Search

Pancreatic solid pseudopapillary neoplasm (SPN) is a low-grade malignant neoplasm with a good prognosis. Clinically aggressive SPNs have rarely been reported but have not been analyzed in detail. In this study, we referred to this highly malignant type of SPN as high-grade SPN (HG-SPN) and compared its clinicopathological and genetic characteristics with conventional SPN (C-SPN) using immunohistochemistry and gene panel analyses. Five HG-SPNs and 15 C-SPNs were evaluated in this study. HG-SPNs share many pathologic characteristics: macroscopically, solid/cystic appearances, microscopically, pseudopapillary/pseudorosette pattern (100%), tumor cell loose cohesiveness (100%), thin/delicate vasculature (100%), tumor cell cytoplasmic vacuolization (100%), immunohistochemical positivity for β-catenin (nuclear expression) (100%), CD10 (80%), CD56 (80%), and vimentin (100%). Conversely, HG-SPNs showed distinct malignant features compared with C-SPNs: mean tumor size (11.7 vs. 2.9 cm, P<0.001); true necrosis (100% vs. 0%, P<0.001); high-grade nuclear atypia (100% vs. 0%, P<0.001); lymphatic and/or venous invasion (100% vs. 20%, P=0.004); mean mitotic count (4.38 vs. 0.05/high-power field, P<0.001); and mean Ki-67 labeling index (33.9% vs. 3.4%, P<0.001). All HG-SPN patients died of primary disease 3 to 36 months after surgery, while all C-SPN patients were alive without disease. Genetic studies have shown that all analyzed HG-SPNs have CTNNB1mutations. Two HG-SPN cases showed RB1mutations with altered immunohistochemical findings for RB1 and p16. Two HG-SPN cases had TP53mutation and/or p53 overexpression. In conclusion, HG-SPNs show distinct malignant features and some genetic alterations that differ from C-SPNs, indicating the importance of differentiating between these 2 subtypes.

Although the oral cavity has been identified as a potential site of infection in hematologic malignancies and oral adverse events (OAEs) have been reported to cause life-threatening systemic morbidity, OAEs-related risk factors in hematopoietic stem cell transplantation (HSCT) recipients remain unclear.

AbstractVancomycin (VM) is used as empirical therapy for bacterial meningitis (BM). We investigated the relationship of the microbiological efficacy of VM for BM with VM minimum inhibitory concentration (MICVM), serum VM trough concentration (VMser) and cerebrospinal fluid (CSF) protein (P)/serum albumin (SA) ratio, which may reflect the extent of blood–brain barrier (BBB) disruption. Twelve BM patients were enrolled and VM was microbiologically effective in seven (58.3%). VMser, MICVM, and CSF-P/SA ratio were not associated with the microbiological efficacy of VM. The microbiological efficacy of VM was significantly associated with CSF-P/SA ratio multiplied by VMserrelative to the MICVM(η = 0.61, p = 0.04). These results indicate that the parameter combining VMser, MICVM, and the extent of BBB disruption could be associated with the microbiological efficacy of VM in BM patients.

Background:

In this study, we constructed a prediction formula for unbound valproic acid (VPA) concentration that was more accurate and widely applicable than previously reported formulae. A total of 136 datasets from 75 patients were analyzed retrospectively. The median of free fraction of VPA was 0.16 (interquartile range: 0.07; range: 0.07–0.45). The parameter that combined total VPA concentration (CtVPA) and serum albumin (SA), (CtVPA[μM] – 2 × SA [μM]), was significantly related to the free fraction of VPA (r = 0.76, p < 0.001). We constructed a combined parameter-based prediction formula for unbound VPA concentration. Analysis using external datasets from patients without severe renal failure showed that the prediction errors of the unbound VPA concentration were lower than those of previously reported formulae. Although the previous formulae showed large prediction errors, especially in the specific range of CtVPAvalues, the constructed formula showed a weak trend with CtVPAor SA. The formula based on (CtVPA[μM] – 2 × SA [μM]) had high prediction accuracy and wide applicability in predicting the unbound VPA concentration in patients without severe renal failure.

Background: Adult-onset Still’s disease (AOSD) is a rare systemic autoinflammatory disease which encompasses patients with heterogenous presentation and a wide range of clinical courses. In this study, we aimed to identify potential subgroups of AOSD and reveal risk factors for relapse. Methods: We included a total of 216 AOSD patients who received treatment in nine hospitals between 2000 and 2019. All patients fulfilled the Yamaguchi classification criteria. We retrospectively collected information about baseline characteristics, laboratory tests, treatment, relapse, and death. We performed latent class analysis and time-to-event analysis for relapse using the Cox proportional hazard model. Results: The median age at disease onset was 51.6 years. The median follow-up period was 36.8 months. At disease onset, 22.3% of the patients had macrophage activation syndrome. The median white blood cell count was 12,600/μL, and the median serum ferritin level was 7230 ng/mL. Systemic corticosteroids were administered in all but three patients (98.6%) and the median initial dosage of prednisolone was 40mg/day. Ninety-six patients (44.4%) were treated with concomitant immunosuppressants, and 22 (10.2%) were treated with biologics. Latent class analysis revealed that AOSD patients were divided into two subgroups: the typical group (Class 1: 71.8%) and the elderly-onset group (Class 2: 28.2%). During the follow-up period, 13 of 216 patients (6.0%) died (12 infections and one senility), and 76 of 216 patients (35.1%) experienced relapses. Overall and relapse-free survival rates at 5 years were 94.9% and 57.3%, respectively, and those rates were not significantly different between Class 1 and 2 (p=0.30 and p=0.19). Time-to-event analysis suggested higher neutrophil count, lower hemoglobin, and age ≥65 years at disease onset as risk factors for death and age ≥65 years at disease onset as a risk factor for relapse. Conclusions: AOSD patients were divided into two subgroups: the typical group and the elderly-onset group. Although the survival of patients with AOSD was generally good, the patients often experienced relapses. Age ≥65 years at disease onset was the risk factor for relapse.

Despite the absolute need for life-long treatment of inherited and genetic diseases, there has been little effort to develop such treatments for most of these conditions due to their rarity. Familial lecithin:cholesterol acyltransferase (LCAT) deficiency is recognized as one such orphan disease. We have been developing an adipocyte-based ex vivogene therapy/regenerative medicine, a novel methodology that differs from the adeno-associated virus-mediated in vivogene therapy or ex vivogene-transduced hematopoietic cell therapy, to treat familial LCAT deficiency. Recently, a first-in-human (FIH) clinical study was conducted under the Act on Securement of Safety of Regenerative Medicine, wherein a patient with familial LCAT deficiency was treated. To obtain approval to put this treatment into practical use, a clinical trial has been designed with reference to the FIH clinical study.

Indocyanine green (ICG) fluorescent lymphography might be useful for assessing patients undergoing lymphatic surgery for secondary lymphedema. The present clinical trial aimed to confirm whether ICG fluorescent lymphography would be useful in evaluating lymphedema, identifying lymphatic vessels suitable for anastomosis, and confirming patency of lymphaticovenular anastomosis in patients with secondary lymphedema.

Nakasone: Takeda Pharmaceutical: Honoraria; Otsuka Pharmaceutical: Honoraria; Bristol-Myers Squibb: Honoraria; Celgene: Honoraria; Pfizer: Honoraria; Novartis: Honoraria; Janssen Pharmaceutical: Honoraria; Eisai: Honoraria; Chugai Pharmaceutical: Honoraria; Nippon Shinyaku: Honoraria. Fujisawa:Takeda Pharmaceutical Company Limited.: Speakers Bureau; Astellas Pharma Inc.: Research Funding, Speakers Bureau; Otsuka Pharmaceutical: Speakers Bureau; Pfizer Japan Inc.: Research Funding, Speakers Bureau; Bristol-Myers Squibb Company: Speakers Bureau; Novartis Pharma KK: Research Funding, Speakers Bureau; Celgene: Speakers Bureau; Janssen Pharmaceutical K.K: Speakers Bureau; NIPPON SHINYAKU CO.,LTD.: Research Funding. Nakaseko:Novartis Pharma KK: Speakers Bureau; Pfizer Japan Inc.: Speakers Bureau. Kanda:Novartis: Honoraria; Kyowa Kirin: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria; Takeda Pharmaceuticals: Honoraria; Alexion Pharmaceuticals: Honoraria; Shire: Honoraria; Daiichi Sankyo: Honoraria; Ono Pharmaceutical: Honoraria; Nippon Shinyaku: Honoraria, Research Funding; Mochida Pharmaceutical: Honoraria; Mundipharma: Honoraria; Sanofi: Honoraria, Research Funding; Meiji Seika Kaisha: Honoraria; Shionogi: Research Funding; Otsuka: Honoraria, Research Funding; Celgene: Honoraria; Chugai Pharma: Honoraria, Research Funding; Eisai: Honoraria, Research Funding; Janssen: Honoraria; Astellas Pharma: Honoraria, Research Funding; Sumitomo Dainippon Pharma: Honoraria; Pfizer: Honoraria, Research Funding; Merck Sharp & Dohme: Honoraria.

To elucidate the possible role of MRI-detected osteophytes as a predictive imaging biomarker for knee osteoarthritis (KOA).

Objective To compare the effects of remifentanil versus fentanyl during light sedation with dexmedetomidine in adults receiving mechanical ventilation (MV) in the intensive care unit.Methods In this retrospective cohort study, we compared the use of remifentanil versus fentanyl in adults receiving MV with dexmedetomidine sedation. The primary outcome was the proportion of time under light sedation (Richmond Agitation–Sedation Scale score between −1 and 0) during MV.Results We included 94 patients and classified 58 into the remifentanil group and 36 into the fentanyl group. The mean proportion of time under light sedation during MV was 66.6% ± 18.5% in the remifentanil group and 39.9% ± 27.3% in the fentanyl group. In the multivariate analysis with control for confounding factors, patients in the remifentanil group showed a significantly higher proportion of time under light sedation than patients in the fentanyl group (mean difference: 24.3 percentage points; 95% confidence interval: 12.9–35.8).Conclusions Remifentanil use might increase the proportion of time under light sedation in patients receiving MV compared with fentanyl administration.

Introduction: So far, no definitive conclusions have been reached regarding the preventive effect of moisturizers on atopic dermatitis (AD). The variability in results may be due to differences in skin care methods, including bathing and washing, among studies and study design. In hot and humid Japan, bathing and gauze washing have been routinely practiced from the neonatal period, but this may impair the skin barrier function. To address this gap, we determined whether a combination of minimally invasive cleaning methods and moisturizing may prevent AD in infants in Japan., Methods: Mothers of children born between January and September 2019 were instructed in traditional skin care methods (control group; 132 subjects), and mothers of children born between January and September 2020 were instructed in a new skin care method combining less invasive washing and moisturizing (intervention group; 140 subjects). Mothers and babies with and without a history of allergy were recruited, and the incidence of AD at 1 year of age was investigated by questionnaire., Results: Skin care-related behaviors such as face washing, hand washing, and use of moisturizers were more frequent in the intervention group than in the control group. At 6 and 12 months of age, there was no difference in the incidence of AD between the two groups. However, for children born between January and March, the prevalence of AD at 12 months was significantly lower in the intervention group than in the control group (2.9% vs. 21.2%, p = 0.0253)., Conclusions: This study suggests that for children born during dry and cold seasons, strengthening the skin barrier function early in life through routine skin care with less invasive washing and moisturizing may prevent AD in Japan. Appropriate skin care practices for newborns and infants may vary in regions and environments., (© 2024 S. Karger AG, Basel.)