External Validation and Update of the Risk Prediction Model for Denosumab-Induced Hypocalcemia Developed From a Hospital-Based Administrative Database.

PURPOSE: Denosumab is used to treat patients with bone metastasis from solid tumors, but sometimes causes severe hypocalcemia, so careful clinical management is important. This study aims to externally validate our previously developed risk prediction model for denosumab-induced hypocalcemia by using data from two facilities with different characteristics in Japan and to develop an updated model with improved performance and generalizability. METHODS: In the external validation, retrospective data of Kameda General Hospital (KGH) and Miyagi Cancer Center (MCC) between June 2013 and June 2022 were used and receiver operating characteristic (ROC)-AUC was mainly evaluated. A scoring-based updated model was developed using the same data set from a hospital-based administrative database as previously employed. Selection of variables related to prediction of hypocalcemia was based on the results of external validation. RESULTS: For the external validation, data from 235 KGH patients and 224 MCC patients were collected. ROC-AUC values in the original model were 0.879 and 0.774, respectively. The updated model consisting of clinical laboratory tests (calcium, albumin, and alkaline phosphatase) afforded similar ROC-AUC values in the two facilities (KGH, 0.837; MCC, 0.856). CONCLUSION: We developed an updated risk prediction model for denosumab-induced hypocalcemia with small interfacility differences. Our results indicate the importance of using data from plural facilities with different characteristics in the external validation of generalized prediction models and may be generally relevant to the clinical application of risk prediction models. Our findings are expected to contribute to improved management of bone metastasis treatment.

Obstetric venous thromboembolism: Evaluation of prophylactic approach based on risk scores, D-dimer levels, and ultrasonography findings in a tertiary hospital in Japan.

AIM: Pulmonary embolism remains a leading cause of maternal mortality in developed countries despite developments in venous thromboembolism prophylaxis strategies. This study aimed to evaluate the effectiveness of our approach involving risk-scoring, D-dimer level assessment, and ultrasonography for obstetric venous thromboembolism. METHODS: This retrospective cohort study included women who delivered at 22-41 weeks of gestation in The University of Tsukuba Hospital, Japan between January and December 2020. Venous thromboembolism risk (determined according to Japanese guidelines) and D-dimer levels were evaluated within 20 weeks of gestation, 30-34 weeks of gestation, and during the pre-delivery period (36 weeks of gestation or any time before preterm delivery). Compression and color Doppler ultrasonography for lower extremity deep vein thrombosis were performed if D-dimer levels were ≥3.2 µg/mL (for those undergoing cesarean delivery, 1.0 µg/mL). RESULTS: Of 1026 women, 6 women had deep vein thrombosis during pregnancy and 1 during the puerperium period. Pulmonary embolism was not observed. The D-dimer screening result was positive for 8 women (2%) within 20 weeks of gestation (deep vein thrombosis was confirmed in 3 of them), 87 women (10%) (no deep vein thrombosis) at 30-34 weeks of gestation, and 367 women (36%) during the pre-delivery period (asymptomatic deep vein thrombosis in one). Based on the Japanese guidelines, 1%, 11%, 33%, and 55% of women had high, intermediate, low, and no postpartum risk factors, respectively. CONCLUSIONS: Our approach appears useful for antenatal venous thromboembolism screening in the first trimester. For postpartum prophylaxis, more cost-effective strategies are needed.

The evidence of a macrophage barrier in the xenotransplantation of human hematopoietic stem cells to severely immunodeficient rats.

BACKGROUND: The human-to-rat hematopoietic stem cell transplantation (HSCT) model is rare, unlike its human-to-mouse counterpart. The rat models are desired, especially in areas of physiology, toxicology, and pharmacology. In addition to lymphocytes, macrophages are also considered to be important for xenotransplantation. We generated a rat xenotransplantation model to prove the role of macrophages as a xenotransplantation barrier. METHODS: Immunodeficiency in SRG rats, which are Sprague-Dawley (SD) rats lacking Rag2 and Il2rg, was confirmed by flow cytometry and spleen immunostaining. Human umbilical cord blood was collected after scheduled cesarean section at the University of Tsukuba Hospital. Cord blood mononuclear cells (CB-MNCs) were transplanted into the SRG rats administered several injections of clodronate liposome (CL), which cause macrophage depletion. Survival of human cells was observed by flow cytometry. Rat macrophage phagocytosis assay was performed to check the species-specific effects of rat macrophages on injected human/rat blood cells. RESULTS: SRG rats were deficient in T/B/NK cells. Without CL pretreatment, human CB-MNCs were removed from SRG rats within 7 hours after transplantation. The rats pretreated with CL could survive after transplantation. Prolonged survival for more than 4 weeks was observed only following a one-time CL injection. Rat macrophages had a species-specific potential for the phagocytosis of human blood cells in vivo. CONCLUSION: In human-to-rat HSCT, the short period of early macrophage control, leading to macrophage immunotolerance, is important for engraftment. The generated model can be useful for the creation of future xenotransplantation models or other clinical research.

How do students deal with difficult physiological knowledge?

Physiology courses are considered to be challenging for students to master due to the highly conceptual nature of the discipline and the substantial cognitive effort required to understand disciplinary knowledge. Students must choose appropriate learning strategies to develop their understanding, as their choices may influence both their understanding and their academic achievement. The primary aim of this study was to develop an understanding of why students experience difficulties with physiology and how they respond when facing the challenge of learning this discipline. Undergraduate allied health students ( n = 231) studying physiology were asked to identify the topics they had difficulty understanding, the strategies they used to deal with that difficult knowledge, and the reasons for their difficulties. Consenting students' responses were subjected to inductive and deductive thematic analyses, and their performance on examinations were collated. Students reported that they found physiology difficult due to their lack of familiarity with it and the level of detail required. To aid their understanding of difficult topics, students commonly reported reviewing information, seeking further information, and seeking social assistance, with more high-achieving students reporting reviewing records, and fewer reporting seeking social assistance than poor-achieving students. Most notably, a disconnect was found between students' reporting of difficult modules and their academic achievement on those modules, with students who cited difficulties performing equally well, if not better, than those who do not. Importantly, these findings suggest that students, in recognizing their difficulties and the reasons for them, can implement effective learning strategies to overcome them.

A case of left ventricular aneurysm caused by localized myocardial infarction.

A 73-year-old man was hospitalized for unstable angina pectoris with no history of myocardial infarction. After undergoing percutaneous coronary intervention, left ventriculography incidentally revealed a cavity in the anterior wall, and echocardiography found the cavity wall to be dyskinetic. Myocardial contrast echocardiography revealed that the wall of the cavity was surrounded by myocardial tissue with low perfusion. Furthermore, radial strain in the wall of the cavity was low. Myocardial scintigraphy showed a localized defect on the anterior wall. The patient was finally diagnosed as true aneurysm after asymptomatic and localized myocardial infarction, and has since been followed up by echocardiography in the outpatient clinic.