Kyoto University Hospital Research Articles

Clinical Characteristics of AKI Associated with Chimeric Antigen Receptor T Cell (CAR-T) Therapy in Kyoto University Hospital

Clinical Characteristics of AKI Associated with Chimeric Antigen Receptor T Cell (CAR-T) Therapy in Kyoto University Hospital

Factors affecting discrepancies in disease activity evaluation between patients and physicians in systemic lupus erythematosus-The importance of symptoms such as fatigue.

There are often discrepancies in the evaluation of disease activity between patients and physicians in systemic lupus erythematosus (SLE). In this study, we examined the factors that affect those evaluations. Physician visual analogue scale (Ph-VAS), patient VAS (Pt-VAS), Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2k), glucocorticoid (GC) usage and dose, age, Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index, and three patient-reported outcomes (SLE symptom checklist [SSC], short-form 36 questionnaire [SF-36], and LupusPRO) were obtained from a study performed in 2019 using 225 SLE outpatients of the Kyoto Lupus Cohort at Kyoto University Hospital. Correlations among Ph-VAS, Pt-VAS, or dif (Pt-VAS-Ph-VAS) (Pt-VAS minus Ph-VAS) and other factors were examined. We found a significant discrepancy between Pt-VAS (median 38.0mm) and Ph-VAS (median 18.7mm) scores (p < 0.001). SSC score showed a significant correlation with Pt-VAS and dif (Pt-VAS-Ph-VAS) (p < 0.001). Among SSC items, fatigue showed the most significant correlation with dif (Pt-VAS-Ph-VAS). We also showed that higher dif (Pt-VAS-Ph-VAS) was associated with lower quality of life (QOL) evaluated by SF-36 and LupusPRO. Pt-VAS scores tended to be higher than Ph-VAS scores, and the discrepancy was influenced mainly by fatigue. Higher dif (Pt-VAS-Ph-VAS) was associated with lower patient QOL.

Subjective symptoms are triggers for the detection of immune checkpoint inhibitor-induced interstitial lung disease and associate with disease severity: a single-center retrospective study

BackgroundInterstitial lung disease (ILD) is one of the most common fatal immune-related adverse events (irAEs). ILD development adversely affects the continuation of anticancer drug therapy, including immune checkpoint inhibitor (ICI) therapy and prognosis. There are no established useful clinical indicators for the early detection of ILD. Furthermore, the factors that lead the attending physician to suspect ICI-induced ILD (ICI-ILD) remain unclear. This study aimed to investigate the ICI-ILD detection based on subjective symptoms and their relationship with disease severity in patients receiving anti-PD-1/PD-L1 antibody.MethodsThis was a retrospective observational study. We enrolled the patients who received anti-PD-1/PD-L1 antibody at Kyoto University Hospital between September 2014 and April 2021. Patients who developed ICI-ILD were stratified into two distinct groups based on factors that triggered the suspicion of ILD development. The “Subjective symptoms” group was defined as patients in whom ILD was detected based on subjective symptoms. Conversely, the “Routine examinations” group was defined as patients in whom ILD was suspected based on scheduled routine examinations. The severity of ILD in each group was assessed and its association with changes in the respiratory symptoms was examined.ResultsOf 926 patients who received anti-PD-1/PD-L1 antibody, 51 patients (5.5%) developed ICI-ILD. The incidence of ICI-ILD in patients with lung cancer was significantly higher than that in patients with other cancers (P < 0.001). Among the patients with ICI-ILD, 27 patients (52.9%) were classified into the “Subjective symptoms” group. The “Subjective symptoms” group exhibited a significantly higher proportion of Grade 3–5 ICI-ILD cases than the “Routine examinations” group (76.2% vs. 23.8%, P = 0.010). At the last visit, before the suspected onset of ILD, 21 of the 27 patients (77.8%) had no symptoms or no change in the respiratory symptoms.ConclusionSubjective symptoms triggered the suspicion of Grade 3–5 ICI-ILD. Enhanced monitoring and patient education could be essential for the early detection of ICI-ILD because ILD may develop rapidly. Our findings might help to manage ICI-ILD in clinical practice.

Predicting invasive disease-free survival in ER-positive, HER2-negative early breast cancer using the PAM50 risk-of-recurrence score: a retrospective analysis using single-center long-term follow-up data of postmenopausal Japanese patients

BackgroundThe prognostic value of the risk-of-recurrence (ROR) score calculated using PAM50 has been validated using clinical trials and patient cohorts. This study aimed to investigate the prognostic value of the PAM50 ROR score in Japanese patients with early breast cancer using long-term follow-up data.MethodsWe enrolled postmenopausal patients with ER-positive, HER2-negative, stage I–II breast cancer who had undergone surgery at the Kyoto University Hospital between 2008 and 2014. The intrinsic subtype and ROR score were calculated using PAM50. The primary endpoint was invasive disease-free survival (IDFS).ResultsWe enrolled 146 patients, of whom 47 (32%) patients had node-positive disease, and 36 (25%) had received neoadjuvant or adjuvant chemotherapy. The proportions of intrinsic subtypes for luminal A, luminal B, HER2-enriched, and basal-like subtypes were 67%, 27%, 3%, and 2%, respectively. The median follow-up duration was 8.4 (range 6.3–10.0) years, and 21 IDFS events were observed. Based on the ROR score, 37%, 33%, and 30% of the patients were classified as low, intermediate, and high risks, respectively. Patients in the high-risk group had a significantly worse 8-year IDFS rate than those in the low-to-intermediate-risk groups (75.1% vs. 91.6%, p = 0.04). The same trend was observed in patients with and without neoadjuvant or adjuvant chemotherapy.ConclusionsUsing long-term follow-up data, this study showed that the ROR score can predict the prognosis of ER-positive, HER2-negative early breast cancer in Japanese postmenopausal patients. Further investigations are required to confirm the prognostic value of the ROR score in Asian populations.

Similarity Analysis of Clinical Notes for Revealing Writing Styles in an Electronic Medical Record System.

One of the disadvantages of medical documentation in Electronic Medical Record (EMR) systems is that records tend to be redundant by "copying and pasting", a writing style to duplicate and revise previous records. In this study, we analyzed the similarity between records to identify the factors affecting the writing style of clinical notes. We analyzed 98,038 records of 4,149 patients from two years in the Department of Obstetricians and Gynecology at Kyoto University Hospital, Japan. We observed the correlation between the distribution of the record similarity and string amounts, as well as the disease codes and ratios of outpatient visit. The patient group with high record similarity and large number of strings was the group with reproductive medicine, followed by the group of malignant tumor follow-up or Women's Healthcare. In reproductive medicine, physicians have a demand for an overarching evaluation, and in follow-up malignancies or in Women's Healthcare, they have a demand to check for subtle differences from the last time. These facts along with our data insist that the writing style in EMR systems is related to the patient's status. We declared that the writing style in EMR systems is affected by the patient's status. The writing style of duplicating and revising is preferred (1) when there is a clinical demand for an overarching evaluation, and (2) when there is a clinical demand to check for subtle differences from the last time.

Efficacy of steroid therapy for improving native liver survival after pediatric acute liver failure with immune activation.

Recent evidence suggests that acute liver failure (ALF) in some patients may reflect a dysregulated immune response, and that corticosteroids improve survival of the native liver in ALF patients with high serum alanine aminotransferase levels, which are an indication of liver inflammation. However, it is unclear whether steroids are effective for pediatric acute liver failure (PALF). The aim of this retrospective case-control study is to examine whether steroid therapy for PALF accompanied by immune activation improves the survival of native liver and to identify factors that predict responses to steroid treatment. Of 38 patients with PALF treated at Kyoto University Hospital from February 2006 to August 2022, 19 receiving steroids who met the specific criteria for identifying the pathophysiology of immune activity in the liver (the "Steroid group"), and seven steroid-free patients who also met the criteria ("Nonsteroid group") were enrolled. Patients in the "Steroid group" were categorized as "responders" or "nonresponders" according to treatment outcome. Clinical and histological data were analyzed. Survival of the native liver in the Steroid group was significantly higher than that in the Nonsteroid group (68% vs. 0%, respectively; p=0.0052). Nonresponders were significantly younger, with higher Model for End-stage Liver Disease and pediatric end-stage liver disease scores, higher prothrombin time - international normalized ratio, and higher serum ferritin levels than responders. Massive hepatic necrosis was more common in nonresponders. Steroid therapy is effective for PALF patients with liver inflammation; however, liver transplantation should be prioritized for young children with ALF accompanied by severe coagulopathy or massive hepatic necrosis.

Additional treatments after curettage of congenital melanocytic nevi in the craniofacial region: A report from a single center in Japan

BackgroundCongenital melanocytic nevus (CMN) is a benign skin lesion present from birth, which may present with a risk of malignant transformation if extensive. Curettage, a treatment method involving the removal of the superficial layer of the nevus, is often used in the early stages of life. However, recurrence of the nevus and postoperative scarring may present as problems. Additional treatments, such as resection and/or laser treatment, are regularly required after curettage, particularly in the craniofacial region. However, no systematic treatment strategy has been reported. This study investigated additional treatments used after curettage to treat CMN in the craniofacial region and compared the frequency of treatments with respect to specific sites. MethodsCMN cases involving curettage as an initial treatment were retrospectively reviewed at Kyoto University Hospital between May 2019 and April 2022. ResultsThis study comprised 23 cases. Curettage was performed at a mean of 3.8 (1–10) months of age. No additional treatments were provided for 80% of head CMN. Additional treatments were performed in all cases, including the forehead and cheek. Laser treatment was performed in 86% of eyelid CMN and 75% of nasal CMN. Tissue expansion and flap closure were used in 33% of forehead CMN and 33% of cheek CMN. ConclusionsAdditional treatments used for CMN in the craniofacial region varied in accordance with the lesion site.

Efficacy and Safety of Branched Chain Amino Acids on Retinitis Pigmentosa: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

The aim of this study was to investigate the efficacy and safety of orally administered branched-chain amino acids (BCAAs) on disease progression in patients with retinitis pigmentosa (RP). A double-blind, randomized, placebo-controlled study was conducted at the Kyoto University Hospital. Seventy patients with RP aged 20years or above were randomly assigned to the TK-98 (a combination of BCAAs in granule form) or placebo group. One packet (4.15g) of the study drug was administered orally thrice daily for 78weeks. There was no significant difference in the rate of change in the total point score, the primary endpoint, between the TK-98 (-52.4 ± 10.3dB/year) and placebo (-42.9 ± 13.8dB/year) groups. Ellipsoid zone length decreased by -76.5 ± 8.9 and -95.5 ± 12.2 µm/year in the TK-98 and placebo groups, respectively; although this difference was not significant, the TK-98 group showed slower degeneration. No serious adverse events were associated with the oral administration of TK-98 in patients with RP. This study did not yield conclusive evidence supporting BCAA combination granules' effectiveness in slowing visual field progression in patients with RP. An insignificant trend toward a slower reduction in ellipsoid zone length was found in morphological tests. Further studies are required to fully understand the potential benefits of BCAA supplementation in RP. Our study demonstrates the safety of administering BCAAs to patients with RP. Accordingly, larger, more homogeneous clinical studies with longer durations may suggest their potential as therapeutic agents.

Differences between pathologic and non-pathologic high myopia in 4-year outcomes of anti-VEGF therapy for macular neovascularization

This retrospective observational study aimed to investigate the difference in 4-year outcomes of ranibizumab or aflibercept therapy for macular neovascularization (MNV) with high myopia between pathologic myopia (PM) and non-PM. This study was conducted at Kyoto University Hospital and included consecutive treatment-naïve eyes with active myopic MNV, in which a single intravitreal ranibizumab or aflibercept injection was administered, followed by a pro re nata (PRN) regimen for 4 years. Based on the META-PM study classification, eyes were assigned to the non-PM and PM groups. This study analyzed 118 eyes of 118 patients (non-PM group, 19 eyes; PM group, 99 eyes). Baseline, 1-year, and 2-year best-corrected visual acuity (BCVA) were significantly better in the non-PM group (P = 0.02, 0.01, and 0.02, respectively); however, the 3-year and 4-year BCVA were not. The 4-year BCVA course was similar in both groups. However, the total number of injections over 4 years was significantly higher in the non-PM than in the PM group (4.6 ± 2.6 vs. 2.9 ± 2.6, P = 0.001). Four-year BCVA significantly correlated only with baseline BCVA in both non-PM (P = 0.047, β = 0.46) and PM groups (P < 0.001, β = 0.59). In conclusion, over the 4-year observation period, the BCVA course after anti-VEGF therapy for myopic MNV was similar in the eyes with non-PM and those with PM; however, more additional injections in a PRN regimen were required in the eyes with non-PM compared to those with PM. Thus, more frequent and careful follow-up is required for the eyes with non-PM compared with those with PM to maintain long-term BCVA.

Comparison of a Novel Head-Mounted Objective Auto-perimetry (Gaze Analyzing Perimeter) and Humphrey Field Analyzer

To evaluate the agreement between 24-2 visual field (VF) test results obtained using the gaze analyzing perimeter (GAP; FINDEX, Tokyo, Japan) and the Humphrey field analyzer (HFA; Carl Zeiss Meditec, Dublin, CA, USA). Cross-sectional study PARTICIPANTS: Patients who underwent HFA 24-2 for suspected or confirmed VF loss and were treated at the Kyoto University Hospital between December 2022 and July 2023. Patients underwent consecutive VF tests on the same eye using HFA and GAP 24-2 tests. Bland-Altman analysis was used to compare GAP and HFA results. Examination points where the sensitivity measured using GAP was ≥10 dB higher than that measured using HFA were reevaluated by referring back to the original gaze data; two ophthalmologists assessed whether the gaze moved linearly toward the new test target. Mean deviation (MD) and elapsed time on an individual basis and sensitivity on an examination point basis. Forty-seven eyes of 47 patients were analyzed. The correlation coefficient of the MD using HFA and GAP was 0.811 (95% confidence interval [CI]: 0.683-0.891). Bland-Altman analysis showed good agreement between HFA and GAP tests. The mean difference (95% limits of agreement [LOA]) in MD between HFA and GAP results was -0.63 dB (-5.81 to 4.54 dB). Although no statistically significant differences were observed in the elapsed time (P = 0.99), measurements completed within 200 s were observed only in the GAP group (11 cases, 23.4%), who had significantly better HFA MD value than others (P=0.001). On an examination point basis for sensitivity, the correlation coefficient between HFA and GAP was 0.691 (95% LOA, 0.670-0.711). Original gaze data assessment revealed that the gaze moved linearly toward the new test target for 70.2% of the examination points with a sensitivity discrepancy. The results indicate that the GAP provides VF assessment outcomes comparable to those of the HFA. The GAP exhibited advantages in terms of testing time, particularly in patients with minimal VF impairment. Furthermore, the GAP records all eye movements, enabling the objective determination of VF abnormalities based on gaze patterns and facilitating easy post-hoc verification.

Investigation of severe acute respiratory syndrome coronavirus 2 infection status in solid organ transplant recipients treated with tixagevimab/cilgavimab

IntroductionTixagevimab and cilgavimab (T/C) are neutralizing antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that can be used to prevent SARS-CoV-2 infection in solid organ transplant (SOT) recipients. However, their neutralizing activity against recent variants was reduced, raising concerns regarding the emergence of breakthrough coronavirus diseases 2019 (COVID-19). This study aimed to investigate the status of the COVID-19 breakthrough after T/C administration. MethodsWe retrospectively investigated breakthrough COVID-19 in SOT recipients administered T/C at Kyoto University Hospital, Japan, from November 2022 to March 2023. Patients were monitored for 6 months after T/C administration. SARS-CoV-2 infection was diagnosed using polymerase chain reaction or antigen tests. The monthly incidence rates of SARS-CoV-2 infection were calculated using the person–time method. ResultsT/C were administered to 67 SOT recipients (liver, 16; lung, 36; and kidney, 15), of whom five were infected with SARS-CoV-2. All five cases were classified as mild, and none of these patients required admission to the intensive care unit (ICU) or died. All infected individuals tested positive for SARS-CoV-2 after March 2023, when T/C-resistant subvariant strains became predominant. The monthly incidence rate of SARS-CoV-2 infection, calculated using the person–time method, suggested an increasing trend. ConclusionsDuring the T/C-resistant variant epidemic, SARS-CoV-2 infections were identified even after T/C administration, suggesting that the prophylactic effects of T/C were invalid. Therefore, emerging variants must be carefully monitored and characterized to determine appropriate antiviral strategies, such as the use of suitable neutralizing antibodies.

Early Diagnosis of Hereditary Angioedema in Japan Based on a US Medical Dataset: Algorithm Development and Validation.

Hereditary angioedema (HAE), a rare genetic disease, induces acute attacks of swelling in various regions of the body. Its prevalence is estimated to be 1 in 50,000 people, with no reported bias among different ethnic groups. However, considering the estimated prevalence, the number of patients in Japan diagnosed with HAE remains approximately 1 in 250,000, which means that only 20% of potential HAE cases are identified. This study aimed to develop an artificial intelligence (AI) model that can detect patients with suspected HAE using medical history data (medical claims, prescriptions, and electronic medical records [EMRs]) in the United States. We also aimed to validate the detection performance of the model for HAE cases using the Japanese dataset. The HAE patient and control groups were identified using the US claims and EMR datasets. We analyzed the characteristics of the diagnostic history of patients with HAE and developed an AI model to predict the probability of HAE based on a generalized linear model and bootstrap method. The model was then applied to the EMR data of the Kyoto University Hospital to verify its applicability to the Japanese dataset. Precision and sensitivity were measured to validate the model performance. Using the comprehensive US dataset, the precision score was 2% in the initial model development step. Our model can screen out suspected patients, where 1 in 50 of these patients have HAE. In addition, in the validation step with Japanese EMR data, the precision score was 23.6%, which exceeded our expectations. We achieved a sensitivity score of 61.5% for the US dataset and 37.6% for the validation exercise using data from a single Japanese hospital. Overall, our model could predict patients with typical HAE symptoms. This study indicates that our AI model can detect HAE in patients with typical symptoms and is effective in Japanese data. However, further prospective clinical studies are required to investigate whether this model can be used to diagnose HAE.

Letermovir prophylaxis for cytomegalovirus in lung-transplant recipients: a comprehensive study with literature review of off-label use and real-world experiences

Letermovir, initially approved for cytomegalovirus (CMV) prophylaxis in hematopoietic stem-cell transplantation, has gained attention for off-label use in lung-transplant (LTx) recipients. Given the high susceptibility of LTx recipients to CMV infection, this study explores the effectiveness and safety of letermovir prophylaxis. A retrospective analysis of using letermovir for LTx recipients at Tohoku University Hospital (January 2000 to November 2023) was conducted. Case summaries from other Japanese transplant centers and a literature review were included. Six cases at Tohoku University Hospital and one at Kyoto University Hospital were identified. Prophylactic letermovir use showed positive outcomes in managing myelosuppression and preventing CMV replication. The literature review supported the safety of letermovir in high-risk LTx recipients. Despite limited reports, our findings suggest letermovir’s potential as prophylaxis for LTx recipients intolerant to valganciclovir. Safety, especially in managing myelosuppression, positions letermovir as a promising option. However, careful consideration is important in judiciously integrating letermovir into the treatment protocol.

Influence of implant length and diameter on implant failure: A retrospective study

ObjectiveDental implants are widely accepted in the dental community. Although several studies have reported high dental implant survival rates, complications can still occur. Implant failure is associated with different risk factors, including implant length and diameter. However, no clear consensus has yet been reached. This study aimed to evaluate the influence of different risk factors associated with implant failure. MethodsThis study included patients who received dental implants at Kyoto University Hospital. The inclusion criteria were dental implants placed between January 1, 2005 and December 31, 2022. Data on patient- and implant-related variables were collected. We used a marginal Cox proportional hazards models to investigate the association between the potential factors and implant failure. ResultsThis study included 147 patients who received 479 dental implants. Eleven of the 147 patients experienced implant failure, whereas 17 of the 479 implants failed. The cumulative survival rate of dental implants at the final time point was 95.3%. Multivariable marginal Cox analysis showed suggestive evidence that implant length (<10 mm) greatly increased the risk of implant failure compared with implant length (≥10 mm) (reference: <10 mm, hazard ratio, 0.07; 95% confidence interval, 0.01–0.34; p = 0.001). ConclusionsA cumulative survival rate comparable to that reported in other studies was achieved over prolonged periods of time. Although implant failure is multifactorial and implant length is only one of many factors contributing to implant loss, clinicians must be aware of the potential influence of implant length and make treatment decisions.

Abstract 4309: Establishment of intratumor heterogeneity using patient derived lung cancer cells

Abstract Overcoming cancer treatment resistance is a problem that must be solved to improve the prognosis of cancer patients. In recent years, genome analysis has revealed the existence of multiple subgroups with different properties within a single tumor, and intratumor heterogeneity is a cause of treatment resistance. It has also been reported that. However, the mechanism of intratumor heterogeneity remains unclear. Previous research on intratumor heterogeneity has mainly focused on analyzing patient cancer cells, classifying subgroups, and estimating characteristic factors. This method has two drawbacks. One is limitations in including all subgroups as research subjects, and other is lack of verification of whether characteristic factors are actually involved in intratumor heterogeneity in patients. Therefore, it is necessary to use a model of "early intratumor heterogeneity" in which monoclonal cells are divided into subgroups with different properties, and to verify the discovered factors using patient-derived cancer cell lines. In alectinib-resistant cell line (H2228-AR1S) created from monoclonal ALK-positive lung cancer cell line (H2228) by exposing to alectinib in vitro, existence of two fractions with different appearances. Using flow cytometry, it was revealed that H2228-AR1S bimodally expresses EpCAM, and the EpCAM-low fraction has high migration ability. In EpCAM-low fraction, epithelial markers were decreased, and mesenchymal markers were increased using immunoblotting. It suggests that EpCAM low subpopulation has undergone epithelial-mesenchymal transition (EMT). Additionally, we established a BRAF-positive lung cancer cell line (KTOR83) collected with consent from patients attending Kyoto University Hospital. Cells after in vitro dabrafenib exposure to KTOR83 showed bimodal EpCAM expression, and the EpCAM-low fraction has high migration ability. We established an intratumor heterogeneous model using commercially available cells and a patient-derived lung cancer cell line. Furthermore, we will explore factors common to the two models and examine factors involved in intratumor heterogeneity. Citation Format: Tomoko Funazo, Hiroaki Ozasa, Takahiro Tsuji, Yusuke Shima, Keiichiro Suminaga, Kentaro Hashimoto, Hiroshi Yoshida, Tatsuya Ogimoto, Kazutaka Hosoya, Hitomi Ajimizu, Takashi Nomizo, Hironori Yoshida, Toyohiro Hirai. Establishment of intratumor heterogeneity using patient derived lung cancer cells [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4309.

Significant association of HLA-A26 with uveitis and gastrointestinal involvement in patients with Behçet's disease in a multicentre study.

Specific human leukocyte antigen (HLA) haplotypes are associated with Behçet's disease. Because the effects of HLA-A26 and its combination with HLA-B51 on organ involvement in Behçet's disease have not been well demonstrated, we aimed to examine them. This multicentre, cross-sectional, observational study enrolled patients with Behçet's disease who visited Kyoto University Hospital between 2018 and 2021 or Kurashiki Central Hospital between 2006 and 2016 (n = 200). Disease severity was evaluated using the Krause score. Uveitis and gastrointestinal involvement were observed in 95/196 and 57/167 patients, respectively. The HLA alleles identified were HLA-B51 (n = 52/106), HLA-A26 (n = 25/88), and HLA-B51 and HLA-A26 (n = 6/88). In patients harbouring HLA-B51, the presence of HLA-A26 was associated with higher frequencies of uveitis (P = .03) and coexistence of uveitis and gastrointestinal involvement (P = .002) and higher Krause scores (P = .02). Furthermore, the presence of HLA-A26 was associated with a higher frequency of uveitis in patients with gastrointestinal involvement (P = .001) and gastrointestinal involvement in patients with uveitis (P = .001). Since specific HLA haplotypes and their combinations are associated with organ involvement, both HLA-A and HLA-B haplotypes should be confirmed when screening for affected organs.

Specific consistency score for rational selection of epilepsy resection surgery candidates.

Degree of indication for epilepsy surgery is determined by taking multiple factors into account. This study aimed to investigate the usefulness of the Specific Consistency Score (SCS), a proposed score for focal epilepsy to rate the indication for epilepsy focal resection. This retrospective cohort study included patients considered for resective epilepsy surgery in Kyoto University Hospital from 2011 to 2022. Plausible epileptic focus was tentatively defined. Cardinal findings were scored based on specificity and consistency with the estimated laterality and lobe. The total points represented SCS. The association between SCS and the following clinical parameters was assessed by univariate and multivariate analysis: (1) probability of undergoing resective epilepsy surgery, (2) good postoperative seizure outcome (Engel I and II or Engel I only), and (3) lobar concordance between the noninvasively estimated focus and intracranial electroencephalographic (EEG) recordings. A total of 131 patients were evaluated. Univariate analysis revealed higher SCS in the (1) epilepsy surgery group (8.4 [95% confidence interval (CI) = 7.8-8.9] vs. 4.9 [95% CI = 4.3-5.5] points; p < .001), (2) good postoperative seizure outcome group (Engel I and II; 8.7 [95% CI = 8.2-9.3] vs. 6.4 [95% CI = 4.5-8.3] points; p = .008), and (3) patients whose focus defined by intracranial EEG matched the noninvasively estimated focus (8.3 [95% CI = 7.3-9.2] vs. 5.4 [95% CI = 3.5-7.3] points; p = .004). Multivariate analysis revealed areas under the curve of .843, .825, and .881 for Parameters 1, 2, and 3, respectively. SCS provides a reliable index of good indication for resective epilepsy surgery and can be easily available in many institutions not necessarily specializing in epilepsy.

Low serum concentrations of bevacizumab and nivolumab owing to excessive urinary loss in patients with proteinuria: a case series.

Proteinuria can cause interindividual variability in the pharmacokinetics of therapeutic antibodies and may affect therapeutic efficacy. Here, we measured the serum and urinary concentrations of bevacizumab (BV) and nivolumab (NIVO) in patients with proteinuria and reported a case series of these patients. Thirty-two cancer patients who received BV every 3 weeks or NIVO every 2 weeks between November 2020 and September 2021 at Kyoto University Hospital were enrolled in this study. The serum and urinary concentrations of BV and NIVO were measured using liquid chromatography-tandem mass spectrometry. We divided the BV-treated patients and the NIVO-treated patients into two groups based on the urine protein-creatinine ratio (UPCR): UPCR 1g/g or higher (BV, n = 9; NIVO, n = 3) and UPCR less than 1g/g (BV, n = 14; NIVO, n = 6). Serum concentrations of the therapeutic antibodies adjusted by their doses were significantly lower in both BV- and NIVO-treated patients with UPCR 1g/g or higher compared to those with less than 1g/g. In patients with UPCR 1g/g or higher, urinary concentrations of the therapeutic antibodies adjusted by their serum concentrations and urinary creatinine concentrations tended to increase. This case-series study suggests a possibility of reduction in serum concentrations of BV and NIVO in patients with proteinuria by urinary excretion of these drugs.

Association Between Pancreatic Cysts and Diabetes Mellitus in Von Hippel-Lindau Disease.

Pancreatic cysts are frequently observed in patients with von Hippel-Lindau disease (VHL), and they are considered clinically not important. This study aimed to evaluate the association between pancreatic cysts and diabetes mellitus (DM) in patients with VHL. Among patients who were on a patient list at the VHL Center at Kyoto University Hospital as of December 2022, those who had undergone an upper abdominal magnetic resonance imaging study after 2010 were retrospectively evaluated. The presence or absence of DM and high glycated hemoglobin (HbA1c) levels (>6.0%) were assessed. Patients were divided into two groups: those with DM or high HbA1c levels, and those without DM or high HbA1c levels. The area of the whole pancreas, including the pancreatic cysts and tumors, the area of the pancreatic cysts, and the percentage of pancreatic cysts, calculated by dividing the area of pancreatic cysts by the area of the whole pancreas, were measured on T2-weighted magnetic resonance images and compared between the two groups. Thirty-six patients with VHL, comprising 22 men and 14 women, with a mean age of 36.4 years (range, 11-79 years), were identified. Seven patients had DM, and two additional patients had high HbA1c levels. The area of the pancreatic cysts (p = 0.0013) was significantly larger and the percentage of the pancreatic cysts (p = 0.0016) was significantly higher in patients with DM or high HbA1c levels (n = 9) than in patients without DM or high HbA1c levels (n = 27); however, the difference in the area of the whole pancreas was not significant (p = 0.068). Our findings suggest that patients with VHL who have a large area covered by pancreatic cysts are more likely to have DM than those without.

Comparison of the safety and cost-effectiveness of nebulized liposomal amphotericin B and amphotericin B deoxycholate for antifungal prophylaxis after lung transplantation

IntroductionFungal infection after lung transplantation can lead to poor clinical outcome, for which lung transplant recipients require prophylaxis. One of the antifungal agents used after lung transplantation is nebulized amphotericin B (AMB). Nebulized AMB causes adverse events such as dyspnea and airway irritation, and long-term use leads to high economic costs. So far, prophylactic regimens employing AMB deoxycholate (AMB-d) and liposomal AMB (L-AMB) have been developed. This study compared the efficacy, safety, and cost of AMB-d and L-AMB. Patients and methodsPatients who underwent lung transplantation at Kyoto University Hospital from January 2021 to May 2023 were included in this study. Thirty-three patients received nebulized AMB-d, whereas 29 received nebulized L-AMB. ResultsBoth regimens maintained comparable prophylactic efficacy regarding the development of fungal infection in the AMB-d and L-AMB groups (3.0% vs. 3.4%, P = 0.877). Patients treated with nebulized L-AMB experienced fewer respiratory-related adverse reactions than those treated with nebulized AMB-d (6.9% vs. 30.3%, P < 0.05), leading to a longer treatment duration with L-AMB than with AMB-d. Additionally, the daily cost of administering L-AMB was lower than that of administering AMB-d (3609 Japanese yen vs. 1792.3 Japanese yen, P < 0.05). DiscussionThese results suggest that nebulized L-AMB is safer and more cost-effective than nebulized AMB-d, with comparable efficacy.