Objectives: In a mouse model, aldehyde dehydrogenase 2 (ALDH2) knockout resulted in lower bone mineral density; however, higher parathyroid hormone receptor expression than wild-type mice. This study aimed to investigate whether ALDH2 polymorphisms influence efficacy of intermittent parathyroid hormone therapy and bone mineral density changes in humans. Methods: Eighty-two patients with primary osteoporosis treated with parathyroid hormone for > 1 year were divided into wild-type ALDH2 (ALDH2*1) and variant (ALDH2*2) groups. Bone mineral densities were measured by dual-energy X-ray absorptiometry. Changes in bone mineral density, treatment response, bone turnover markers, and new fracture incidence were evaluated. Furthermore, bone mineral density was analyzed using a mixed-effects model. Results: Femoral neck bone mineral density increased by 1.0 ± 7.4% in the ALDH2*1 group and 4.3 ± 8.1% in the ALDH2*2 group (P < 0.05), whereas lumbar spine bone mineral density increased by 5.7 ± 8.2% and 9.4 ± 9.1% without significance. Treatment success rates were higher in ALDH2*2 group (femoral neck 38.7%, lumbar spine 68.8%) compared with ALDH2*1 (16.3%, 51.0%). Statistical significance was observed only at the femoral neck. Bone turnover markers and fracture incidence were comparable between groups. Mixed-effects analysis adjusting for confounders showed a significant ALDH2 genotype × duration interaction for femoral neck, indicating genotype-related differences in the rate of bone mineral density increase over time. For lumbar spine, the genotype main effect was significant, whereas the interaction was not. Conclusions These findings suggest that ALDH2 polymorphisms may influence the therapeutic response to PTH treatment and highlight the need for larger future studies.

Background: The potassium voltage-gated channel subfamily Q member 1 (KCNQ1) gene has recently received much attention as a candidate susceptibility gene for type 2 diabetes mellitus, especially in Asian populations. We previously reported that Kcnq1 mutant mice exhibit reduced insulin secretion and hyperglycemia due to a decrease in pancreatic β-cell mass. Through in vivo and in vitro analyses, we ascertained that this mechanism is the result of the downregulation of the non-coding RNA ‘Kcnq1ot1,’ which is expressed in the paternal allele of the Kcnq1 gene region, causing an increase in the expression of the cell cycle inhibitor cyclin dependent kinase inhibitor 1C (Cdkn1c). It was found that decreased Kcnq1ot1 expression resulted in pancreatic β-cell failure; however, the degree of pancreatic β-cell volume reduction was not severe. Methods: We induced obesity in Kcnq1ot1 truncation mice by feeding them a high-fat diet and evaluated pancreatic β-cell mass. Results: In the present study, we reveal that CCAAT/enhancer binding protein beta (C/EBPβ), which is expressed at higher levels in pancreatic β-cells in obese individuals, further increases the expression of Cdkn1c, which is upregulated by the Kcnq1 gene mutation. We found that simultaneous Cdkn1c hypomethylation and C/EBPβ overexpression in pancreatic β-cells causes a synergistic decrease in pancreatic β-cell mass. Conclusion This finding suggests that the synergistic effect of genetic factors such as Kcnq1 gene mutations and environmental factors such as obesity and overeating, which lead to increased expression of C/EBPβ, contribute to the regulation of pancreatic β-cell mass. This study is the first to show that the Kcnq1 gene is related to pancreatic β-cell mass through genetic-environment interactions.

In this revision, we have attempted to align the Model Core Curriculum for Medical Education competency, "problem-solving ability based on specialized knowledge," with the "Standards of National Examination for Medical Practitioners." The major diseases and syndromes in "Essential Fundamentals" correspond to the basic diseases in Table 1 of the Core Curriculum, symptoms, physical and laboratory examinations, and treatment in "General Medicine" correspond to the items in Table 2 of the Core Curriculum, and the diseases in "Medical Theory" correspond to the diseases in PS-02 of the Core Curriculum. The validity of the diseases in the Core Curriculum was verified using the evaluation results of the examination level classification of the "Research for Revision of National Examination Criteria." Approximately 690 diseases were conclusively selected. This revision mentions the number of diseases in the Core Curriculum for the first time. Hopefully, this will lead to a deeper examination of diseases that should be studied in medical schools in the future.

Nephroblastomatosis (NBM) is a precursor of Wilms tumor. We herein report a case in which Wilms tumor was initially suspected and the affected kidney was removed.The tumor was subsequently diagnosed as intralobar NBM and a favorable outcome was achieved with postoperative chemotherapy. A 2-year-old boy who presented with gross hematuria was found to have an enlarged left kidney with hydronephrosis.Needle biopsy of the left kidney suggested Wilms tumor and left nephrectomy was performed. The tumor was histopathologically diagnosed as intralobar NBM.Although NBM is regarded as a precancerous lesion, a definite treatment plan has not yet been established. In the present case, we used a similar chemotherapy regimen to that for Wilms tumor. Eight years after the completion of chemotherapy, Wilms tumor has not developed or recurred. Appropriate management plans need to be developed by accumulating similar cases.

A 76-year-old female was admitted with complaints of dyspnea on exertion and lower leg edema. She had undergone an aortic valve replacement thirty-nine years before and a redo aortic valve replacement and mitral valve replacement twenty-eight years before. She also had hemolytic anemia with jaundice. Echocardiography showed severe paravalvular leakage in the aortic and mitral valves, and a blood flow in the aortic annulus that flows from the aortic side into the left atrium. We diagnosed heart failure and hemolytic anemia due to paravalvular leakage and decided to perform a double-valve replacement for the third time. On operation, after removing the aortic valve through aortotomy, aorto- mitral fibrous continuity was extensively calcified and perforated, and its strength was not enough to sew the prosthetic valve to it. Therefore, we decided to perform the Commando procedure. Aortotomy was extended between the noncoronary aortic sinus and the left coronary aortic sinus until it reached the dome of the left atrium. After the prosthetic mitral valve was excised, annuloplasty of the posterior mitral annulus was performed using a bovine pericardial patch, and the new prosthesis mitral valve was implanted. The anterior part of the annulus corresponding to the aorto-mitral fibrous continuity was reconstructed by sewing the base of a two-tongued triangular bovine pericardial patch to the sewing cuff of the mitral prosthesis. After closing the left atrial ceiling with the posterior patch, the aortic prosthesis was secured to the aortic annulus and the pericardial patch. The anterior patch was used to close the right side of the aortotomy. The postoperative course was uneventful, and postoperative echocardiography revealed no paravalvular leakage.

The case patient was a 61-year-old man who fell while working on the back of a truck and bruised his abdomen. Immediately thereafter, the patient started experiencing lumbar pain and weakness in both lower limbs. He was then transported to our hospital by ambulance. Based on the abdominal CT findings, he was diagnosed with acute lower limb ischemia due to a ruptured abdominal aortic aneurysm. The patient underwent graft replacement surgery within 3.5 hours after the onset of the rupture. The patient had no adverse findings, such as ischemia-reperfusion injury and compartment syndrome, after resumption of blood flow (6.5 hours after the onset) and both lower limbs were well perfused. Although there was mild muscle weakness and numbness in the distal left lower limb, the patient was discharged 9 days after surgery.

The patient was a 73-year-old man who was referred to our hospital due to an abnormal thoracic shadow. CT scans revealed Kommerell's diverticulum and saccular aortic arch aneurysm accompanied by abnormal origins of the right aortic arch and the left subclavian artery. Although there were no subjective symptoms, a surgical operation was planned considering the risk of a rupture of the saccular aneurysm. For the surgery, a median sternotomy approach was employed. Under cardiopulmonary bypass, the aortic arch was detached using the open distal method. Further, an open stent graft was inserted, and the aortic arch was replaced with a four-branched artificial blood vessel. After weaning off the cardiopulmonary bypass, coil embolization was performed on the left subclavian artery, and the site was checked to ensure that there was no endoleak. Although hoarseness was noted postoperatively due to paralysis of the right vocal cord, the patient progressed without any other major complications and was discharged 30 days after the operation.

Objective: Monitoring the prevalence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants is important due to concerns regarding infectivity, transmissibility, immune evasion and disease severity. We evaluated the temporal and regional replacement of previous SARS-CoV-2 variants by the emergent strains, Alpha and Delta. Methods: We obtained the results of polymerase chain reaction screening tests for variants conducted in multiple commercial laboratories. Assuming that all previous strains would be replaced by one variant, the new variant detection rate was estimated by fitting a logistic growth model. We estimated the transmission advantage of each new variant over the pre-existing virus strains. Results: The variant with the N501Y mutation was first identified in the Kinki region in early February 2021, and by early May, it had replaced more than 90% of the previous strains. The variant with the L452R mutation was first detected in the Kanto-Koshin region in mid-May, and by early August, it comprised more than 90% of the circulating strains. Compared with pre-existing strains, the variant with the N501Y mutation showed transmission advantages of 48.2% and 40.3% in the Kanto-Koshin and Kinki regions, respectively, while the variant with the L452R mutation showed transmission advantages of 60.1% and 71.9%, respectively. Discussion In Japan, Alpha and Delta variants displayed regional differences in the replacement timing and their relative transmission advantages. Our method is efficient in monitoring and estimating changes in the proportion of variant strains in a timely manner in each region.

The Japanese Society of Hepato-Biliary-Pancreatic Surgery launched the clinical practice guidelines for the management of biliary tract cancers (cholangiocarcinoma, gallbladder cancer, and ampullary cancer) in 2007, then published the 2nd version in 2014. In this 3rd version, clinical questions (CQs) were proposed on six topics. The recommendation, grade for recommendation, and statement for each CQ were discussed and finalized by an evidence-based approach. Recommendations were graded as grade 1 (strong) or grade 2 (weak) according to the concepts of the grading of recommendations assessment, development, and evaluation system. The 31 CQs covered the six topics: (1) prophylactic treatment, (2) diagnosis, (3) biliary drainage, (4) surgical treatment, (5) chemotherapy, and (6) radiation therapy. In the 31 CQs, 14 recommendations were rated strong and 14 recommendations weak. The remaining three CQs had no recommendation. Each CQ includes a statement of how the recommendations were graded. This latest guideline provides recommendations for important clinical aspects based on evidence. Future collaboration with the cancer registry will be key for assessing the guidelines and establishing new evidence.