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1.
Cancer Sci ; 115(4): 1317-1332, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38279512

RESUMO

T-cell acute leukemia and lymphoma have a poor prognosis. Although new therapeutic agents have been developed, their therapeutic effects are suboptimal. α-Pinene, a monoterpene compound, has an antitumor effect on solid tumors; however, few comprehensive investigations have been conducted on its impact on hematologic malignancies. This report provides a comprehensive analysis of the potential benefits of using α-pinene as an antitumor agent for the treatment of T-cell tumors. We found that α-pinene inhibited the proliferation of hematologic malignancies, especially in T-cell tumor cell lines EL-4 and Molt-4, induced mitochondrial dysfunction and reactive oxygen species accumulation, and inhibited NF-κB p65 translocation into the nucleus, leading to robust apoptosis in EL-4 cells. Collectively, these findings suggest that α-pinene has potential as a therapeutic agent for T-cell malignancies, and further investigation is warranted.


Assuntos
Monoterpenos Bicíclicos , Neoplasias Hematológicas , Neoplasias , Humanos , NF-kappa B/metabolismo , Linfócitos T/metabolismo , Apoptose , Linhagem Celular Tumoral , Proliferação de Células
2.
Transfusion ; 63(7): 1344-1353, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37293978

RESUMO

BACKGROUND: Granulocyte transfusion therapy is a rational therapeutic option for patients with prolonged, severe neutropenia. Although high molecular weight hydroxyethyl starch (hHES) facilitates the separation of red blood cells during granulocyte collection, renal dysfunction has been noted as a potential side effect. HES130/0.4 (Voluven®) is a medium molecular weight HES (mHES) with superior safety profiles compared to hHES. Although HES130/0.4 is reportedly effective in the collection of granulocytes, we lack studies comparing the efficiency of granulocyte collection using HES130/0.4 and hHES. STUDY DESIGN AND METHODS: We retrospectively collected the data from 60 consecutive apheresis procedures performed on 40 healthy donors at the Okayama University Hospital between July 2013 and December 2021. All procedures were performed using the Spectra Optia system. Based on the HES130/0.4 concentration in the separation chamber, granulocyte collection methods using HES130/0.4 were classified into m0.46, m0.44, m0.37, and m0.8 groups. We used HES130/0.4 and hHES groups to compare the various sample collection methods. RESULTS: The median granulocyte collection efficiency (CE) was approximately 24.0% and 28.1% in the m0.8 and hHES groups, respectively, which were significantly higher than those in the m0.46, m0.44, and m0.37 groups. One month following granulocyte collection with HES130/0.4, no significant changes were observed in serum creatinine levels compared to those before the donation. CONCLUSION: Therefore, we propose a granulocyte collection approach employing HES130/0.4, which is comparable to the use of hHES in terms of the granulocyte CE. A high concentration of HES130/0.4 in the separation chamber was considered crucial for granulocyte collection.


Assuntos
Remoção de Componentes Sanguíneos , Neutropenia , Humanos , Peso Molecular , Estudos Retrospectivos , Granulócitos , Derivados de Hidroxietil Amido
3.
Transfusion ; 62(5): 1065-1072, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35322885

RESUMO

BACKGROUND: CD34+ cell collection efficiency (CE) is the determining factor when calculating processed blood volume (PBV) for leukapheresis (LP). However, the factors affecting CE in the continuous mononuclear cell collection (cMNC) protocol performed by the Spectra Optia apheresis system are not well established. STUDY DESIGN AND METHODS: We retrospectively collected the data from 147 consecutive apheresis procedures across 106 healthy donors and 27 patients completed between July 2016 and December 2020 at the Okayama University Hospital. All procedures were performed using the Optia cMNC protocol. RESULTS: The median CD34+ CE2 was significantly higher in the donor samples (64.3%) than in the patient samples (46.8%) (p < .0001). WBC counts, hematocrit, and platelet counts were all significantly higher in the donors than in the patients, and there was a moderate positive correlation between CD34+ CE2 and hematocrit (r = .47, p < .0001), with the equation of the line being y = 1.23x + 12.23. In contrast, there was only a very weak correlation between CD34+ CE2 and WBC or platelet count. In addition, low hematocrit correlated with an increased time to interface formation. CONCLUSION: These data revealed the negative impact of low hematocrit on the efficiency of CD34+ cell collection when using the Optia cMNC protocol and suggest that hematocrit values should also be considered when determining PBV.


Assuntos
Remoção de Componentes Sanguíneos , Mobilização de Células-Tronco Hematopoéticas , Antígenos CD34 , Remoção de Componentes Sanguíneos/métodos , Hematócrito , Mobilização de Células-Tronco Hematopoéticas/métodos , Humanos , Leucaférese/métodos , Leucócitos Mononucleares , Estudos Retrospectivos
4.
Transfus Apher Sci ; 61(6): 103453, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35577683

RESUMO

Active infection at the time of allogeneic hematopoietic stem cell transplantation (HSCT) is a risk for non-relapse mortality (NRM) after HSCT. Granulocyte transfusion (GTX) has been used to prevent or treat life-threatening infections in patients with severe neutropenia. However, data are limited on the clinical benefits of GTX during HSCT. We retrospectively analyzed the transplant outcomes of HSCT patients who had undergone GTX between 2012 and 2020. Altogether, 20 patients with documented infection had received 55 GTXs during HSCT. No adverse events were observed during the GTX infusion. The average number of granulocytes was 0.40 (range, 0.10-1.59) × 109/kg. The median neutrophil increment one day after GTX was 515 (range, -6 to 6630)/µl, which was significantly correlated with the infused granulocyte dose (p = 0.0007). A total of 17 of 20 patients achieved neutrophil engraftment. The number of infused granulocytes tended to higher in clinical responders (p = 0.12), and patients receiving ≥ 0.5 × 109/kg showed trend toward to better transplant outcomes (GTX-high vs. GTX-low, 1-year OS; 33% vs. 11%, p = 0.19. 1-year NRM; 44% vs.77%, p = 0.11). The type of red blood sedimenting agents was significantly correlated with the amounts of granulocyte collection. In conclusion, GTX, especially with a high amount of containing granulocytes, could be a safe bridging therapy for neutrophil engraftment after HSCT in patients with active infection.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Neutrófilos , Adulto , Humanos , Estudos Retrospectivos , Transfusão de Leucócitos/efeitos adversos , Granulócitos/metabolismo , Transplante Homólogo
5.
Acta Neurochir (Wien) ; 164(9): 2465-2471, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35869331

RESUMO

BACKGROUND: Meningiomas have vascular supply from the tumor attachment on the dura mater. Gamma Knife radiosurgery (GKS) is known to have a vascular obliterating effect. This study aims to determine the benefits of high-dose irradiation to the tumor attachment compared to conventional dose planning in the long-term control of tumor growth with GKS. METHODS: Two different dose plannings were retrospectively compared in 75 patients with meningioma treated with GKS as a primary treatment. Forty-three patients were irradiated over 20 Gy to the tumor attachment. The remaining 32 patients were treated with conventional-dose planning. Tumor growth control, reduction of enhancement on the gadolinium-enhanced magnetic resonance imaging (MRI), and neurological status were retrospectively assessed. RESULTS: The maximum dose on the tumor attachment was significantly higher in the high-dose group (23 Gy) than in the conventional group (16 Gy). The tumor margin was irradiated with the median of the 50% isodose line in both groups. The prescription doses resulted in 14 Gy and 12 Gy, respectively. The tumor control rate achieved 91% in both groups during the median follow-up period of 54 months. A decrease of enhancement on follow-up MRI was noted in one patient in each group. Kaplan-Meier analysis revealed no statistical difference in the progression-free survival between the two groups. The number of patients with improved neurological status showed no statistical difference. CONCLUSIONS: No obvious benefit of high-dose irradiation to the tumor attachment and margin was found in tumor control and neurological status in the long term.


Assuntos
Neoplasias Meníngeas , Meningioma , Radiocirurgia , Seguimentos , Humanos , Neoplasias Meníngeas/diagnóstico por imagem , Neoplasias Meníngeas/radioterapia , Neoplasias Meníngeas/cirurgia , Meningioma/diagnóstico por imagem , Meningioma/radioterapia , Meningioma/cirurgia , Radiocirurgia/métodos , Estudos Retrospectivos , Resultado do Tratamento
6.
Acta Med Okayama ; 76(5): 609-615, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36352810

RESUMO

A 69-year-old Japanese man with acute leukemia received post-transplant cyclophosphamide-based haploidentical stem cell transplantation (PTCY-haplo-SCT) but was readmitted with dyspnea and ground-glass-opacities of the lungs. Bronchoscopy showed inflammatory changes with no signs of infection. He received steroids but required intubation as his condition deteriorated. In addition to antithymocyte globulin and cyclophosphamide, we administered ruxolitinib but failed to save him. Autopsy findings revealed fibrotic nonspecific interstitial pneumonia (NSIP) without evidence of organizing pneumonia or infection. Thus, we diagnosed idiopathic pneumonia syndrome (IPS). As far as our knowledge, this is the first case of IPS with NSIP histology after PTCY-haplo-SCT.


Assuntos
Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas , Pneumonia , Humanos , Masculino , Idoso , Autopsia , Ciclofosfamida/uso terapêutico , Condicionamento Pré-Transplante , Pulmão , Estudos Retrospectivos
7.
Transfus Apher Sci ; 60(4): 103147, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33931360

RESUMO

Peripheral blood progenitor cells (PBPCs) are a predominant graft source in allogeneic hematopoietic cell transplantation. Citrate-induced hypocalcemia remains the most frequent side effect of PBPC apheresis. Although the method for preventing severe adverse events is established, more efficient prophylaxis is required so that volunteer donors can donate PBPCs without pain and anxiety. We studied 80 healthy donors who underwent PBPC harvest between February 2014 and June 2020. Of these, 23 donors who underwent apheresis between February 2014 and December 2015 received only the standard prophylaxis of intravenous calcium gluconate. Oral calcium drinks were provided to 57 donors who underwent apheresis from January 2016 to June 2020 to supplement intravenous calcium gluconate prophylaxis. The ionized calcium (ICa) levels at multiple time intervals and the hypocalcemic symptoms were evaluated. Oral supplementation with a calcium drink maintained significantly higher ICa levels. Analysis using the inverse probability weighted regression adjustment method suggested that calcium drinks reduced the frequency of citrate-related reactions by 39.2 %. Administering a prophylactic oral calcium drink before apheresis with intravenous administration of calcium gluconate is promising to further reduce citrate-induced hypocalcemia in volunteer donors.


Assuntos
Gluconato de Cálcio/administração & dosagem , Ácido Cítrico , Suplementos Nutricionais , Mobilização de Células-Tronco Hematopoéticas , Células-Tronco de Sangue Periférico/metabolismo , Doadores de Tecidos , Administração Oral , Adulto , Remoção de Componentes Sanguíneos , Cálcio/administração & dosagem , Ácido Cítrico/efeitos adversos , Ácido Cítrico/farmacologia , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Masculino , Pessoa de Meia-Idade
8.
J Infect Chemother ; 25(12): 1065-1069, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31227382

RESUMO

Cunninghamella is a member of the class Zygomycetes. Cunninghamella species include ubiquitous filamentous fungi; infections caused by Cunninghamella species are less frequent but have higher mortality rates than infections caused by Mucorales group members such as Rhizopus and Mucor. Herein, we reported a rare fatal case of endobronchial metastasis from breast cancer accompanied with Cunninghamella bertholletiae tracheobronchial mycetoma. A 73-year-old female with a history of right-sided breast cancer who had undergone mastectomy 11 years previously and had no recurrence presented to our emergency department with a 1-week history of left-sided back pain. Chest X-ray revealed left lung atelectasis; bronchoscopy revealed an endobronchial mass lesion in the left main bronchus. Pathological examination revealed fungal mycetoma but malignant lesions were not detected. Endobronchial and lung mycetoma caused by Cunninghamella bertholletiae were initially diagnosed; liposomal amphotericin B was administered, but her condition deteriorated. Rigid endoscopy showed growth of hemorrhagic tissue occupying the left main bronchus just under the carina. Pathological examination of the shaved lesion revealed metastasis from breast cancer covered with abundant necrotic tissue. No mold was observed in the necrotic tissue; this was probably due to liposomal amphotericin B treatment. To our knowledge, this is the first case of endobronchial metastasis from breast cancer accompanied with Cunninghamella bertholletiae mycetoma. Distinguishing endobronchial metastases from breast cancer and atypical presentations of Cunninghamella endobronchial mycetomas can be very difficult. Repeated bronchoscopies maybe helpful in establishing an accurate diagnosis when clinical prognosis does not match the initial diagnosis.


Assuntos
Neoplasias da Mama/patologia , Neoplasias Brônquicas/complicações , Cunninghamella/isolamento & purificação , Pneumopatias Fúngicas/diagnóstico , Mucormicose/diagnóstico , Micetoma/diagnóstico , Idoso , Anfotericina B/uso terapêutico , Antifúngicos/uso terapêutico , Neoplasias da Mama/cirurgia , Brônquios/diagnóstico por imagem , Brônquios/microbiologia , Neoplasias Brônquicas/secundário , Broncoscopia , Evolução Fatal , Feminino , Humanos , Pneumopatias Fúngicas/tratamento farmacológico , Pneumopatias Fúngicas/microbiologia , Mastectomia , Mucormicose/tratamento farmacológico , Mucormicose/microbiologia , Micetoma/tratamento farmacológico , Micetoma/microbiologia
9.
Transpl Infect Dis ; 20(2): e12850, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29359846

RESUMO

A 52-year-old man suffered from progressive multifocal leukoencephalopathy (PML) after human leukocyte antigen (HLA)-haploidentical transplantation with post-transplantation cyclophosphamide (PTCY). Mirtazapine, mefloquine, and cytarabine failed to improve his symptoms, and he finally died 4.5 months after PML onset. This is the first case report of a patient with PML after HLA-haploidentical transplantation with PTCY. Although T-cell replete HLA-haploidentical transplantation with PTCY has enabled early immune reconstitution, PML should be considered if a patient's mental condition deteriorates.


Assuntos
Ciclofosfamida/uso terapêutico , Doença Enxerto-Hospedeiro/prevenção & controle , Antígenos HLA/genética , Leucoencefalopatia Multifocal Progressiva/etiologia , Transplante de Células-Tronco/efeitos adversos , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Linfoma Folicular/complicações , Linfoma Difuso de Grandes Células B/terapia , Masculino , Pessoa de Meia-Idade , Transplante Haploidêntico
10.
Acta Neurochir (Wien) ; 160(4): 727-730, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29285680

RESUMO

Extensive large dumbbell-shaped hypoglossal schwannoma is extremely rare, and total resection is nearly impossible. We present a case of a 61-year-old male with a giant-size hypoglossal schwannoma with moderate tongue atrophy. The tumor extended from the enlarged hypoglossal canal to the brainstem intradurally and the high cervical region extradurally. Through the extreme lateral infrajugular transcondylar (ELITE) skull base approach, the tumor was totally removed in a single-stage operation. Single-stage total resection is feasible by an experienced skull base team utilizing transcondylar skull base techniques and high cervical dissection.


Assuntos
Neoplasias dos Nervos Cranianos/patologia , Neoplasias dos Nervos Cranianos/cirurgia , Doenças do Nervo Hipoglosso/patologia , Doenças do Nervo Hipoglosso/cirurgia , Neurilemoma/patologia , Neurilemoma/cirurgia , Procedimentos Neurocirúrgicos/métodos , Atrofia , Neoplasias dos Nervos Cranianos/diagnóstico por imagem , Humanos , Doenças do Nervo Hipoglosso/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neurilemoma/diagnóstico por imagem , Base do Crânio/cirurgia , Tomografia Computadorizada por Raios X , Língua/patologia , Resultado do Tratamento
11.
Acta Neurochir (Wien) ; 159(11): 2127-2135, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28905114

RESUMO

BACKGROUND: There is still no clear guideline for surgical treatment for patients with medically refractory trigeminal neuralgia (TN). When it comes to which surgical treatment to choose, microvascular decompression (MVD) or Gamma Knife surgery (GKS), we should know the long-term outcome of each treatment. METHODS: We analyzed 179 patients undergoing MVD and 52 patients undergoing GKS followed for 1 year or longer. We evaluated the patient's neurological status including pain relief, complications and recurrence. Results were assessed with Barrow Neurological Institute (BNI) pain intensity and facial numbness scores. Overall outcomes were compared between the two groups based on pain relief and complications. RESULTS: BNI pain intensity and facial numbness scores at the final visit were significantly lower in the MVD group than in the GKS group (P < 0.001, P = 0.04, respectively). Overall outcomes were superior following MVD than following GKS (P < 0.001). Following whichever treatment, there were initially high rates of pain-free status "without medication": 96.6% in the MVD group and 96.2% in the GKS group. However, 6.1% in the MVD group and 51.9% in the GKS group fell into a "with medication" state within median periods of 1.83 and 3.92 years, respectively (P < 0.001). Kaplan-Meier analysis revealed that pain recurred more often and later in the GKS group than in the MVD group (P < 0.001). CONCLUSIONS: Considering the long-term outcomes, MVD should be chosen as the initial surgical treatment for patients with medically refractory TN.


Assuntos
Cirurgia de Descompressão Microvascular/métodos , Radiocirurgia/métodos , Neuralgia do Trigêmeo/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Hipestesia/epidemiologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Dor/etiologia , Medição da Dor , Complicações Pós-Operatórias/epidemiologia , Recidiva , Estudos Retrospectivos , Resultado do Tratamento , Neuralgia do Trigêmeo/complicações , Adulto Jovem
12.
Acta Neurochir (Wien) ; 159(4): 681-688, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28108856

RESUMO

BACKGROUND: Trigeminal neuralgia (TN) caused solely by venous compression is uncommon. An appropriate vein management protocol for microvascular decompression (MVD) has not been established. We evaluated the management of veins for TN solely due to venous involvement. METHOD: We analyzed 31 patients with TN in whom only veins were manipulated during MVD. The culprit veins smaller in diameter than the vein of the cerebellopontine fissure (VCPF) were coagulated and divided in 20 patients (divided group), while transposition was performed for larger veins in the remaining 11 patients (non-divided group). Postoperative outcomes were assessed by Barrow Neurological Institute (BNI) pain intensity score and BNI facial numbness score. RESULTS: Preoperative contrast-enhanced T1 spoiled gradient recalled (SPGR) imaging exhibited higher detection rates for veins (93.5%) than non-contrast fast imaging employing a steady-state acquisition image (74.2%). The transverse pontine vein (TPV) was the most frequently involved vessel. All the divided veins were small TPVs except one. The non-divided group included seven cases of large TPVs and four involving the main trunk of the superior petrosal vein or its large tributaries. The median follow-up duration was 33 months. Pain relief was achieved immediately after the surgery in 28 (90.3%) and within a month in the remaining 3 (9.7%) patients. Numbness was present in seven (22.6%) patients at the final follow-up. Recurrence was observed in only two (10.0%) patients in the divided group compared with four (36.4%) patients in the non-divided group. Comparison at the final follow-up revealed that the divided group had superior outcome compared to the non-divided group. CONCLUSIONS: Contrast-enhanced T1 SPGR imaging is crucial to detect small veins in the preoperative diagnosis. Division of the culprit veins is recommended if the diameter is smaller than the VCPF as it provides a better outcome and lower recurrence rate than transposition.


Assuntos
Hipestesia/etiologia , Cirurgia de Descompressão Microvascular/efeitos adversos , Complicações Pós-Operatórias/etiologia , Neuralgia do Trigêmeo/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Veias Cerebrais/patologia , Veias Cerebrais/cirurgia , Feminino , Humanos , Masculino , Cirurgia de Descompressão Microvascular/métodos , Pessoa de Meia-Idade , Neuralgia do Trigêmeo/diagnóstico
13.
J Clin Rheumatol ; 23(2): 87-93, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28225510

RESUMO

OBJECTIVE: The current study demonstrated the potential use of calcineurin inhibitor (CNI) in combination therapy for interstitial lung disease (ILD) complicated with dermatomyositis (DM) and polymyositis (PM). METHODS: Thirty DM/PM patients with ILD were enrolled in this study. Continuous intravenous administration of cyclosporine A (IV-CsA) was simultaneously started with corticosteroid in patients presenting more than two respiratory distress factors as follows: <70 mmHg of PaO2, percentage of vital capacity <70%, and/or exertional dyspnea. Other patients took CNI orally with corticosteroid. When a patient presented exacerbation of ILD, intravenous cyclophosphamide pulse therapy (IVCY) was additionally administrated. Clinical outcomes were compared with those of 21 patients who had been previously treated in our hospital before starting this study, as the historical comparison group. RESULTS: Seven patients underwent IV-CsA, maintaining the drug concentration in blood between 300 and 350 ng/mL, and six of them had favorable outcomes without any adverse events. Eight out of the 30 patients additionally required IVCY. Meanwhile, the frequency of death ascribable to respiratory failure was 6.7%, which was significantly lower than that of the historical comparison group (P = 0.043). Furthermore, longer survival free from exacerbation and severe adverse event was significantly shown (P = 0.029). CONCLUSIONS: For repressing the activity of ILD in DM/PM patients, stabilizing the blood concentration of CNI immediately is a reasonable treatment as well as initiating immunosuppressive therapy in the early phase of the illness. IV-CsA may be a useful option for achieving this purpose in patients with severe ILD.


Assuntos
Inibidores de Calcineurina , Ciclosporina/administração & dosagem , Dermatomiosite/complicações , Glucocorticoides/administração & dosagem , Doenças Pulmonares Intersticiais , Polimiosite/complicações , Adulto , Idoso , Inibidores de Calcineurina/administração & dosagem , Inibidores de Calcineurina/sangue , Protocolos Clínicos , Monitoramento de Medicamentos/métodos , Quimioterapia Combinada/métodos , Feminino , Humanos , Imunossupressores/administração & dosagem , Japão/epidemiologia , Doenças Pulmonares Intersticiais/diagnóstico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/epidemiologia , Doenças Pulmonares Intersticiais/etiologia , Masculino , Pessoa de Meia-Idade , Gravidade do Paciente , Testes de Função Respiratória/métodos , Resultado do Tratamento
14.
Mod Rheumatol ; 24(3): 525-8, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24506572

RESUMO

We report a patient with polyarteritis nodosa (PN) who showed frequent episodes of acute-onset central nervous system (CNS) involvement mimicking relapsing-remitting multiple sclerosis (MS) for 22 years. Long-term use of oral prednisolone successfully avoided recurrence of neurological symptoms. PN can sometimes affect the CNS, and is an important item in the differential diagnosis of neurological manifestations with lesion dissemination in time and space, as seen in MS.


Assuntos
Esclerose Múltipla Recidivante-Remitente/diagnóstico , Poliarterite Nodosa/diagnóstico , Adulto , Encéfalo/patologia , Diagnóstico Diferencial , Feminino , Humanos , Imageamento por Ressonância Magnética , Esclerose Múltipla Recidivante-Remitente/patologia , Poliarterite Nodosa/patologia , Substância Branca/patologia
15.
Respir Med Case Rep ; 41: 101794, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36583058

RESUMO

Although immune checkpoint inhibitors (ICIs) can be used for lung cancer treatment, the activated immune response may cause immune-related adverse effects (irAEs). We present here a case of cytomegalovirus (CMV) enterocolitis during steroid therapy for an irAE. A 70-year-old man diagnosed with small-cell lung carcinoma (limited disease) received radiotherapy plus two chemotherapy cycles of cisplatin and etoposide. The tumor exhibited complete response but recurred after 3 years. After treatment with two cycles of carboplatin, etoposide, and atezolizumab, an inhibitors of programmed cell death receptor-1, he was switched to atezolizumab every 3 weeks for maintenance therapy. Diarrhea occurred after nine atezolizumab doses. With a strong suspicion of ICI-induced colitis, we administered methylprednisolone 500 mg for 3 days, followed by oral prednisolone 40 mg/day. Total colonoscopy during the treatment revealed mucosal inflammation of the total colon, suggesting immune-related colitis. Biopsies from the ulceration revealed crypt abscess with highly infiltrative plasma cells and lymphocytes. Furthermore, immunohistochemical staining showed positivity for CMV. With no improvement in watery diarrhea, the prednisolone dose was increased to 80 mg/day on the 11th day, and ganciclovir was additionally administered twice daily on the 26th day. On the 28th day, the patient had abdominal pain, and abdominal computed tomography revealed free air, resulting in the diagnosis of colon perforation. He underwent subtotal colectomy followed by ileostomy as emergency surgery. A colon specimen revealed colitis with CMV infection. We describe colon perforation in a patient with CMV enterocolitis complicated by refractory immune-related colitis.

16.
Biol Pharm Bull ; 35(3): 317-20, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22382316

RESUMO

PURPOSE: Cytochrome P450 (CYP)2C19 polymorphisms may partly explain the variability of thalidomide concentration and adverse drug effects by altering its metabolism. To compare the genetic and clinical factors responsible for the adverse effects and efficacy of thalidomide treatment, we investigated CYP2C19 genetic polymorphisms in Japanese subjects. MATERIALS AND METHODS: Variations in the CYP2C19 gene in 6 patients treated with thalidomide were analyzed. The dosage of thalidomide, concentrations of (R)- and (S)-thalidomide in whole blood, and clinical laboratory test results were used as pharmacokinetic and pharmacodynamic indices. Using genomic DNA, CYP2C19*2 and *3 allele frequencies were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assays. RESULTS: The frequencies of CYP2C19 PM and hetero EM (hetEM) genotypes in Japanese patients taking thalidomide were 2 (33.3%) and 4 (66.7%), respectively. The areas under the curve (AUC) of (R)-thalidomide were 3.42 and 5.33 µg·h/L, and those of (S)-thalidomide were 1.64 and 2.46 µg·h/L for hetEM and PM, respectively. CONCLUSIONS: This study provided new insights regarding the contribution of CYP2C19 gene variations to adverse responses to thalidomide. Genotyping of CYP2C19*2 and *3 can be considerably simplified by using KOD FX as a polymerase for prediction of adverse effects to thalidomide by the PCR-RFLP method. CYP2C19 PM patients tend to have high serum thalidomide concentrations.


Assuntos
Antineoplásicos/farmacocinética , Hidrocarboneto de Aril Hidroxilases/genética , Talidomida/farmacocinética , Idoso , Amiloidose/metabolismo , Antineoplásicos/efeitos adversos , Antineoplásicos/sangue , Povo Asiático/genética , Citocromo P-450 CYP2C19 , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/metabolismo , Polimorfismo Genético , Talidomida/efeitos adversos , Talidomida/sangue
17.
BMC Musculoskelet Disord ; 13: 228, 2012 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-23173570

RESUMO

BACKGROUND: To investigate whether or not coadministration of tacrolimus (TAC) with prednisolone (PSL) can produce a beneficial effect in the treatment of polymyositis/ dermatomyositis (PM/DM). METHODS: We reviewed medical records of 32 PM/DM patients who had been admitted to our hospital, and abstracted those who had received TAC in addition to oral PSL for treatment. The clinical usefulness of TAC in PM/DM was objectively evaluated focusing upon the manual muscle strength test (MMT) score, serum creatine kinase (CK) and tapering of PSL. RESULTS: Nine patients with PM and 6 with DM were enrolled in this study. TAC was added because of difficulty in reduction of PSL in 12 patients and recurrence with corticosteroid-induced complications in the remaining 3. Both PM and DM patients showed significant increases in the MMT score and significant decreases in serum CK 1 to 3 months after starting TAC compared with before. Skin symptoms in a clinically amyopathic DM patient also improved 1 month after starting TAC. The daily dosage of PSL could be significantly reduced in both PM and DM after starting TAC compared with before. No serious adverse events ascribable to TAC occurred in any patients. CONCLUSION: Additional use of TAC with PSL may safely promote improvement of PM/DM and also accelerate tapering of the latter.


Assuntos
Corticosteroides/uso terapêutico , Dermatomiosite/tratamento farmacológico , Imunossupressores/uso terapêutico , Músculo Esquelético/efeitos dos fármacos , Prednisolona/uso terapêutico , Tacrolimo/uso terapêutico , Administração Oral , Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Creatina Quinase/sangue , Dermatomiosite/sangue , Dermatomiosite/diagnóstico , Dermatomiosite/fisiopatologia , Esquema de Medicação , Quimioterapia Combinada , Feminino , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Masculino , Pessoa de Meia-Idade , Força Muscular/efeitos dos fármacos , Músculo Esquelético/metabolismo , Músculo Esquelético/fisiopatologia , Prednisolona/administração & dosagem , Prednisolona/efeitos adversos , Recuperação de Função Fisiológica , Estudos Retrospectivos , Tacrolimo/administração & dosagem , Tacrolimo/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
18.
Cureus ; 14(3): e23411, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35481309

RESUMO

Pneumonia secondary to coronavirus disease 2019 (COVID-19) is exacerbated by a disproportionate increase in the systemic inflammatory response and cytokine storm due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Herein, we report the successful treatment of severe COVID-19 pneumonia using a combination of tocilizumab and baricitinib in a patient with combined pulmonary fibrosis and emphysema (CPFE). A 67-year-old male with type 2 diabetes mellitus and CPFE presented with fever and dyspnea and was diagnosed with COVID-19. Upon admission, his respiratory failure was managed using high-flow nasal cannula (HFNC) therapy; however, despite treatment with remdesivir and systemic steroids, his respiratory failure continued to worsen. Therefore, baricitinib was administered from the ninth day of hospitalization for 14 days. Furthermore, his blood interleukin-6 (IL-6) levels showed an increase until day 13. Thus, tocilizumab was administered on the 13th day, which led to symptomatic improvement by day 18. The patient was discharged from our hospital on day 42. This case indicates that combination therapy with tocilizumab and baricitinib improves the efficacy of COVID-19 treatment in patients with comorbidities.

19.
Respirol Case Rep ; 10(1): e0890, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34934507

RESUMO

Urachal carcinoma is a rare malignancy of all bladder carcinomas. Metastatic lung tumours showing multiple nodules are rare without a local recurrence. We describe a case of multiple metastatic lung cancer from urachal carcinoma that required differentiation from primary lung cancer.

20.
Allergy Asthma Clin Immunol ; 18(1): 14, 2022 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-35183225

RESUMO

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is a vasculitis characterized by abnormally high eosinophils and frequent peripheral neuropathy. Mepolizumab is an approved therapy for EGPA, but its efficacy against peripheral neuropathy remains unknown. CASE PRESENTATION: A 41-year-old woman was admitted in the hospital with dyspnea and neuropathy. Ground glass opacity and infiltrative shadow in the bilateral lungs were evident on chest computed tomography images. Eosinophils were increased in serum, in bronchoalveolar lavage fluid (BALF), and in transbronchial lung biopsy, and bacteria were not detected in BALF. EGPA resulting in severe eosinophilic asthma, sinusitis, pulmonary infiltrates, and peripheral neuropathy was diagnosed. Prednisolone (50 mg/day) caused remission of eosinophilic pneumonia and sinusitis, but not peripheral neuropathy. During prednisolone tapering (7 mg/day, 10 months after treatment), eosinophils were increased, and peripheral neuropathy relapsed. The humanized anti-IL-5 antibody mepolizumab (300 mg) was initially administered, followed by prednisolone. Mepolizumab caused sustained peripheral neuropathy remission and effective prednisolone tapering. CONCLUSIONS: Introduction of mepolizumab combined with prednisolone may improve peripheral neuropathy.

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