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1.
Front Pharmacol ; 15: 1419044, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38895635

RESUMO

Glioblastoma multiforme (GBM) is one of the most prevalent and lethal primary central nervous system malignancies. GBM is notorious for its high rates of recurrence and therapy resistance and the PI3K/Akt pathway plays a pivotal role in its malignant behavior. Crebanine (CB), an alkaloid capable of penetrating the blood-brain barrier (BBB), has been shown to have inhibitory effects on proinflammatory molecules and multiple cancer cell lines via pathways such as PI3K/Akt. This study aims to investigate the efficacy and mechanisms of CB treatment on GBM. It is the first study to elucidate the anti-tumor role of CB in GBM, providing new possibilities for GBM therapy. Through a series of experiments, we demonstrate the significant anti-survival, anti-clonogenicity, and proapoptotic effects of CB treatment on GBM cell lines. Next-generation sequencing (NGS) is also conducted and provides a complete list of significant changes in gene expression after treatment, including genes related to apoptosis, the cell cycle, FoxO, and autophagy. The subsequent protein expressions of the upregulation of apoptosis and downregulation of PI3K/Akt are further proved. The clinical applicability of CB to GBM treatment could be high for its BBB-penetrating feature, significant induction of apoptosis, and blockage of the PI3K/Akt pathway. Future research is needed using in vivo experiments and other therapeutic pathways shown in NGS for further clinical or in vivo studies.

2.
Int J Biol Macromol ; 270(Pt 2): 132240, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38744360

RESUMO

Current treatment of snakebite relies on immunoglobulin-rich antivenoms. However, production of these antivenoms is complicated and costly. Aptamers - single-stranded DNAs or RNAs with specific folding structures that bind to specific target molecules - represent excellent alternatives or complements to antibody-based therapeutics. However, no studies have systematically assessed the feasibility of using aptamers to mitigate venom-induced toxicity in vivo. ß-bungarotoxin is the predominant protein responsible for the toxicity of the venom of Bungarus multicinctus, a prominent venomous snake inhabiting Taiwan. In this study, we reported the screening and optimization of a DNA aptamer against ß-bungarotoxin and tested its utility in a mouse model. After 14 rounds of directed evolution of ligands by exponential enrichment, an aptamer, called BB3, displaying remarkable binding affinity and specificity for ß-bungarotoxin was obtained. Following structural prediction and point-modification experiments, BB3 underwent truncation and was modified with 2'-O-methylation and a 3'-inverted dT. This optimized aptamer showed sustained, high-affinity binding for ß-bungarotoxin and exhibited remarkable nuclease resistance in plasma. Importantly, administration of this optimized aptamer extended the survival time of mice treated with a lethal dose of ß-bungarotoxin. Collectively, our data provide a compelling illustration of the potential of aptamers as promising candidates for development of recombinant antivenom therapies.


Assuntos
Aptâmeros de Nucleotídeos , Bungarotoxinas , Animais , Aptâmeros de Nucleotídeos/farmacologia , Aptâmeros de Nucleotídeos/química , Bungarotoxinas/farmacologia , Bungarotoxinas/química , Camundongos , Modelos Animais de Doenças , Bungarus , Mordeduras de Serpentes/tratamento farmacológico , Técnica de Seleção de Aptâmeros
4.
Rev Sci Instrum ; 95(5)2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38717266

RESUMO

In the field of precision industries, measuring micro-angular errors plays a crucial role in improving the accuracy of equipment. Therefore, this study aims to develop a two-degree-of-freedom (two-DOF) angular error measurement system for simultaneously measuring the assembly angle errors of the bond head in a die bonding machine. This system is based on the laser collimation method and constructed by using components such as a fiber laser and position-sensitive detectors. It utilizes the angular drift compensation of the laser beam and averaging function to improve the measurement accuracy. In addition, the mathematical model of the proposed system was established by using skew-ray tracing. Through experiments, the measuring accuracy of ±0.25 arcsec and measuring repeatability of 0.3 arcsec could be achieved.

5.
J Clin Med ; 13(8)2024 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-38673691

RESUMO

Background: Various diseases involving the cavernous sinus can cause a condition called cavernous sinus syndrome (CSS), which is characterized by ophthalmoplegia or sensory deficits over the face resulting from the compression effect of internal structure. While tumor compression is the most reported cause of CSS, statistical data on CSS caused by infections are limited. Its risk factors, treatment methods, and clinical outcomes are not well-documented. Methods: In this retrospective study, we reviewed the data of patients admitted to a tertiary medical center from 2015 to 2022 with a diagnosis of acute and chronic sinusitis and at least one diagnostic code for CSS symptoms. We manually reviewed whether patients were involved in two or more of the following cranial nerves (CN): CN III, CN IV, CN V, or CN VI, or at least one of these nerves with a neuroimaging-confirmed lesion in the cavernous sinus. Results: Nine patients were diagnosed with rhinosinusitis-related CSS. The most common comorbidity was type 2 diabetes, and the most common clinical manifestations were diplopia and blurred vision. The sphenoid sinus was the most affected sinus. One patient expired due to a severe brain abscess infection without surgery. The remaining patients underwent functional endoscopic sinus surgery, and 50% of the pathology reports indicated fungal infections. Staphylococcus spp. was the most cultured bacteria, and Amoxycillin/Clavulanate was the most used antibiotic. Only four patients had total recovery during the follow-up one year later. Conclusions: CSS is a rare but serious complication of rhinosinusitis. Patients with diabetes and the elderly may be at a higher risk for this complication. Even after treatment, some patients may still have neurological symptoms.

6.
J Cancer ; 15(8): 2403-2411, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38495506

RESUMO

Background: Breast cancer is the most prevalent cancer among women worldwide. The potential involvement of Epstein-Barr virus (EBV) in breast cancer pathogenesis has been a subject of debate, but its correlation with clinical outcomes remains uncertain. Methods: In this study, we collected 276 pathologically confirmed breast cancer tissue samples from the tissue bank of MacKay Memorial Hospital and the National Health Research Institutes in Taiwan. DNA was extracted from frozen tissue using The QIAamp DNA Mini Kit. The Taqman quantitative PCR method was employed to assess the EBV copy number per cell in these samples, using NAMALWA cells as a reference. We performed statistical analyses, including 2 × 2 contingency tables, Cox regression analysis, and Kaplan-Meier survival curves, to explore the association between clinicopathologic factors and survival outcomes in breast cancer patients. We analyzed both relapse survival, which reflects the period patients remain free from cancer recurrence post-treatment, and overall survival, which encompasses all-cause mortality. Results: Our results revealed a significant association between EBV status and relapse survival (hazard ratio: 2.75, 95% CI: 1.30, 5.86; p = 0.008) in breast cancer patients. However, no significant association was found in overall survival outcomes. Additionally, we observed significant associations between ER status and tumor histologic grade with both overall and relapse survival. Patients with EBV-positive tumors exhibited higher recurrence rates compared to those with EBV-negative tumors. Furthermore, we noted significant correlations between EBV status and HER-2 (p = 0.0005) and histological grade (p = 0.02) in our cohort of breast cancer patients. Conclusions: The presence of EBV in breast cancer tumors appears to exert an impact on patient outcomes, particularly concerning recurrence rates. Our findings highlight the significance of considering EBV status as a potential prognostic marker in breast cancer patients. Nonetheless, further research is essential to elucidate the underlying molecular mechanisms and develop novel therapeutic approaches.

8.
Cancer Imaging ; 24(1): 43, 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38532511

RESUMO

BACKGROUND: Automatic segmentation of hepatocellular carcinoma (HCC) on computed tomography (CT) scans is in urgent need to assist diagnosis and radiomics analysis. The aim of this study is to develop a deep learning based network to detect HCC from dynamic CT images. METHODS: Dynamic CT images of 595 patients with HCC were used. Tumors in dynamic CT images were labeled by radiologists. Patients were randomly divided into training, validation and test sets in a ratio of 5:2:3, respectively. We developed a hierarchical fusion strategy of deep learning networks (HFS-Net). Global dice, sensitivity, precision and F1-score were used to measure performance of the HFS-Net model. RESULTS: The 2D DenseU-Net using dynamic CT images was more effective for segmenting small tumors, whereas the 2D U-Net using portal venous phase images was more effective for segmenting large tumors. The HFS-Net model performed better, compared with the single-strategy deep learning models in segmenting small and large tumors. In the test set, the HFS-Net model achieved good performance in identifying HCC on dynamic CT images with global dice of 82.8%. The overall sensitivity, precision and F1-score were 84.3%, 75.5% and 79.6% per slice, respectively, and 92.2%, 93.2% and 92.7% per patient, respectively. The sensitivity in tumors < 2 cm, 2-3, 3-5 cm and > 5 cm were 72.7%, 92.9%, 94.2% and 100% per patient, respectively. CONCLUSIONS: The HFS-Net model achieved good performance in the detection and segmentation of HCC from dynamic CT images, which may support radiologic diagnosis and facilitate automatic radiomics analysis.


Assuntos
Carcinoma Hepatocelular , Aprendizado Profundo , Neoplasias Hepáticas , Humanos , Processamento de Imagem Assistida por Computador , Veia Porta , Tomografia Computadorizada por Raios X
9.
Transplant Proc ; 56(3): 742-745, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38519267

RESUMO

BACKGROUND: Numerous successful pregnancy outcomes have been reported after kidney transplantation, but until now, there have been no reports of healthy twin deliveries through in vitro fertilization treatment in high-gestation aged women with a long post-transplant duration. In our report, we present a case of a high-gestation aged kidney transplant recipient who successfully delivered healthy twins with the aid of in vitro fertilization. CASE PRESENTATION: At the age of 29, a woman with end-stage kidney disease caused by immunoglobin A nephropathy underwent kidney transplantation. She had a history of premature ovarian failure and had been on continuous ambulatory peritoneal dialysis since the age of 18. Eleven years after starting dialysis, she received a cadaveric kidney transplant. Despite being infertile for 7 years after transplantation, she wished to have children. In vitro fertilization embryo transfer was conducted after failure of ovarian stimulation, considering her age and premature ovarian failure. The patient successfully delivered twins at 29 weeks gestation via cesarean section, as the first fetus presented in breech position. The first newborn weighed 945 g and the second weighed 855 g, with no other congenital abnormalities found. One year after childbirth, neither the recipient nor her babies experienced any fatal complications. CONCLUSIONS: A woman who underwent kidney transplantation and has stage 3 CKD may successfully deliver healthy twins through in vitro fertilization embryo transfer, even if she is of advanced maternal age and has a long post-transplant period. However, there is a risk of preterm premature rupture of membrane in such cases.


Assuntos
Fertilização in vitro , Transplante de Rim , Humanos , Feminino , Gravidez , Adulto , Gravidez de Gêmeos , Resultado da Gravidez , Falência Renal Crônica/cirurgia , Transferência Embrionária
10.
Comput Biol Med ; 172: 108244, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38457931

RESUMO

The primary objective of this study is to enhance the prediction accuracy of intradialytic hypotension in patients undergoing hemodialysis. A significant challenge in this context arises from the nature of the data derived from the monitoring devices and exhibits an extreme class imbalance problem. Traditional predictive models often display a bias towards the majority class, compromising the accuracy of minority class predictions. Therefore, we introduce a method called UnderXGBoost. This novel methodology combines the under-sampling, bagging, and XGBoost techniques to balance the dataset and improve predictive accuracy for the minority class. This method is characterized by its straightforward implementation and training efficiency. Empirical validation in a real-world dataset confirms the superior performance of UnderXGBoost compared to existing models in predicting intradialytic hypotension. Furthermore, our approach demonstrates versatility, allowing XGBoost to be substituted with other classifiers and still producing promising results. Sensitivity analysis was performed to assess the model's robustness, reinforce its reliability, and indicate its applicability to a broader range of medical scenarios facing similar challenges of data imbalance. Our model aims to enable medical professionals to provide preemptive treatments more effectively, thereby improving patient care and prognosis. This study contributes a novel and effective solution to a critical issue in medical prediction, thus broadening the application spectrum of predictive modeling in the healthcare domain.


Assuntos
Hipotensão , Humanos , Reprodutibilidade dos Testes , Hipotensão/etiologia , Diálise Renal/efeitos adversos , Diálise Renal/métodos
11.
Artigo em Inglês | MEDLINE | ID: mdl-38491916

RESUMO

INTRODUCTION: We aimed to evaluate the effect of transcatheter arterial embolization (TAE) with iodized oil (Lipiodol) on temperature change during cryoablation (CA) for renal cell carcinoma (RCC). MATERIAL AND METHODS: We retrospectively reviewed patients receiving CA for RCC from February 2020 to July 2021, including those who received Lipiodol TAE prior to CA (TAE group) and those who underwent only CA with comparable clinical and tumor characteristics (non-TAE group). Clinical data and tumor characteristics of both groups were recorded. The temperature readings of each cryoprobe at every 15 s and 'time to -100 °C' were compared between the groups. RESULTS: A total of 17 patients with 18 RCCs were recruited (seven in the TAE group and 11 in the non-TAE group). The 'time to -100 °C' was significantly longer in the TAE group than in the non-TAE group (64.5 ± 24.3 s vs. 48.8 ± 9.7 s, p = 0.018). Positive correlation between 'time to -100 °C' and tumor maximal diameter, RENAL nephrometry and PADUA score were observed in the non-TAE group, while no corresponding correlation was found in the TAE group. CONCLUSIONS: Pre-embolization with iodized oil influences the temporal temperature changes during cryoablation by disrupting the positive correlation between the time to reach the target temperature and tumor characteristics.

12.
Mol Cell Endocrinol ; 584: 112175, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38341020

RESUMO

Testicular hyperthermia has been noted in men who work in high ambient temperatures. Scrotal temperatures above the normal range caused germ cell loss in the testes and resulted in male subfertility. In adult male rats, exercising at a higher environmental temperature (36 °C with relative humidity of 50%, 52 min) caused exertional heat stroke (EHS) characterized by scrotal hyperthermia, impaired sperm quality, dysmorphology in testes, prostates and bladders, and erectile dysfunction. Here, we aim to ascertain whether hyperbaric oxygen preconditioning (HBOP: 100% O2 at 2.0 atm absolute [ATA] for 2 h daily for 14 days consequently before the onset of EHS) is able to prevent the problem of EHS-induced sterility, testes, prostates, and bladders dysmorphology and erectile dysfunction. At the end of exertional heat stress compared to normobaric air (NBA or non-HBOP) rats, the HBOP rats exhibited lower body core temperature (40 °C vs. 43 °C), lower scrotal temperature (34 °C vs. 36 °C), lower neurological severity scores (2.8 vs. 5.8), higher erectile ability, (5984 mmHg-sec vs. 3788 mmHg-sec), higher plasma testosterone (6.8 ng/mL vs. 3.5 ng/mL), lower plasma follicle stimulating hormone (196.3 mIU/mL vs. 513.8 mIU/mL), lower plasma luteinizing hormone (131 IU/L vs. 189 IU/L), lower plasma adrenocorticotropic hormone (5136 pg/mL vs. 6129 pg/mL), lower plasma corticosterone (0.56 ng/mL vs. 1.18 ng/mL), lower sperm loss and lower values of histopathological scores for epididymis, testis, seminal vesicle, prostate, and bladder. Our data suggest that HBOP reduces body core and scrotal hyperthermia and improves sperm loss, testis/prostate/bladder dysmorphology, and erectile dysfunction after EHS in rats.


Assuntos
Disfunção Erétil , Golpe de Calor , Oxigenoterapia Hiperbárica , Humanos , Adulto , Masculino , Ratos , Animais , Testículo/patologia , Temperatura , Disfunção Erétil/patologia , Sêmen , Espermatozoides , Golpe de Calor/complicações , Golpe de Calor/terapia
13.
Int J Biol Macromol ; 262(Pt 2): 130080, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38354918

RESUMO

Animal testing has been the primary approach to assess the neutralization potency of antivenom for decades. However, the necessity to sacrifice large numbers of experimental animals during this process has recently raised substantial welfare concerns. Furthermore, the laborious and expensive nature of animal testing highlights the critical need to develop alternative in vitro assays. Here, we developed an antibody-detection enzyme-linked immunosorbent assay (ELISA) technique as an alternative approach to evaluate the neutralization potency of hyperimmunized equine plasma against B. multicinctus, a medically important venomous snake in Taiwan. Firstly, five major protein components of B. multicinctus venom, specifically, α-BTX, ß-BTX, γ-BTX, MTX, and NTL, were isolated. To rank their relative medical significance, a toxicity score system was utilized. Among the proteins tested, ß-BTX presenting the highest score was regarded as the major toxic component. Subsequently, antibody-detection ELISA was established based on the five major proteins and used to evaluate 55 hyperimmunized equine plasma samples with known neutralization potency. ELISA based on ß-BTX, the most lethal protein according to the toxicity score, exhibited the best sensitivity (75.6 %) and specificity (100 %) in discriminating between high-potency and low-potency plasma, supporting the hypothesis that highly toxic proteins offer better discriminatory power for potency evaluation. Additionally, a phospholipase A2 (PLA2) competition process was implemented to eliminate the antibodies targeting toxicologically irrelevant domains. This optimization greatly enhanced the performance of our assay, resulting in sensitivity of 97.6 % and specificity of 92.9 %. The newly developed antibody-detection ELISA presents a promising alternative to in vivo assays to determine the neutralization potency of antisera against B. multicinctus during the process of antivenom production.


Assuntos
Bungarotoxinas , Bungarus , Animais , Cavalos , Bungarus/metabolismo , Bungarus multicinctus , Antivenenos , Taiwan , Ensaio de Imunoadsorção Enzimática
14.
Front Cardiovasc Med ; 11: 1290610, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38374999

RESUMO

Background: Postoperative atrial fibrillation (POAF) is a frequent complication that may increase morbidity and mortality risk following cardiac surgery. The systemic immune-inflammation index (SII) is an emerging biomarker that provides an integrated measure of inflammation by incorporating neutrophil, lymphocyte, and platelet counts. Recent studies have reported associations between elevated SII and increased POAF risk; however, significant heterogeneity exists regarding its predictive efficacy. This meta-analysis aimed to assess SII's diagnostic efficacy for predicting POAF risk. Methods: To synthesize existing evidence on the ability of perioperative SII for predicting POAF in patients undergoing cardiac surgery, a systematic review and meta-analysis was conducted. In August 2023, a comprehensive literature search was performed to identify relevant studies reporting SII cutoff values with corresponding sensitivity and specificity. The primary aim was to evaluate SII's diagnostic utility for predicting POAF, whereas secondary outcomes included the pooled incidence of POAF and the relationship between the SII and POAF. Results: Eight studies published between 2021 and 2023 with 3,245 patients were included. Six studies involved coronary artery bypass grafting (CABG) surgery; one encompassed various cardiac procedures, and another focused solely on mitral valve surgery. The pooled incidence of POAF was 23.6% [95% confidence interval (CI), 18.7%-29.2%]. Elevated SII significantly increased the odds of POAF by 3.24-fold (odds ratio, 3.24; 95% CI, 1.6-6.55; p = 0.001). SII's pooled sensitivity and specificity for predicting POAF were 0.80 (95% CI, 0.68-0.89) and 0.53 (95% CI, 0.23-0.8), respectively. The SII had moderate predictive accuracy based on a hierarchical summary receiver operating characteristic (HSROC) area under the curve of 0.78 (95% CI, 0.74-0.81). Subgroup analyses, whether focusing on CABG alone or CABG with cardiopulmonary bypass (CPB), both indicated an area under the HSROC curve of 0.78 (95% CI, 0.74-0.81). Conclusion: Elevated SII is significantly correlated with an increased POAF risk following cardiac surgery, highlighting its utility as a predictive biomarker. Considering its moderate diagnostic accuracy, further research is essential for clarifying SII's clinical effectiveness, either as an independent predictor or combined with other risk factors, for stratifying patients at high POAF risk. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier [CRD42023456128].

15.
Liver Cancer ; 13(1): 29-40, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38344446

RESUMO

Introduction: Outcomes of transarterial chemoembolization (TACE) for intermediate-stage hepatocellular carcinoma (HCC) are diverse because of the heterogeneity of tumor burden. Radiologic pattern is one criterion for determining whether TACE is unsuitable. However, additional evidence is required. This study determined the influence of radiologic morphology on the outcomes of initial and subsequent TACE. Methods: From January 2007 to September 2021, 633 treatment-naive patients with HCC with intermediate-stage HCC undergoing TACE were retrospectively enrolled. Of these patients, 386 patients received repeated TACE. The radiological features of HCC were evaluated by two radiologists and classified into encapsulated nodular type, simple nodular type with extranodular growth, confluent multinodular type, and infiltrative type. The objective response rate (ORR) and survival rate after initial and subsequent TACE among various radiologic morphologies were compared. Results: After initial TACE, encapsulated nodular type HCC had the highest ORR (58%), followed by extranodular type (45.8%), confluent multinodular type (29%), and infiltrative type (19.5%). Notably, radiologic pattern was highly associated with tumor burden. Tumor burden and radiologic morphology were significantly associated with ORR and overall survival (OS) in the multivariate analysis. In 386 patients with subsequent TACE, encapsulated nodular type HCC had the highest ORR (48.7%), followed by extranodular type (37.3%), confluent multinodular type (26.2%), and infiltrative type (10%). In the multivariate analysis, radiologic features were significant independent predictors of ORR and OS after receiving subsequent TACE. Conclusion: Radiologic patterns determine the outcomes of initial and subsequent TACE. Systemic therapy should be considered for patients with intermediate-stage HCC with unfavorable radiologic patterns.

16.
Resuscitation ; 196: 110120, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38266768

RESUMO

BACKGROUND: Early recognition of cardiac arrest and early initiation of bystander cardiopulmonary resuscitation can increase the survival of patients with out-of-hospital cardiac arrest (OHCA). We compared dispatcher-assisted cardiopulmonary resuscitation (DACPR) effectiveness before and after using different communication models in the dispatching center. METHOD: We analyzed dispatch recordings of non-trauma origin OHCA cases received by the Taichung dispatch center between May 1 to September 30, 2021, and November 1, 2021, to March 31, 2022. The dispatchers underwent an 8-hour training intervention consisting of targeted education using a new communication model for DACPR. Several outcome measures were evaluated, including the sustained return of spontaneous circulation and the time to first chest compression. RESULTS: We included 640 cases in the preintervention group and 580 cases in the postintervention group. The return of spontaneous circulation (ROSC) rate, the time to first chest compression, and good neurological outcome were significantly improved in the postintervention group (20.9% vs. 31.0%, p < 0.001;168 seconds vs. 151 seconds, p = 0.004; 2.8% vs. 5.3%, p = 0.024, respectively). In subgroup analyses, the intervention was related to a statistical improvement in ROSC rate among patients whose caller was a family member (18.7% vs. 31.4%, p < 0.001). Among patients whose caller was female, both ROSC and good neurological outcome significantly improved after the intervention (19.8% vs. 36.6%, p < 0.001; 2.7% vs. 7.5%, p = 0.006, respectively). There was a statistical difference between the pre-intervention and post-intervention group with respect to ROSC rate among patients whose caller was family (the adjusted odds ratio:1.78, 95% CI: 0.59-1.25], p < 0.001.) or female (the adjusted odds ratio:3.18,95% CI: 1.77-5.70], p = 0.008.) in the multivariable regression model. CONCLUSION: The new communication model has enhanced the effectiveness of DACPR in terms of the ROSC rate, particularly when the caller was a family member or female, leading to improved rates of ROSC and favorable neurological outcomes.


Assuntos
Reanimação Cardiopulmonar , Parada Cardíaca Extra-Hospitalar , Humanos , Feminino , Comunicação Persuasiva , Comunicação , Cognição , Parada Cardíaca Extra-Hospitalar/terapia
17.
J Formos Med Assoc ; 123(4): 487-495, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37852875

RESUMO

OBJECTIVE: The approved standard dose of pembrolizumab (200 mg administrated every 3 weeks) for cancer treatment imposes a significant financial burden on patients. However, no study has analyzed the clinical outcomes of low-dose pembrolizumab among individuals diagnosed with gynecologic cancer. The primary objective of this study was to assess the effectiveness and safety of a low-dose pembrolizumab regimen in real-world clinical practice. METHODS: We retrospectively assessed the efficacy and safety data of patients with gynecologic malignancies who received pembrolizumab between 2017 and 2022 at Kaohsiung Chang Gung Memorial Hospital. Furthermore, we conducted a comparative analysis of the objective response rate (ORR) and progression-free survival (PFS) between patients with deficient mismatch repair (dMMR) and proficient MMR (pMMR). RESULTS: A total of thirty-nine patients were included and received pembrolizumab at fixed dosages of 50 mg (5.1%), 100 mg (84.6%) and 200 mg (10.3%) per cycle. Compared to the pMMR group, the dMMR group exhibited a tendency toward improved ORR (45.5% vs. 13.0%, p = 0.074), and notably, the median duration of response remained unreached. There was no significant difference in PFS between the dMMR and pMMR groups; however, the patients with dMMR in tumor tissue had a trend of better survival (p = 0.079). Incidence of immune-related adverse events (irAEs) of any grade was observed in 13 patients (33.3%), with 3 individuals (7.7%) experiencing grade 3 or 4 events. CONCLUSION: Low-dose pembrolizumab may be a cost-effective and safe treatment option without compromising clinical outcomes in patients with refractory gynecologic cancers.


Assuntos
Neoplasias dos Genitais Femininos , Humanos , Feminino , Neoplasias dos Genitais Femininos/tratamento farmacológico , Neoplasias dos Genitais Femininos/genética , Neoplasias dos Genitais Femininos/induzido quimicamente , Estudos Retrospectivos , Anticorpos Monoclonais Humanizados/efeitos adversos , Intervalo Livre de Progressão
18.
Int Urol Nephrol ; 56(4): 1307-1313, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38044410

RESUMO

PURPOSE: Renal cysts are typically a benign condition, and parapelvic cysts are a type of renal cyst that occur adjacent to the renal pelvis or renal sinus. Parapelvic cysts can increase the risk for injury to adjacent organs or urine leakage during laparoscopic surgery. Flexible ureteroscopes with laser assistance were used to make internal incisions in cysts. Perioperative outcomes of this method were compared with those of laparoscopic surgery. METHODS: Eight-three patients, who underwent surgical treatment for renal cysts at the authors' medical center between January 2019 and June 2022, were evaluated. Two patients were excluded because they originally opted for RIRS but subsequently converted to laparoscopic surgery. Patients were divided into 2 groups based on surgery type: laparoscopic; and RIRS for internal incision. Outcomes in both groups were analyzed. RESULTS: Of the 81 patients analyzed, 60 [74% (group 1)] underwent laparoscopic surgery and 21 [26% (group 2)] underwent RIRS for internal incision. The median operative durations for groups 1 and 2 were 87 and 56 min, respectively (p < 0.001). Relative to RIRS, laparoscopic surgery resulted in greater postoperative painkiller use (laparoscopic surgery versus [vs.] RIRS, 43% vs. 19%; p = 0.047). The median length of hospital stay was 2 and 1 days, respectively (p < 0.001). CONCLUSIONS: RIRS demonstrated several advantages over laparoscopic surgery for the internal incision of parapelvic cysts, including shorter operative duration, shorter hospital stay, and less postoperative pain control. These findings may guide the selection of appropriate surgical approaches for patients with renal cysts.


Assuntos
Cistos , Cálculos Renais , Doenças Renais Císticas , Neoplasias Renais , Laparoscopia , Humanos , Laparoscopia/efeitos adversos , Laparoscopia/métodos , Ureteroscópios , Pelve Renal/cirurgia , Doenças Renais Císticas/cirurgia , Neoplasias Renais/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Cálculos Renais/cirurgia
19.
J Clin Anesth ; 92: 111306, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-37883902

RESUMO

STUDY OBJECTIVE: This meta-analysis aimed to compare the risk of brain swelling during craniotomy between propofol-based and volatile-based anesthesia. DESIGN: Meta-analysis of randomized controlled trials (RCTs). SETTING: Operating room. INTERVENTION: Propofol-based anesthesia. PATIENTS: Adult patients undergoing craniotomy. MEASUREMENTS: Databases, including EMBASE, MEDLINE, Google Scholar, and Cochrane Library, were searched from inception to April 2023. The primary outcome was the risk of brain swelling, while the secondary outcomes included the impact of anesthetic regimens on surgical and recovery outcomes, as well as the risk of hemodynamic instability. MAIN RESULTS: Our meta-analysis of 17 RCTs showed a significantly lower risk of brain swelling (risk ratio [RR]: 0.85, p = 0.03, I2 = 21%, n = 1976) in patients receiving propofol than in those using volatile agents, without significant differences in surgical time or blood loss between the two groups. Moreover, propofol was associated with a lower intracranial pressure (ICP) (mean difference: -4.06 mmHg, p < 0.00001, I2 = 44%, n = 409) as well as a lower risk of tachycardia (RR = 0.54, p = 0.005, I2 = 0%, n = 822) and postoperative nausea/vomiting (PONV) (RR = 0.59, p = 0.002, I2 = 19%, n = 1382). There were no significant differences in other recovery outcomes (e.g., extubation time), risk of bradycardia, hypertension, or hypotension between the two groups. Subgroup analysis indicated that propofol was not associated with a reduced risk of brain swelling when compared to individual volatile agents. Stratified by craniotomy indications, propofol reduced brain swelling in elective craniotomy, but not in emergency craniotomy (e.g., traumatic brain injury), when compared to volatile anesthetics. CONCLUSIONS: By reviewing the available evidence, our results demonstrate the beneficial effects of propofol on the risk of brain swelling, ICP, PONV, and intraoperative tachycardia. In emergency craniotomy for traumatic brain injury and subarachnoid hemorrhage, brain swelling showed no significant difference between propofol and volatile agents. Further large-scale studies are warranted for verification.


Assuntos
Anestésicos Inalatórios , Edema Encefálico , Lesões Encefálicas Traumáticas , Propofol , Adulto , Humanos , Anestesia por Inalação , Anestésicos Intravenosos/efeitos adversos , Edema Encefálico/epidemiologia , Edema Encefálico/etiologia , Edema Encefálico/prevenção & controle , Craniotomia/efeitos adversos , Náusea e Vômito Pós-Operatórios/epidemiologia , Náusea e Vômito Pós-Operatórios/etiologia , Náusea e Vômito Pós-Operatórios/prevenção & controle , Propofol/efeitos adversos , Taquicardia , Ensaios Clínicos Controlados Aleatórios como Assunto
20.
JAMA Oncol ; 10(3): 325-334, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38127335

RESUMO

Importance: The incidence of brain metastasis is increasing in patients with metastatic breast cancer. Treatments to extend the control of brain metastasis are urgently required. Objective: To investigate whether the addition of an induction treatment of bevacizumab, etoposide, and cisplatin (BEEP) improves brain-specific progression-free survival (PFS) after whole-brain radiotherapy (WBRT). Design, Setting, and Participants: This open-label, randomized, multicenter clinical trial assessed patients with brain metastases from breast cancer (BMBC) in Taiwan from September 9, 2014, to December 24, 2018, with survival follow-up until December 31, 2021. Key inclusion criteria included metastatic brain tumors not suitable for focal treatment, WBRT naivety, age 20 to 75 years, and at least 1 measurable brain metastatic lesion. The primary end point was brain-specific PFS, with an expected hazard ratio of 0.60, a 2-sided α ≤ .20, and power of 0.8. Interventions: Eligible patients were randomly assigned at a ratio of 2:1 to the experimental arm, which involved 3 cycles of BEEP followed by WBRT, or the control arm, which involved WBRT alone. Main Outcomes and Measures: The primary end point was the determination of brain-specific PFS by local investigators according to the Response Evaluation Criteria in Solid Tumors, version 1.1, the initiation of other brain-directed treatment after WBRT, or death. Other key end points included brain-specific objective response rate after 8 weeks of BEEP treatment or WBRT and 8-month brain-specific PFS rate, PFS, and overall survival. Results: A total of 118 patients with BMBC were randomized, with the intention-to-treat cohort comprising 112 patients. The median age was 56 years (range, 34-71 years), and 61 patients (54.5%) had ERBB2 (formerly HER2 or HER2/neu)-positive disease. The median (range) brain-specific PFS was 8.1 (0.3-29.5) vs 6.5 (0.9-25.5) months in the experimental and control arms, respectively (hazard ratio, 0.71; 95% CI, 0.44-1.13; P = .15; significant at predefined α ≤ .20). The brain-specific objective response rate at 2 months was not significantly different (BEEP treatment vs WBRT, 41.9% vs 52.6%), but the 8-month brain-specific PFS rate was significantly higher in the experimental group (48.7% vs 26.3%; P = .03). Adverse events were generally manageable with prophylactic granulocyte colony-stimulating factor treatment. Conclusions and Relevance: The findings show that induction BEEP before WBRT may improve the control of BMBC compared with using upfront WBRT, which could address an unmet need for an effective systemic treatment for intractable brain and extracranial metastases from metastatic breast cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT02185352.


Assuntos
Neoplasias Encefálicas , Neoplasias da Mama , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Bevacizumab/uso terapêutico , Encéfalo/patologia , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/radioterapia , Cisplatino/uso terapêutico , Etoposídeo/uso terapêutico
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