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We previously reported that sodium-glucose cotransporter 2 (SGLT2) inhibitors exert sustained fluid homeostatic actions through compensatory increases in osmotic diuresis-induced vasopressin secretion and fluid intake. However, SGLT2 inhibitors alone do not produce durable amelioration of fluid retention. In this study, we examined the comparative effects of the SGLT2 inhibitor dapagliflozin (SGLT2i group, n = 53) and the combined use of dapagliflozin and conventional diuretics, including loop diuretics and/or thiazides (SGLT2i + diuretic group, n = 23), on serum copeptin, a stable, sensitive, and simple surrogate marker of vasopressin release and body fluid status. After six months of treatment, the change in copeptin was significantly lower in the SGLT2i + diuretic group than in the SGLT2i group (-1.4 ± 31.5% vs. 31.5 ± 56.3%, p = 0.0153). The change in the estimated plasma volume calculated using the Strauss formula was not significantly different between the two groups. Contrastingly, changes in interstitial fluid, extracellular water, intracellular water, and total body water were significantly lower in the SGLT2i + diuretic group than in the SGLT2i group. Changes in renin, aldosterone, and absolute epinephrine levels were not significantly different between the two groups. In conclusion, the combined use of the SGLT2 inhibitor dapagliflozin and conventional diuretics inhibited the increase in copeptin levels and remarkably ameliorated fluid retention without excessively reducing plasma volume and activating the renin-angiotensin-aldosterone and sympathetic nervous systems.
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Follicular lymphoma (FL) is an indolent lymphoma that becomes aggressive due to histological transformation (HT), leading to reduced survival. Patients with FL have different clinical courses and various treatment options. Some patients exhibit shorter survival and experience disease progression within 24 months of diagnosis/treatment (POD24); the optimal treatment remains an unmet needs. Thus, identifying factors that predict shorter survival is essential to stratify treatment and prolong the survival of patients with FL. To analyze risk factors for POD24 and HT in patients treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) as first-line treatment, we performed this post-hoc analysis of patients with advanced indolent B-cell lymphoma in a randomized clinical trial wherein six cycles of R-CHOP were administered every 2-3 weeks. The primary analysis showed no differences in outcomes, which enabled the analysis of 248 patients with FL, assigned to two arms. All histopathological specimens from the 300 enrolled patients were reviewed by three expert hematopathologists. Multivariable analysis implicated Follicular Lymphoma International Prognostic Index (FLIPI) intermediate (odds ratio [OR] 2.531, 95% confidence interval [CI] 0.676-9.466) and high- (OR 2.236, 95% CI 0.160-31.226) risks, B symptoms (OR 2.091, 95% CI 0.747-5.851), and grade 3A (G3A) (OR 1.833, 95% CI 0.634-5.299) as risk factors for POD24. Furthermore, multivariable analysis through a median follow-up of 15.9 years implicated G3A (OR 2.628, 95% CI 0.806-8.575) and high-risk FLIPI (OR 4.401, 95% CI 0.186-104.377) as risk factors for HT. However, an analysis limited to the first 10 years revealed that the prognostic factors elucidated from the longer-term analysis had a greater impact on HT. G3A and high-risk FLIPI may independently predict POD24 and HT, thereby informing treatment stratification of patients with untreated advanced-stage FL in future trials, particularly to address the unmet needs of patients with POD24.
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Linfoma Folicular , Humanos , Rituximab/uso terapêutico , Vincristina/efeitos adversos , Prednisona/efeitos adversos , Seguimentos , Ciclofosfamida/efeitos adversos , Doxorrubicina/uso terapêutico , Progressão da Doença , Fatores de Risco , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
BACKGROUND: That the peroneus tertius muscle (PT) is a separate entity has been debated. PT has been reported to be part of the extensor digitorum longus muscle, part of the extensor digitorum brevis, or a separate muscle. While pigs have a PT as well as primates, there are no reports of its association with the extensor digitorum longus muscle or extensor digitorum brevis. MATERIALS AND METHODS: In this study, we used gross dissection and Sihler's staining to determine the origin, course, insertion, and innervation of the pig PT. RESULTS: The PT and extensor digitorum longus muscles jointly originated from the femur and ran between the tibialis cranialis and peroneus longus muscles. The PT was inserted at the retinaculum of the metatarsal extensors, tarsal bone, and second metatarsal bone. The branches of the common fibular nerve to the extensor digitorum longus muscle were distributed to the PT. CONCLUSIONS: The innervations suggest that the PT and extensor digitorum longus muscles of the pig were derived from the same muscle mass during development but were named separately due to differences in their morphology. Furthermore, morphological features suggest that pig PT and human PT are probably different muscles.
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Secondary central nervous system involvement (sCNSi) in diffuse large B-cell lymphoma (DLBCL) is fatal. However, its features in patients with sCNSi who are categorized as lower risk by international prognostic index (IPI) or CNS-IPI are not yet fully understood. In the present analysis, we evaluated DLBCL patients who developed sCNSi at their first progression and who participated in JCOG0601, most of whom were lower risk by IPI. Of 409 patients, 21 (5.1%) developed sCNSi during a median follow-up of 4.9 years. Five-year cumulative incidence of sCNSi were 5.1%; and 4.0%, 5.3%, and 11.5% at low, intermediate, and high risk of CNS-IPI, respectively. The most common locations of extranodal lesions at the time of registration in patients with sCNSi were the stomach (n = 4), paranasal cavity (n = 3), and bone marrow (n = 2). In univariable analysis, paranasal cavity lesion was a high-risk factor for sCNSi (subdistribution hazard ratio, 4.34 [95% confidence interval 1.28-14.73]). Median overall survival after sCNSi was 1.3 years, with a 2-year overall survival rate of 39.3%. The incidence of sCNSi in DLBCL patients at lower risk of CNS-IPI was low, as previously reported, but paranasal cavity lesion might indicate high risk for organ involvement. CLINICAL TRIAL REGISTRATION: JCOG0601 was registered in the UMIN Clinical Trials Registry (UMIN000000929, date of registration; December 04, 2007) and the Japan Registry of Clinical Trials (jRCTs031180139, date of registration; February 20, 2019).
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Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias do Sistema Nervoso Central , Ciclofosfamida , Doxorrubicina , Linfoma Difuso de Grandes Células B , Prednisona , Rituximab , Vincristina , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/epidemiologia , Rituximab/uso terapêutico , Masculino , Feminino , Vincristina/uso terapêutico , Vincristina/administração & dosagem , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Idoso , Doxorrubicina/uso terapêutico , Ciclofosfamida/uso terapêutico , Ciclofosfamida/administração & dosagem , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Adulto , Prednisona/uso terapêutico , Prednisona/administração & dosagem , Idoso de 80 Anos ou mais , Seguimentos , Taxa de SobrevidaRESUMO
Chimeric antigen receptor T (CAR-T) cells targeting multiple antigens (Ag), may reduce the risk of immune escape following the loss of the target Ag and further increase the efficacy of treatment. We developed dual-targeting CAR-T cells that target CD19 and CD37 Ags and evaluated their antitumor effects. CD19/CD37 dual CAR-T cells were generated using cotransduction and simultaneous gene transfer of two types of lentiviral vectors transferring CD19CAR or CD37CAR genes, including the intracellular domains of CD28 and CD3ζ signaling domains. These dual CAR-T cells contained three fractions: CD19/CD37 bispecific CAR-T cells, single CD19CAR-T cells, and single CD37CAR-T cells. In the functional evaluation of CAR-T cells in vitro, CD19/CD37 dual CAR-T cells showed adequate proliferation and cytokine production in response to CD19 and CD37 antigen stimulation alone or in combination. Evaluation of intracellular signaling revealed that dual CAR-T cell-mediated signals were comparable with single CAR-T cells in response to CD19- and CD37-positive B-cell tumors. Although the cytotoxicity of CD19/CD37 dual CAR-T cells in both CD19- and CD37-positive B-cell tumors was similar to that of single CD19 and CD37CAR-T cells, against CD19 and CD37 Ag-heterogeneous tumor, dual CAR-T cells demonstrated significantly superior tumor lysis compared with single CAR-T cells. Furthermore, CD19/CD37 dual CAR-T cells effectively suppressed Ag-heterogeneous Raji cells in a xenograft mouse model. Collectively, these results suggest that CD19/CD37 dual CAR-T cells may be effective target-Ag-loss B-cell tumor models in vitro and in vivo, which represents a promising treatment for patients with relapsed/refractory B-cell malignancies.
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Neoplasias , Receptores de Antígenos Quiméricos , Humanos , Camundongos , Animais , Imunoterapia Adotiva/métodos , Receptores de Antígenos Quiméricos/genética , Linfócitos T , Antígenos de Neoplasias , Antígenos CD19 , TetraspaninasRESUMO
Anti-CD20 antibody in combination with chemotherapy extends overall survival (OS) in untreated advanced-stage follicular lymphoma (FL), yet the optimal associated therapy is unclear. Data on the cumulative incidence of secondary malignancies postrelapse after conventional immunochemotherapy are scarce. A long-term analysis of rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) as first-line treatment was conducted in a randomised clinical trial. A six-cycle R-CHOP regimen was administered every 2 or 3 weeks without rituximab maintenance. A prespecified evaluation was conducted 15 years after the completion of enrolment, following initial analysis results that showed no significant differences in outcomes at the 3-year mark. In-depth analyses were performed on the cohort of 248 patients with FL who were allocated to the two treatment arms. With a median follow-up period of 15.9 years, the 15-year OS was 76.2%. There were no protocol treatment-related deaths, nor were there any fatal infections attributable to subsequent lymphoma treatment. At 15 years, the cumulative incidence of non-haematological and haematological malignancies was 12.8% and 3.7% respectively. Histological transformation appeared after a median of 8 years. R-CHOP maintains safety and efficacy in patients with advanced FL over extended follow-up, making it a viable first-line option for patients with advanced-stage FL.
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Linfoma Folicular , Humanos , Rituximab , Vincristina , Linfoma Folicular/tratamento farmacológico , Prednisona , Seguimentos , Anticorpos Monoclonais Murinos/uso terapêutico , Ciclofosfamida , Doxorrubicina , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Resultado do TratamentoRESUMO
Sodium glucose cotransporter 2 (SGLT2) inhibitors have both glucose-lowering and diuretic effects. We recently reported that the SGLT2 inhibitor dapagliflozin exerts short-term fluid homeostatic action in patients with chronic kidney disease (CKD). However, the long-term effects of SGLT2 inhibitors on body fluid status in patients with CKD remain unclear. This was a prospective, non-randomized, open-label study that included a dapagliflozin treatment group (n = 73) and a control group (n = 24) who were followed for 6 months. Body fluid volume was measured using a bioimpedance analysis device. The extracellular water-to-total body water ratio (ECW/TBW), a predictor of renal outcomes, was used as a parameter for body fluid status (fluid retention, 0.400 ≤ ECW/TBW). Six-month treatment with dapagliflozin significantly decreased ECW/TBW compared with the control group (-0.65% ± 2.03% vs. 0.97% ± 2.49%, p = 0.0018). Furthermore, dapagliflozin decreased the ECW/TBW in patients with baseline fluid retention, but not in patients without baseline fluid retention (-1.47% ± 1.93% vs. -0.01% ± 1.88%, p = 0.0017). Vasopressin surrogate marker copeptin levels were similar between the control and dapagliflozin groups at 6 months (32.3 ± 33.4 vs. 30.6 ± 30.1 pmol/L, p = 0.8227). However, dapagliflozin significantly increased the change in copeptin levels at 1 week (39.0% ± 41.6%, p = 0.0010), suggesting a compensatory increase in vasopressin secretion to prevent hypovolemia. Renin and aldosterone levels were similar between the control and dapagliflozin groups at 6 months, while epinephrine and norepinephrine (markers of sympathetic nervous system activity) were significantly lower in the dapagliflozin group than in the control group. In conclusion, the SGLT2 inhibitor dapagliflozin ameliorated fluid retention and maintained euvolemic fluid status in patients with CKD, suggesting that SGLT2 inhibitors exert sustained fluid homeostatic actions in patients with various fluid backgrounds. Clinical trial registration: https://www.umin.ac.jp/ctr/, identifier [UMIN000048568].
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The knee joint capsules composed of a fibrous layer and a synovial layer. The knee meniscus consists of the superficial network, lamellar layer, tie fibre and circumferential bundles. However, the continuous structure of the knee joint capsule and meniscus has not been reported. Fetal and adult pigs were used to investigate the structural relationship between the stifle joint capsule and meniscus based on the gross anatomy and histological findings. In the gross anatomical examination, the joint capsule appeared to have separated attachments to the meniscus, except for the lower aspect of the popliteal hiatus. Histologically, the lower half of the popliteal hiatus was found to have separated attachments, with vessels running between the attachments of the joint capsules. The synovial layer of the joint capsule continued to the superficial network, and the fibrous layer of the joint capsule continued to the lamellar layer and tie fibres. There were two routes of arterial entry into the meniscus: intracapsular and intercapsular. It appeared that the presence of separated attachments of the joint capsule was necessary to allow the intercapsular route. This study clarified for the first time the routes of feeding vessels entering the meniscus and proposed to call this entry point the meniscus hilum. We consider that this detailed anatomical information is important for understanding the continuation between the joint capsule and the meniscus.
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Articulação do Joelho , Menisco , Animais , Suínos , Articulação do Joelho/anatomia & histologia , Membrana Sinovial , Feto , Meniscos Tibiais/anatomia & histologiaRESUMO
BACKGROUND: Some reports have used pigs to establish models of meniscus injury. However, accurate information on the origin, course, and access of the arteries supplying the menisci remains unclear. This information is important to avoid damaging vital arteries when creating the meniscus injury model. MATERIALS AND METHODS: In this study, fetal and adult pigs were employed to investigate the arterial supply of the menisci in pigs using gross anatomical and histological methods. RESULTS: Macro-anatomically, the anterior horn, body, and posterior horn of the medial meniscus were found to be supplied by the medial superior genicular artery, medial inferior genicular artery, and posterior middle genicular artery. The anterior and posterior horns of the lateral meniscus were supplied by the cranial tibial recurrent artery and the middle genicular artery, respectively. Anastomosis was observed in some cases, but appeared to be infrequent and too thin to expect the anastomotic branches to provide adequate blood flow. The histological examination showed that the arteries entered the meniscus along the tie-fiber. The access process of the artery was the same irrespective of whether it was in fetal or mature pigs, the medial or lateral meniscus, or the anterior horn or body or posterior horn. The medial inferior genicular artery ran along the medial meniscus in the circumferential direction. Therefore, the clinical longitudinal incision should take into account the characteristics of the vessel course in order to protect the blood vessels from damage. CONCLUSIONS: Based on the results of this study, the protocol for creating a pig meniscus injury model should be reconsidered.
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Patient-derived xenograft (PDX) mouse models are useful for deepening our understanding of the biology of malignant lymphoma; however, factors associated with the success of the PDX lymphoma model are largely unknown. We retrospectively analyzed the characteristics of 66 xenotransplantations from 65 patients. In all, 43 (65%) specimens were obtained from patients aged > 60 years, and 42 (64%) specimens were obtained at diagnosis. Specimens were obtained from patients with the following diseases: diffuse large B-cell lymphoma (n = 30), intravascular large B-cell lymphoma (n = 12), follicular lymphoma (n = 8), peripheral T-cell lymphoma (n = 7), mantle cell lymphoma (n = 2), and other (n = 7). The specimens were sourced mainly from bone marrow (n = 31, 47%) and extranodal tumors (n = 13, 20%). Engraftment was successful in 33/66 (50%) xenotransplantations. The median age of patients who provided successful specimens was significantly higher than that for unsuccessful specimens (p = 0.013). Specimens with a high proportion of tumor cells in the graft and those obtained from patients with relapsed/refractory disease showed higher tendencies toward successful engraftment. Taken together, these data suggest that tumor cells with a highly malignant potential might have a high likelihood of engraftment.
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Linfoma Folicular , Linfoma Difuso de Grandes Células B , Linfoma de Célula do Manto , Humanos , Animais , Camundongos , Adulto , Estudos Retrospectivos , Linfoma Difuso de Grandes Células B/terapia , Linfoma Difuso de Grandes Células B/patologia , Linfoma Folicular/patologia , Linfoma de Célula do Manto/patologia , Linfócitos/patologiaRESUMO
CD19-targeted chimeric antigen receptor T-cell (CAR-T) therapy has shown promise as treatment of relapsed or refractory B-cell malignancies. However, the clinical utility of early CAR-T monitoring within 1 month after infusion has not been elucidated. In this study, we quantitatively measured CAR-T kinetics in peripheral blood on days 2, 4, 7, 9, 11, 14, 21, and 28 post-infusion using flow cytometry and quantitative polymerase chain reaction in 13 patients with relapsed refractory diffuse large B-cell lymphoma (DLBCL) treated with tisagenlecleucel (tisa-cel). No relationships were identified between bulk CAR-T kinetics and treatment outcomes. Interestingly, the magnitude of CD4+ CAR-T expansion was higher in responders than in nonresponders, while CD8+ CAR-T expansion was minimal in responders. Additionally, CAR-T proliferation was more pronounced in patients with cytokine release syndrome. Our results suggest that CD4+ CAR-T cellular kinetics within 1 month after CAR-T infusion may predict its efficacy after tisa-cel therapy in adult patients with DLBCL.
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Linfoma Difuso de Grandes Células B , Receptores de Antígenos Quiméricos , Adulto , Humanos , Receptores de Antígenos Quiméricos/uso terapêutico , Receptores de Antígenos de Linfócitos T/uso terapêutico , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfócitos T , Imunoterapia Adotiva/métodos , Antígenos CD19/uso terapêuticoRESUMO
Axicabtagene ciloleucel (axi-cel) is an autologous, CD19-targeting chimeric antigen receptor Tcell therapy. We recently reported the 3-month follow-up results of a phase 2, multicenter, openlabel, single-arm study of axi-cel in Japanese patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) (JapicCTI-183914). Here, we present 1-year efficacy and safety data and biomarker analysis data regarding mechanisms of resistance to axi-cel. Primary and secondary endpoints included investigator-assessed objective response rate (ORR), serious adverse events, and treatment-emergent adverse events. Axi-cel pharmacokinetics were also examined. Biomarker analysis was performed by cytokine measurement, immunohistochemistry, RNA sequencing, and whole-exome sequencing. At a median follow-up of 13.4 months, ORR was 86.7% (13/15 patients), and the complete response (CR) rate improved to 53.3% (8/15 patients) due to response conversion. Seven patients experienced disease progression, and one achieved CR after re-treatment with axi-cel. No new safety concerns were detected. Plausible resistance mechanisms to axi-cel varied among patients but included CD19 downregulation, programmed death-ligand 1 upregulation, and increased macrophage and angiogenesis signatures. The 1-year efficacy and safety of axi-cel were confirmed in Japanese patients with R/R LBCL. Resistance to treatment may involve multiple factors, including target antigen loss and an unfavorable tumor environment.Clinical trial registration: Japan Clinical Trials Information; JapicCTI-183914.
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Imunoterapia Adotiva , Linfoma Difuso de Grandes Células B , Humanos , Seguimentos , Japão , Imunoterapia Adotiva/efeitos adversos , Imunoterapia Adotiva/métodos , Linfoma Difuso de Grandes Células B/terapia , Linfoma Difuso de Grandes Células B/patologia , Antígenos CD19/uso terapêuticoRESUMO
Nanoparticles (NPs) enhance soybean growth; however, their precise mechanism is not clearly understood. To develop a more effective method using NPs for the enhancement of soybean growth, fiber crosslinked with zinc oxide (ZnO) NPs was prepared. The solution of ZnO NPs with 200 nm promoted soybean growth at the concentration of 10 ppm, while fibers crosslinked with ZnO NPs promoted growth at a 1 ppm concentration. Soybeans grown on fiber cross-linked with ZnO NPs had higher Zn content in their roots than those grown in ZnO NPs solution. To study the positive mechanism of fiber crosslinked with ZnO NPs on soybean growth, a proteomic technique was used. Proteins categorized in photosynthesis and secondary metabolism accumulated more in soybeans grown on fiber crosslinked with ZnO NPs than in those grown in ZnO NPs solution. Furthermore, significantly accumulated proteins, which were NADPH oxidoreductase and tubulins, were confirmed using immunoblot analysis. The abundance of NADPH oxidoreductase increased in soybean by ZnO NPs application. These results suggest that fiber crosslinked with ZnO NPs enhances soybean growth through the increase of photosynthesis and secondary metabolism. Additionally, the accumulation of NADPH oxidoreductase might relate to the effect of auxin with fiber crosslinked with ZnO NPs on soybean growth.
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Fabaceae , Nanopartículas , Óxido de Zinco , Fabaceae/metabolismo , NADP/metabolismo , Oxirredutases/metabolismo , Proteômica , Plântula/metabolismo , Glycine max/metabolismo , Zinco/metabolismo , Óxido de Zinco/químicaRESUMO
PURPOSES: Central blood pressure is a stronger predictor of cardiovascular prognosis rather than brachial blood pressure. The reflection wave reaches the abdominal aorta sooner than ascending aorta. Thus, the contribution of central pulse pressure (cPP) to renal events may differ from that of cardiovascular events. METHODS: The subanalysis of the ABC-J II study was performed. Subjects were 3434 treated hypertensive patients with a mean follow-up of 4.7 years. Left ventricular hypertrophy, an index of cardiovascular risk, correlated with cPP better than central systolic blood pressure in this cohort. The contribution of brachial pulse pressure (bPP) and cPP to cardiovascular and renal events was analysed. RESULTS: Cox proportional-hazard analysis revealed that sex (p < 0.001), height (p < 0.05), history of cardiovascular diseases (p < 0.001), number of antihypertensive drugs (p < 0.05), and cPP (p < 0.05) contributed to cardiovascular events. However, Cox proportional-hazard analysis disclosed that baseline serum creatinine (p < 0.001) and bPP (p < 0.05) predicted renal events. After adjusting for the history of cardiovascular diseases, Cox regression demonstrated only sex as a significant predictor of cardiovascular events. After adjusting for baseline serum creatinine, no parameters were shown to predict renal events. CONCLUSIONS: The present findings support our previous data that the absence of cardiovascular or renal diseases is an important determinant for event-free survival, and suggest that cPP and bPP contribute to cardiovascular and renal events in treated hypertensive patients.
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Doenças Cardiovasculares , Hipertensão , Pressão Sanguínea , Artéria Braquial , Creatinina , Humanos , Hipertensão/tratamento farmacológico , Análise de Onda de Pulso , Fatores de RiscoRESUMO
The Recurrent Stroke Prevention Clinical Outcome (RESPECT) Study and its pooled analysis showed that intensive blood pressure (BP) lowering reduced recurrent stroke risk by 22% in patients with a history of stroke. Here, we report the effect of intensive BP lowering on the risk of recurrent stroke subtypes in patients with a history of ischemic stroke. RESPECT was a randomized clinical trial among 1280 people with a history of cerebral infarction or intracerebral hemorrhage. Participants were assigned to the intensive blood pressure control group (blood pressure < 120/80 mmHg) or standard blood pressure control group (blood pressure < 140/90 mmHg). In this post hoc analysis, we analyzed 1074 patients with a history of cerebral infarction. The mean BP at baseline was 140.7/81.4 mmHg. Throughout the follow-up period, the mean BP was 133.4/77.5 (95% CI, 132.7-134.1/76.9-78.2) mmHg in the standard group and 126.7/74.1 (95% CI, 126.0-127.4/73.5-74.8) mmHg in the intensive group. During a mean follow-up of 3.9 years, 78 first recurrent strokes occurred. Intensive treatment tended to reduce overall annual stroke recurrence (1.74% in intensive vs. 2.17% in standard; P = 0.351 by log-rank test) and did not change the risk of ischemic stroke (1.74% vs. 1.75%, P = 0.999) but markedly reduced the risk of hemorrhagic stroke (0.00% vs. 0.39%, P = 0.005). Beneficial effects of intensive BP control were observed for the risk of hemorrhagic stroke in patients with a history of ischemic stroke. The findings of this study indicate the benefit of intensive BP control for patients with a history of ischemic stroke at high risk of hemorrhagic stroke.
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Acidente Vascular Cerebral Hemorrágico , Hipertensão , AVC Isquêmico , Acidente Vascular Cerebral , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/fisiologia , Infarto Cerebral/induzido quimicamente , Infarto Cerebral/tratamento farmacológico , Humanos , Hipertensão/induzido quimicamente , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Acidente Vascular Cerebral/induzido quimicamente , Resultado do TratamentoRESUMO
To elucidate the long-term outcomes of non-anthracycline-containing therapies and central nervous system (CNS) events in patients with extranodal NK/T-cell lymphoma, nasal type (ENKTL), the clinical data of 313 patients with ENKTL diagnosed between 2000 and 2013 in a nationwide retrospective study in Japan were updated and analyzed. At a median follow-up of 8.4 years, the 5-year overall survival (OS) and progression-free survival (PFS) were 71% and 64%, respectively, in 140 localized ENKTL patients who received radiotherapy-dexamethasone, etoposide, ifosfamide, and carboplatin (RT-DeVIC) in clinical practice. Nine (6.4%) patients experienced second malignancies. In 155 localized ENKTL patients treated with RT-DeVIC, 10 (6.5%) experienced CNS relapse (median, 12.8 months after diagnosis). In five of them, the events were confined to the CNS. Nine of the 10 patients who experienced CNS relapse died within 1 year after CNS relapse. Multivariate analysis identified gingival (hazard ratio [HR], 54.35; 95% confidence interval [CI], 8.60-343.35) and paranasal involvement (HR, 7.42; 95% CI, 1.78-30.89) as independent risk factors for CNS relapse. In 80 advanced ENKTL patients, 18 received steroid (dexamethasone), methotrexate, ifosfamide, L-asparaginase, and etoposide (SMILE) chemotherapy as first-line treatment. Patients who received SMILE as their first-line treatment tended to have better OS than those who did not (p = 0.071). Six (7.5%) advanced ENKTL patients experienced isolated CNS relapse (median, 2.6 months after diagnosis) and died within 4 months of relapse. No second malignancies were documented in advanced ENKTL patients. In the entire cohort, the median OS after first relapse or progression was 4.6 months. 12 patients who survived 5 years after PFS events were disease-free at the last follow-up. Of those, 11 (92%) underwent hematopoietic stem cell transplantation. Our 8-year follow-up revealed the long-term efficacy and safety of RT-DeVIC and SMILE. The risk of CNS relapse is an important consideration in advanced ENKTL.
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Linfoma Extranodal de Células T-NK , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Asparaginase , Carboplatina , Sistema Nervoso Central/patologia , Dexametasona , Etoposídeo , Humanos , Ifosfamida , Células Matadoras Naturais/patologia , Linfoma Extranodal de Células T-NK/diagnóstico , Linfoma Extranodal de Células T-NK/tratamento farmacológico , Metotrexato , Recidiva Local de Neoplasia/tratamento farmacológico , Estudos RetrospectivosRESUMO
A left ventricular assist device (LVAD) is a treatment option for patients with end-stage heart failure; however, a certain number of patients on durable LVADs are diagnosed with malignancy. Radiation therapy (RT) for patients with durable LVADs has safety concerns, because RT may interfere with the device. Herein, we report a case of RT during durable LVAD management. A 48-year-old man with a durable LVAD was diagnosed with sinusitis. As his symptoms were resistant to drug therapy, endoscopic sinus surgery was performed, and extranodal NK/T-cell lymphoma, nasal type (ENKL) was pathologically detected. Since RT was the first-line treatment for ENKL, we conducted two types of irradiation experiments to determine whether RT can be safely performed in patients with durable LVADs as follows: (1) assessing the extent of the radiation levels at each site and evaluating device malfunction by irradiating the lesion sites in the patient model with the same protocol as planned, and (2) evaluating device malfunction by directly irradiating the durable LVAD equipment once at the scheduled total dose. The radiation doses at the pump, driveline, system controller, power cable, and power module of the durable LVAD reached 7.86 cGy, 6.34 cGy, 0.66 cGy, 0.38 cGy, and 0.14 cGy, respectively. In both experiments, durable LVAD malfunction or any type of alarm was not observed. We concluded that RT could be safely performed with chemotherapy in this patient and our irradiation experiments can be applied to RT for other malignancies.
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Insuficiência Cardíaca , Coração Auxiliar , Linfoma de Células T , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) typically arises from sites such as the stomach, where there is no organized lymphoid tissue. Close associations between Helicobacter pylori and gastric MALT lymphoma or Campylobacter jejuni and immunoproliferative small intestinal disease (IPSID) have been established. A subset of tumors is associated with chromosomal rearrangement and/or genetic alterations. This disease often presents as localized disease, requiring diverse treatment approaches, from antibiotic therapy to radiotherapy and immunochemotherapy. Eradication therapy for H. pylori effectively cures gastric MALT lymphoma in most patients. However, treatment strategies for H. pylori-negative gastric MALT lymphoma are still challenging. In addition, the effectiveness of antibiotic therapy has been controversial in intestinal MALT lymphoma, except for IPSID. Endoscopic treatment has been noted to usually achieve complete remission in endoscopically resectable colorectal MALT lymphoma with localized disease. MALT lymphoma has been excluded from post-transplant lymphoproliferative disorders with the exception of Epstein-Barr virus (EBV)-positive marginal zone lymphoma (MZL). We also describe the expanding spectrum of EBV-negative MZL and a close association of the disease with the gastrointestinal tract.
RESUMO
Double inferior vena cava (IVC) is known as a variation in which the additional IVC is found on the left side of the abdominal aorta. Their developmental process has been well documented, but the venous development around the lumbosacral region is controversial. In the present double IVC case, the left IVC entered the left renal vein at the L2 level, and the renal veins on each side flowed into the right IVC at the L1 level. The internal and external iliac veins were merged at the S1 level on each side. Besides, a venous communication (3-mm-width) was found horizontally between the internal iliac veins near their origin at the S1 level. It had also an extra narrow branch (1-mm-width), which ran obliquely upward and reached the left IVC at the level of L5. The median sacral artery (MSA) ran at the ventral side of the horizontal communication but at the dorsal side of its extra oblique branch. These results suggest that the oblique branch is a remnant of the anastomosis between the right and left posterior cardinal veins. Furthermore, the horizontal vein corresponds to the sacral venous plexus, suggesting that the anastomosis can be formed between the IVC and sacral venous plexus.
Assuntos
Veias Renais , Veia Cava Inferior , Aorta Abdominal , Cadáver , Humanos , Veia IlíacaRESUMO
Fetal age is estimated widely by body length and weight and skeletal or dental development and maturation. Regarding dental development, dental development charts reported by Schour and Massler and Ubelaker are well known. We tried to calculate the calcification rate of the deciduous teeth, mandibular cortical bone, and clavicle in fetuses utilizing postmortem computed tomography (CT) image analysis. The CT values within the circumferential area of the region of interest were automatically calculated using a software, and the calcification rate was calculated by performing single regression analysis. Our results showed that deciduous tooth calcification could be detected in over 19-week-old fetuses using CT images. The calcification of bones (mandibular cortical bone and clavicle) started earlier than the calcification of deciduous teeth. However, the calcification rate of the bones was slower compared to that of the deciduous teeth. The calcification rate of the deciduous teeth in fetuses using CT value may be effective to estimate fetal age and evaluate deciduous teeth development, suggesting that our established method is effective for age estimation in forensic dentistry.