case presentation: We treated a 69-year-old Japanese male who was histologically diagnosed with Richter's syndrome after 6 years of CLL. His lymphadenopathy had systemically progressed for years, with lymphocyte counts of less than 10,000 cells/µL and a disease status of Rai classification stage I and Binet classification B. He had high fever and hepatosplenomegaly upon Richter's transformation. The patient was treated with ofatumumab for refractory CLL, which relieved his febrile lymphadenopathy. He received a total of 11 ofatumumab courses and achieved partial remission. On the day of the 12th course of ofatumumab, his disease relapsed with febrile lymphadenopathy. Computed tomography revealed multiple liver masses and systemic lymphadenopathy, while a liver biopsy confirmed T-cell lymphoma. Concomitantly, CD20-lacking CLL cells were detected in his peripheral blood and bone marrow, and pathological examination of his left cervical lymph node biopsy showed CD20-positive DLBCL. The final diagnosis was three different types of lymphoma pathologies: (1) CD20-positive DLBCL of the lymph nodes, (2) CD20-lacking CLL of the peripheral blood and bone marrow, and (3) peripheral T-cell lymphoma (PTCL) of the liver. He received intravenous and oral dexamethasone therapy as palliative care. He died because of the rapid progression of abdominal masses 2 months after the diagnosis of triple transformation CLL. An autopsy revealed aggressive PTCL with aggressive systemic involvement of the liver, spleen, gall bladder, pericardium, bone marrow, and mediastinal-paraaortic-intraceliac lymph nodes. T-cell receptor study of an autopsy specimen supported the diagnosis of PTCL that spread to the intraceliac organs and lymph nodes. We concluded that his pathogenicity progressed to a mixture of triple lymphoma as a result of double malignant transformations, which included PTCL from CLL, CD20-negative CLL, and CD20-positive DLBCL by Richter's transformation. Conclusions: Our case provides information on the biology of CLL, to transform from a low-grade chemosensitive status to a malignant chemoresistant status.

18.
Rare Tumors ; 10: 2036361318773847, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29785257

RESUMO

Acute erythroid leukemia, also known as acute myeloid leukemia-M6, may be associated with previous chemotherapy or immunosuppressive therapy. For 10 years, a 69-year-old Japanese female patient with pure erythroid leukemia (or acute myeloid leukemia-M6b) was treated for polymyositis with 50-100 mg/day azathioprine. She complained of dyspnea with low-grade fever and was diagnosed as having pure erythroid leukemia. Chromosomal analysis revealed a complex karyotype abnormality, with the deletion of 5q, -6, -7 and addition of 11q13. No morphological myelodysplastic changes were observed in her bone marrow cells. In this study, azathioprine accumulation was considered to be associated with the patient's leukemogenesis.

19.
Int J Oncol ; 52(5): 1738-1748, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29568932

RESUMO

Small-cell lung cancer (SCLC) is intractable due to its high propensity for relapse. Novel agents are thus needed for SCLC treatment. Lemongrass essential oil (LG-EO) and its major constituent, citral, have been reported to inhibit the proliferation and survival of several types of cancer cells. However, the precise mechanisms through which LG-EO and citral exert their effects on SCLC cells have not been fully elucidated. SCLC cells express Src and have high levels of Src-tyrosine kinase (Src-TK) activity. In most SCLC cell lines, constitutive phosphorylation of Stat3(Y705), which is essential for its activation, has been detected. Src-TK can phosphorylate Stat3(Y705), and activated Stat3 promotes the expression of the anti-apoptotic factors Bcl-xL and Mcl-1. In the present study, LG-EO and citral prevented Src-TK from phosphorylating Stat3(Y705), resulting in decreased Bcl-xL and Mcl-1 expression, in turn suppressing the proliferation/survival of SCLC cells. To confirm these findings, the wild-type-src gene was transfected into the LU135 SCLC cell line (LU135­wt-src), in which Src and activated phospho-Stat3(Y705) were overexpressed. The suppression of cell proliferation and the induction of apoptosis by treatment with LG-EO or citral were significantly attenuated in the LU135-wt-src cells compared with the control LU135-mock cells. The signal transducer and activator of transcription 3 (Stat3) signaling pathway is also associated with intrinsic drug resistance. LU135-wt-src cells were significantly resistant to conventional chemotherapeutic agents compared with LU135-mock cells. The combined effects of citral and each conventional chemotherapeutic agent on SCLC cells were also evaluated. The combination treatment exerted additive or more prominent effects on LU135-wt-src, LU165 and MN1112 cells, which are relatively chemoresistant SCLC cells. These findings suggest that either LG-EO or citral, alone or in combination with chemotherapeutic agents, may be a novel therapeutic option for SCLC patients.

20.
Transpl Infect Dis ; 20(4): e12886, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29570914

RESUMO

BACKGROUND: Voriconazole (VRCZ) is a broad-spectrum antifungal agent that can be administered both orally and intravenously. A high level of intra- and interindividual variability in serum drug therapeutic concentrations has been reported. We analyzed the influence of corticosteroid use on serum VRCZ concentration by assessing the correlation between corticosteroid dose and VRCZ trough level. METHODS: Immunocompromised patients treated with VRCZ with or without corticosteroid use from June 2010 to March 2017 (6 years and 8 months) were reviewed in our institute. VRCZ and the corticosteroids were administered orally or intravenously. Corticosteroid treatment was considered as "concurrent" only if it was administered within 3 days before or after the initiation of VRCZ. All corticosteroids were converted to a prednisolone-based dosage according to their anti-inflammatory effect (relative glucocorticoid activity). VRCZ concentration was measured at the trough point on the day of steady state. RESULTS: A total of 85 samples were obtained from 38 patients. The medical records of 23 women and 15 men, with a median age of 61 years (range: 35-86), were reviewed. Twenty-one patients (55.3%, 21/38) received chemotherapy, and 28 (73.7%, 28/38) received corticosteroid therapy. The average and median daily doses of corticosteroids were 59.2 and 89.8 mg, respectively (range: 0.714-377). VRCZ concentration was inversely correlated with corticosteroid dose (r = -.26). The VRCZ concentration was significantly decreased in the corticosteroid user compared to nonuser (P = .013). We evaluated the association of VRCZ concentration and corticosteroid dose in 3 patients among our cohorts for whom more than 5 points of data were available. Intraindividual analysis revealed the trough level of VRCZ concentration decreased as the corticosteroid dose increased. The patients' underlying diseases were hematological diseases (n = 25) and immunological diseases (n = 13). Among accrual patients, no patients were undergoing stem cell transplantation, and no patients were treated with known confounders such as calcineurin inhibitors or phenytoin. CONCLUSIONS: VRCZ might be metabolized by an enzyme induced by corticosteroid treatment; therefore, intraindividual variation in VRCZ metabolism should be considered prior to concurrent treatment, especially for patients with hematological malignancies treated with corticosteroids.


Assuntos
Antifúngicos/sangue , Glucocorticoides/farmacologia , Doenças Hematológicas/tratamento farmacológico , Micoses/tratamento farmacológico , Voriconazol/sangue , Administração Intravenosa , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Antifúngicos/farmacologia , Antifúngicos/uso terapêutico , Variação Biológica da População , Comorbidade , Relação Dose-Resposta a Droga , Interações de Medicamentos , Monitoramento de Medicamentos , Feminino , Glucocorticoides/uso terapêutico , Doenças Hematológicas/sangue , Doenças Hematológicas/epidemiologia , Doenças Hematológicas/imunologia , Humanos , Hospedeiro Imunocomprometido , Masculino , Pessoa de Meia-Idade , Micoses/sangue , Micoses/epidemiologia , Micoses/imunologia , Voriconazol/farmacologia , Voriconazol/uso terapêutico
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