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1.
J Cardiol Cases ; 30(2): 47-50, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39170921

RESUMO

A 65-year-old man with no-option chronic limb-threatening ischemia underwent percutaneous deep venous arterialization (pDVA). An arteriovenous fistula (AVF) was created using a modified venous arterialization simplified technique. During the balloon dilation of the AVF site, the venous puncture site was accidentally also dilated, resulting in massive bleeding. The angiographic bleeding was controlled by stent graft deployment, and the final angiography revealed good DVA flow. Two weeks post-pDVA, the patient developed right shin pain. Suspecting a subcutaneous hematoma and infection, extensive debridement was performed. The patient's wounds completely healed approximately 7 months after the pDVA. Learning Objective: Modified venous arterialization simplified technique (m-VAST) is a feasible technique for percutaneous deep venous arterialization; however, it may lead to unexpected complications. When performing m-VAST, the possibility of puncture site complications should be carefully considered.

2.
ACS Pharmacol Transl Sci ; 7(8): 2401-2413, 2024 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-39144550

RESUMO

In the field of radiopharmaceutical development targeting cancer, an albumin binder (ALB) is commonly used to improve accumulation of radioligands in tumors because it has high binding affinity for albumin and extends the circulation time of radioligands. The further development of ALB-containing radioligands is also expected to regulate their pharmacokinetics. In this study, we newly designed and synthesized [111In]In-PNT-DA1 derivatives, prostate-specific membrane antigen (PSMA)-targeting radioligands including a functional linker (d-glutamic acid or 4-(aminomethyl)benzoic acid), and evaluated the relationships among the structure, albumin-binding affinity, and pharmacokinetics. These derivatives showed a different binding affinity for albumin by the introduction of a linker. Biodistribution studies revealed that the introduction of a linker affects the pharmacokinetics of each derivative. The biodistribution studies also suggested that moderate albumin-binding affinity enhances the tumor/kidney ratio of the derivative. SPECT imaging using [111In]In-PNT-DA3 with the highest tumor/kidney ratio among [111In]In-PNT-DA1 derivatives led to clear visualization of a PSMA-positive LNCaP tumor. The results suggest that the appropriate introduction of linker entities may be necessary to improve the pharmacokinetics of PSMA-targeting radioligands.

3.
PLoS One ; 19(8): e0307978, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39141600

RESUMO

The generalization of deep neural network algorithms to a broader population is an important challenge in the medical field. We aimed to apply self-supervised learning using masked autoencoders (MAEs) to improve the performance of the 12-lead electrocardiography (ECG) analysis model using limited ECG data. We pretrained Vision Transformer (ViT) models by reconstructing the masked ECG data with MAE. We fine-tuned this MAE-based ECG pretrained model on ECG-echocardiography data from The University of Tokyo Hospital (UTokyo) for the detection of left ventricular systolic dysfunction (LVSD), and then evaluated it using multi-center external validation data from seven institutions, employing the area under the receiver operating characteristic curve (AUROC) for assessment. We included 38,245 ECG-echocardiography pairs from UTokyo and 229,439 pairs from all institutions. The performances of MAE-based ECG models pretrained using ECG data from UTokyo were significantly higher than that of other Deep Neural Network models across all external validation cohorts (AUROC, 0.913-0.962 for LVSD, p < 0.001). Moreover, we also found improvements for the MAE-based ECG analysis model depending on the model capacity and the amount of training data. Additionally, the MAE-based ECG analysis model maintained high performance even on the ECG benchmark dataset (PTB-XL). Our proposed method developed high performance MAE-based ECG analysis models using limited ECG data.


Assuntos
Eletrocardiografia , Redes Neurais de Computação , Humanos , Eletrocardiografia/métodos , Masculino , Feminino , Aprendizado de Máquina Supervisionado , Pessoa de Meia-Idade , Curva ROC , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Esquerda/diagnóstico , Idoso , Algoritmos , Ecocardiografia/métodos , Aprendizado Profundo , Adulto
4.
Nucl Med Biol ; 138-139: 108945, 2024 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-39153354

RESUMO

INTRODUCTION: Prostate-specific membrane antigen (PSMA) is a promising target for treating metastatic castration-resistant prostate cancer. Our previous report presented 111In- or 225Ac-labeled PSMA-NAT-DA1 (PNT-DA1) as a PSMA-targeted ligand. To improve its therapeutic efficiency, PNT-DA1 contains 4-(p-iodophenyl)butyric acid (IPBA), which is known as an albumin binder (ALB) moiety. However, few reports have examined the relationship between the chemical modification of the ALB moiety and pharmacokinetics of PSMA-targeted radioligands. To assess this relationship, we designed, synthesized, and evaluated four [111In]In-PNT-DA1 analogues with ALB moieties different from IPBA. METHODS: The [111In]In-PNT-DA1 analogues were synthesized from their corresponding precursors through ligand substitution reaction. The stability of [111In]In-PNT-DA1 analogues in mouse plasma, their affinity for human serum albumin (HSA), their binding to mouse plasma proteins, and their affinity for PSMA were evaluated in vitro. The tissue distribution profile of the radioligands was assessed in biodistribution studies using LNCaP tumor-bearing nude mice. RESULTS: All [111In]In-PNT-DA1 analogues were obtained at a high radiochemical yield and purity. These analogues were highly stable in mouse plasma after 24 h. The binding affinity for HSA significantly varied among the different ALB moieties. Moreover, high affinity for mouse plasma proteins was observed for all [111In]In-PNT-DA1 analogues compared with their counterparts without an ALB moiety. The affinity for PSMA was comparable for all radioligands. In the biodistribution assay, the pharmacokinetics of [111In]In-PNT-DA1 analogues varied markedly depending on the type of ALB moiety. In particular, tumor area under the curve (AUC) values were increased for radioligands with higher blood retention, while some previous studies reported that compounds with moderate blood retention exhibited the highest tumor AUC values. CONCLUSION: The introduction of an appropriate ALB moiety into the ligand may lead to the development of more useful PSMA-targeted radioligands with higher tumor accumulation.

5.
J Orthop Res ; 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39162144

RESUMO

To clarify the relevance of physical activity (PA) with respect to a decrease in minimal joint space (MJS) of the nonoperative hip in female patients at 24 months post-contralateral total hip arthroplasty (THA). This prospective cohort study was conducted from six to 24 months post-THA. The subjects were 85 female patients with hip osteoarthritis (OA) who had undergone unilateral THA. The primary outcome was a change in MJS (ΔMJS). Daily step counts and moderate to vigorous physical activity were measured. To identify factors related to ΔMJS, a generalized linear model approach was used, with adjustment factors, Kellgren-Lawrence (KL) grade, PA, and interaction terms between PA and KL grade as explanatory variables. The interaction term between daily step count and KL grade was significant. The regression coefficient of the daily step count for ΔMJS was significant in the KL ≥ 1 group, but not in the KL = 0 group. A model with adjustment factors, an interaction term, and PA showed that the daily step count increased ΔMJS. PA was related to ΔMJS of the nonoperative hip in female patients with KL grade ≥1, but was not related to ΔMJS in patients without OA post-THA. Excessive daily step count may be a risk factor for a decrease in MJS of the nonoperative hip.

6.
J Labelled Comp Radiopharm ; 67(10): 341-348, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39107085

RESUMO

Radioimmunoconjugates (RICs) composed of tumor-targeting monoclonal antibodies and radionuclides have been developed for diagnostic and therapeutic application. A new radiolabeling method using microfluidic devices is expected to facilitate simpler and more rapid synthesis of RICs. In the microfluidic method, microfluidic chips can promote the reaction between reactants by mixing them efficiently, and pumping systems enable automated synthesis. In this study, we synthesized RICs by the pre-labeling method, in which the radiometal is coordinated to the chelator and then the radiolabeled chelator is incorporated into the antibodies, using microfluidic devices for the first time. As a result of examining the reaction parameters including the material of mixing units, reaction temperature, and flow rate, RICs with radiochemical purity (RCP) exceeding 90% were obtained. These high-purity RICs were successfully synthesized without any purification simply by pumping three solutions of a chelating agent, radiometal, and antibody into microfluidic devices. Under the same conditions, the RCP of RICs labeled by conventional methods was below 50%. These findings indicate the utility of microfluidic devices for automatic and rapid synthesis of high-quality RICs.


Assuntos
Imunoconjugados , Marcação por Isótopo , Imunoconjugados/química , Técnicas Analíticas Microfluídicas/métodos , Técnicas Analíticas Microfluídicas/instrumentação , Anticorpos Monoclonais/química , Quelantes/química , Dispositivos Lab-On-A-Chip , Automação , Compostos Radiofarmacêuticos/química , Compostos Radiofarmacêuticos/síntese química
7.
J Arrhythm ; 40(4): 991-997, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39139888

RESUMO

Background: Insertion of electrode catheters into the coronary sinus (CS) through the right internal jugular vein (RIJV) carries risks of pneumothorax and severe hematoma formation. This study was performed to compare the safety and feasibility of catheterization through the left cubital superficial vein versus the RIJV. Methods: This prospective nonrandomized study involved consecutive patients who underwent catheter ablation from September 2021 to February 2023. Blind puncture techniques were used in the left cubital vein group; ultrasound-guided insertion was performed in the RIJV group. The success rates of sheath insertion and CS catheterization, the procedure and fluoroscopy times of CS cannulation, and complications were compared between groups. Results: The left cubital vein group comprised 152 patients, and the RIJV group comprised 58 patients. The sheath insertion success rate was significantly lower in the cubital vein group than in the RIJV group (84.9% vs 100%, respectively; p = .0008). In the cubital vein group, blind puncture attempts failed in 20 patients; three patients developed guidewire-induced venous injury. One arterial puncture occurred in the RIJV group. After successful sheath insertion, no significant differences were observed in the CS cannulation success rate (97% vs 100%, p = .55), procedure time (median [range], 93 [51-174] vs 74 [44-129] s; p = .19), or fluoroscopy time (median [range], 66 [36-134] vs 48 [30-92] s; p = .17). No serious complications requiring procedural discontinuation occurred. Conclusion: The left cubital vein approach is practical, offering a viable alternative to the RIJV approach.

9.
Artigo em Inglês | MEDLINE | ID: mdl-39102067

RESUMO

PURPOSE: This study examined whether patient-reported measures (PRMs) addressing quality of life, personal agency, functional impairment, and treatment satisfaction at hospital discharge were associated with future readmission during a 12-month follow-up period. The study also examined whether readmission influenced changes in the same measures. METHODS: A multicenter prospective cohort study was conducted at 21 psychiatric hospitals in Japan. Participants completed the EuroQol-five-dimensions-five-level (EQ-5D), the Five-item Subjective Personal Agency Scale, and the Sheehan Disability Scale (SDS) at the time of index admission (T1), discharge from index admission (T2), and 6 months (T3) and 12 months (T4) after discharge. Inpatient treatment satisfaction was assessed at T2. Readmission and variables potentially associated with hospitalization and PRMs were evaluated using mixed-effects logistic regression models and mixed models for repeated measures. RESULTS: A total of 491 participants were followed for 12 months (attrition rate: 19.4%), and 480 were included in the EQ-5D analysis. The most common diagnoses were schizophrenia (59%), depression (14%), and bipolar disorder (13%). No patient-reported measures were significantly associated with readmission over the follow-up period. Interaction of readmission and time did not significantly affect changes in EQ-5D. Readmission did significantly influence SDS score changes between T2 and T3 (B = 1.78, 95% CI = 0.30-3.25, p = 0.018) and between T3 and T4 (B = 1.43, 95% CI = 0.14-2.72, p = 0.029). The same influence of readmission on SDS score changes was not observed in the model which adjusted for all potential covariates. CONCLUSION: Readmission was potentially associated with changes in self-reported functional impairment. Findings highlight the potential role of intensive post-discharge services in preventing readmission, rather than relying on time-of-discharge PRMs in order to predict readmission risk. TRIAL REGISTRATION: This study was registered in UMIN Clinical Trials Registry (UMIN000034220).

10.
Ann Nucl Med ; 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38976087

RESUMO

OBJECTIVE: Prostate-specific membrane antigen (PSMA) is a well-known biomarker of prostate cancer. Previously, our group reported that the succinimidyl-cystatin-urea-glutamate (SCUE) moiety has a high affinity for PSMA. In this study, we developed the novel technetium-99m-labeled PSMA-targeting probe "[99mTc]Tc-(Ham-SCUE)2" based on a hydroxamamide chelate with a bivalent SCUE and evaluated its potential as a SPECT imaging probe for the diagnosis of PSMA-expressing prostate cancer. METHODS: Ham-SCUE was synthesized by a one-step reaction with Ham-Mal and cysteine-urea-glutamine. Then, Ham-SCUE was reacted with [99mTc]NaTcO4 for 10 min at room temperature to obtain [99mTc]Tc-(Ham-SCUE)2. [99mTc]Tc-(Ham-SCUE)2 was added to LNCaP (high PSMA expression) cells or PC3 (low PSMA expression) cells, and their radioactivity was measured 60 min after administration. The blocking study was performed by co-incubation of LNCaP cells with various concentrations of 2-PMPA (a PSMA inhibitor) for 15 min before adding [99mTc]Tc-(Ham-SCUE)2. The biodistribution of [99mTc]Tc-(Ham-SCUE)2 in LNCaP/PC3 dual xenografted C.B.-17/Icr scid/scid Jcl mice was evaluated for 120 min after intravenous injection. The blocking study was performed by pretreatment of mice with 2-PMPA (10 mg/kg weight). RESULTS: [99mTc]Tc-(Ham-SCUE)2 was acquired at radiochemical yields of 56% with a radiochemical purity of over 95%. The cellular uptake level of [99mTc]Tc-(Ham-SCUE)2 by LNCaP cells was significantly higher than that by PC3 cells (LNCaP: 11.12 ± 0.71 vs. PC3: 1.40 ± 0.13%uptake/mg protein, p < 0.01), and the uptake was significantly suppressed by pretreatment with 2-PMPA (2.56 ± 0.37%uptake/mg protein, p < 0.05). IC50 of 2-PMPA was 245 ± 47 nM. In the in vivo study, the radioactivity of LNCaP tumor tissue was significantly higher than that of PC3 tumor tissue at 120 min after the administration of [99mTc]Tc-(Ham-SCUE)2 (LNCaP: 9.97 ± 2.79, PC3: 1.16 ± 0.23%ID/g, p < 0.01), and was suppressed by pretreatment with 2-PMPA (2.50 ± 0.45%ID/g, p < 0.01). CONCLUSION: [99mTc]Tc-(Ham-SCUE)2 has the potential to be a SPECT imaging agent for diagnosing high PSMA-expressing prostate cancer.

11.
Sci Rep ; 14(1): 15359, 2024 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965290

RESUMO

We sought to validate the ability of a novel handheld ultrasound device with an artificial intelligence program (AI-POCUS) that automatically assesses left ventricular ejection fraction (LVEF). AI-POCUS was used to prospectively scan 200 patients in two Japanese hospitals. Automatic LVEF by AI-POCUS was compared to the standard biplane disk method using high-end ultrasound machines. After excluding 18 patients due to infeasible images for AI-POCUS, 182 patients (63 ± 15 years old, 21% female) were analyzed. The intraclass correlation coefficient (ICC) between the LVEF by AI-POCUS and the standard methods was good (0.81, p < 0.001) without clinically meaningful systematic bias (mean bias -1.5%, p = 0.008, limits of agreement ± 15.0%). Reduced LVEF < 50% was detected with a sensitivity of 85% (95% confidence interval 76%-91%) and specificity of 81% (71%-89%). Although the correlations between LV volumes by standard-echo and those by AI-POCUS were good (ICC > 0.80), AI-POCUS tended to underestimate LV volumes for larger LV (overall bias 42.1 mL for end-diastolic volume). These trends were mitigated with a newer version of the software tuned using increased data involving larger LVs, showing similar correlations (ICC > 0.85). In this real-world multicenter study, AI-POCUS showed accurate LVEF assessment, but careful attention might be necessary for volume assessment. The newer version, trained with larger and more heterogeneous data, demonstrated improved performance, underscoring the importance of big data accumulation in the field.


Assuntos
Inteligência Artificial , Volume Sistólico , Função Ventricular Esquerda , Humanos , Feminino , Masculino , Pessoa de Meia-Idade , Volume Sistólico/fisiologia , Idoso , Função Ventricular Esquerda/fisiologia , Ecocardiografia/métodos , Ultrassonografia/métodos , Estudos Prospectivos , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/fisiopatologia
12.
J Dent Sci ; 19(3): 1540-1545, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39035278

RESUMO

Background/purpose: Implant-supported fixed partial dentures (IFPDs) are a treatment option for partially edentulous dentition with missing posterior-most molars despite the concept of a shortened dental arch (SDA). This study aimed to evaluate the effect of IFPD treatment on oral health-related quality of life (OHRQoL) in patients with unilateral SDA missing two adjacent molars and to compare the effects of single- and two-unit IFPDs. Materials and methods: Forty patients with unilateral SDA missing two adjacent molars (Kennedy Class II) participated in this study; 11 patients received one implant placement in the first molar and were treated with a single-unit IFPD (single-unit group), and 29 received two implant placements and were treated with a two-unit IFPD (two-unit group). The Oral Health Impact Profile (OHIP) questionnaire for OHRQoL assessment and the gummy jelly test for objective masticatory performance were administered before and after IFPD treatment. The Wilcoxon signed-rank test for all patients and Mann-Whitney U test were performed for pre- and post-treatment comparisons and between-group comparisons, respectively. Results: The OHIP summary score and gummy jelly glucose concentration in all patients showed significant improvements after treatment (all P < 0.05). No significant differences were observed between the single- and two-unit groups for any of the items. Using the minimal important difference in the OHIP summary score, 63.6 % and 58.6 % of patients in the single- and two-unit groups, respectively, showed improvement by 6 points or more. Conclusion: IFPD treatment for patients with SDA missing two adjacent molars may provide clinically meaningful improvements in OHRQoL.

13.
J Dent Sci ; 19(3): 1667-1672, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39035296

RESUMO

Background/purpose: In cases of missing posterior teeth, treatment modalities based on the shortened dental arch (SDA) concept may be a viable alternative. However, the association between oral health-related quality of life (OHRQoL) and patients' treatment decisions remains unclear. This study aimed to investigate the association between OHRQoL and the decision to be treated with implant-supported fixed partial dentures (IFPDs) or take a wait-and-see approach in patients with an SDA missing a single second molar and to clarify the impact of IFPD treatment on the OHRQoL. Materials and methods: The Oral Health Impact Profile (OHIP) questionnaire was administered twice (pre- and post-treatment) and once to 41 patients with a unilateral SDA missing a single second molar who chose IFPD treatment (IFPD group, n = 22) and the wait-and-see approach (no treatment group, n = 19), respectively. Logistic regression analysis was performed with IFPD treatment choice as the objective variable and the four OHIP dimension scores, age, and sex as covariates. The pre- and post-treatment values of the OHIP summary and four-dimension scores were compared using a paired t-test. Results: The IFPD treatment choice was significantly associated with sex (male), higher Oral Function dimension scores, and lower Psychosocial Impact dimension scores (all P < 0.05). The OHIP summary and four-dimension scores were significantly lower following IFPD treatment (all P < 0.05). Conclusion: IFPD treatment for a single missing second molar may be clinically beneficial for improving the OHRQoL of patients with an SDA who experience a decline in masticatory function.

14.
Phys Ther ; 2024 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-39058652

RESUMO

OBJECTIVE: Regaining hip and knee muscle strength is important after total hip arthroplasty (THA). However, it is unclear if muscles other than those of the operated hip also lose strength. This study aimed to identify deficits in hip and knee strength on the surgical and nonsurgical sides in female patients up to 12 months after THA. METHODS: Participants were 91 female patients who had hip osteoarthritis and underwent unilateral THA. Forty-six community-dwelling women who were asymptomatic were selected as control participants. Patients with locomotor disorders or postsurgical complications were excluded. Maximal isometric strength of the hip flexors, extensors, and abductors, and knee extensors and flexors on the surgical and nonsurgical sides were measured before THA and 3, 6, and 12 months thereafter. RESULTS: Twelve months after THA, hip flexion, extension, and abduction strength on the surgical side were 84.6%, 83.5%, and 76.2%, respectively, of those in individuals who were asymptomatic; at the same time point, those on the nonsurgical side were 94.8%, 83.9%, and 79.4%, respectively. Knee extension strength on the surgical side was 89.3% of that in individuals who were asymptomatic. Compared to individuals who were asymptomatic, nearly all muscles showed significantly lower strength on both sides up to 6 months after THA. CONCLUSION: At 12 months after THA, hip and knee strength on both the surgical and nonsurgical sides did not recover to the level observed in individuals who were asymptomatic. In particular, hip abductor strength on the surgical and nonsurgical sides were 76% and 79%, respectively, of that in individuals who were asymptomatic. IMPACT STATEMENT: At 12 months after THA, hip and knee strength on the surgical and nonsurgical sides did not recover to the level observed in individuals who were asymptomatic, suggesting that the nonsurgical side may be inappropriate as a control to assess strength recovery on the surgical side.

15.
Function (Oxf) ; 5(4)2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38985004

RESUMO

A neurological dogma is that the contralateral effects of brain injury are set through crossed descending neural tracts. We have recently identified a novel topographic neuroendocrine system (T-NES) that operates via a humoral pathway and mediates the left-right side-specific effects of unilateral brain lesions. In rats with completely transected thoracic spinal cords, unilateral injury to the sensorimotor cortex produced contralateral hindlimb flexion, a proxy for neurological deficit. Here, we investigated in acute experiments whether T-NES consists of left and right counterparts and whether they differ in neural and molecular mechanisms. We demonstrated that left- and right-sided hormonal signaling is differentially blocked by the δ-, κ- and µ-opioid antagonists. Left and right neurohormonal signaling differed in targeting the afferent spinal mechanisms. Bilateral deafferentation of the lumbar spinal cord abolished the hormone-mediated effects of the left-brain injury but not the right-sided lesion. The sympathetic nervous system was ruled out as a brain-to-spinal cord-signaling pathway since hindlimb responses were induced in rats with cervical spinal cord transections that were rostral to the preganglionic sympathetic neurons. Analysis of gene-gene co-expression patterns identified the left- and right-side-specific gene co-expression networks that were coordinated via the humoral pathway across the hypothalamus and lumbar spinal cord. The coordination was ipsilateral and disrupted by brain injury. These findings suggest that T-NES is bipartite and that its left and right counterparts contribute to contralateral neurological deficits through distinct neural mechanisms, and may enable ipsilateral regulation of molecular and neural processes across distant neural areas along the neuraxis.


Assuntos
Transdução de Sinais , Animais , Ratos , Sistemas Neurossecretores/metabolismo , Lesões Encefálicas/metabolismo , Lesões Encefálicas/fisiopatologia , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/fisiopatologia , Masculino , Medula Espinal/metabolismo , Lateralidade Funcional/fisiologia , Membro Posterior/inervação
16.
J Labelled Comp Radiopharm ; 67(8): 295-304, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38837480

RESUMO

Cathepsin B (CTSB) is a lysosomal protease that is overexpressed in tumor cells. Radioimmunoconjugates (RICs) composed of CTSB-recognizing chelating agents are expected to increase the molecular weights of their radiometabolites by forming conjugates with CTSB in cells, resulting in their improved retention in tumor cells. We designed a novel CTSB-recognizing trifunctional chelating agent, azide-[111In]In-DOTA-CTSB-substrate ([111In]In-ADCS), to synthesize a RIC, trastuzumab-[111In]In-ADCS ([111In]In-TADCS), and evaluated its utility to improve tumor retention of the RIC. [111In]In-ADCS and [111In]In-TADCS were synthesized with satisfactory yield and purity. [111In]In-ADCS was markedly stable in murine plasma until 96 h postincubation. [111In]In-ADCS showed binding to CTSB in vitro, and the conjugation was blocked by the addition of CTSB inhibitor. In the internalization assay, [111In]In-TADCS exhibited high-level retention in SK-OV-3 cells, indicating the in vitro utility of the CTSB-recognizing unit. In the biodistribution assay, [111In]In-TADCS showed high-level tumor accumulation, but the retention was hardly improved. In the first attempt to combine a CTSB-recognizing unit and RIC, these findings show the fundamental properties of the CTSB-recognizing trifunctional chelating agent to improve tumor retention of RICs.


Assuntos
Catepsina B , Quelantes , Imunoconjugados , Catepsina B/metabolismo , Quelantes/química , Quelantes/síntese química , Animais , Camundongos , Imunoconjugados/química , Imunoconjugados/farmacocinética , Distribuição Tecidual , Linhagem Celular Tumoral , Humanos , Radioisótopos de Índio/química , Técnicas de Química Sintética , Trastuzumab/química
17.
PCN Rep ; 3(2): e189, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38868083

RESUMO

Aim: The mental healthcare system in Japan is transitioning from institution-based to community-based treatment. To prevent prolonged hospitalization and community integration of psychiatric patients, mental health social workers (MHSWs) are pivotal in coordinating post-discharge arrangements for psychiatric inpatients. This study aimed to propose a care model to improve clinical outcomes in psychiatric emergency wards in Japan. Methods: We conducted a mail-in questionnaire survey targeting medical facilities with psychiatric emergency wards. We collected data of the psychiatric care system, including facility profiles, staffing conditions and caseloads, and the provided psychiatric services and treatment options. Using multiple regression analyses, we explored associations between these data and clinical outcomes, focusing on the average number of days for hospitalization and the integration of patients into a community. Results: Data were collected from 82 facilities (response rate, 45.8%). The average number of days for hospitalization and community integration were 64.7 and 327.9 days, respectively. The caseloads for MHSWs were significantly associated with longer hospitalization (ß = 0.31, p = 0.009) and shorter duration of community living (ß = -0.28, p = 0.027). Conclusion: The clinical performance in psychiatric emergency wards surpassed the Japanese government's targets regarding these outcomes. We found that heavy caseloads on MHSWs were associated with worse clinical outcomes for patients in psychiatric emergency wards. These findings suggest that reducing MHSW caseloads (≤20 cases) may be a potential interventional strategy to prevent prolonged hospitalization and promote successful community integration of patients.

18.
PCN Rep ; 3(2): e192, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38868084

RESUMO

Aim: The large number of new long-stay (NLS) patients and high readmission rates in psychiatric hospitals are longstanding concerns in Japan despite reforms to encourage multidisciplinary support of such patients. Staffing shortages of specialists, especially mental health social workers (MHSWs), may be one of the reasons for these problems to remain unsolved. Methods: The authors examined the effectiveness of the MHSW-centered multidisciplinary care model in preventing NLSs and rehospitalization in terms of both patient dynamics and cost by retrospective comparison of before and after program implementation. Results: After our program was introduced, NLS was almost completely prevented. In addition, a significant decrease in readmissions of involuntarily admitted patients was also observed. On the other hand, the resulting decrease in treatment costs and hospital revenues was mismatched by an increase in personnel costs. Conclusion: While MHSW-centered multidisciplinary care is effective for the community integration of patients, there are cost challenges. State policy changes are needed to resolve staffing problems, along with the introduction of appropriate indicators of community integration.

19.
Cancers (Basel) ; 16(11)2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38893277

RESUMO

With cancer diagnosis occurring at older ages, the use of immune checkpoint inhibitors (ICIs) has extended to older adults. However, the safety of immune-related adverse events (irAEs) in this population remains unclear and relies on data extrapolated from younger adults. This multicenter retrospective study aimed to examine irAE prevalence and tolerability in older adults. We included 436 patients with non-small lung cancer undergoing ICI therapy and dichotomized them into two age groups (< or ≥75 years). Incidence of any irAE grade, grade ≥3 irAEs, and steroid usage after irAE occurrence was similar between younger (n = 332) and older groups (n = 104). While the younger patients with irAEs showed prolonged overall survival in the 12-month landmark Kaplan-Meier analysis (Hazard ratio (HR) 0.59, 95% confidence interval (CI) 0.38-0.89, p = 0.013), the older cohort did not (HR 0.80, 95% CI 0.36-1.78, p = 0.588). Although no differences were observed with ICI continuation or re-challenge after irAE onset, the elderly cohort had double the irAE cases that required a transition to best supportive care (BSC) (11.3% vs. 22.4%, p = 0.026). In conclusion, although irAE prevalence remains consistent regardless of age, the increased conversion to BSC post-irAE onset in older adults suggests diminished tolerability and the potential absence of favorable prognosis associated with irAEs in this population.

20.
Yakugaku Zasshi ; 144(6): 691-695, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38825478

RESUMO

In Japan, only few hospitals have pharmacists in their secondary emergency rooms to record medication history and provide drug information in real time. In this study, we investigated the benefits of pharmacist intervention in secondary emergency rooms by comparing the time taken by the pharmacists and non-pharmacists in the emergency room to record the medication history in the electronic medical record and the accuracy of its content. The study period was from September 1 to September 30, 2022, and included patients who were transported to our hospital for emergency care between 9:00 and 16:30. We compared the time taken between the patient's arrival until the recording of their medication history and the accuracy of the record by the emergency room pharmacists and non-pharmacists (paramedics or medical clerks). The study included 58 patients whose medication histories were collected by pharmacists, and 11 patients whose histories were collected by non-pharmacists. For pharmacists, the median time to record medication history in the electronic medical record was 12 min, whereas for non-pharmacists, it was 19 min, which was significantly different (p=0.015). The pharmacists accurately recorded the medication history of 98.3% (57/58) of patients, whereas non-pharmacists accurately recorded it for only 54.5% (6/11) of patients, with a significant difference (p<0.01). We observed that in secondary emergency rooms, when pharmacists were responsible for recording the patients' medication histories, it resulted in rapid and accurate sharing of medication history.


Assuntos
Registros Eletrônicos de Saúde , Serviço Hospitalar de Emergência , Farmacêuticos , Humanos , Masculino , Feminino , Fatores de Tempo , Idoso , Pessoa de Meia-Idade , Japão , Papel Profissional , Anamnese , Serviço de Farmácia Hospitalar , Idoso de 80 Anos ou mais , Adulto
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