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1.
J Clin Med ; 12(16)2023 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-37629454

RESUMO

Diffuse idiopathic skeletal hyperostosis (DISH) is a noninflammatory spondyloarthropathy characterized by ectopic calcification of spinal cord tissue. Its etiology is possibly polygenic. However, its pathogenesis and systemic effects remain unclear. Recent studies have reported a high prevalence of DISH in heart failure patients. The authors investigated how the incidence and severity of DISH are associated with vascular calcification and the occurrence of cardiovascular events. In this retrospective chart review study, 500 patients with cardiovascular disease who underwent surgery (cardiovascular events group) and 500 patients with non-cardiovascular disease who underwent computed tomography scans (non-cardiovascular events group) were randomly selected to investigate the degree of ossification of the anterior longitudinal ligament and the incidence of DISH. We found that the incidence of DISH was higher in patients with cardiovascular events and that patients with DISH had more calcification of the coronary arteries and aorta. Next, we examined the relationship between the degree of coronary and aortic calcification, the incidence of DISH, and the degree of ossification of the anterior longitudinal ligament in the non-cardiovascular event group. The prevalence of DISH in the cardiovascular and non-cardiovascular groups was 31.4% and 16.5%, respectively (p = 0.007). Aortic calcification and a predominant degree of vascular calcification with a certain level of ossification of the anterior longitudinal ligament suggest some correlation between DISH and cardiovascular events. This study is important in understanding the pathophysiology and pathogenesis of DISH.

2.
Cancer Rep (Hoboken) ; 6(4): e1768, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36494178

RESUMO

BACKGROUND AND AIM: Non-invasive breast carcinoma is considered to be localized disease and is distinguished from invasive ductal and lobular carcinomas. The local recurrence of non-invasive carcinoma after surgery may lead to development of invasive carcinoma and promote distant metastasis, which worsens the prognosis for breast cancer mortality. The distant metastasis of non-invasive carcinoma may involve the ductal microvasculature without invasion. The outcomes of non-invasive breast carcinoma were examined in this retrospective cohort study. METHODS AND RESULTS: Of 872 primary breast cancers diagnosed at a single center between May 2008 and March 2022, 93 (10.6%) were found to be non-invasive carcinomas and were examined in this study. The breast cancer recurrence and survival rates of patients with non-invasive carcinoma were analyzed retrospectively. The median follow-up period was 1891 (range, 5-4804) days. All patients underwent surgical treatment [mastectomy with sentinel lymph node biopsy (SLNB) and partial mastectomy with or without SLNB, tumorectomy, and microdochectomy]. Postoperatively, radiation therapy was administered to 73 (78.4%) of the patients and endocrine therapy was administered to 64 (81.0%) of 79 patients with hormone-receptor positivity. Of 26 patients who underwent partial mastectomy with SLNB, 24 (92.3%) showed isolated tumor cells in the SLNs on one-step nucleic acid amplification. Local recurrence was observed in three (0.3%) patients; no distant metastasis was observed. One patient died of a noncancerous disease. The overall survival rate was 98.0% and the breast cancer-specific survival rate was 100.0%. CONCLUSIONS: Non-invasive breast carcinoma, like invasive breast carcinoma, causes local recurrence, but has a good prognosis without distant metastasis. The clinical significance of isolated tumor cells in the SLNs as a systemic component of non-invasive breast carcinoma remains to be elucidated.


Assuntos
Neoplasias da Mama , Carcinoma Lobular , Humanos , Feminino , Neoplasias da Mama/patologia , Mastectomia , Estudos Retrospectivos , Recidiva Local de Neoplasia/patologia
3.
J Endovasc Ther ; 30(5): 676-681, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-35416069

RESUMO

PURPOSE: Postoperatively persistent type II endoleaks (T2ELs) in abdominal endovascular aneurysm repair (EVAR) are known risk factors for long-term aneurysm enlargement. Therefore, various measures have been proposed to prevent T2ELs. Notably, the Kilt technique, which can be used in patients with dumbbell-shaped morphology, employs an aortic cuff deployed in the distal seal zone before the main body. Although previous studies have successfully applied this technique for preventing T2ELs, the mid- and long-term outcomes remain unclear. This study aimed to report the early- to mid-term outcomes in cases where an aortic cuff technique was used to prevent T2ELs. MATERIALS AND METHODS: This retrospective single-center study analyzed 9 patients (mean age, 79 years; range, 69-88 years; 8 men) with abdominal aortic aneurysms. All patients underwent EVAR using an aortic cuff to prevent T2ELs. The primary end points were technical success (successful deployment) and clinical success (no T2ELs). Secondary end points included morbidity, reintervention, and aortic remodeling during follow-up. RESULTS: The technical success rate was 100%. There were no intraprocedural or postoperative complications. No deaths or reinterventions occurred. Postoperative computed tomography showed no endoleaks in 6 patients, while T2ELs from the lumbar artery outside the aortic cuff deployment range were noted in 3 patients. However, no T2ELs were observed in the artery in the aortic cuff deployment range in any patient. The average number of successfully occluded arteries was 4.2 (range, 2-8). All patients had follow-up >6 (mean, 18.6; range, 6-36) months. Aneurysm sac shrinkage occurred in 5 patients during the follow-up period, whereas aneurysm size was stable in 3 patients. In contrast, only 1 patient showed transient dilation of the aneurysm sac enlargement; however, this dilation remained unchanged even after 1.5 years. CONCLUSION: The aortic cuff technique is a favorable endovascular method for preventing T2ELs in EVAR. The present study showed that a single aortic cuff could easily and reliably occlude arteries branched from the aneurysm sac.


Assuntos
Aneurisma da Aorta Abdominal , Implante de Prótese Vascular , Procedimentos Endovasculares , Masculino , Humanos , Idoso , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/cirurgia , Aneurisma da Aorta Abdominal/complicações , Correção Endovascular de Aneurisma , Estudos Retrospectivos , Procedimentos Endovasculares/efeitos adversos , Implante de Prótese Vascular/efeitos adversos , Resultado do Tratamento , Endoleak/diagnóstico por imagem , Endoleak/etiologia , Endoleak/prevenção & controle , Fatores de Risco
4.
Cancer Rep (Hoboken) ; 6(1): e1643, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35655440

RESUMO

BACKGROUND: Recurrence after primary treatment is an important obstacle to the curing of primary breast cancer. Less-immunosuppressive anesthetic techniques, such as local anesthesia with lidocaine, intravenous anesthesia (IVA) with propofol, and/or sedation with midazolam under spontaneous breathing may reduce breast cancer recurrence compared with standard general anesthesia techniques such as IVA and inhalation anesthesia with opioids under mechanical ventilation. AIM: The aim of this study was to analyze the factors involved in breast cancer recurrence in patients who underwent breast-conserving surgery (BCS) under non-mechanically ventilated anesthesia. METHODS: The study included 491 consecutive patients with stages 0-III breast cancer who underwent BCS/axillary lymph-node management with local anesthesia and IVA and/or sedation under non-mechanical ventilation between May 2008 and September 2021. Survival and recurrence were assessed by retrospective cohort analysis. RESULTS: The median follow-up period was 2565 days (range, 28-4834 days). The overall and breast cancer-specific survival rates were 92.9% and 95.6%, respectively. Twenty-one deaths, of which 11 were breast cancer-related, occurred. Disease recurred in 29 (5.9%) patients, of whom 15 patients received neoadjuvant chemotherapy (NAC) and 14 patients received adjuvant therapy (chemotherapy in 12 cases). The surgical procedure performed, but not other clinicopathological factors [recurrence site, P stage, tumor subtype, and disease-free interval (DFI)], differed between the NAC and adjuvant therapy groups. The DFI tended to be shorter in the NAC group than in the adjuvant therapy group. The pathological therapeutic effect grade after NAC was 1 in 12 patients and ≥2 in 3 patients. CONCLUSION: More than 50% (15/29) of patients with recurrence who underwent BCS were given NAC, but most patients did not respond to it. Similarly, adjuvant chemotherapy may not have contributed to the eradication of residual tumor cells after BCS. To reduce breast cancer recurrence in patients undergoing BCS, treatment strategies, especially for patients who do not respond to NAC or adjuvant chemotherapy, need to be developed. Non-mechanical ventilation anesthesia may also affect the incidence of breast cancer recurrence.


Assuntos
Anestesia , Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/cirurgia , Neoplasias da Mama/tratamento farmacológico , Mastectomia Segmentar , Estudos Retrospectivos , Taxa de Sobrevida
5.
J Artif Organs ; 25(2): 117-124, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34689296

RESUMO

Hematocrit (Hct) values after the initiation of cardiopulmonary bypass (CPB) must be maintained appropriately to avoid perioperative complications. Therefore, an accurate prediction is required. However, the standard prediction equation often results in actual values that are lower than the predicted values. This study aimed to clarify the limits of agreement (LOA) and bias of the prediction equations and investigate better the prediction equations. A retrospective study was performed on adult patients between April 2015 and December 2020. Study 1 included 158 patients, and Study 2 included 55 patients. The primary outcomes were the LOA and bias between the predicted and measured Hct values after the initiation of CPB, and two studies were conducted. In Study 1, total blood volume (TBV) was estimated, and the new blood volume index (BVI) was calculated. BVI was also evaluated for the overall value and gender differences. Therefore, the patient's background was compared by gender differences. In, Study 2 the conventional predicted equation (Eq. 1), the predicted equation using the new BVI (Eq. 2), and the predicted equation using the new BVI including physiological factors in the TBV equation (Eq. 3) were compared. In Study 1, BVI was 53 (44-67) mL/kg. In Study 2, bias ± LOA was - 2.5 ± 6.8% for Eq. 1, 0.1 ± 6.6% for Eq. 2, and 0.4 ± 6.2% for Eq. 3. The new equation is expected to predict the Hct value after the initiation of CPB with better LOA and bias than the conventional equation.


Assuntos
Volume Sanguíneo , Ponte Cardiopulmonar , Adulto , Volume Sanguíneo/fisiologia , Ponte Cardiopulmonar/efeitos adversos , Hematócrito , Humanos , Estudos Retrospectivos
6.
Mod Rheumatol ; 32(5): 946-952, 2022 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34918126

RESUMO

OBJECTIVES: We encountered the case in whom the results of autoantibodies tests became transiently positive after high-dose immunoglobulin therapy and investigated the effect of administration of these preparations on autoantibodies tests in subjects with autoimmune diseases who had received high-dose immunoglobulin therapy. METHODS: We measured the autoantibodies in residual serum samples after routine clinical testing from eight subjects with autoimmune diseases who had received high-dose immunoglobulin therapy. We also measured the autoantibodies in available immunoglobulin preparations. RESULTS: Tests for autoantibodies conducted before and after immunoglobulin therapy revealed a positive conversion of the results for anti-Sjogren's syndrome antigen A (SS-A) antibody, anti-glutamic acid decarboxylase (GAD) antibody, anti-thyroglobulin (Tg) antibody, and anti-thyroid peroxidase (TPO) antibody. In five cases in which changes in the antibody titres of anti-SS-A antibody after the high-dose immunoglobulin administration, it was found that the titres decreased by about 50% from 10 to 20 days after and the test result became negative 25- 30 days later. CONCLUSIONS: In patients receiving high-dose immunoglobulin therapy, there appears to be a high likelihood of positive conversion of tests for anti-SS-A antibody, GAD antibody, Tg antibody, and TPO antibody after the treatment, so that cautious interpretation of the results is of importance.


Assuntos
Doenças Autoimunes , Síndrome de Sjogren , Autoanticorpos , Humanos
8.
J Cardiothorac Surg ; 16(1): 219, 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34348745

RESUMO

BACKGROUND: There are a lot of reports of the renal failure and heart failure due to coarctation of the aorta. However, there are no case reports in which revascularization dramatically improved left ventricular function in patients with progressive decline in left ventricular function. Herein, we present a rare case in which the left ventricular function was dramatically improved by surgical treatment for progressive left ventricular dysfunction due to atypical coarctation of the aorta. CASE PRESENTATION: A 58-year-old man underwent left axillary artery-bilateral femoral artery bypass at another hospital for atypical coarctation of the aorta due to Takayasu's arteritis. Approximately 10 years later, he was re-hospitalized for heart failure, and the left ventricular ejection fraction gradually decreased to 28%. Computed tomography showed severe calcification and stenosis at the same site from the peripheral thoracic descending aorta to the lower abdominal aorta of the renal artery, and aortography showed delayed bilateral renal artery blood flow. An increase in plasma renin activity was also observed. Despite the administration of multiple antihypertensive drugs, blood pressure control was insufficient. We decided to perform surgical treatment to improve progressive cardiac dysfunction due to increased afterload and activated plasma renin activity. Descending thoracic aorta-abdominal aorta bypass and revascularization of the bilateral renal arteries via the great saphenous vein grafts were performed. Postoperative blood pressure control was improved, and the dose of antihypertensive drugs could be reduced. Plasma renin activity decreased, and transthoracic echocardiography 1.5 years later showed an improvement in contractility with a left ventricular ejection fraction of 58%. CONCLUSION: In atypical coarctation of the aorta in patients with decreased bilateral renal blood flow, heart failure due to renal hypertension, and progressive decrease in left ventricular contractility, descending thoracic aorta-abdominal aortic bypass and bilateral renal artery recirculation can be extremely effective.


Assuntos
Aorta Abdominal , Coartação Aórtica , Insuficiência Cardíaca , Arterite de Takayasu , Antagonistas de Receptores de Angiotensina , Inibidores da Enzima Conversora de Angiotensina , Aorta Abdominal/diagnóstico por imagem , Aorta Abdominal/cirurgia , Aorta Torácica/diagnóstico por imagem , Aorta Torácica/cirurgia , Coartação Aórtica/complicações , Coartação Aórtica/diagnóstico por imagem , Coartação Aórtica/cirurgia , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Circulação Renal , Volume Sistólico , Arterite de Takayasu/complicações , Arterite de Takayasu/cirurgia , Função Ventricular Esquerda
9.
mSphere ; 6(2)2021 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-33692195

RESUMO

Genomic analysis revealed that the vaccine seed lot of Mycobacterium bovis bacillus Calmette-Guérin (BCG) Tokyo 172 contains two subclones (types I and II), but their phenotypic differences have not been elucidated. In this study, we compared the susceptibility of bacilli types I and II to oxidative stress in vitro and within host cells. Notably, the subclones displayed similar superoxide dismutase activity; however, foam height in the catalase test and lysate catalase/peroxidase activity were higher for type I bacilli than for type II bacilli. Additionally, type I bacilli were less susceptible to hydrogen peroxide (H2O2) than type II bacilli. After exposure to H2O2, antioxidative stress response genes katG, ahpC, sodA, and trxA were more strongly induced in type I bacilli than in type II bacilli. Further, we investigated cell survival in macrophages. Fewer type II bacilli were recovered than type I bacilli. However, in the presence of apocynin, a specific inhibitor of NADPH oxidase, type II recovery was greater than that of type I. The production of interleukin 1ß (IL-1ß), IL-12 p40, and tumor necrosis factor alpha (TNF-α) was higher in type I bacillus-infected macrophages than in type II bacillus-infected macrophages. The proportions of type I and type II bacilli in vaccine lots over 3 years (100 lots) were 97.6% ± 1.5% and 2.4% ± 1.5%, respectively. The study results illustrated that type I bacilli are more resistant to oxidative stress than type II bacilli. Overall, these findings provide important information in terms of the quality control and safety of BCG Tokyo 172 vaccine.IMPORTANCE This study revealed the difference of in vivo and in vitro antioxidative stress properties of BCG Tokyo 172 types I and II as one of the bacteriological characteristics. In particular, the bacilli exhibited differences in catalase/peroxidase activity, which could explain their different protective effects against infection. The differences correlated with survival in the host cell and the production of proinflammatory cytokines to protect against infection by Mycobacterium tuberculosis The proportion of bacilli types I and II in all commercial lots of BCG Tokyo 172 over 3 years (100 lots) was constant. The findings also highlighted the importance of analyzing their content for quality control during vaccine production.


Assuntos
Peróxido de Hidrogênio/farmacologia , Macrófagos/microbiologia , Mycobacterium bovis/efeitos dos fármacos , Mycobacterium bovis/genética , Estresse Oxidativo/efeitos dos fármacos , Animais , Vacina BCG/imunologia , Citocinas/imunologia , Genoma Bacteriano , Humanos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Camundongos , Mycobacterium bovis/classificação , Mycobacterium tuberculosis/imunologia , Células RAW 264.7 , Células THP-1 , Tóquio , Tuberculose/imunologia , Tuberculose/microbiologia , Tuberculose/prevenção & controle
10.
Eur J Cardiothorac Surg ; 60(1): 164-174, 2021 07 14.
Artigo em Inglês | MEDLINE | ID: mdl-33517384

RESUMO

OBJECTIVES: Ischaemic spinal cord injury (SCI) is one of the most serious complications of aortic surgery. Ischaemic SCIs occur due to various aetiologies, and prediction of the risk is difficult. Magnetic resonance imaging (MRI) is useful to detect the details of spinal cord infarction. There are few studies about MRI for evaluating ischaemic SCI after cardiovascular surgery and aortic events. We report 9 cases of postoperative ischaemic SCI and analyse their MRI features. METHODS: T2-weighted MRI scans of 9 patients who developed ischaemic SCI due to cardiovascular surgery and aortic events between 2012 and 2017 were evaluated. RESULTS: In all patients, high-intensity areas were observed on T2-weighted magnetic resonance images. The site of infarction was the thoracic spinal cord level (9 cases) and additionally at the lumbar spinal cord level (5 cases). The area of infarction area was categorized based on the arterial territory: anterior spinal artery territory (3 cases), posterior spinal artery territory (2 cases), spinal sulcal artery territory (1 case) and artery of Adamkiewicz territory (3 cases). CONCLUSIONS: MRI revealed the infarction sites in all cases and the differences in the infarction patterns in each case. MRI could thus be useful for investigating the aetiology of ischaemic SCI following aortic surgeries and events.


Assuntos
Traumatismos da Medula Espinal , Isquemia do Cordão Espinal , Humanos , Infarto , Imageamento por Ressonância Magnética , Medula Espinal/diagnóstico por imagem , Isquemia do Cordão Espinal/diagnóstico por imagem , Isquemia do Cordão Espinal/etiologia
11.
Transl Oncol ; 14(1): 100927, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33157515

RESUMO

Immune activation plays an important role in achieving the pathological and therapeutic effects of preoperative chemotherapy in patients with breast cancer. We evaluated how the immune response contributes to various therapeutic effects. This study was conducted on 43 patients with stages II-IV breast cancer who received preoperative chemotherapy followed by surgery. Peripheral natural killer (pNK) cell activity and the neutrophil-lymphocyte ratio, lymphocyte-monocyte ratio, and platelet-lymphocyte ratio (PLR) were assessed before and after chemotherapy. Tumor-infiltrating lymphocytes (TILs) and levels of 14 tumor microenvironmental factors, analyzed by next-generation sequencing, were assessed in formalin-fixed, paraffin-embedded sections of preoperative biopsy samples and surgical specimens. Univariate analysis showed that grade 2 (G2) and better therapeutic effects were significantly associated with human epidermal growth factor receptor 2 (HER-2)-positive cancer, lower PLRs, and higher NK cell and interleukin-6 levels after chemotherapy. The disappearance of axillary lymph-node metastasis was significantly associated with HER-2-positive cancer; increased pNK cell activity and lower PLRs and vascular endothelial growth factor (VEGF) levels after chemotherapy; and increased cytotoxic T lymphocyte antigen 4 (CTLA-4) levels in regulatory T cells (Tregs) and ≥5% TILs before chemotherapy. Multivariate analysis showed that G2 and better therapeutic effects tended to be associated with higher NK cell levels after chemotherapy (odds ratio = 1.02; 95% confidence interval, 0.99-1.05; P = 0.07). The activation of local and systemic immune responses by downregulation of immunosuppressive factors, such as VEGF and CTLA-4 in Tregs, had variable pathological and therapeutic effects after preoperative chemotherapy in patients with breast cancer.

12.
Ann Med Surg (Lond) ; 60: 365-371, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33224492

RESUMO

The use of general anesthesia (GA) with inhalational anesthetics for breast cancer surgery may be associated with breast cancer recurrence and increased mortality due to the immunosuppressive effects of these drugs. Less-immunosuppressive anesthetic techniques may reduce breast cancer recurrence. We evaluated the feasibility, safety, and efficacy of outpatient breast-conserving surgery (BCS) for breast cancer in a breast clinic in terms of the anesthetic technique used, complications occurring, recurrence, and survival. Methods: The sample comprised 456 consecutive patients with stage 0-III breast cancer who underwent BCS/axillary lymph node (ALN) management using local and intravenous anesthesia and/or sedation between May 2008 and January 2020. Most patients received adjuvant chemotherapy and/or endocrine therapy and radiotherapy after surgery. Patient outcomes were evaluated retrospectively. Results: All patients recovered and were discharged after resting for 3-4 h postoperatively. No procedure-related severe complication or death occurred. Sixty-four complications (14.0%) were observed: 14 wound infections, 17 hematomas, and 33 axillary lymphoceles. The median follow-up period was 2259 days (range, 9-4190 days), during which disease recurrence was observed in 25 (5.4%) patients. The overall survival and breast cancer-specific survival rates were 92.3% and 94.7%, respectively. Conclusions: Outpatient surgery for breast cancer involving BCS and ALN management under local and intravenous anesthesia and/or sedation can be performed safely, without serious complication or death. Less-immunosuppressive anesthetic techniques with spontaneous breathing may reduce the recurrence of breast cancer and improve survival relative to GA.

13.
Brain Res ; 1747: 147040, 2020 11 15.
Artigo em Inglês | MEDLINE | ID: mdl-32771405

RESUMO

Ischemic spinal cord injury (iSCI) is a devastating complication of aortic surgery, with few strategies for prevention. Intravenous infusion of mesenchymal stem cells (MSCs) for iSCI has been shown to provide functional improvement through protection of gray matter. The purpose of this study was to investigate additional mechanisms which may exert therapeutic efficacy in iSCI. Severe iSCI was created to occlude the descending aorta, which was cross-clamped 5 mm distal to the left subclavian artery for 16 min. One day after iSCI induction, iSCI rats were randomized into two groups: one received intravenous infusion of MSCs (MSC-group), the other received vehicle (no cells; vehicle-group). Locomotor function and in vivo MRI were recorded. H&E, Nissl and toluidine blue stainings, immunohistochemical analysis, diffusion tensor imaging (DTI), and the assessment of blood-spinal cord barrier (BSCB) stability were performed. MSC treated animals exhibited gradual improvement in hind-limb locomotor function during the 4-week study period; however the vehicle-treated group displayed persistent motor deficits. In the MSC-treated group we observed the protection of white and gray matter volume reduction of axonal and neuronal loss or degeneration and preservation of microvasculature including BSCB function. Intravenous infusion of MSCs may provide therapeutic efficacy to improve functional outcomes in a rat model of severe iSCI via protection of white and gray matter.


Assuntos
Substância Cinzenta/patologia , Células-Tronco Mesenquimais , Atividade Motora/fisiologia , Isquemia do Cordão Espinal/terapia , Substância Branca/patologia , Administração Intravenosa , Animais , Modelos Animais de Doenças , Substância Cinzenta/diagnóstico por imagem , Imageamento por Ressonância Magnética , Ratos , Isquemia do Cordão Espinal/diagnóstico por imagem , Isquemia do Cordão Espinal/patologia , Substância Branca/diagnóstico por imagem
14.
Metallomics ; 12(6): 868-875, 2020 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-32315022

RESUMO

Copper (Cu) is an essential trace element and acts as a redox cofactor for many enzymes; however, excess Cu is toxic to cells. Hydrogen sulfide (H2S) is a well-known toxic gaseous molecule, but it has various biological effects such as neuromodulation and vasodilation. H2S was recently demonstrated to be involved in the detoxification of heavy metals, including zinc and cadmium, suggesting that H2S helps to maintain the homeostasis of heavy metals in cells. However, it is unclear how H2S impacts cellular Cu dynamics. In this study, we examined the effects of H2S on Cu cytotoxicity. Human neuroblastoma SH-SY5Y cells were exposed to CuSO4 in the presence of the H2S donor NaHS. CuSO4 alone slightly induced cell injury, whereas the combination of CuSO4 and NaHS (Cu/NaHS) increased Cu cytotoxicity. The Cu chelator bathocuproinedisulfonic acid mitigated Cu/NaHS-induced cytotoxicity. Compared with CuSO4 alone, Cu/NaHS markedly promoted ROS generation, mitochondrial dysfunction, and a decrease in ATP production. In addition, reporter assay using the metal responsive element (MRE)-driven reporter plasmid revealed that Cu/NaHS augmented Cu-dependent MRE activation. The amount of intracellular Cu was significantly higher in cells treated with Cu/NaHS than in those treated with CuSO4 alone. Moreover, Cu/NaHS markedly suppressed the level of the Cu exporter ATP7A, but not ATP7B, protein, whereas the combination did not affect that of the Cu importer CTR1 protein. Taken together, we conclude that the marked decrease in the ATP7A protein level by Cu/NaHS promotes intracellular Cu accumulation and leads to increased Cu cytotoxicity.


Assuntos
Trifosfato de Adenosina/metabolismo , Cobre/metabolismo , Sulfeto de Hidrogênio/metabolismo , Animais , Humanos , Metais Pesados/metabolismo , Transdução de Sinais , Sulfetos/metabolismo
15.
Eur J Surg Oncol ; 46(1): 77-84, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31563296

RESUMO

PURPOSE: To evaluate immune responses paralleling the pathological and therapeutic effects of neoadjuvant chemotherapy (NAC) in the tumor microenvironment of breast cancer. PATIENTS AND METHODS: 38 patients with stages II and III breast cancer received NAC followed by surgery in 2012-2018. Peripheral natural killer (pNK) cell activity, tumor-infiltrating lymphocytes (TILs), and levels of tumor microenvironmental factors were assessed before and after NAC. RESULTS: In univariate analysis, grade 2 (G2) and better therapeutic effects were significantly associated with high post-NAC levels of NK cells and interleukin-6, and tended to be associated with higher CD4, CD8 and CTLA-4 transcripts. Disappearance of axillary lymph node metastasis (Ax+) was significantly associated with 1) increased NK and pNK levels, 2) decreased vascular endothelial growth factor (VEGF) transcripts after NAC, 3) the presence of ≥5% TILs, and tended to be associated with higher CTLA-4 levels before NAC. Multivariate analysis showed that G2 and better therapeutic effects were significantly associated with higher NK levels after NAC (OR = 1.07, 95% CI 1.00-1.14; p = 0.0255), and that disappearance of Ax+ was significantly associated with the presence of ≥5% pre-NAC TILs (OR = 19.87, 95% CI 2.24-175.80; p = 0.0072). CONCLUSIONS: Increased NK cells after NAC, together with increased CD4+ and CD8+ T-cells, and decreased CTLA-4+ T cells and VEGF correlate with beneficial therapeutic effects. Systemic activation of pNK cell activity and the presence of pre-NAC TILs may improve the elimination of Ax + together with decreased immunosuppression by VEGF in tumors.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/imunologia , Quimioterapia Adjuvante , Microambiente Tumoral/imunologia , Adulto , Idoso , Biomarcadores Tumorais/sangue , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Terapia Neoadjuvante , Gradação de Tumores , Estadiamento de Neoplasias
16.
Gen Thorac Cardiovasc Surg ; 68(3): 290-294, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30632025

RESUMO

We present two consecutive patients with secondary aortoesophageal fistula (AEF) who successfully underwent total repair including partial esophagectomy, removal of infected vascular prosthesis, graft replacement, and esophageal reconstruction using gastric tube concomitant to omental wrapping for staged operation in short phase. One 81-year-old male who had undergone thoracic endovascular aortic repair and another 69-year-old male who had undergone graft replacement of the descending thoracic aorta were referred to our hospital for treatment of AEF. In the first operation, partial esophagectomy, removal of infected vascular prosthesis, and graft replacement were performed via left rib-cross thoracotomy. About half a day after the operation when the patients became hemodynamically stable, esophageal reconstruction was started. The gastric tube was prepared via median laparotomy and introduced to the left thoracic cavity with the omentum through the enlarged hiatus. Thereafter, the gastric tube was anastomosed to the oral side of the esophageal stump via left thoracotomy with the same wound similar to the first operation. Finally, the graft positioned parallel to the gastric tube was completely wrapped by the omentum. Both patients could ingest orally 4 weeks after surgery and maintained no recurrence of infection.


Assuntos
Aorta Torácica/cirurgia , Doenças da Aorta/cirurgia , Implante de Prótese Vascular , Prótese Vascular , Fístula Esofágica/cirurgia , Fístula Vascular/cirurgia , Idoso , Idoso de 80 Anos ou mais , Aneurisma da Aorta Torácica/cirurgia , Fístula Esofágica/complicações , Esofagectomia , Humanos , Masculino , Omento/transplante , Toracotomia
18.
J Card Surg ; 34(3): 143-146, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30742333

RESUMO

A 74-year-old man had undergone two-vessel coronary artery bypass grafting (CABG), 19 years ago, with the left internal mammary artery (LITA) to the left anterior descending artery and the saphenous vein graft (SVG) to the posterior descending artery. In outpatient care, a thoracic aortic aneurysm was suspected by the chest X-ray. In the computed tomography, appeared the distal arch aortic aneurysm, abdominal aortic aneurysm (AAA), and giant right coronary artery aneurysm (rCAA). The diameter of rCAA was 70 mm and it oppressed the right atrium and ventricle of the heart. The patient was referred to our hospital. After the initial treatment of distal arch aneurysm and AAA, surgical treatment for the rCAA was performed. The rCAA was resected completely and CABG with new SVG was performed without cardiopulmonary bypass. The histopathology of rCAA wall revealed that the etiology was an atherosclerotic change. The postoperative course was good, the oppressed right heart system was released and the hemodynamics of the tricuspid valve showed improvement.


Assuntos
Aneurisma Coronário/cirurgia , Ponte de Artéria Coronária/métodos , Vasos Coronários/cirurgia , Idoso , Aneurisma da Aorta Abdominal/diagnóstico por imagem , Aneurisma da Aorta Abdominal/cirurgia , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/cirurgia , Aneurisma Coronário/diagnóstico por imagem , Aneurisma Coronário/etiologia , Doença da Artéria Coronariana/complicações , Vasos Coronários/diagnóstico por imagem , Humanos , Masculino , Veia Safena/transplante , Tomografia Computadorizada por Raios X , Resultado do Tratamento
19.
Cancer Immunol Immunother ; 68(4): 577-585, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30673828

RESUMO

Tumor-infiltrating lymphocytes are an important prognostic factor after neoadjuvant chemotherapy (NAC) in patients with breast cancer. Natural killer (NK) cells play critical roles in antitumor immune surveillance. Here, we assessed the relationship between peripheral natural killer (pNK) cell activity, tumor microenvironmental factors (TMEFs), and the therapeutic efficacy of preoperative chemotherapy in patients with breast cancer. In a cohort of 39 patients diagnosed with stage II-IV breast cancer who received NAC, we measured pNK cell activity by chromium release assay and assessed TMEF levels by next-generation sequencing. Following NAC, pNK cell activity was increased in 24/39 patients but decreased in 15/39 patients. Increased pNK cell activity following preoperative chemotherapy was associated significantly with the disappearance of axillary lymph node metastasis (Ax+; p = 0.0235). Increased pNK cell activity remained significantly associated with the disappearance of Ax+ in multivariate logistic regression analysis (OR 5.41, 95% CI 1.19-24.52, p = 0.0283). A Grade 2 or higher effect of NAC was associated with high pre-NAC cytotoxic T lymphocyte-associated protein 4 (CTLA-4) levels (p = 0.0281) and elevated post-NAC NK (p = 0.0005) cells and transforming growth factor-beta (TGF-ß; p = 0.0350) levels. The disappearance of Ax+ was associated with high pre-NAC CTLA-4 levels (p = 0.0278) and elevated CD4 levels after NAC (p = 0.0250). The systemic activation of pNK cells after NAC may improve metastatic tumor elimination in patients with breast cancer owing to a release from local immunosuppression, and immune activation in the tumor microenvironment.


Assuntos
Neoplasias da Mama/imunologia , Neoplasias da Mama/terapia , Células Matadoras Naturais/imunologia , Adulto , Idoso , Biomarcadores , Biomarcadores Tumorais , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Feminino , Expressão Gênica , Humanos , Células Matadoras Naturais/metabolismo , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Cuidados Pré-Operatórios , Resultado do Tratamento , Microambiente Tumoral
20.
Interact Cardiovasc Thorac Surg ; 28(4): 629-634, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30364942

RESUMO

OBJECTIVES: Some patients achieve complete recovery through false lumen remodelling in the descending aorta after surgery for acute type A aortic dissection. Our goal was to investigate the relationship between false lumen remodelling during later postoperative stages and quantitative analysis of the true lumen shape during the early postoperative stages. METHODS: We examined 88 surgical patients between January 2007 and December 2016. Three points of the descending aorta were assessed from the 6th (T6), the 9th (T9) and the 11th (T11) vertebral levels. The shape of the true lumen was evaluated during the early postoperative stages, and false lumen remodelling 1 year after surgery was the end point. The parameters obtained by evaluating the shape of the true lumen comprised the first principal component analysis using elliptic Fourier analysis, the minor diameter ratio and the ratio of the area of the true lumen to that of the descending aorta, and the number of contact points on the true lumen wall during the early stages. RESULTS: Using univariate analysis, we detected significant differences in the first principal components, the minor diameter ratio, the area ratio and the number of contact points at each thoracic vertebral level (P < 0.05). The cut-off value of the minor diameter ratio was 0.55, and the area ratio was 0.48 as determined by analysis of the receiver operating characteristic. Multivariable logistic analysis indicated that the first principal component was the most significant predictor from the proximal to the middle descending aorta. CONCLUSIONS: Quantitative evaluation of shape of the true lumen in the early postoperative stages after surgery for acute type A dissection can serve as a viable predictor for false lumen remodelling in later stages. Furthermore, the first principal component could serve as a more astute predictor than other quantitative parameters according to multivariate analysis.


Assuntos
Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/diagnóstico , Dissecção Aórtica/diagnóstico , Implante de Prótese Vascular/métodos , Procedimentos Endovasculares/métodos , Remodelação Vascular/fisiologia , Idoso , Dissecção Aórtica/fisiopatologia , Dissecção Aórtica/cirurgia , Aorta Torácica/fisiopatologia , Aorta Torácica/cirurgia , Aneurisma da Aorta Torácica/fisiopatologia , Aneurisma da Aorta Torácica/cirurgia , Feminino , Humanos , Masculino , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
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