Shiga Medical Center

Since comprehensive data on the pathogenic variants of ABCG5 and ABCG8 and clinical features in sitosterolemia remain limited, we aimed to compile a catalog through an extensive literature search of case reports from 2002 to 2024, as well as an evaluation of variants reported in review articles. We compiled 155 cases of sitosterolemia from 133 families with nonsynonymous variants in ABCG5 and ABCG8, along with data on clinical information from case reports. Pathogenic variants were defined either as 1) protein-truncating variants, 2) classified as pathogenic or likely pathogenic variants according to the ACMG guidelines, or 3) serum sitosterol level of the case was measured at ≥ 1 mg/dL. Xanthoma was observed in 69.2% of patients, ischemic heart disease in 14.2%, and hematologic abnormalities in 57.9%. Fifty-three variants in ABCG5 and 52 in ABCG8 were evaluated for their pathogenicity, in which 33 in ABCG5 and 29 in ABCG8 were protein-truncating variants. Additionally, based on the ACMG criteria and serum sitosterol levels, 50 variants in ABCG5 and 51 variants in ABCG8 were finally classified as pathogenic. Among them, the frequently observed R446X and R389H in ABCG5 were highly prevalent in East Asians, while W361X and S107X in ABCG8 were predominantly found in Europeans. We provided the largest catalog of clinical features and pathogenic variants of ABCG5 and ABCG8 in the world. This study may help clarify the pathogenicity of variants in ABCG5 and ABCG8 and provide a valuable reference for the genetic diagnosis of sitosterolemia.

We evaluated the prognostic significance and implications of a major pathologic response (MPR) after preoperative treatment for pancreatic ductal adenocarcinoma (PDAC). Preoperative treatment is increasingly used for PDAC to improve oncologic outcomes. The pathologic response represents a potential indicator of treatment efficacy; however, its prognostic value in PDAC remains unclear. We retrospectively analyzed 739 patients who underwent pancreatectomy for PDAC after preoperative treatment at 21 institutions in Japan. The pathologic response was graded using Evans' classification, with MPR defined as Evans grade III/IV. Survival outcomes and prognostic factors were evaluated, and factors associated with achieving MPR were analyzed to develop a predictive model. MPR was achieved in 11.5% of patients. The MPR group had a significantly longer median overall survival (71.5 vs. 40.9mo) and recurrence-free survival (55.5 vs. 15.2mo) than the non-MPR group. Multivariate analysis identified MPR as an independent prognostic factor for overall survival. In the MPR subgroup, neither overall nor recurrence-free survival differed according to adjuvant chemotherapy administration; multivariate analysis did not identify adjuvant therapy as an independent prognostic factor. Predictive factors for achieving MPR included chemoradiotherapy, preoperative duration ≥6 months, normal carbohydrate antigen 19-9 after preoperative treatment, and complete or partial radiologic response. Finally, we developed a simplified predictive model for achieving MPR. MPR was independently associated with favorable survival in PDAC. The prognostic impact of adjuvant chemotherapy was not observed among patients who achieved MPR, suggesting that MPR may inform individualized postoperative management and warrants prospective validation.

Self-expanding metal stents (SEMS) are widely used as a bridge to surgery in obstructive colon cancer, offering short-term benefits by reducing postoperative complications and avoiding emergency stoma creation. Additionally, early initiation of systemic chemotherapy may improve oncological outcomes. However, the safety and feasibility of preoperative chemotherapy following SEMS placement remain unclear. This study aims to evaluate the safety and efficacy of neoadjuvant CAPOX chemotherapy after SEMS placement in patients with obstructive colon cancer. This is a prospective, multicenter, single-arm Phase II trial involving patients with clinical stage II or III obstructive colon cancer. Eligible patients undergo successful SEMS placement followed by two cycles of CAPOX chemotherapy prior to elective surgery. The primary endpoint is the incidence of severe perioperative complications, defined as a composite of stent-related adverse events and Clavien - Dindo Grade III or higher postoperative complications. Secondary endpoints include chemotherapy-related adverse events, pathological response, and 2-year relapse-free survival. A total of 75 patients are planned for enrollment across 16hospitals in Japan over 1.5 years. The study is registered in the Japan Registry of Clinical Trials (jRCTs051240077).

BackgroundThe measurement of computed tomography dose index 100 (CTDI100), which is feasible only through axial scanning, requires that the clinical spiral protocols be replaced with those for axial scanning. The real‐time ionization chamber detects the integral of radiation dose rate profile, enabling the direct verification of the volume CTDI on spiral CT scanning (CTDIvolSpiral).PurposeThis study aimed to develop a direct measurement technique for CTDIvolSpiral and compare its accuracy with that measured using axial scanning (CTDIvolAxial) or that displayed on the console (CTDIvolDisplayed).MethodsA CTDI phantom with a real‐time ionization chamber was placed on the headrest or examination table. CTDI100Axial was measured with following parameters: tube voltage = 120 kV, effective mAs = 100, and rotation time = 1.00 s. The parameters for measuring CTDI100Spiral were set identical to those used for axial scanning, except for rotation times = 0.33, 0.50, and 1.00, pitch = 0.35, 0.50, 0.75, 1.00, 1.25, and 1.50, and the scanning range = 15 cm. CTDI100Spiral was extracted from the integral of radiation dose rate profile. CTDIvolSpiral was subsequently calculated and compared with CTDIvolAxial and CTDIvolDisplayed. Finally, CTDIvolSpiral was measured for 10 clinical protocols and compared with CTDIvolDisplayed.ResultsThe differences between CTDIvolAxial and CTDIvolDisplayed, CTDIvolSpiral and CTDIvolDisplayed, and CTDIvolAxial and CTDIvolSpiral for the head and body phantoms were all < −2.0%. The differences between CTDIvolDisplayed and CTDIvolSpiral for scans on clinical protocols with and without automatic exposure control were < 11.9% and < 10.5%, respectively; these large differences were observed in the dual‐energy twin‐beam protocol. Excluding this protocol yielded differences between the measurements with and without automatic exposure control of < 2.0% and < −3.9%, respectively.ConclusionsThe results showed an excellent agreement between CTDIvolAxial and CTDIvolSpiral, supporting the use of the clinical spiral CT scanning to verify CTDIvolDisplayed using a real‐time ionization chamber.

BackgroundPatients with rheumatoid arthritis (RA) are at a higher risk for sarcopenia than the general population. Exercise therapy can improve muscle strength in older adults; however, its efficacy in older patients with RA has not been fully established. This study aimed to evaluate the efficacy of a personalized exercise program on physical function in older patients with RA at high risk for sarcopenia.MethodsA single-centre, parallel-group, two-arm, superiority randomized controlled trial was conducted in patients with RA aged 60–85 years who were at risk of sarcopenia. The intervention group (n = 69) underwent a 16-week personalized exercise program in addition to nutritional guidance and standard care, whereas the control group (n = 65) received only nutritional guidance and standard care. The primary outcome was the change in the total Short Physical Performance Battery (SPPB) scores from baseline to week 16.ResultsA total of 140 patients were randomized. Of these, 134 initiated the assigned intervention. There was a 0.2-point difference in SPPB total score from baseline to week 16 between the intervention group (+ 0.4 points) and the control group (+ 0.2 points); 95% confidence interval: -0.1 to 0.5; p = 0.206. Regarding the secondary outcomes at week 16, there was a tendency for improvement in the chair-stand test, grip strength, and the mental component score.ConclusionThe 16-week personalized exercise therapy did not improve the total SPPB scores. However, the intervention may improve standing ability, grip strength, and mental health-related quality of life in older patients with RA at high risk of sarcopenia.Trial registrationThis study was registered with UMINCTR (trial number: UMIN000044930).Supplementary InformationThe online version contains supplementary material available at 10.1186/s13075-026-03751-8.

ObjectiveThe treatment effects of lymphadenectomy in early-stage ovarian clear cell carcinoma (OCCC) reported in previous studies may have been overestimated owing to confounding factors. This study aimed to investigate the treatment effect of pelvic and para-aortic lymphadenectomy (PeNPAN) in early-stage OCCC, with careful adjustment for potential confounders.MethodsThis retrospective multi-center cohort study involved women with preoperatively suspected stage I OCCC. We included patients who underwent surgery for OCCC between 2005 and 2019 at 11 affiliated institutions. The exposure (PeNPAN) group comprised patients who underwent PeNPAN. The primary outcome was disease-free survival (DFS). Additionally, hazard ratios (HRs) of lymphadenectomy for DFS were estimated using unadjusted and propensity score-weighted Cox regression models and biased models applied in previous studies. To identify strong confounders, we further examined factors associated with recurrence that differed between the groups.ResultsWe analyzed 304 women who underwent surgery for preoperatively suspected stage I OCCC. The unadjusted HR for DFS was 0.63 (95% confidence interval [CI]=0.36–1.09; p=0.10), and the propensity-score adjusted HR was 0.82 (95% CI=0.42–1.58; p=0.55). The biased model showed a statistically significant HR of 0.59 (95% CI=0.36–1.00; p=0.048). Adhesions in the Douglas’ pouch and cardiovascular disease were associated with recurrence and were more prevalent in the control group, suggesting potential confounders.ConclusionAfter adjusting for potential confounders, the observed treatment effects of lymphadenectomy in the biased models were no longer statistically significant. Future investigations should carefully account for possible confounders, including intraoperative adhesions and comorbidities.

ABSTRACTThe Japan Primary Care Association (JPCA) was established in 2010 through the merger of three academic societies: the Japanese Medical Society of Primary Care, the Japanese Academy of Family Medicine, and the Japanese Society of General Medicine. This article reviews the historical development of these predecessor organizations, the context and process of their unification, and the evolution of JPCA. Over the past 15 years, JPCA has promoted clinical practice, education, and research while enhancing inter‐professional collaboration and certification systems for physicians, nurses, and pharmacists. Its proactive response to disasters, involvement during the COVID‐19 pandemic, and participation in healthcare policies reflect its dedication to addressing Japan's changing healthcare landscape. As the leading academic organization for primary care in Japan, JPCA continues to foster integrated community‐based care and aims to strengthen its presence both nationally and internationally in the advancing field of primary care.

ABSTRACTPurposePronounced apex‐distal joint line obliquity (JLO) complicates total knee arthroplasty (TKA) by challenging patellofemoral tracking and medial tibial bone support. Joint line obliquity–modified kinematic alignment (JLO‐KA)—a selective modification of kinematic alignment (KA) that omits femoral cartilage‐wear compensation and reallocates correction to the tibial side—was developed. This study quantified postoperative component and limb alignment with JLO‐KA versus true KA.MethodsRetrospective comparison of 20 JLO‐KA knees and 15 true‐KA knees with preoperative apex‐distal JLO (CPAK I–III). Pre‐/postoperative computed tomography (CT) measured lateral distal femoral angle (LDFA), medial proximal tibial angle (MPTA), femoral component rotation (FCR), arithmetic hip–knee–ankle angle (aHKA), and JLO; postoperative Coronal Plane Alignment of the Knee (CPAK) distribution was analysed (Δ = JLO‐KA minus true KA).ResultsGroups were similar at baseline: preoperative LDFA 87.7° versus 87.6°, MPTA 83.5° versus 83.5°, aHKA −4.3° versus −4.1°, JLO 171.2° versus 171.2° (all p > 0.05). Postoperatively, JLO‐KA increased LDFA to 90.4° ± 2.3° versus 87.0° ± 1.9° (Δ = +3.4°, 95% confidence interval [CI]: 1.9–4.8; p < 0.0001), MPTA to 88.0° ± 1.4° versus 85.6° ± 2.0° (Δ = +2.4°, 1.1–3.7; p = 0.0015), and FCR to 3.1° ± 2.0° versus 0.1° ± 2.0° (Δ = +2.9°, 1.5–4.3; p = 0.0002), while aHKA was similar (−2.4° ± 3.1° vs. −1.4° ± 2.8°; Δ = −1.0°; p = 0.324). JLO was closer to neutral with JLO‐KA (178.4° ± 2.2° vs. 172.7° ± 2.8°; Δ = +5.8°; p < 0.001). Neutral‐JLO CPAK types (IV–VI) occurred in 16/20 (80%) versus 2/15 (13%) (p = 0.00013). The restricted KA 90° ± 5° range for LDFA and MPTA was met by 19/20 (95%) versus 7/15 (47%) (p = 0.0019).ConclusionReallocating cartilage‐wear compensation from the medial femur to the medial tibia within the same calliper‐verified workflow reduced femoral valgus, limited tibial varus, and increased femoral external rotation by ≈3° while maintaining aHKA. Shifts were consistent with lateralizing the prosthetic trochlear groove and preserving medial tibial bone support, positioning JLO‐KA as a targeted option for apex‐distal knees (CPAK I–III).Level of EvidenceLevel III, retrospective comparative study.