In vivo最新文献

Background/aim: Body weight loss (BWL) after gastrectomy for gastric cancer (GC) decreases postoperative quality of life and survival in patients with GC. This study aimed to evaluate the effect of oral nutritional supplements composed of high protein on BWL in the early period following gastrectomy.

Patients and methods: Pre- and postoperative body weight and skeletal muscle mass were measured using bioelectrical impedance analysis in patients undergoing radical gastrectomy for GC and analyzed retrospectively. Patients received either a regular diet (control group, n=43) or 250 ml (320 kcal) per day of a high-protein oral nutritional supplement (ONS) (22 g protein) in addition to their regular diet (ONS group, n=40) for four weeks after gastrectomy. The actual daily intake of ONS was recorded by patients themselves. The BWL and skeletal muscle loss (SML) at one month after surgery were compared between the two groups.

Results: BWL and SML at one month after surgery were similar between the two groups. In the ONS group, patients were divided into two subgroups (ONS-H and ONS-L) according to whether their ONS intake amount was above or below the average value of 216 kcal. The ONS-H group (ONS intake ≥216 kcal) showed significantly lower BWL compared to the control group (-4.6±2.6% vs. -6.2±2.5%; p=0.03). Moreover, the ONS group showed significantly lower BWL at one month after surgery than the control group in cases of total or proximal gastrectomy (-5.9±3.0% vs. -7.8±1.9%; p=0.04), although no significant difference was observed between the two groups in distal gastrectomy. The hematological nutritional parameters were similar between the two groups.

Conclusion: The administration of ONS composed of high protein for four weeks after gastrectomy did not improve BWL at one month after gastrectomy. However, adequate amount of ONS intake and ONS intake after total or proximal gastrectomy might improve BWL.

Background/aim: Diabetic retinopathy (DR), a complication of diabetes, causes damage to retinal blood vessels and can lead to vision impairment. Persistent high blood glucose levels contribute to this damage, and despite ongoing research, effective treatment options for DR remain limited. Dimethyl sulfoxide (DMSO) has shown anti-inflammatory and antioxidant properties in both in vivo and in vitro studies; however, its potential as an anti-inflammatory agent in the context of DR has not yet been explored. This study aimed to assess the effects of subconjunctival injection of DMSO on the progression of DR.

Materials and methods: DR was induced in rats using intraperitoneal injections of streptozotocin (55 mg/kg), confirmed by measuring blood glucose levels and electroretinography (ERG). The rats were divided into five groups: a normal control group (CON), a DR control group receiving PBS injections (DMSO 0), and three DR groups receiving different concentrations of DMSO (98%, 50%, and 10%). Retinal function was evaluated using ERG at weeks 10 and 14, and histological analysis at week 16.

Results: The DMSO 50 group had significantly higher B-wave amplitude in ERG compared to the DMSO 0 group (p<0.05). Flicker response amplitudes were also significantly greater in the DMSO 50 and DMSO 10 groups compared to DMSO 0 (p<0.05). Histological examination revealed thinner retinal layers in the DMSO 0 group compared to the CON group, while the DMSO-treated groups showed improved retinal thickness.

Conclusion: Subconjunctival injection of 50% DMSO appears to improve retinal function in a rat model of DR.

Background/aim: Despite the seriousness of lung adverse events (AEs) associated with lenvatinib, comprehensive data on these events remain limited. This study was conducted to examine the disproportionality, time to onset, incidence rates, and outcomes of lenvatinib-associated lung AEs using the Japanese Adverse Drug Event Report database.

Patients and methods: We analysed data for the period from April 2004 to May 2023. Data on lung AEs were extracted and the relative disproportionality of AEs was estimated using reporting odds ratios (RORs). Weibull distribution parameters were also calculated.

Results: Among the 2,230,863 reports analysed, 7,684 reports of AEs associated with lenvatinib were identified, including 380 lung AEs. Signals were detected for three lung AEs: tracheal fistula, tracheo-oesophageal fistula, and tracheal haemorrhage. Fatal outcomes were observed for tracheal fistula and tracheal haemorrhage. A histogram of median times to onset indicated that lung AEs associated with lenvatinib occurred 15-111 days after administration. Weibull distributions showed that the incidence of these AEs remained constant throughout the exposure period (random failure type).

Conclusion: The present study highlights post-marketing AEs associated with lenvatinib, with a particular focus on lung AEs. Tracheal fistula and tracheal haemorrhage were identified as AEs with potentially serious outcomes following lenvatinib administration. Monitoring patients for early signs of these AEs is important not only at treatment initiation, but also throughout the entire course of therapy.

Background/aim: Atrial fibrillation (AF) and heart failure (HF) commonly co-occur, significantly increasing morbidity and mortality. Poorly controlled AF can contribute to complications like HF and is associated with conditions, such as stroke and pulmonary embolism (PE). This report involves a man with AF who had persistent respiratory symptoms and left-sided chest pain, initially suspected to be PE, but eventually diagnosed as HF.

Case report: A 43-year-old male experienced increasing breathlessness, cough, and fatigue. Initially suspected to have a respiratory infection, his persistent symptoms raised concern for PE. The patient had a history of AF, unsuccessful cardioversion, and long-term non-adherence to beta blockers. Initial assessment revealed persistent respiratory symptoms and elevated levels of C-reactive protein, D-dimer, N-terminal pro-B-type natriuretic peptide, and Troponin T. Chest X-ray showed pulmonary congestion, and echocardiogram confirmed a severely impaired ejection fraction (EF <20%). While the differential diagnosis included community-acquired pneumonia, PE, and HF, the final diagnosis was worsening AF and HF with reduced EF, not PE.

Conclusion: PE symptoms can overlap with HF, making careful differential diagnosis essential, particularly in AF patients with elevated D-dimer levels, where false positives necessitate caution. This case underscores the importance of thorough differential diagnosis and clinical judgment before ordering tests to avoid misdiagnosis. Long-term non-adherence to beta blockers exacerbated the patient's symptoms, emphasising the critical role of consistent medication use in managing AF and preventing complications like HF. This case report also highlights the importance of thorough investigations, guideline-based treatments and multidisciplinary care in complex AF-HF cases.

Background/aim: Apalutamide induces severe skin adverse events (sAEs) in 14.7% of Japanese patients, leading to treatment discontinuation. To maximize the management of sAEs in patients taking apalutamide for prostate cancer, we conducted pharmacist outpatient clinics for patients receiving apalutamide in the outpatient setting. During these sessions, patients were informed about skin care management, including the application of moisturizers to prevent sAEs. This study aimed to evaluate the usefulness of pharmacist-led outpatient services in managing sAEs.

Patients and methods: Patients with castration-resistant prostate cancer without distant metastases or prostate cancer with distant metastases, receiving 240 mg apalutamide once daily, were divided into pharmacist intervention and nonintervention groups and retrospectively investigated. The primary endpoint was the incidence of all sAEs.

Results: The incidence of sAEs of any grade was significantly lower in the intervention group (n=26) than in the nonintervention group (n=16) (30.8% vs. 68.8%, respectively, p=0.03), without a significant difference in the incidence of grade 3 or more sAEs (3.8% vs. 25.0%, respectively, p=0.05). At the pharmacist outpatient clinics, pharmacists gave 84 recommendations to urologists, with 98.8% of them reflected in prescriptions. The most frequently prescribed moisturizers were heparinoid oil-based creams, with a significantly higher prescription rate in the intervention compared to the nonintervention group (30.0 g/28 days vs. 0 g/28 days, p<0.01).

Conclusion: As far as we are aware, our study is the first to show that intervention by pharmacist outpatient clinics reduces apalutamide-induced sAEs. Pharmacist outpatient clinics can assist in the appropriate skin management of patients taking apalutamide.

Patients affected by metastatic carcinoma of the colon/rectum (mCRC) harboring mutations in the BRAF gene (MBRAF) respond poorly to conventional therapy and have a prognosis worse than that of patients without mutations. Despite the promising outcomes of targeted therapy utilizing multi-targeted inhibition of the mitogen-activated protein kinase (MAPK) signaling system, the therapeutic efficacy, especially for the microsatellite stable/DNA proficient mismatch repair (MSS/PMMR) subtype, remains inadequate. Patients with MBRAF/mCRC and high microsatellite instability or DNA deficient mismatch repair (MSI-H/DMMR) exhibit a substantial tumor mutation burden, suggesting a high probability of response to immunotherapy. It is widely acknowledged that MSS/pMMR/mCRC is an immunologically "cold" malignancy that exhibits resistance to immunotherapy. The integration of targeted therapy and immunotherapy may enhance clinical outcomes in patients with MBRAF/mCRC. Efforts to enhance outcomes are exclusively focused on MSS/DMMR-BRAF mutant cancers, which constitute the largest proportion. This review evaluates the clinical efficacy and advancement of novel immune checkpoint blockade therapies for MSI-H/DMMR and MSS/PMMR BRAF mutant mCRC. We examine potential indicators in the tumor immune milieu for forecasting immunotherapeutic response in BRAF mutant mCRC.

Background/aim: Brain arteriovenous malformations (AVMs) are vascular malformations characterized by dysmorphic, aberrant vasculature. During previous surgeries of compact nidus brain AVMs (representing the majority of cases), we have observed a "shiny" plane between nidal and perinidal AVM vessels and the surrounding grey and white matter and hypothesized that preoperative neuroimaging of brain AVMs may show a neuroradiological correlate of these intraoperative observations.

Patients and methods: We retrospectively reviewed and analyzed multiplanar and multisequence 3-Tesla magnetic resonance (3T MR) imaging in five consecutive brain AVMs with special attention on imaging characteristics of the brain-AVM interface, i.e., the perivascular and perinidal regions.

Results: In all five patients, we identified T2-hypertinense perivascular perinidal spaces, which were predominantly observed around the AVM nidus and less prominently around the feeding arteries or draining veins.

Conclusion: The identification of T2-hypertinense perivascular spaces surrounding brain AVMs on neuroradiological imaging may provide insights into the anatomico-radiological relationships of brain AVMs and the surrounding grey and white matter parenchyma. These findings could have future implications for our understanding of brain AVM biology and may influence neurosurgical approaches to these lesions.

Background/aim: A standard mouse model of pulmonary fibrosis has been created by intratracheal or intraperitoneal administration of bleomycin. However, a difficulty presented by this traditional method is its high mortality rate of more than 50% after bleomycin administration. In this study, we aimed to establish a unilateral lung disease model and to assess its feasibility and usefulness.

Materials and methods: After 6-week-old C57BL/6 mice were anesthetized, a 1.7Fr microcatheter was advanced into the trachea using an otoscope. Then, 1.0 mg/kg of bleomycin was injected into bilateral lung at the trachea (n=13) or unilateral lung (n=14) after advancing the microcatheter to the left main bronchus under fluoroscopy. Body weight change and survival of bilateral and unilateral lung disease group mice at day 28 were compared using Mann-Whitney and log-rank tests. Lungs were extracted and evaluated using Masson trichrome staining.

Results: Body weights decreased 75.7%±14.0% in the bilateral lung disease group, but were greater, 94.1%±11.4%, in the unilateral lung disease group (p=0.03). Overall survival rates at day 28 were 30.8% and 85.7% in the bilateral and unilateral lung disease groups, respectively. Survival was significantly better in the unilateral lung disease model (p=0.01). Histological evaluation confirmed collagen deposition only in the bleomycin injected lung in the unilateral lung disease model.

Conclusion: Establishing both a healthy and a diseased lung in the same individual model was feasible, achieving lessened body weight loss and more favorable survival. This technique allows for a more efficacious research design, where both the efficacy and adverse effects of a pharmaceutical agent can be evaluated in a single animal.

Background/aim: The effect of left ventricular systolic dysfunction (LVSD), a risk factor for postoperative mortality, in older adult patients with gastric cancer has not been fully elucidated. This study aimed to evaluate the impact of low preoperative left ventricular ejection fraction (EF) on short- and long-term outcomes in older adult patients with gastric cancer.

Patients and methods: This retrospective study enrolled 237 older adult patients with gastric cancer (≥75 years old) who underwent preoperative echocardiography and curative gastrectomy. LVSD was defined as an EF <50%. Postoperative complications and prognosis were compared between patients with low- and normal-EF using the Fisher's exact or Chi-square test, log-rank test, Kaplan-Meier method, and Cox regression analysis.

Results: Thirteen patients (5.4%) exhibited LVSD. The incidence of postoperative complications was not significantly different between the two groups (p=0.470), although the incidence of pneumonia was high (p=0.003) and overall survival was significantly worse in the low-EF group compared to the normal-EF group (p=0.016). Multivariate analysis revealed that decreased EF, low preoperative body mass index, and advanced pathological stage were significant prognostic factors in older adult patients with gastric cancer.

Conclusion: LVSD increases the risk of postoperative pneumonia and has a negative prognostic impact on older adult patients with gastric cancer.

Background/aim: Cancer cachexia is characterized by weight loss with a specific decrease in skeletal muscle and adipose tissue. In Japan, anamorelin, which has a novel mechanism of action, was approved in 2021 for the treatment of cancer cachexia. However, little information is available on its safety in routine clinical care, in particular the occurrence of conduction defects as adverse reactions. Therefore, this study evaluated the risk and time to onset of anamorelin-related conduction defects by performing a literature review and evaluating the Japanese pharmacovigilance database.

Patients and methods: We reviewed the literature from April 2000 to June 2024 to identify reports of anamorelin-related conduction defects and analyzed data from April 2004 to December 2023 in the Japanese Adverse Drug Event Report (JADER) database. Using the database, we calculated reporting odds ratios (RORs) with 95% confidence intervals (CIs) and adjusted RORs (95%CIs) by considering whether patients were taking concomitant medications that can cause QT prolongation. In addition, we investigated outcomes and time to onset.

Results: The literature review identified seven cases of conduction defects. All cases occurred within approximately three weeks after starting treatment, and all patients recovered. The JADER database contained 537 cases of adverse reactions to anamorelin. The adjusted ROR (95%CI) of conduction defects was 20.00 (14.86-26.91), and the median time to onset was 13 days. Poor clinical outcomes occurred in only a few cases.

Conclusion: Performing frequent cardiac electrograms for two to three weeks after starting anamorelin may help to quickly identify anamorelin-related conduction defects.