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The deposition of α-synuclein (α-Syn) fibrils in neuronal cells has been implicated as a causative factor in Parkinson's disease (PD) and dementia with Lewy Bodies (DLB). α-Syn can be degraded by autophagy, proteasome, and chaperone-mediated autophagy, and previous studies have suggested the potency of certain cathepsins, lysosomal proteases, for α-Syn degradation. However, no studies have comprehensively evaluated all cathepsins. Here, we evaluated the efficacy of all 15 cathepsins using a cell model of α-Syn fibril propagation and found that overexpression of cathepsin L (CTSL) was the most effective in preventing the accumulation of α-Syn aggregates. CTSL-mediated degradation of α-Syn aggregates was dependent on the autophagy machinery, and CTSL itself promoted autophagy flux. Interestingly, CTSL was effective in autophagic degradation of wild-type (WT) α-Syn, but not in the case of A53T and E46K missense mutations, which are causative for familial PD. These results suggest that CTSL is a potential therapeutic strategy for sporadic PD pathology in WT α-Syn.
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Doença de Parkinson , alfa-Sinucleína , Humanos , alfa-Sinucleína/genética , alfa-Sinucleína/metabolismo , Catepsina L/genética , Catepsina L/metabolismo , Doença de Parkinson/metabolismo , Mutação de Sentido Incorreto , Complexo de Endopeptidases do Proteassoma/metabolismoRESUMO
INTRODUCTION AND HYPOTHESIS: This study evaluated the association between pelvic organ prolapse (POP), frailty, and sarcopenia to explore how POP treatment can extend healthy life expectancy in elderly women. METHODS: We conducted a retrospective study of prospectively collected data, comparing women with mild POP (stages 0-II) with those with advanced POP (stages III and IV). The inclusion criteria for this study were women who visited the clinic with at least one symptom of pelvic floor dysfunction and underwent imaging studies between April 2020 and November 2022. Initially, 119 patients met these inclusion criteria. Patients were excluded if they had a history of previous POP treatment, did not respond to the study survey, or were lost to follow-up. After applying these exclusion criteria, 82 patients were included in the final analysis, of whom 65 underwent surgery (laparoscopic sacrocolpopexy, colpocleisis, tension-free vaginal tape, and native tissue repair). Assessments included POP Quantification, Kihon Checklist, Pelvic Organ Prolapse Quality of Life (P-QOL) questionnaire, International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score (OABSS), and Incontinence Symptom Questionnaire (ICIQ-SF). Pelvic muscles were measured using MRI or CT. Immunohistochemical analysis of estrogen receptor alpha (ERα), estrogen receptor beta , and androgen receptor was performed on surgical specimens from 43 patients. RESULTS: The median age of participants was 75 years. Of the 82 patients, 48 (58.5%) were classified as frail or pre-frail, and 22 (26.8%) exhibited motor impairment. Advanced POP (stages 3 and 4) was seen in 41 patients. These patients had more motor function impairments (advanced, 16; mild, 6; p = 0.01). Patients with advanced POP had poorer P-QOL, ICIQ-SF (median: 9.5 vs 4, p = 0.006) and OABSS (7 vs 4, p = 0.008) scores, and smaller pubococcygeus muscle diameter (2.5 vs 3 cm, p = 0.017). Postoperatively, significant improvements were seen in P-QOL (all domains except personal relationships: p < 0.001), total IPSS (11 vs 4, p < 0.001), OABSS (6 vs 5, p = 0.033), and ICIQ-SF scores (6 vs 2, p < 0.001). ERα expression was associated with preoperative frailty (r = -0.37, p = 0.014). CONCLUSIONS: Advanced POP correlates with poorer QOL, worse urinary symptoms, and reduced pubococcygeus muscle diameter, consistent with sarcopenia, compared with mild POP.
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BACKGROUND: Although the second-generation androgen receptor inhibitors and taxanes have recently been recommended for the initial treatment of metastatic prostate cancer, bicalutamide and flutamide are still used in a large number of cases. Therefore, it is important to elucidate the clinical characteristics of these treated CRPC cases and their sensitivity to the currently used therapeutic agents. We aimed to examine the outcomes of metastatic castration-resistant prostate cancer following combined androgen blockade as initial therapy at our institution. METHODS: Ninety-four patients who developed metastatic castration-resistant prostate cancer after hormonal treatment with combined nonsteroidal androgen receptor antagonists and continuous androgen deprivation therapy between January 2015 and December 2020 were included. The presence of visceral metastases, duration of efficacy of each treatment, and overall survival after castration-resistant prostate cancer were evaluated. RESULTS: Patients with a longer duration of castration-resistant prostate cancer tended to have a longer response duration to subsequent enzalutamide administration (p = 0.003). Patients who achieved a 90% reduction in prostate-specific antigen levels with enzalutamide had a significantly better castration-resistant prostate cancer prognosis (p = 0.002). Meanwhile, those with visceral metastases at the time of castration-resistant prostate cancer diagnosis had a significantly poorer prognosis (p < 0.001). A positive correlation was observed between the treatment efficacy of abiraterone and taxanes for castration-resistant prostate cancer. CONCLUSION: The study provides scientific evidence to support that patients with longer time to castration-resistant prostate cancer are more sensitive to enzalutamide, and the use of abiraterone between docetaxel and cabazitaxel has favorable prognostic impact. These findings provide instrumental evidence that can enable better treatment selection for prostate cancer patients.
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Androgênios , Neoplasias de Próstata Resistentes à Castração , Masculino , Humanos , Neoplasias de Próstata Resistentes à Castração/patologia , Antagonistas de Androgênios/uso terapêutico , Taxoides , Resultado do Tratamento , Antígeno Prostático Específico , Receptores AndrogênicosRESUMO
BACKGROUND: This study aimed to assess initial results and patient characteristics of prostatic urethral lift (PUL) compared with those of bipolar transurethral enucleation of the prostate (TUEB) in the treatment of benign prostatic hyperplasia (BPH) in older patients. METHODS: This retrospective study was conducted at a single institution and involved 25 consecutive patients with BPH who underwent PUL between April 2022 and May 2023. Patient characteristics, operative details, and pre- and postoperative symptom scores were evaluated. The results were compared with those of a previously reported TUEB group (n = 55). RESULTS: The mean age of the patients in the PUL group was 74.6 years, and the mean prostate volume was 47.5 ml. The PUL procedure significantly improved urinary symptoms, particularly incomplete emptying (p = 0.041), intermittency (p = 0.005), and weak stream (p = 0.001). The PUL group had higher comorbidity scores (p = 0.048) and included older patients (p = 0.002) than the TUEB group. TUEB showed better improvements in some symptoms and maximum flow rate (p = 0.01) than PUL; however, PUL had a shorter operative time and fewer complications than TUEB (p < 0.001). CONCLUSION: The initial results demonstrate the efficacy and safety of PUL in older patients with BPH. Despite TUEB showing better outcomes in certain aspects than PUL, PUL offers advantages such as shorter operative time and fewer complications. Therefore, PUL can be considered a viable option for high-risk older patients with BPH.
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Hiperplasia Prostática , Ressecção Transuretral da Próstata , Masculino , Humanos , Idoso , Próstata/cirurgia , Estudos Retrospectivos , Hiperplasia Prostática/complicações , Ressecção Transuretral da Próstata/métodos , Qualidade de Vida , Resultado do TratamentoRESUMO
BACKGROUND: Residual regurgitation after transcatheter edge-to-edge mitral valve repair (TMVR) is a predictor of poor prognosis in patients with functional mitral regurgitation (FMR). This study sought to identify the mitral valve (MV) parameters measured by three-dimensional transesophageal echocardiography (3D-TEE) and MV leaflet features that predict residual mitral regurgitation (MR) after TMVR in patients with FMR. METHODS: Consecutive patients with FMR who underwent TMVR were classified into two groups based on the degree of residual MR just after TMVR: < 2+ in the optimal MR reduction group and ≥ 2+ in the suboptimal MR reduction group. The two groups were compared with respect to 3D-TEE parameters and the MV leaflet features, including the following parameters: stiffness, defined as a leaflet that remains at a fixed angle even during diastole, and thickness, measured in both clear and rough zones. RESULTS: Thirty-four of 46 patients (74%) were classified as the optimal MR reduction group. Multivariable analysis showed that anterior mitral leaflet + posterior mitral leaflet length/anteroposterior annulus diameter (p = .044) and MV leaflet stiffness (p = .007) were independent predictors of residual MR. CONCLUSION: MV leaflet stiffness and the ratio of MV leaflet lengths to the annulus diameter may be good predictors of residual MR after TMVR in patients with FMR.
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Procedimentos Cirúrgicos Cardíacos , Ecocardiografia Tridimensional , Implante de Prótese de Valva Cardíaca , Insuficiência da Valva Mitral , Humanos , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/cirurgia , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Ecocardiografia Tridimensional/métodos , Ecocardiografia Transesofagiana/métodos , Resultado do TratamentoRESUMO
Distal transradial access (dTRA) is a novel alternative to conventional radial artery access for coronary catheterization. However, the feasibility and safety of repeated use of dTRA have not been fully elucidated. This study aimed to evaluate the feasibility and safety of the repeated use of dTRA for coronary angiography and intervention in the same arm. A total of 1717 patients underwent angiography or angioplasty via dTRA. We retrospectively analyzed the catheterization records of patients who underwent repeated puncture of the distal radial artery in the same arm. The incidence of successive applications of dTRA and the reasons for dropout were retrospectively investigated. A total of 416 patients, including three who underwent coronary catheterization with the bilateral dTRA in the initial attempt were analyzed. A 3-, 4-, 5-, or 6-French sheath or sheathless guide catheter was used in the initial procedure. A maximum of four successive coronary catheterization procedures were performed. The second procedure with dTRA on the same arm was successfully performed in 395 cases (94.3%), with a successive rate of 89.6% for both the third and fourth dTRA procedures. Conversion to another approach site (n = 30) was attributed to radial artery occlusion (n = 9), narrowing of the distal radial artery (n = 19), and puncture failure (n = 2). The current data indicate that the repeated use of dTRA is safe and feasible, and this approach may become a standard approach site in the future.
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Arteriopatias Oclusivas , Intervenção Coronária Percutânea , Braço , Angiografia Coronária/efeitos adversos , Estudos de Viabilidade , Humanos , Intervenção Coronária Percutânea/efeitos adversos , Artéria Radial/diagnóstico por imagem , Estudos Retrospectivos , Resultado do TratamentoRESUMO
OBJECTIVE: To compare the surgical outcomes of laparoscopic sacrocolpopexy for pelvic organ prolapse between a group in which only sutures were used (standard method), and a group in which a combination of tackers and sutures were used (tacker combination method). METHODS: A total of 77 patients who underwent laparoscopic sacrocolpopexys from June 2016 to October 2019 were divided into a suture group (36 patients) and a suture + tacker group (41 patients). We retrospectively compared operation time, amount of blood loss, postoperative length of hospital stay, incidence of perioperative complications and anatomical cure rate 1 year after surgery. Lower urinary tract symptoms were evaluated using symptom questionnaires and objective parameters. RESULTS: Operation time in the suture + tacker group was shorter (104.9 ± 27.0 vs 147.5 ± 33.7 min; P < 0.0001). The incidence of perioperative complications in the suture group and the suture + tacker group was 2.8% and 2.4%, respectively (P = 0.9409). Anatomical cure rates at 1 year after surgery were 94.4% and 100%, respectively (P = 0.2153). Both groups showed significant improvement after 1 year for International Prostate Symptom Score total and quality of life score, Overactive Bladder Symptom Score total score, voided volume, maximum urinary flow rate and post-void residual. [Corrections added on 7 September 2021 after first online publication: the first two P-values have been updated.] CONCLUSIONS: The combined use of sutures and tackers in laparoscopic sacrocolpopexy simplifies the procedure and translates into shorter operation time. Surgical outcomes at 1 year and improvement of lower urinary tract symptoms are similar regardless of the technique.
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Laparoscopia , Prolapso de Órgão Pélvico , Feminino , Procedimentos Cirúrgicos em Ginecologia/efeitos adversos , Humanos , Laparoscopia/efeitos adversos , Masculino , Prolapso de Órgão Pélvico/cirurgia , Qualidade de Vida , Estudos Retrospectivos , Telas Cirúrgicas , Resultado do TratamentoRESUMO
During the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, patients with ST-elevation myocardial infarction (STEMI) should be treated as possibly infected individuals. Therefore, more time is considered necessary to conduct primary percutaneous coronary intervention (PCI). In this study, we sought to evaluate the impact of the SARS-CoV-2 pandemic on primary PCI for STEMI. Between March 2019 and March 2021, 259 patients with STEMI underwent primary PCI. Patients were divided into 2 groups: the pre-pandemic group (March 2019-February 2020) and the pandemic group (March 2020-February 2021). The patient demographics, reperfusion time including onset-to-door time, door-to-balloon time (DTBT), computed tomography (CT), peak creatinine phosphokinase (CPK), and 30-day mortality rate were investigated. The mean age of the patients was 70.4 ± 12.9 years, and 71.6% were male. There were 117 patients before the pandemic and 142 during the pandemic. The median DTBT was 29 (21.25-41.25) minutes before the pandemic and 48 minutes (31-73 minutes) during the pandemic (P < 0.001). The median door-to-catheter-laboratory time was 13.5 (10-18.75) minutes before the pandemic and 29.5 (18-47.25) minutes during the pandemic (P < 0.001). CT evaluation was performed before PCI in 39 (33.3%) patients and 63 (44.4%) patients (P = 0.08); their peak CPK levels were 1480 (358-2737.5) IU and 1363 (621-2722.75) IU (P = 0.56), and the 30-day mortality rates were 4.3% and 2.1% (P = 0.48), respectively. The SARS-CoV-2 pandemic changed the diagnostic procedure in the emergency department and affected the DTBT in patients with STEMI. Nonetheless, no adverse effects on the 30-day mortality rate were observed.
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COVID-19/complicações , Creatina Quinase/sangue , Intervenção Coronária Percutânea/estatística & dados numéricos , Infarto do Miocárdio com Supradesnível do Segmento ST/cirurgia , Idoso , Idoso de 80 Anos ou mais , COVID-19/diagnóstico , COVID-19/epidemiologia , COVID-19/virologia , Feminino , Avaliação do Impacto na Saúde/estatística & dados numéricos , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Intervenção Coronária Percutânea/métodos , Intervenção Coronária Percutânea/mortalidade , Estudos Retrospectivos , SARS-CoV-2/genética , Infarto do Miocárdio com Supradesnível do Segmento ST/epidemiologia , Infarto do Miocárdio com Supradesnível do Segmento ST/mortalidade , Infarto do Miocárdio com Supradesnível do Segmento ST/virologia , Fatores de Tempo , Tempo para o Tratamento/tendênciasRESUMO
Glottal incompetence, i.e., reduced ability to produce effective glottal closure, is a problem often associated with aging. The study protocol is presented to determine whether blood substance P (SP) serves as an indicator of glottal closure function among the elderly. SP is involved in the neuromuscular mechanisms of cough; reduced concentration of SP may be a marker for increased risk of aspiration pneumonia. The antihypertensive angiotensin-converting enzyme inhibitor, which also inhibits degradation of SP, has been found to be effective in preventing aspiration pneumonia by strengthening the cough reflex. In this study, we will employ National Hospital Organization self-controlled vocal exercise (NHOEx), which has been shown to improve glottal closure by strengthening the laryngeal adduction muscles. We hypothesize that improved glottal closure by NHOEx may lead to the increase in the plasma concentration of SP, which reflects effective cough reflex. Maximum phonation time (MPT), an indicator of glottal closure, will be measured to assess improvement of glottis-closing function. The study will include 180 patients over 65 years old with dysphonia, dysphagia, or MPT of less than 15 seconds. Based on the speculation that the improved MPT may be associated with changes in SP expression, we will measure the plasma SP before and after 6-month treatment of glottal incompetence using NHOEx. The goal is to verify the reliability of SP as an indicator for glottal closure and swallowing function. Measurement of plasma SP may be helpful for earlier detection of subjects with higher risk of aspiration pneumonia among the elderly.
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Glote/fisiologia , Substância P/sangue , Idoso , Determinação de Ponto Final , Terapia por Exercício , Humanos , Tamanho da AmostraRESUMO
A macroring composed of three Cu(ii) porphyrins (CuP) and three slipped-cofacial Zn(ii) porphyrin (ZnP2) dimers exhibited near-IR emission from the CuP part. The emission lifetime of the macroring (15 µs) was 500 times longer compared to that of a Cu porphyrin monomer (e.g., Cu(ii)TPP; TPP = meso-tetraphenylporphyrin). The observed emission is ascribed to emission via the reservoir mechanism from the trip-doublet (2T1) state in CuP thermally activated from the T1 state of ZnP2, which is located ca. 1030 cm-1 below the 2T1 state of CuP. The near-IR emission of the macroring was significantly quenched by O2, whereas that of the Cu porphyrin monomer was hardly quenched, indicating that the quenching event mainly occurred on the T1 state of the ZnP2 parts. The nonemissive triplet state of a Zn porphyrin at room temperature was visualized through emission from a neighboring Cu porphyrin.
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OBJECTIVES: To evaluate the effect of a self-controlled vocal exercise in elderly people with glottal closure insufficiency. DESIGN: Parallel-arm, individual randomized controlled trial. METHODS: Patients who visited one of 10 medical centers under the National Hospital Organization group in Japan for the first time, aged 60 years or older, complaining of aspiration or hoarseness, and endoscopically confirmed to have glottal closure insufficiency owing to vocal cord atrophy, were enrolled in this study. They were randomly assigned to an intervention or a control group. The patients of the intervention group were given guidance and a DVD about a self-controlled vocal exercise. The maximum phonation time which is a measure of glottal closure was evaluated, and the number of patients who developed pneumonia during the six months was compared between the two groups. RESULTS: Of the 543 patients enrolled in this trial, 259 were allocated into the intervention group and 284 into the control; 60 of the intervention group and 75 of the control were not able to continue the trial. A total of 199 patients (age 73.9 ±7.25 years) in the intervention group and 209 (73.3 ±6.68 years) in the control completed the six-month trial. Intervention of the self-controlled vocal exercise extended the maximum phonation time significantly ( p < 0.001). There were two hospitalizations for pneumonia in the intervention group and 18 in the control group, representing a significant difference ( p < 0.001). CONCLUSION: The self-controlled vocal exercise allowed patients to achieve vocal cord adduction and improve glottal closure insufficiency, which reduced the rate of hospitalization for pneumonia significantly. CLINICAL TRIAL: gov Identifier-UMIN000015567.
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Transtornos de Deglutição/reabilitação , Exercício Físico/fisiologia , Glote/fisiopatologia , Pneumonia Aspirativa/prevenção & controle , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/fisiologia , Transtornos de Deglutição/complicações , Transtornos de Deglutição/diagnóstico , Humanos , Japão , Laringoscopia/métodos , Pessoa de Meia-Idade , Cooperação do Paciente/estatística & dados numéricos , Pneumonia Aspirativa/etiologia , Prognóstico , Recuperação de Função Fisiológica , Valores de Referência , Medição de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Resultado do TratamentoRESUMO
Chronic total occlusion (CTO) in a non-infarcted-related artery was reported to worsen immediate clinical outcome in acute myocardial infarction (AMI) patients. However, the prognosis of such patients with preserved left ventricular function after successful primary percutaneous coronary intervention (PCI) has not yet been clarified. The aim of the present study was to evaluate whether the presence of CTO contributes to a worse prognosis even in patients with preserved left ventricular function after primary PCI.We retrospectively analyzed 353 consecutive patients with acute myocardial infarction, whose left ventricular ejection fraction (LVEF) was not less than 40% in the echocardiography performed 1 day after primary PCI. We divided the patients into two groups according to the presence (n = 25) or absence (n = 328) of CTO in the non-infarct-related coronary artery, and compared the clinical outcome of patients between the two groups.The LVEF estimated by echocardiography after primary PCI was similar between patients with and without CTO (55.1 ± 8.6% versus 58.0 ± 9.4%; P = 0.07). The peak creatine kinase value was also similar between the two groups (1539 versus 1921 U/L; P = 0.33); however, CTO patients were significantly more likely to undergo intra-aortic balloon pumping (56.0% versus 12.5%; P < 0.001) during primary PCI, and 30-day mortality was significantly higher in CTO patients (12.0% versus 0.9%; P < 0.001). By multivariate analysis, cardiogenic shock at arrival was significantly correlated with 30-day mortality.Even though the LVEF of AMI patients with CTO was preserved after successful PCI, a high mortality rate was observed.
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Oclusão Coronária , Vasos Coronários , Infarto do Miocárdio , Intervenção Coronária Percutânea/estatística & dados numéricos , Idoso , Oclusão Coronária/diagnóstico , Oclusão Coronária/epidemiologia , Oclusão Coronária/fisiopatologia , Vasos Coronários/patologia , Vasos Coronários/fisiopatologia , Feminino , Humanos , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/fisiopatologia , Infarto do Miocárdio/terapia , Prognóstico , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Análise de Sobrevida , Função Ventricular EsquerdaRESUMO
Cardiorenal anemia syndrome has recently been receiving greater attention; however, data regarding the relationship between chronic kidney disease (CKD)/anemia on presentation and in-hospital outcome in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI) are still limited in Japan.A total of 1,447 primary PCI-treated AMI patients were classified into 4 groups according to the presence of CKD and/or anemia on hospital admission (with CKD/with anemia n = 222, with CKD/without anemia n = 299, without CKD/with anemia n = 151, without CKD/without anemia n = 775). Angiographic acute results of primary PCI were similar among the 4 groups. The patients with CKD had a significantly higher in-hospital overall mortality rate than the patients without CKD, and in the presence or absence of CKD, patients with anemia tended to have a higher in-hospital mortality rate than the patients without anemia. According to a multivariate analysis, anemia on admission was found to be an independent predictor of in-hospital mortality, whereas admission CKD and admission eGFR were statistically not independent predictors. Moreover, the multivariable adjusted odds ratio of in-hospital death in AMI patients with CKD alone was 1.855 (95% CI 0.929-3.706), and that in AMI patients with CKD/with anemia was 3.384 (95% CI 1.697-6.748).These results suggest that among real-world, unselected Japanese AMI patients undergoing primary PCI, the combination of CKD and anemia on admission confers significant adverse effects on in-hospital mortality.
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Anemia/diagnóstico , Infarto do Miocárdio/cirurgia , Admissão do Paciente , Intervenção Coronária Percutânea , Insuficiência Renal Crônica/diagnóstico , Medição de Risco/métodos , Idoso , Feminino , Seguimentos , Mortalidade Hospitalar/tendências , Humanos , Incidência , Japão/epidemiologia , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Complicações Pós-Operatórias , Prognóstico , Estudos Retrospectivos , Fatores de RiscoRESUMO
Myocardial perfusion scintigraphy is a popular minimally invasive method for evaluating chronic coronary disease (CCD). We performed myocardial scintigraphy to assess CCD in a 74-year-old man with a history of allergy to contrast media. The patient developed anaphylactic shock immediately after the administration of the technetium (99mTc)-tetrofosmin preparation. This is the first report of anaphylactic shock due to 99mTc-tetrofosmin administration during myocardial perfusion scintigraphy.
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BACKGROUND: A new subtype of prostate cancer called treatment-related neuroendocrine prostate carcinoma (t-NEPC) was added to the revised World Health Organization classification of prostate cancer in 2022. t-NEPC cases are increasing, and there is no established standard treatment. METHODS: A 49-year-old male patient was referred to our department for dysuria. A rectal examination and a prostate biopsy revealed stony hardness and prostate adenocarcinoma, respectively. Imaging studies confirmed the presence of multiple bone and lymph node metastases. The patient was started on upfront treatment with androgen deprivation therapy and an androgen receptor signaling inhibitor, which resulted in a significant (>90%) decrease in prostate-specific antigen (PSA) levels. The patient experienced postrenal failure 6 months later, attributable to local disease progression. Concurrently, there was an elevation in neuron-specific enolase (NSE) levels and an enlargement of pelvic lymph node metastases, without PSA progression. RESULTS: Biopsy specimen for cancer genome profiling revealed deletion of BRCA 2 and PTEN, AR amplification, and the presence of the TMPRSS2-ERG fusion gene. Based on increased NSE and BRCA2 mutations, a diagnosis of t-NEPC with BRCA2 mutation was eventually made. The patient received docetaxel chemotherapy and pelvic radiotherapy. Subsequently, he was treated with olaparib. His NSE levels decreased, and he achieved a complete response (CR). However, 18 months following the olaparib administration, brain metastases appeared despite the absence of pelvic tumor relapse, and the patient's PSA levels remained low. Consequently, the patient underwent resection of the brain metastases using gamma knife and whole-brain radiotherapy but died approximately 3 months later. CONCLUSION SUBSECTIONS: Platinum-based chemotherapy is often administered for the treatment of t-NEPC, but there are few reports on the effectiveness of olaparib in patients with BRCA2 mutations. In a literature review, this case demonstrated the longest duration of effectiveness with olaparib alone without platinum-based chemotherapy. Additionally, the occurrence of relatively rare, fatal brain metastases in prostate cancer after a long period of CR suggests the necessity of regular brain imaging examinations.
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Neoplasias Encefálicas , Carcinoma , Ftalazinas , Piperazinas , Neoplasias da Próstata , Masculino , Humanos , Pessoa de Meia-Idade , Neoplasias da Próstata/genética , Neoplasias da Próstata/terapia , Neoplasias da Próstata/diagnóstico , Antígeno Prostático Específico , Antagonistas de Androgênios/uso terapêutico , Próstata/patologia , Metástase Linfática , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/tratamento farmacológico , Carcinoma/tratamento farmacológico , Proteína BRCA2RESUMO
Data regarding relationship between pulse pressure (PP) at admission and in-hospital outcome in patients with acute myocardial infarction (AMI) undergoing primary percutaneous coronary intervention (PCI) are still lacking. A total of 1413 primary PCI-treated AMI patients were classified into quintiles based on admission PP (<40, n = 280; 40-48, n = 276; 49-57, n = 288; 58-70, n = 288; and ≥71 mmHg, n = 281). The patients with PP < 40 mmHg tended to have higher prevalence of male, smoking, and Killip class ≥3 at admission; right coronary artery, left main trunk (LMT), or multivessels as culprit lesions; larger number of diseased vessels; lower Thrombolysis in Myocardial Infarction (TIMI) grade in the infarct-related artery before/after primary PCI; and higher value of peak creatine phosphokinase concentration. Patients with PP < 40 mmHg had highest mortality, while patients with PP 49-57 mmHg had the lowest: 11.8 % (<40), 7.2 % (40-48), 2.8 % (49-57), 5.9 % (58-70), and 6.0 % (≥71 mmHg). On multivariate analysis, Killip class ≥3 at admission, LMT or multivessels as culprit lesions, chronic kidney disease, and age were the independent positive predictors of the in-hospital mortality, whereas admission PP 49-57 mmHg, hypercholesterolemia, and TIMI 3 flow before/after PCI were the negative ones, but admission PP < 40 mmHg was not. These results suggest that admission PP 49-57 mmHg might be correlated with better in-hospital prognosis in Japanese AMI patients undergoing primary PCI.
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Pressão Sanguínea , Infarto do Miocárdio/terapia , Admissão do Paciente , Intervenção Coronária Percutânea , Idoso , Idoso de 80 Anos ou mais , Distribuição de Qui-Quadrado , Feminino , Humanos , Japão , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/fisiopatologia , Razão de Chances , Intervenção Coronária Percutânea/efeitos adversos , Intervenção Coronária Percutânea/mortalidade , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
Benign prostatic hyperplasia (BPH) is prevalent in older men. As surgery can be high risk in this group, minimally invasive procedures are preferrable. This study aimed to assess the initial results of minimally invasive Rezum water vapor thermal therapy (WVTT) in patients with BPH. This single-center retrospective study included 25 consecutive patients with BPH who underwent WVTT between September 2022 and July 2023. Parameters including age, Charlson Comorbidity Index and Geriatric 8 (G8) scores, operative time, and number of vapor injections were evaluated. The International Prostate Symptom Score (IPSS), Overactive Bladder Symptom Score, and Core Lower Urinary Tract Symptom Score (CLSS) were used to assess symptoms before the procedure, and at 1 and 3 months after it. Urinary function indicators such as single voiding volume, maximum flow rate (MFR), and post-void residual volume were assessed at the same time points. The mean patient age was 76.0 years and the mean prostate volume was 54.8 mL. The mean G8 score was 14.4 and the Charlson Comorbidity Index score averaged 1.2. The mean operative time was 6.84 min, and included a mean of 4.8 vapor injections. Three months after WVTT, significant improvements were observed in the maximum flow rate (Pâ =â .02), post-void residual volume (Pâ =â .001), and urine volume (Pâ <â .001), as well as in the IPSS incomplete emptying (Pâ =â .01) and weak stream (Pâ =â .01) domains. No significant changes were observed in the remaining IPSS domains or in the Overactive Bladder Symptom Score or CLSS. This study provides the first report on Rezum WVTT outcomes in Japan using the CLSS assessment tool. The initial results indicate a promising experience with this new treatment method. With a rapidly aging population, the incidence of BPH is expected to increase, making the minimally invasive Rezum system a valuable addition to BPH treatment options.
Assuntos
Sintomas do Trato Urinário Inferior , Hiperplasia Prostática , Bexiga Urinária Hiperativa , Masculino , Humanos , Idoso , Hiperplasia Prostática/cirurgia , Hiperplasia Prostática/diagnóstico , Vapor , Resultado do Tratamento , Bexiga Urinária Hiperativa/complicações , Japão , Estudos Retrospectivos , Sintomas do Trato Urinário Inferior/etiologia , Sintomas do Trato Urinário Inferior/terapia , Sintomas do Trato Urinário Inferior/diagnóstico , Qualidade de VidaRESUMO
For the purpose of analyzing mechanisms related to the cis-diamminedichloroplatinum resistance in head and neck squamous cell carcinoma, we analyzed RPMI2650 and its derived previously established cis-diamminedichloroplatinum resistant cell line RPMI2650CR. To identify resistant phenotype-related microRNAs, we compared microRNA expressions between RPMI2650CR and RPMI2650 by microarray. One of the microRNAs as downregulated, miR-34a, was further investigated. Decreased expression of miR-34a in RPMI2650CR was confirmed by quantitative reverse transcription-polymerase chain reaction, but introduction of the miR-34a precursor into RPMI2650CR or the inhibitor of miR-34a into RPMI2650 did not change cis-diamminedichloroplatinum sensitivities. However, 24 patients with sinonasal squamous cell carcinomas treated with intra-arterial infusion of cis-diamminedichloroplatinum showed a significant association between decreased expression of miR-34a and poor disease specific survival (P = 0.0015), poor disease free survival (P = 0.0019), and poor local control rates (P = 0.017) (median follow-up period: 53 months). Furthermore, multivariate analyses demonstrated significant associations between miR-34a expression and the hazard ratios of disease free survival at 0.005 (95% confidence interval [CI] 0.00-0.29, P = 0.011) and local control rate at 0.008 (95% CI 0.00-0.44, P = 0.019), although other parameters such as age, gender, treatment method, T and N stages did not show any similar association. These results strongly suggest that miR-34a expression can be an independent prognostic biomarker in patients with sinonasal squamous cell carcinoma who are undergoing treatment with cis-diamminedichloroplatinum.
Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Cisplatino/uso terapêutico , MicroRNAs/genética , Neoplasias dos Seios Paranasais/tratamento farmacológico , Neoplasias dos Seios Paranasais/genética , Adulto , Idoso , Antineoplásicos/farmacologia , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/mortalidade , Linhagem Celular Tumoral , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias dos Seios Paranasais/mortalidade , PrognósticoRESUMO
Although cisplatin is indispensable for the chemotherapy treatment of many malignancies, cisplatin-associated thrombosis is attracting increasing attention. However, experience of primary percutaneous coronary intervention (PCI) and intravascular ultrasound imaging (IVUS) for coronary thrombosis, possibly due to cisplatin-based chemotherapy, has been limited. Case 1 with postoperative gastric cancer developed acute myocardial infarction (AMI) on the sixth day of the second chemotherapy course with conventional doses of cisplatin and tegafur gimeracil oteracil potassium. Emergency coronary angiography (CAG) showed a filling defect in the proximal left anterior descending coronary artery (LAD) concomitant with no reflow in the distal LAD. Case 2 with advanced lung cancer and brain metastasis suffered AMI on the fifth day of the first chemotherapy course with conventional doses of cisplatin and gemcitabine. Emergency CAG delineated a total occlusion in the proximal right coronary artery. In both cases, thrombectomy using aspiration catheter alone obtained optimal angiographic results and subsequent IVUS revealed no definite atherosclerotic plaque, while slow flow still remained even after selective intra-coronary infusion of vasodilator in the case 1. These cases suggest that primary PCI using thrombus-aspiration catheter might be safe and effective for coronary thrombosis due to cisplatin-based chemotherapy.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Trombose Coronária/diagnóstico por imagem , Trombose Coronária/terapia , Intervenção Coronária Percutânea , Ultrassonografia de Intervenção , Adulto , Cisplatino/efeitos adversos , Angiografia Coronária , Trombose Coronária/induzido quimicamente , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/induzido quimicamente , Infarto do Miocárdio/diagnóstico por imagem , Infarto do Miocárdio/terapia , Valor Preditivo dos Testes , Neoplasias Gástricas/tratamento farmacológico , Trombectomia , Resultado do TratamentoRESUMO
Fish bones are one of the most frequently observed ingested foreign bodies in the pharynx-esophagus. Fish bones have a tendency to stick and penetrate the mucosa, which can occasionally lead to severe or lethal complications. The extraluminal migration of fish bones in the upper digestive tract is a rare event, and it is even more unlikely that the foreign body will remain in the neck for a prolonged period. We report the unique case of a 69-year-old woman who remained asymptomatic, while a fish bone was lodged in her neck for 9 months. Finally, after her anterior neck had become swollen, she underwent neck exploration, which revealed that the fish bone was embedded in the scar tissue running from within the thyroid gland to outside of the thyroid. Treatment proceeded without complications, and the foreign body was removed successfully. The length of the fish bone was 34 mm. Intraoperative ultrasonography was able to identify the fish bone in situ using real-time imaging; therefore, we recommend this technique for locating migrated foreign bodies in the neck.