Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 244
Filtrar
1.
JMIR Med Inform ; 12: e63010, 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39357052

RESUMO

BACKGROUND: Generative artificial intelligence (GAI) systems by Google have recently been updated from Bard to Gemini and Gemini Advanced as of December 2023. Gemini is a basic, free-to-use model after a user's login, while Gemini Advanced operates on a more advanced model requiring a fee-based subscription. These systems have the potential to enhance medical diagnostics. However, the impact of these updates on comprehensive diagnostic accuracy remains unknown. OBJECTIVE: This study aimed to compare the accuracy of the differential diagnosis lists generated by Gemini Advanced, Gemini, and Bard across comprehensive medical fields using case report series. METHODS: We identified a case report series with relevant final diagnoses published in the American Journal Case Reports from January 2022 to March 2023. After excluding nondiagnostic cases and patients aged 10 years and younger, we included the remaining case reports. After refining the case parts as case descriptions, we input the same case descriptions into Gemini Advanced, Gemini, and Bard to generate the top 10 differential diagnosis lists. In total, 2 expert physicians independently evaluated whether the final diagnosis was included in the lists and its ranking. Any discrepancies were resolved by another expert physician. Bonferroni correction was applied to adjust the P values for the number of comparisons among 3 GAI systems, setting the corrected significance level at P value <.02. RESULTS: In total, 392 case reports were included. The inclusion rates of the final diagnosis within the top 10 differential diagnosis lists were 73% (286/392) for Gemini Advanced, 76.5% (300/392) for Gemini, and 68.6% (269/392) for Bard. The top diagnoses matched the final diagnoses in 31.6% (124/392) for Gemini Advanced, 42.6% (167/392) for Gemini, and 31.4% (123/392) for Bard. Gemini demonstrated higher diagnostic accuracy than Bard both within the top 10 differential diagnosis lists (P=.02) and as the top diagnosis (P=.001). In addition, Gemini Advanced achieved significantly lower accuracy than Gemini in identifying the most probable diagnosis (P=.002). CONCLUSIONS: The results of this study suggest that Gemini outperformed Bard in diagnostic accuracy following the model update. However, Gemini Advanced requires further refinement to optimize its performance for future artificial intelligence-enhanced diagnostics. These findings should be interpreted cautiously and considered primarily for research purposes, as these GAI systems have not been adjusted for medical diagnostics nor approved for clinical use.


Assuntos
Inteligência Artificial , Humanos , Diagnóstico Diferencial , Estudos Transversais
2.
PLoS One ; 19(9): e0309834, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39240836

RESUMO

BACKGROUND: Prognostic implications of peritoneal washing cytology (CY) in patients with localized pancreatic ductal adenocarcinoma (PDAC) undergoing surgical resection following preoperative chemoradiotherapy (CRT) remain unclear. This study aimed to elucidate the prognostic significance and predictors of a positive CY status (CY+) after preoperative CRT. METHODS: Clinical data from 141 patients with localized PDAC who underwent curative-intent resection after preoperative CRT were retrospectively analyzed to examine the association between CY+ and clinicopathological factors and survival. RESULTS: CY+ was observed in six patients (4.3%). The CY+ group exhibited significantly higher preoperative serum levels of CA19-9 and a substantially greater incidence of tumor location in the pancreatic body or tail, along with pathological invasion to the anterior pancreatic capsule, than the CY- group. The CY+ group had a significantly higher incidence of peritoneal recurrence compared with the CY- group (83.3% vs. 18.5%, p = 0.002). Overall survival (OS) and recurrence-free survival (RFS) after surgery were significantly shorter in the CY+ group than in the CY- group (CY+ vs. CY-: 18.3 vs. 46.2 months, p = 0.001, and 8.9 vs. 17.7 months, p = 0.009, respectively). Multivariate analyses identified CY+ as an independent prognostic factor for worse OS (hazard ratio 5.00, 95% confidence interval 1.03-12.31) and RFS (hazard ratio 2.58, 95% confidence interval 1.04-6.43). Local invasion grade on imaging before CRT, limited histological response to CRT, and absence of adjuvant chemotherapy were independent predictors of worse OS and RFS. CONCLUSION: Despite the relatively low incidence of CY+ after preoperative CRT, it emerged as an independent prognostic factor in patients with localized PDAC undergoing curative-intent resection following preoperative CRT.


Assuntos
Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Feminino , Masculino , Carcinoma Ductal Pancreático/terapia , Carcinoma Ductal Pancreático/patologia , Carcinoma Ductal Pancreático/cirurgia , Idoso , Pessoa de Meia-Idade , Prognóstico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/cirurgia , Estudos Retrospectivos , Quimiorradioterapia , Adulto , Idoso de 80 Anos ou mais , Lavagem Peritoneal/métodos , Citodiagnóstico/métodos , Recidiva Local de Neoplasia/patologia , Citologia
3.
Surg Today ; 2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39080038

RESUMO

PURPOSE: Despite descriptions of different pancreatojejunostomy procedures using robotic pancreaticoduodenectomy (RPD), a standardized procedure has not yet been established. No prior report has described pancreatojejunostomy by RPD combined with modified Blumgart anastomosis with continuous suturing for duct-to-mucosa anastomosis. This study investigated this surgical technique and evaluated the short-term outcomes of the simplified pancreatojejunostomy procedure. METHODS: Between December 2021 and March 2024, 36 patients underwent pancreatojejunostomy using modified Blumgart anastomosis with continuous suturing for duct-to-mucosa anastomosis using RPD. Patients were divided into an early group (n = 15), without the use of the new four-needle three-loop suture device during the modified Blumgart anastomosis and a late group (n = 21) that did use this device. RESULTS: The late group had a significantly shorter pancreatojejunostomy duration (60 min vs. 49 min, p = 0.004) than the early group. Both groups showed equivalent postoperative outcomes; however, the late group exhibited a trend toward a lower rate of postoperative pancreatic fistula grade ≥ B (26.7% vs. 4.8%, p = 0.138). CONCLUSIONS: Pancreatojejunostomy using modified Blumgart anastomosis with a four-needle three-loop suture device and continuous suture for duct-to-mucosa anastomosis in patients undergoing RPD is simple and effective. This new suturing device may further reduce the incidence of postoperative pancreatic fistulas.

4.
Surg Laparosc Endosc Percutan Tech ; 34(5): 472-478, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38989675

RESUMO

BACKGROUND: Minimally invasive spleen-preserving distal pancreatectomy with Warshaw procedure (MI-WP), has gained widespread recognition for the treatment of benign and low-grade malignant tumors of the pancreatic body and tail. However, the comparative advantages of the robotic Warshaw procedure (R-WP) over the laparoscopic Warshaw procedure (L-WP) remain uncertain. This study aimed to compare the surgical outcomes between R-WP and L-WP. MATERIALS AND METHODS: Among the 146 cases of MI-DP conducted between October 2020 and December 2023 (L-DP:115, R-DP:31), 33 cases of MI-WP were subjected to analysis, comprising the R-WP group (n=10) and the L-WP group (n=23). RESULTS: R-WP successfully completed all procedures under a purely laparoscopic approach, whereas L-WP necessitated conversion to open surgery in 2 cases (8.7%). Despite the significantly prolonged operative time in R-WP compared with L-WP (R-WP vs. L-WP: 421vs. 300 min), there was no significant difference in estimated blood loss between the 2 groups (R-WP vs. L-WP: 19 vs. 20 mL). Although the rate of major complications did not significantly differ between the 2 groups, 2 cases (8.7%) of L-WP required reoperation, including splenectomy in 1 instance. Furthermore, the incidence of postoperative splenic infarction was significantly higher in L-WP than in R-WP (R- vs. L-WP:0 vs. 43.5%, P =0.015). The length of hospital stay after surgery did not exhibit a significant difference between the 2 groups (R-WP vs. L-WP: 11 vs. 12 d). DISCUSSION: R-WP demonstrated superiority to L-WP for reducing the incidence of postoperative splenic infarction, potentially contributing to enhancing the spleen preservation rate.


Assuntos
Laparoscopia , Duração da Cirurgia , Tratamentos com Preservação do Órgão , Pancreatectomia , Complicações Pós-Operatórias , Procedimentos Cirúrgicos Robóticos , Infarto do Baço , Humanos , Procedimentos Cirúrgicos Robóticos/métodos , Masculino , Pancreatectomia/métodos , Pancreatectomia/efeitos adversos , Feminino , Laparoscopia/métodos , Laparoscopia/efeitos adversos , Pessoa de Meia-Idade , Infarto do Baço/cirurgia , Infarto do Baço/prevenção & controle , Infarto do Baço/etiologia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Incidência , Tratamentos com Preservação do Órgão/métodos , Idoso , Estudos Retrospectivos , Neoplasias Pancreáticas/cirurgia , Adulto , Baço/cirurgia , Baço/irrigação sanguínea , Tempo de Internação , Esplenectomia/métodos , Resultado do Tratamento
5.
Res Pract Thromb Haemost ; 8(4): 102439, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38993620

RESUMO

Background: Joint bleeding can lead to synovitis and arthropathy in people with hemophilia, reducing quality of life. Although early diagnosis is associated with improved therapeutic outcomes, diagnostic ultrasonography requires specialist experience. Artificial intelligence (AI) algorithms may support ultrasonography diagnoses. Objectives: This study will research, develop, and evaluate the diagnostic precision of an AI algorithm for detecting the presence or absence of hemarthrosis and synovitis in people with hemophilia. Methods: Elbow, knee, and ankle ultrasound images were obtained from people with hemophilia from January 2010 to March 2022. The images were used to train and test the AI models to estimate the presence/absence of hemarthrosis and synovitis. The primary endpoint was the area under the curve for the diagnostic precision to diagnose hemarthrosis and synovitis. Other endpoints were the rate of accuracy, precision, sensitivity, and specificity. Results: Out of 5649 images collected, 3435 were used for analysis. The area under the curve for hemarthrosis detection for the elbow, knee, and ankle joints was ≥0.87 and for synovitis, it was ≥0.90. The accuracy and precision for hemarthrosis detection were ≥0.74 and ≥0.67, respectively, and those for synovitis were ≥0.83 and ≥0.74, respectively. Analysis across people with hemophilia aged 10 to 60 years showed consistent results. Conclusion: AI models have the potential to aid diagnosis and enable earlier therapeutic interventions, helping people with hemophilia achieve healthy and active lives. Although AI models show potential in diagnosis, evidence is unclear on required control for abnormal findings. Long-term observation is crucial for assessing impact on joint health.

6.
Surg Case Rep ; 10(1): 165, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38954117

RESUMO

BACKGROUND: Hepatopancreatoduodenectomy (HPD) is a high-risk surgical procedure. Delayed division of the pancreatic parenchyma (DDPP) was reported as a novel technique in HPD for reducing postoperative pancreatic fistula. However, it is often difficult to dissect the pancreatic head nerve plexus while leaving the pancreatic parenchyma intact, particularly in patients with a bulky tumor with vascular invasion. Of the various reported approaches to the superior mesenteric artery, the right lateral approach can provide a useful surgical field to conduct DDPP in HPD. CASE PRESENTATION: A 78-year-old man visited a local clinic with itching and jaundice. Laboratory tests revealed elevated hepatobiliary enzyme, total bilirubin, and tumor markers. Enhanced computed tomography, endoscopic retrograde cholangiopancreatography, and intraductal ultrasonography of the bile duct were performed, and he was diagnosed with perihilar cholangiocarcinoma with invasion to the right hepatic artery (40 × 15 mm, Bismuth IIIa, cT3N0M0 cStage III). After neoadjuvant chemotherapy, he underwent left hepatectomy with caudate lobectomy, pancreatoduodenectomy, and combined resection of right hepatic artery using DDPP with a right lateral approach to the superior mesenteric artery. The pathological diagnosis was perihilar cholangiocarcinoma ypT3N1M0 ypStage IIIC, R0 resection. He was discharged on postoperative day 57 in good health and has been doing well for 6 months since the surgery. CONCLUSIONS: We present an effective application of the right lateral approach to the superior mesenteric artery in DDPP during HPD. This procedure can provide a clear surgical field to easily divide the pancreatic head nerve plexus before transection of the pancreatic parenchyma.

7.
Asian J Endosc Surg ; 17(3): e13336, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38923310

RESUMO

Achieving margin-negative resection is crucial in treatment of solid pseudopapillary neoplasm (SPN) of the pancreas, while preserving the spleen during distal pancreatectomy is highly desirable in pediatric cases. Laparoscopic Warshaw procedure (Lap-WT) is invaluable when tumor involvement in splenic vessels complicates preservation. However, the feasibility of Lap-WT in pediatric patients remains contentious. This study presents the clinical outcomes of three pediatric SPN cases who underwent Lap-WT. The median age was 10 years, with a median tumor size of 50 mm. Lap-WT demonstrated successful outcomes with a median operation time of 311 min and blood loss of 12 mL. No postoperative complications occurred, with a median length of hospital stay of 8 days. Long-term follow-up showed mild thrombocytopenia and increased spleen volume in two cases, perigastric varices in one, with no bleeding complications. No instances of tumor recurrence were observed. Lap-WT emerges as a feasible approach for pediatric SPN, ensuring spleen preservation without compromising oncological outcomes.


Assuntos
Estudos de Viabilidade , Laparoscopia , Pancreatectomia , Neoplasias Pancreáticas , Humanos , Laparoscopia/métodos , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/patologia , Criança , Feminino , Pancreatectomia/métodos , Masculino , Resultado do Tratamento , Adolescente , Carcinoma Papilar/cirurgia , Carcinoma Papilar/patologia , Duração da Cirurgia
8.
Surg Case Rep ; 10(1): 140, 2024 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-38861107

RESUMO

BACKGROUND: Absence of portal bifurcation is an extremely rare anomaly that should be recognized preoperatively, especially prior to a major hepatectomy. CASE PRESENTATION: A 45-year-old woman presented with abdominal pain, and abdominal computed tomography (CT) revealed dilatation of both the common bile duct (CBD) and intrahepatic bile duct (IHBD). Endoscopic retrograde cholangiopancreatography (ERCP) showed CBD and IHBD stones (B2 and B4). The CBD stones were removed, but the IHBD stones could not be, yet there was no evidence of malignancy at the site of IHBD stenosis. Enhanced CT revealed a dilated IHBD, while three-dimensional CT images showed the left portal vein running through the ventral side of the middle hepatic vein, which was diagnosed as the absence of portal vein bifurcation (APB). Laparoscopic left hepatectomy was successfully performed using real-time indocyanine green (ICG) fluorescence imaging. CONCLUSION: Surgeons should be aware of the possibility of APB, a rare portal vein anomaly, before performing major hepatectomy. Real-time ICG fluorescence imaging may be helpful to ensure the precise anatomy of the liver during laparoscopic surgery.

9.
J Cardiol Cases ; 29(6): 269-271, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38826769

RESUMO

Ductus venosus stenting via a transumbilical approach for pulmonary venous obstruction in infracardiac total anomalous pulmonary venous connection has been described. In a 902-gram infant who was diagnosed with asplenia syndrome and infracardiac total anomalous pulmonary venous connection, ductus venosus stenting was attempted by a transumbilical approach. However, ductus venosus stenting was discontinued due to bleeding from the portal vein. The bleeding subsided in time spontaneously, and total anomalous pulmonary venous connection repair with pulmonary artery banding was performed on 21 days after birth. To our knowledge, this is the first report that describes total anomalous pulmonary venous connection repair in a neonate under 1000 g body weight. Learning objective: Ductus venosus stenting is an effective palliative option, especially in the presence of high surgical risk, such as heterotaxy syndrome and a low birth weight. However, ductus venosus stenting should carefully be evaluated by assessment of anatomical configuration of umbilical vein and ductus venosus. If ductus venosus stenting is anatomically difficult, primary surgical repair may be an option even in an extremely low birth weight infant.

10.
Transl Psychiatry ; 14(1): 216, 2024 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-38806495

RESUMO

Genetic factors significantly affect the pathogenesis of psychiatric disorders. However, the specific pathogenic mechanisms underlying these effects are not fully understood. Recent extensive genomic studies have implicated the protocadherin-related 15 (PCDH15) gene in the onset of psychiatric disorders, such as bipolar disorder (BD). To further investigate the pathogenesis of these psychiatric disorders, we developed a mouse model lacking Pcdh15. Notably, although PCDH15 is primarily identified as the causative gene of Usher syndrome, which presents with visual and auditory impairments, our mice with Pcdh15 homozygous deletion (Pcdh15-null) did not exhibit observable structural abnormalities in either the retina or the inner ear. The Pcdh15-null mice showed very high levels of spontaneous motor activity which was too disturbed to perform standard behavioral testing. However, the Pcdh15 heterozygous deletion mice (Pcdh15-het) exhibited enhanced spontaneous locomotor activity, reduced prepulse inhibition, and diminished cliff avoidance behavior. These observations agreed with the symptoms observed in patients with various psychiatric disorders and several mouse models of psychiatric diseases. Specifically, the hyperactivity may mirror the manic episodes in BD. To obtain a more physiological, long-term quantification of the hyperactive phenotype, we implanted nano tag® sensor chips in the animals, to enable the continuous monitoring of both activity and body temperature. During the light-off period, Pcdh15-null exhibited elevated activity and body temperature compared with wild-type (WT) mice. However, we observed a decreased body temperature during the light-on period. Comprehensive brain activity was visualized using c-Fos mapping, which was assessed during the activity and temperature peak and trough. There was a stark contrast between the distribution of c-Fos expression in Pcdh15-null and WT brains during both the light-on and light-off periods. These results provide valuable insights into the neural basis of the behavioral and thermal characteristics of Pcdh15-deletion mice. Therefore, Pcdh15-deletion mice can be a novel model for BD with mania and other psychiatric disorders, with a strong genetic component that satisfies both construct and surface validity.


Assuntos
Transtorno Bipolar , Temperatura Corporal , Caderinas , Modelos Animais de Doenças , Locomoção , Camundongos Knockout , Animais , Masculino , Camundongos , Comportamento Animal , Transtorno Bipolar/genética , Transtorno Bipolar/fisiopatologia , Caderinas/genética , Ritmo Circadiano/genética , Ritmo Circadiano/fisiologia , Locomoção/genética , Camundongos Endogâmicos C57BL , Inibição Pré-Pulso/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Proteínas Proto-Oncogênicas c-fos/genética , Protocaderinas
11.
PLoS One ; 19(5): e0292628, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38748746

RESUMO

Hepatic ischemia-reperfusion injury causes liver damage during surgery. In hepatic ischemia-reperfusion injury, the blood coagulation cascade is activated, causing microcirculatory incompetence and cellular injury. Coagulation factor Xa (FXa)- protease-activated receptor (PAR)-2 signaling activates inflammatory reactions and the cytoprotective effect of FXa inhibitor in several organs. However, no studies have elucidated the significance of FXa inhibition on hepatic ischemia-reperfusion injury. The present study elucidated the treatment effect of an FXa inhibitor, edoxaban, on hepatic ischemia-reperfusion injury, focusing on FXa-PAR-2 signaling. A 60 min hepatic partial-warm ischemia-reperfusion injury mouse model and a hypoxia-reoxygenation model of hepatic sinusoidal endothelial cells were used. Ischemia-reperfusion injury mice and hepatic sinusoidal endothelial cells were treated and pretreated, respectively with or without edoxaban. They were incubated during hypoxia/reoxygenation in vitro. Cell signaling was evaluated using the PAR-2 knockdown model. In ischemia-reperfusion injury mice, edoxaban treatment significantly attenuated fibrin deposition in the sinusoids and liver histological damage and resulted in both anti-inflammatory and antiapoptotic effects. Hepatic ischemia-reperfusion injury upregulated PAR-2 generation and enhanced extracellular signal-regulated kinase 1/2 (ERK 1/2) activation; however, edoxaban treatment reduced PAR-2 generation and suppressed ERK 1/2 activation in vivo. In the hypoxia/reoxygenation model of sinusoidal endothelial cells, hypoxia/reoxygenation stress increased FXa generation and induced cytotoxic effects. Edoxaban protected sinusoidal endothelial cells from hypoxia/reoxygenation stress and reduced ERK 1/2 activation. PAR-2 knockdown in the sinusoidal endothelial cells ameliorated hypoxia/reoxygenation stress-induced cytotoxicity and suppressed ERK 1/2 phosphorylation. Thus, edoxaban ameliorated hepatic ischemia-reperfusion injury in mice by protecting against micro-thrombosis in sinusoids and suppressing FXa-PAR-2-induced inflammation in the sinusoidal endothelial cells.


Assuntos
Inibidores do Fator Xa , Fígado , Sistema de Sinalização das MAP Quinases , Piridinas , Receptor PAR-2 , Traumatismo por Reperfusão , Tiazóis , Animais , Masculino , Camundongos , Modelos Animais de Doenças , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/metabolismo , Inibidores do Fator Xa/farmacologia , Fígado/efeitos dos fármacos , Fígado/metabolismo , Fígado/patologia , Fígado/irrigação sanguínea , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Piridinas/farmacologia , Receptor PAR-2/efeitos dos fármacos , Receptor PAR-2/metabolismo , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Tiazóis/farmacologia , Tiazóis/uso terapêutico
12.
Cancer Diagn Progn ; 4(3): 244-249, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38707740

RESUMO

Background/Aim: The regimen with nanoliposomal irinotecan plus 5-fluorouracil and L-leucovorin (nal-IRI/FL) is used for metastatic pancreatic cancer. A clinical study has indicated that the uridine diphosphate-glucuronosyltransferase (UGT) 1A1 polymorphism is associated with neutropenia during nal-IRI/FL treatment; however, no studies have reported risk factors for the occurrence of adverse events in the clinical setting. This study aimed to explore the risk factors for adverse events of nal-IRI/FL. Patients and Methods: This study included patients with metastatic pancreatic cancer who started nal-IRI/FL treatment. Patient information, including laboratory data before nal-IRI/FL initiation and adverse events during nal-IRI/FL treatment, was retrospectively obtained from medical records. Results: This study consisted of 36 patients, including 16, 16, and 4 with UGT1A1*6 or *28 wild-type (-/-), heterozygous (+/-), and homozygous (+/+), respectively. Patients with UGT1A1*6 or *28 (+/+) exhibited significantly lower nadir counts of white blood cells (p=0.033) and neutrophils (p=0.043). Multiple regression analyses revealed that the decreased white blood cell count was significantly associated with the genotype of UGT1A1*6 or *28 (+/+) (p=0.009), high aspartate aminotransferase (AST) value before the therapy (p=0.019), and pancreatic head cancer (p=0.030). Also, the decreased neutrophil count was significantly related to the genotype of UGT1A1*6 or *28 (+/+) (p=0.017). Conclusion: Patients with UGT1A1*6 or *28 (+/+) should be especially concerned about neutropenia and leukopenia during nal-IRI/FL treatment. Additionally, high AST value and pancreatic head cancer may be risk factors for leukopenia during nal-IRI/FL treatment.

13.
Crohns Colitis 360 ; 6(2): otae024, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38711858

RESUMO

Background: Real-world data regarding ustekinumab (UST) for ulcerative colitis (UC) particularly in biologics-naïve patients is currently limited. This study aimed to elucidate the real-world effectiveness and safety of UST for UC. Methods: Overall, 150 patients with UC treated with UST from March 2020 to January 2023 were enrolled across 7 referral hospitals. To assess the clinical efficacy and persistence of UST, retrospective analyses were conducted from weeks 8 to 56. Predictive factors concerning the response and persistence of UST were examined through univariate and multivariate analyses. Results: Of the 150 patients, 125 received UST for remission induction, including 36% biologics-naïve. The response and remission rates were 72.8% and 56.0% at week 8 and 73.2% and 63.4% at week 56, respectively. Biologics-naïve patients represented higher response and remission rates at week 8 (84.4% and 73.3%) than those with biologics exposure (66.2% and 46.2%). Patients with prior antitumor necrosis factor (anti-TNF) and vedolizumab (VDZ) exposure had relatively lower response and remission rates (34.5% and 24.1%, respectively). The 1-year cumulative persistence rate was 84.0%. Multivariate analysis revealed that the chronic continuous type and prior anti-TNF and VDZ exposure were negative predictive factors for week 8 responsiveness. Clinical response at week 8 was a predictor of 1-year persistence. Adverse event incidence remained notably low at 6.4%. Conclusions: This study highlights the safety and effectiveness of UST as an induction and maintenance therapy for UC. Chronic continuous type and previous anti-TNF and VDZ exposure negatively contributed to short-term effectiveness, whereas short-term effectiveness provided good persistency.

14.
Ther Drug Monit ; 46(5): 687-691, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38648649

RESUMO

BACKGROUND: Brexpiprazole is a second-generation antipsychotic approved in Japan in 2018; however, information on placental passage and breast milk transfer remains limited. In this report, the patient, a 30-year-old pregnant woman with schizophrenia, was medicated with brexpiprazole, risperidone, and quetiapine. METHODS: The study used high-performance liquid chromatography-tandem mass spectrometry to determine the concentrations of brexpiprazole, quetiapine, risperidone, and its active metabolite (paliperidone) in maternal and neonatal plasma, cord venous plasma, and breast milk. Maternal plasma samples were obtained approximately 2 and 8 hours after the last administration of antipsychotics on the day of delivery and at the estimated drugs' trough time on days 1, 3, and 5 after delivery. RESULTS: The maternal plasma concentrations of brexpiprazole, quetiapine, and paliperidone increased by approximately 3.5-fold on the fifth day compared with those on the day of delivery, whereas the risperidone concentration remained almost constant. Moreover, the neonatal plasma concentrations of the 4 drugs immediately after birth were indistinguishable from the umbilical cord concentrations and gradually decreased, except for risperidone. Relative infant doses of these compounds were below 1.1%. CONCLUSIONS: Pregnancy status notably alters the pharmacokinetic properties of antipsychotics. Therefore, close and careful monitoring of clinical symptoms should be considered during pregnancy and after delivery. Although brexpiprazole is transferred to neonates through the placenta, breastfeeding is still possible because the relative infant dose value of this drug was much less than 10%.


Assuntos
Antipsicóticos , Leite Humano , Palmitato de Paliperidona , Período Pós-Parto , Fumarato de Quetiapina , Quinolonas , Risperidona , Esquizofrenia , Tiofenos , Humanos , Feminino , Palmitato de Paliperidona/farmacocinética , Palmitato de Paliperidona/uso terapêutico , Adulto , Fumarato de Quetiapina/farmacocinética , Fumarato de Quetiapina/uso terapêutico , Antipsicóticos/farmacocinética , Antipsicóticos/sangue , Antipsicóticos/uso terapêutico , Gravidez , Risperidona/farmacocinética , Risperidona/sangue , Risperidona/uso terapêutico , Leite Humano/metabolismo , Leite Humano/química , Recém-Nascido , Esquizofrenia/tratamento farmacológico , Esquizofrenia/metabolismo , Tiofenos/farmacocinética , Tiofenos/sangue , Quinolonas/farmacocinética , Quinolonas/sangue , Quinolonas/uso terapêutico , Espectrometria de Massas em Tandem/métodos , Sangue Fetal/química , Sangue Fetal/metabolismo , Complicações na Gravidez/tratamento farmacológico
15.
Surg Today ; 54(8): 953-963, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38581555

RESUMO

PURPOSE: Predicting nonalcoholic fatty liver disease (NAFLD) following pancreaticoduodenectomy (PD) is challenging, which delays therapeutic intervention and makes its prevention difficult. We conducted this study to assess the potential application of preoperative computed tomography (CT) radiomics for predicting NAFLD. METHODS: The subjects of this retrospective study were 186 patients with PD from a single institution. We extracted the predictors of NAFLD after PD statistically from conventional clinical and radiomic features of the estimated remnant pancreas and whole liver region on preoperative nonenhanced CT images. Based on these predictors, we developed a machine-learning predictive model, which integrated clinical and radiomic features. A comparative model used only clinical features as predictors. RESULTS: The incidence of NAFLD after PD was 43.5%. The variables of the clinicoradiomic model included one shape feature of the pancreas, two texture features of the liver, and sex; the variables of the clinical model were age, sex, and chemoradiotherapy. The accuracy%, precision%, recall%, F1 score, and area under the curve of the two models were 75.0, 72.7, 66.7, 69.6, and 0.80; and 69.6, 68.4, 54.2, 60.5, and 0.69, respectively. CONCLUSIONS: Preoperative CT-derived radiomic features from the pancreatic and liver regions are promising for the prediction of NAFLD post-PD. Using these features enhances the predictive model, enabling earlier intervention for high-risk patients.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Pancreaticoduodenectomia , Complicações Pós-Operatórias , Tomografia Computadorizada por Raios X , Humanos , Pancreaticoduodenectomia/efeitos adversos , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Hepatopatia Gordurosa não Alcoólica/etiologia , Masculino , Estudos Retrospectivos , Feminino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/diagnóstico por imagem , Complicações Pós-Operatórias/epidemiologia , Idoso , Aprendizado de Máquina , Valor Preditivo dos Testes , Pâncreas/diagnóstico por imagem , Pâncreas/patologia , Adulto , Fígado/diagnóstico por imagem , Fígado/patologia , Período Pré-Operatório , Incidência , Idoso de 80 Anos ou mais , Radiômica
16.
Cureus ; 16(4): e57516, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38572179

RESUMO

Introduction In our previous work, we investigated the analgesic effects of ibuprofen gargle after mandibular third molar extractions. However, a subsequent detailed review of individual patient data revealed variations in postoperative pain reduction among patients. Consequently, the present study was designed to conduct post-hoc subanalyses that identified factors contributing to variation in the analgesic response to ibuprofen gargle after third molar extractions. Materials and methods This study involved thirty-five Japanese patients from a prior randomized, double-blind, placebo-controlled, crossover study, which focused on the analgesic effects of ibuprofen gargle after mandibular third molar extractions. Participants were categorized as responders (n = 13) and non-responders (n = 22) based on the within-subject difference (ibuprofen-placebo, IP) of visual analog scale (VAS) changes. Baseline characteristics were compared, along with variables, such as age, sex, the reason for extraction, extraction site, Pell Gregory (space and depth) classification, Winter's classification, surgeon's experience, and surgery time. Baseline characteristics predicting responder status were examined using multivariate logistic regression. Results In the univariate analysis, variables such as age, sex, and baseline VAS scores with p-values <0.2 were evaluated using a stepwise approach. This analysis identified age (per -10 years) with an odds ratio of 4.163 (95% confidence interval (CI): 1.170-31.952, p = 0.0233) and sex (female) with an odds ratio of 9.977 (95% CI: 1.336-208.256, p = 0.0213) as significant predictors of responder status. Conclusions In young and female patients, ibuprofen gargle decreased postoperative pain after mandibular third molar extractions.

17.
Bioorg Chem ; 147: 107316, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38583246

RESUMO

Ras GTPases and other CaaX proteins undergo multiple post-translational modifications at their carboxyl-terminus. These events initiate with prenylation of a cysteine and are followed by endoproteolytic removal of the 'aaX' tripeptide and carboxylmethylation. Some CaaX proteins are only subject to prenylation, however, due to the presence of an uncleavable sequence. In this study, uncleavable sequences were used to stage Ras isoforms in a farnesylated and uncleaved state to address the impact of CaaX proteolysis on protein localization and function. This targeted strategy is more specific than those that chemically inhibit the Rce1 CaaX protease or delete the RCE1 gene because global abrogation of CaaX proteolysis impacts the entire CaaX protein proteome and effects cannot be attributed to any specific CaaX protein of the many concurrently affected. With this targeted strategy, clear mislocalization and reduced activity of farnesylated and uncleaved Ras isoforms was observed. In addition, new peptidomimetics based on cleavable Ras CaaX sequences and the uncleavable CAHQ sequence were synthesized and tested as Rce1 inhibitors using in vitro and cell-based assays. Consistently, these non-hydrolyzable peptidomimetic Rce1 inhibitors recapitulate Ras mislocalization effects when modeled on cleavable but not uncleavable CaaX sequences. These findings indicate that a prenylated and uncleavable CaaX sequence, which can be easily applied to a wide range of mammalian CaaX proteins, can be used to probe the specific impact of CaaX proteolysis on CaaX protein properties under conditions of an otherwise normally processed CaaX protein proteome.


Assuntos
Proteínas ras , Humanos , Proteínas ras/metabolismo , Proteínas ras/antagonistas & inibidores , Proteínas ras/genética , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , Bibliotecas de Moléculas Pequenas/síntese química , Proteólise/efeitos dos fármacos , Estrutura Molecular , Peptidomiméticos/farmacologia , Peptidomiméticos/química , Peptidomiméticos/síntese química , Endopeptidases
18.
JMIR Med Inform ; 12: e55627, 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38592758

RESUMO

BACKGROUND: In the evolving field of health care, multimodal generative artificial intelligence (AI) systems, such as ChatGPT-4 with vision (ChatGPT-4V), represent a significant advancement, as they integrate visual data with text data. This integration has the potential to revolutionize clinical diagnostics by offering more comprehensive analysis capabilities. However, the impact on diagnostic accuracy of using image data to augment ChatGPT-4 remains unclear. OBJECTIVE: This study aims to assess the impact of adding image data on ChatGPT-4's diagnostic accuracy and provide insights into how image data integration can enhance the accuracy of multimodal AI in medical diagnostics. Specifically, this study endeavored to compare the diagnostic accuracy between ChatGPT-4V, which processed both text and image data, and its counterpart, ChatGPT-4, which only uses text data. METHODS: We identified a total of 557 case reports published in the American Journal of Case Reports from January 2022 to March 2023. After excluding cases that were nondiagnostic, pediatric, and lacking image data, we included 363 case descriptions with their final diagnoses and associated images. We compared the diagnostic accuracy of ChatGPT-4V and ChatGPT-4 without vision based on their ability to include the final diagnoses within differential diagnosis lists. Two independent physicians evaluated their accuracy, with a third resolving any discrepancies, ensuring a rigorous and objective analysis. RESULTS: The integration of image data into ChatGPT-4V did not significantly enhance diagnostic accuracy, showing that final diagnoses were included in the top 10 differential diagnosis lists at a rate of 85.1% (n=309), comparable to the rate of 87.9% (n=319) for the text-only version (P=.33). Notably, ChatGPT-4V's performance in correctly identifying the top diagnosis was inferior, at 44.4% (n=161), compared with 55.9% (n=203) for the text-only version (P=.002, χ2 test). Additionally, ChatGPT-4's self-reports showed that image data accounted for 30% of the weight in developing the differential diagnosis lists in more than half of cases. CONCLUSIONS: Our findings reveal that currently, ChatGPT-4V predominantly relies on textual data, limiting its ability to fully use the diagnostic potential of visual information. This study underscores the need for further development of multimodal generative AI systems to effectively integrate and use clinical image data. Enhancing the diagnostic performance of such AI systems through improved multimodal data integration could significantly benefit patient care by providing more accurate and comprehensive diagnostic insights. Future research should focus on overcoming these limitations, paving the way for the practical application of advanced AI in medicine.

20.
Life Sci Alliance ; 7(5)2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38373797

RESUMO

Skeletal muscle development is a highly ordered process orchestrated transcriptionally by the myogenic regulatory factors. However, the downstream molecular mechanisms of myogenic regulatory factor functions in myogenesis are not fully understood. Here, we identified the RNA-binding protein Musashi2 (Msi2) as a myogenin target gene and a post-transcriptional regulator of myoblast differentiation. Msi2 knockdown in murine myoblasts blocked differentiation without affecting the expression of MyoD or myogenin. Msi2 overexpression was also sufficient to promote myoblast differentiation and myocyte fusion. Msi2 loss attenuated autophagosome formation via down-regulation of the autophagic protein MAPL1LC3/ATG8 (LC3) at the early phase of myoblast differentiation. Moreover, forced activation of autophagy effectively suppressed the differentiation defects incurred by Msi2 loss. Consistent with its functions in myoblasts in vitro, mice deficient for Msi2 exhibited smaller limb skeletal muscles, poorer exercise performance, and muscle fiber-type switching in vivo. Collectively, our study demonstrates that Msi2 is a novel regulator of mammalian myogenesis and establishes a new functional link between muscular development and autophagy regulation.


Assuntos
Desenvolvimento Muscular , Músculo Esquelético , Animais , Camundongos , Miogenina/genética , Miogenina/metabolismo , Músculo Esquelético/metabolismo , Desenvolvimento Muscular/genética , Autofagia/genética , Proteínas de Ligação a RNA/genética , Mamíferos/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA