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Sarcopenia is a poor prognosis factor in some cancer patients, but little is known about the mechanisms by which malignant tumors cause skeletal muscle atrophy. Tryptophan metabolism mediated by indoleamine 2,3-dioxygenase is one of the most important amino acid changes associated with cancer progression. Herein, we demonstrate the relationship between skeletal muscles and low levels of tryptophan. A positive correlation was observed between the volume of skeletal muscles and serum tryptophan levels in patients with diffuse large B-cell lymphoma. Low levels of tryptophan reduced C2C12 myoblast cell proliferation and differentiation. Fiber diameters in the tibialis anterior of C57BL/6 mice fed a tryptophan-deficient diet were smaller than those in mice fed a standard diet. Metabolomics analysis revealed that tryptophan-deficient diet downregulated glycolysis in the gastrocnemius and upregulated the concentrations of amino acids associated with the tricarboxylic acid cycle. The weights and muscle fiber diameters of mice fed the tryptophan-deficient diet recovered after switching to the standard diet. Our data showed a critical role for tryptophan in regulating skeletal muscle mass. Thus, the tryptophan metabolism pathway may be a promising target for preventing or treating skeletal muscle atrophies.

We compared the predictive ability of the International Prognostic Index (IPI), a frequently used prognostic model for peripheral T-cell lymphoma (PTCL), with that of a type-specific prognostic model, the Prognostic Index for PTCL-U (PIT). We retrospectively analyzed 113 patients diagnosed with PTCL. The median age was 67 years (range, 16–88 years), 75 patients (66%) were male, and the most common disease type was PTCL, not otherwise specified (69%). With a median follow-up of 6.8 years (interquartile range, 2.7–9.9 years), 5-year survival rates for the four groups in IPI were 85%, 62%, 49%, and 13%, respectively. Similarly, 5-year survival rates for the four groups in PIT were 83%, 64%, 49%, and 19%, respectively. The area under the receiving operating characteristic curve for predicting mortality from PIT (0.725) was not significantly different from that from the IPI (0.685, P  = 0.134). Multivariable analysis showed that performance status ≥ 2 ( P  < 0.0001) and extranodal lesions ≥ 2 ( P  = 0.029) were significantly associated with lower overall survival. The present study found no significant difference in prognostic ability between the IPI and PIT for PTCL, and both models appear useful as predictive models.

Background Long-term use of proton pump inhibitors (PPIs) has been found to significantly lower serum magnesium levels in patients in the USA and Europe. The package inserts of PPIs in these countries clearly state that healthcare professionals should consider monitoring magnesium levels prior to initiation of PPI treatment and periodically thereafter. However, the package inserts of PPIs in Japan do not clearly mention the monitoring of magnesium levels. In this study, we evaluated the relationship between long-term use of PPIs and the lower serum magnesium concentrations in elderly Japanese patients. Methods Using a retrospective observational approach, a total of 264 Japanese outpatients were included in the study. Patients over the age of 75 years were considered elderly. Serum magnesium levels of the patients were measured in units of 0.1 mg/dL between January 2016 and June 2022 at the Higo Internal Medicine Clinic and Ai Pharmacy in Kyoto, Japan. Results Four of the 264 eligible patients were diagnosed with hypomagnesemia. Three were PPI non-users, and one was a PPI user. Serum magnesium concentrations were significantly lower in PPI users ( n  = 47) than in non-users ( n  = 85; 2.1 ± 0.2 vs. 2.2 ± 0.3 mg/dL, p  < 0.05) in the 132 elderly patients. Comorbidity included diabetes mellitus in both PPI users (23.4%) and non-users (57.6%) and hyperlipidemia in both PPI users (61.7%) and non-users (41.2%). Conclusion PPIs are commonly used oral drugs for elderly patients. There was an association between the long-term use of PPIs and lower serum magnesium concentrations in elderly patients. Although the difference in the decrease in serum magnesium concentrations was within the normal range of serum magnesium levels, health care professionals should consider monitoring serum magnesium levels periodically in elderly patients receiving long-term PPIs.

The SARS-CoV-2 pandemic disrupted healthcare systems worldwide, particularly affecting hematopoietic stem cell transplantation (HSCT) activities. Understanding the impact of the SARS-CoV-2 pandemic on transplant practices, especially in Japan, where cord blood transplantation (CBT) is prevalent, is crucial. A total of 40,444 allogeneic HSCT cases in Japan between 2011 and 2021 were examined using an interrupted time series analysis to assess the impact of COVID-19 on CBT utilization. Following the SARS-CoV-2 pandemic, CBT cases demonstrated a significant increase (11.06 [95% confidence interval (CI): 1.87 to 20.25] cases per month), whereas bone marrow transplantation cases decreased, by 10.74 cases per month (95% CI, −19.84 to −1.63 cases per month). Total HSCT cases remained stable with a level change of 5.47 cases per month (95% CI, −10.07 to 21.01 cases per month) and a trend change of −1.11 cases per month (95% CI, −2.22 to 0.004 cases per month). The interrupted time series analysis showed significantly increased CBT cases in Japan, highlighting its crucial role as an alternative transplant source during the pandemic. CBT offset the impact of the decrease in bone marrow transplantation and contributed to the maintenance of HSCT activity in Japan during the unprecedented crisis.

Background A simple suspension method is used in medical practice to administer several orexin receptor antagonists for patients with dysphagia; however, detailed suspension and passage through catheter evaluations have not been performed. Therefore, to safely administer orexin receptor antagonists using the simple suspension method in patients with dysphagia, this study evaluated the disintegration, suspension, passage through the catheter, and drug recovery after passage of Belsomra ® 20 mg (suvorexant), Dayvigo ® 10 mg (lemborexant), and Quviviq ® 50 mg (daridorexant) tablets through a catheter. Methods Disintegration and suspension of Belsomra ® 20 mg, Dayvigo ® 10 mg, and Quviviq ® 50 mg tablets, and passage through the catheter were visually confirmed. Drug recovery after passage through the catheter was quantified using liquid chromatography-mass spectrometry. Results In this study, there was no disintegration and suspension of Belsomra ® 20 mg tablets. However, Dayvigo ® 10 mg and Quviviq ® 50 mg tablets demonstrated disintegration and suspension, including passage through the catheter after rapid and complete disintegration. Drug recovery after catheter passage was >80% for Dayvigo ® 10 mg without flushing and for Quviviq ® 50 mg after two flushes. Conclusion As the disintegration and suspension properties of Belsomra ® 20 mg tablet could not be confirmed, the conventional simple suspension method is not suitable for this product. However, Dayvigo ® 10 mg and Quviviq ® 50 mg tablets showed potential suitability for the simple suspension method.

ObjectivesTo identify prognostic factors for TAFRO syndrome, a rare inflammatory disorder of unknown etiology characterized by thrombocytopenia, anasarca, fever, reticulin myelofibrosis, renal dysfunction, and organomegaly.MethodsData of patients with TAFRO syndrome were extracted from a Japanese patient registry. Patients were divided into groups according to the clinical and laboratory parameters at initial presentation. Cut-off values for the laboratory parameters were determined using receiver operating characteristic curve analysis and by clinical relevance. Patient survival was analyzed by the Kaplan–Meier method. Univariable analysis was performed using log-rank tests. Multivariable analyses were performed with the logistic regression model and the Cox proportional hazards model.ResultsWe extracted the data of 83 patients with TAFRO syndrome from the registry. Univariable analysis identified several potential prognostic factors. Of these factors, age ≥60 years and D-dimer ≥18 μg/dL remained significant predictors of poor overall survival in the multivariable Cox proportional hazards model. Based on these results, we developed a simple prognostic scoring system for TAFRO syndrome (TS-PSS).ConclusionPatients in our cohort were stratified into low, intermediate, and high-risk groups by the TS-PSS. This system should be verified with independent patient cohorts in future studies.

Background Epcoritamab, a bispecific CD3×CD20 antibody, offers a promising treatment for relapsed diffuse large B‐cell lymphoma (DLBCL). Its efficacy and safety after allogeneic hematopoietic stem cell transplantation (allo‐HSCT) remain unclear. Case Report In a 64‐year‐old man with relapsed DLBCL, epcoritamab showed limited efficacy, achieving stable disease prior to allo‐HSCT; nevertheless, re‐administration after donor T‐cell engraftment resulted in a complete response without severe graft‐versus‐host disease or cytokine release syndrome. Conclusions This observation suggests that donor‐derived T‐cell redirection with epcoritamab may enhance antitumor efficacy while maintaining safety in the post‐transplant setting, supporting its potential as a salvage therapy for relapsed DLBCL post‐allo‐HSCT.

Hepatic immune regulation is associated with the progression from simple steatosis to non-alcoholic steatohepatitis, a severe condition of inflamed fatty liver. Indoleamine 2,3-dioxygenase (IDO), an intracellular enzyme that mediates the catabolism of L-tryptophan to L-kynurenine, plays an important role in hepatic immune regulation. In the present study, we examined the effects of IDO gene silencing on high-fat diet (HFD)-induced liver inflammation and fibrosis in mice. After being fed a HFD for 26 weeks, the IDO-knockout (KO) mice showed a marked infiltration of inflammatory cells, especially macrophages and T lymphocytes, in the liver. The expression levels of F4/80, IFNγ, IL-1β, and IL-6 mRNA in the liver and the expression levels of F4/80 and TNF-α mRNA in the white adipose tissue were significantly increased in IDO-KO mice, although hepatic steatosis, the accumulation of intrahepatic triglycerides, and the amount of oxidative stress were lower than those in IDO-wild-type mice. IDO-KO mice also developed marked pericellular fibrosis in the liver, accumulated hepatic hydroxyproline, and exhibited increased expression levels of hepatic TGF-β1 mRNA. These findings suggest that IDO-KO renders the mice more susceptible to HFD-induced hepatic inflammation and fibrosis. Therefore, IDO may have a protective effect against hepatic fibrosis, at least in this HFD-induced liver injury model.

Background Pharmaceutical care of capecitabine-related hand–foot syndrome (HFS) is extremely important to avoid the progression of the syndrome. Protocol-based pharmacotherapy management (PBPM) of HFS by community pharmacists has been introduced in our community, whereby the community pharmacist instructs patients to use steroid creams if they develop HFS of grade 2 or higher. This study aimed to evaluate the effectiveness of PBPM in cancer patients with HFS by comparing it to conventional pharmaceutical care using monitoring reports for pharmacotherapy management by community pharmacists. Methods From September 2017 to August 2019, we retrospectively investigated the medical records of 396 cancer patients who received capecitabine adjuvant chemotherapy. Before PBPM implementation, conventional pharmaceutical care was administered from September 2017 to August 2018; these patients served as the control group. Care was switched to PBPM in September 2018, and PBPM was applied from September 2018 to August 2019; these patients served as the PBPM group. We excluded patients who received both conventional pharmaceutical care and PBPM. We categorized all cases into two groups: age ≤ 69 years and age ≥ 70 years. Results In all, 396 cases were included, of which 227 were ineligible, such as those of cancer patients who received both conventional pharmaceutical care and PBPM. Among patients aged higher than 70 years, the incidence and severity of HFS associated with PBPM were significantly lower than those associated with conventional care (grade 0: 59.5% [44/74] vs. 30.6% [11/36], grade 1: 33.8% [25/74] vs. 63.9% [23/36]). All patients continued to receive the capecitabine, HFS severity improved to grade 1 during the study period, and treatment of HFS was not stopped. Conclusion Our findings suggest that PBPM is effective for addressing capecitabine-related HFS among cancer patients aged higher than 70 years, in that it helps prevent an increase in HFS severity.

Indoleamine 2,3-dioxygenase (IDO), a tryptophan-catabolizing intracellular enzyme of the L-kynurenine pathway, causes preneoplastic cells and tumor cells to escape the immune system by inducing immune tolerance; this mechanism might be associated with the development and progression of human malignancies. In the present study, we investigated the role of IDO in diethylnitrosamine (DEN)-induced hepatocarcinogenesis by using IDO-knockout (KO) mice. To induce hepatocellular carcinoma (HCC), hepatic adenoma, and preneoplastic hepatocellular lesions termed foci of cellular alteration (FCA), male IDO-wild-type (WT) and IDO-KO mice with a C57BL/6J background received a single intraperitoneal injection of DEN at 2 weeks of age. The mice were sacrificed to evaluate the development of FCA and hepatocellular neoplasms. HCC overexpressed IDO and L-kynurenine compared to surrounding normal tissue in the DEN-treated IDO-WT mice. The number and cell proliferative activity of FCAs, and the incidence and multiplicity of HCC were significantly greater in the IDO-WT than in the IDO-KO mice. The expression levels of the IDO protein, of L-kynurenine, and of IFN-γ, COX-2, TNF-α, and Foxp3 mRNA were also significantly increased in the DEN-induced hepatic tumors that developed in the IDO-WT mice. The mRNA expression levels of CD8, perforin and granzyme B were markedly increased in hepatic tumors developed in IDO-KO mice. Moreover, Foxp3-positive inflammatory cells had infiltrated into the livers of DEN-treated IDO-WT mice, whereas fewer cells had infiltrated into the livers of IDO-KO mice. Induction of IDO and elevation of L-kynurenine might play a critical role in both the early and late phase of liver carcinogenesis. Our findings suggest that inhibition of IDO might offer a promising strategy for the prevention of liver cancer.