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Abstract Rationale To detect pulmonary arterial hypertension (PAH) at any early stage is a promising approach to optimize the outcome. Objectives To investigate the impact of school ECG-based screening on detecting idiopathic or heritable (I/H)-PAH in the general pediatric population. Methods This was a nationwide survey of patients with I/H-PAH newly diagnosed at 3 months to 18 years of age in Japan during 2005–2012. Measurements and Main Results Eighty-seven eligible patients (age range, 1–16 yr) were recruited. Among 68 (78%) patients diagnosed at greater than or equal to 6 years of age (the age of the first ECG-based screening), 28 (41%) were detected by the ECG-based screening (screening group) and 40 (59%) were recognized by their symptoms (n = 37) or coincidental occasions (n = 3; nonscreening group). In the screening group, the proportion of patients in World Health Organization functional class I/II at diagnosis was higher (96% vs. 60%; P < 0.001), plasma brain natriuretic peptide level was lower (149 ± 290 vs. 398 ± 559 pg/ml; P = 0.045), and 6-minute-walk distance was longer (420 ± 109 vs. 327 ± 104 m; P < 0.001) than the nonscreening group, despite similar values in mean pulmonary artery pressure (58 ± 17 vs. 61 ± 17 mm Hg; P = 0.42) and pulmonary vascular resistance index (18 ± 8 vs. 21 ± 11 Wood units ⋅ m2; P = 0.24) between groups. The proportion of patients on intravenous epoprostenol at the final visit was lower in the screening group than the nonscreening group (14% vs. 50; P = 0.004). Conclusions These findings suggest that the ECG-based screening detects a unique subpopulation of pediatric patients with I/H-PAH that is associated with already established pulmonary hypertension but without obvious right heart failure and warrants investigating the prognostic significance of this system.

We report the importance of evaluating the right coronary artery (RCA) by two-dimensional echocardiography (2DE) in the acute phase of Kawasaki disease (KD), based on our experience with three patients whose coronary artery lesions (CAL) involving the RCA were missed in the acute phase of KD. Two patients had asymptomatic occlusion of the RCA, and it was speculated that one patient had a cardiac arrest due to CAL of the RCA. An abnormal Q wave in lead III in all 3 patients had indicated stenotic lesions of the RCA. Because it is difficult to diagnose CAL by 2DE in the late period, it is essential to identify the proximal RCA using a right parasternal approach while the patient is lying in the right lateral position.

Background: Regular visits with healthcare professionals are important for preventing serious complications in patients with diabetes. The purpose of this retrospective cohort study was to clarify whether there was any suppression of physician visits among patients with diabetes during the spread of the novel coronavirus 2019 (COVID-19) in Japan and to assess whether telemedicine contributed to continued visits.Methods: We used the JMDC Claims database, which contains the monthly claims reported from July 2018 to May 2020 and included 4,595 (type 1) and 123,686 (type 2) patients with diabetes. Using a difference-in-differences analysis, we estimated the changes in the monthly numbers of physician visits or telemedicine per 100 patients in April and May 2020 compared with the same months in 2019.Results: For patients with type 1 diabetes, the estimates for total overall physician visits were −2.53 (95% confidence interval [CI], −4.63 to 0.44) in April and −8.80 (95% CI, −10.85 to −6.74) in May; those for telemedicine visits were 0.71 (95% CI, 0.47–0.96) in April and 0.54 (95% CI, 0.32–0.76) in May. For patients with type 2 diabetes, the estimates for overall physician visits were −2.50 (95% CI, −2.95 to −2.04) in April and −3.74 (95% CI, −4.16 to −3.32) in May; those for telemedicine visits were 1.13 (95% CI, 1.07–1.20) in April and 0.73 (95% CI, 0.68–0.78) in May.Conclusion: The COVID-19 pandemic was associated with suppression of physician visits and a slight increase in the utilization of telemedicine among patients with diabetes during April and May 2020.

We previously reported that dye was effective to prevent the leakage of enzyme solutions from pancreatic glands during an islet isolation procedure. However, the dye used for islet isolation has not yet been optimized. In this study, we focused on pyoktanin blue (PB), diagnogreen (DG), and indigo carmine (IC) as potential candidates among clinically established dyes. A serial dilution assay was performed to determine minimal effective concentrations of each dye for detecting damaged pancreatic tissues. According to the outcome of serial dilution assays, double minimum effective concentrations of each dye were used for in vitro toxicity assays on islets and used in the isolation procedure to investigate whether they adversely affect islet isolation efficiency. The evaluations included islet yield, ADP/ATP, ATP/DNA, glucose stimulation test, and insulin/DNA assays. Islet viability cultured with PB contained medium was significantly lower than the other dyes. DG and IC appeared to be non-toxic to the islets. In isolation experiments, the islet yield in the DG group was considerably lower than that in the Control group, suggesting that DG might inhibit enzyme activity. The present study demonstrates that IC could be a promising candidate for an effective dye to detect damaged pancreatic tissues without affecting the enzyme activity and islet quality.

Optimizing the collagenase G (ColG):collagenase H (ColH) ratio is a key strategy for achieving tailored donor-tissue specific islet isolation. Collagen V (Col V) and collagen III (Col III) are crucial target matrices of ColG and ColH, respectively. We herein investigated the relevance between the expression of target matrices in pancreatic tissues and influence of ColG:ColH ratio on islet isolation outcome. Islet isolation was performed in Lewis and SD rats using different ColG:ColH ratios (5:1, 1:1 and 1:5; n = 7/group). The composition of Col III and Col V was examined using immunohistochemical staining, real-time polymerase chain reaction (PCR), Western blotting and mass spectrometry. Chain types in collagen I (Col I) were also assessed using mass spectrometry. No beneficial effects were observed by increasing the ColG amount, irrespective of the rat strain. In contrast, the islet yield in Lewis rats was considerably increased by high amounts of ColH but decreased in SD rats, suggesting that Lewis pancreas contains more Col III than SD pancreas. Neither immunohistochemical nor real-time PCR showed correlation with isolation outcome. However, Western blotting revealed that Lewis contained considerably higher amount of Col III than SD (p = 0.10). Likewise, Col-I(α1)/Col-III(α1) and Col-I(α2)/Col-III(α1) were significantly lower in Lewis than in SD rats (p = 0.007, respectively). Furthermore, the isolation outcome was considerably correlated with the composition of homotrimeric Col I. The Col III expression and the composition of homotrimeric Col I in pancreatic tissues determined using mass analyses appeared useful for optimizing the ColG:ColH ratio in islet isolation.

Background Anatomical resections have been reported to achieve better long-term outcomes compared with partial resections for the treatment of hepatocellular carcinoma (HCC). Despite this, laparoscopic anatomical resections are very challenging operations, especially when approaching the posterosuperior segments of the liver (IVa, VII, and VIII). We report a full laparoscopic anatomical segment 8 resection focusing on the technical aspects of the Glissonian approach. Methods A routine follow-up CT scan of an 80-year-old women affected by hepatitis C-related liver cirrhosis showed a 3-cm HCC in segment 8. Three-dimensional reconstruction was performed to evaluate the liver anatomy, the relationship of the lesion with major vessels, and the borders of segment 8. A true anatomical segmentectomy was performed by using selective occlusion of segment’s 8 Glissonian pedicle, which was identified from the liver hilum. Indocyanine green (ICG) dye demarcation was used as a guidance during parenchymal transection. 1 – 4 Results Operative time was 420 min, and blood loss was 261 mL. The patient had an uneventful postoperative course and was discharged home after 8 days. Conclusions Full laparoscopic anatomical segment 8 resection is a technically challenging operation. The use of the Glissonian approach and the aid of ICG dye could be of help, but advanced laparoscopic skills are necessary to complete such a difficult procedure safely. 5 – 13

The global coronavirus disease-2019 (COVID-19) pandemic is associated with reduced rate of percutaneous coronary intervention (PCI). However, there were a few data showing how emergency medical system (EMS) and management strategies for acute coronary syndrome (ACS) changed during the pandemic. We sought to clarify changes on characteristics, treatments, and in-hospital mortality of patients with ACS transported via EMS between pre- and post-pandemic. We examined consecutive 656 patients with ACS admitted to Sapporo City ACS Network Hospitals between June 2018 and November 2021. The patients were divided into pre- and post-pandemic groups. The number of ACS hospitalizations declined significantly during the pandemic (proportional reduction 66%, coefficient −0.34, 95% CI −0.50 to −0.18, p < 0.001). The median time from an EMS call to hospital was significantly longer in post-pandemic group than in pre-pandemic group (32 [26–39] vs. 29 [25–36] min, p = 0.008). There were no significant differences in the proportion of patients with ACS receiving PCI, and in-hospital mortality between the groups. The COVID-19 pandemic had a significant impact on EMS and management in patients with ACS. Although a significant decline was observed in ACS hospitalizations, the proportion of patients with ACS receiving emergency PCI remained during the pandemic.

Acute coronary syndrome (ACS) requires rapid transportation by the emergency medical system (EMS). In snowy areas, traffic conditions may delay EMS transport times and increase mortality rate of ACS. However, there is a paucity of systemic data showing how snowfall affects the EMS and mortality in patients with ACS. This study aimed to investigate the impact of snowfall on the EMS transport times and in-hospital death in patients with ACS. We examined 2387 consecutive ACS patients who were transported via EMS to hospitals participating in the Sapporo City ACS network between April 2013 and April 2023. The patients were divided into two groups based on their arrival on either a snowy day (n = 612, 26%) or a non-snowy day (n = 1775, 74%), as determined by historical weather records from the Japan Meteorological Agency for the Sapporo area. The median age was 68 years, 1754 (74.6%) patients were male. Patients in the snowy day group had longer median time from an EMS call to hospital than those in the non-snowy day group (33 min [IQR 26–40] vs. 29 min [IQR 24–36], P  < 0.001). Quantity of snowfall was associated with a delayed time from EMS call to hospital. The proportion of in-hospital death was higher in the snowy day group compared to the non-snowy day group (7.3% vs. 4.6%, P  = 0.011). Multivariable logistic regression analysis showed that the snowfall was independently associated with higher incidence of in-hospital death (odds ratio 1.57, 95% confidence interval 1.00–2.47, P  = 0.048). In conclusion, snowfall had a significant impact on the EMS and mortality in patients with ACS in an urban city in Japan.

BackgroundRegular visits with healthcare professionals are important for preventing serious complications in patients with diabetes. The purpose of this retrospective cohort study was to clarify whether there was any suppression of physician visits among patients with diabetes during the spread of COVID-19, in Japan and to assess whether telemedicine contributed to continued visits.MethodsWe used the JMDC Claims database which contains the monthly claims reported from July 2018 to May 2020 and included 4595 (type 1) and 123,686 (type 2) patients with diabetes.Using a difference-in-differences analysis, we estimated the changes in the monthly numbers of physician visits or telemedicine per 100 patients in April and May 2020 compared with the same months in 2019.ResultsFor patients with type 1 diabetes, the estimates for total overall physician visits were -2.53 (95% CI, -4.63 to 0.44) in April and -8.80 (-10.85 to -6.74) in May; those for telemedicine visits were 0.71 (0.47 to 0.96) in April and 0.54 (0.32 to 0.76) in May. For patients with type 2 diabetes, the estimates for overall physician visits were -2.50 (-2.95 to -2.04) in April and -3.74 (-4.16 to -3.32) in May; those for telemedicine visits were 1.13 (1.07 to 1.20) in April and 0.73 (0.68 to 0.78) in May.ConclusionsThe COVID-19 pandemic was associated with suppression of physician visits and a slight increase in the utilisation of telemedicine among patients with diabetes during April and May 2020.

Acute myeloid leukemia (AML) is an aggressive hematological malignancy with genetic alterations. The FMS-like tyrosine kinase 3 (FLT3) gene is frequently mutated in adult de novo AML, with two types of mutations: internal tandem duplication (ITD) and point mutations in the tyrosine kinase domain. This study aimed to investigate the impact of FLT3 inhibitors and hematopoietic cell transplantation (HCT) on survival outcomes in patients with FLT3-ITD AML in a real-world setting. We retrospectively analyzed 139 patients with FLT3-ITD-positive AML between 2012 and 2021. The median age was 63 years. In the propensity score-matched cohort, FLT3 inhibitors improved overall survival (OS) compared with patients treated without FLT3 inhibitors (3-year OS: 33.7% vs. 25.8%, p = 0.021). Patients who underwent HCT had superior outcomes to those without HCT (3-year OS: 45.3% vs. 2.2%, p < 0.0001). The combination of FLT3 inhibitors and HCT resulted in the highest OS and relapse-free survival (RFS) rates (3-year OS: 62.4%; 3-year RFS: 44.4%). Disease status before transplantation did not predict the prognosis, but use of FLT3 inhibitors increased survival in patients without complete remission before HCT. These results demonstrate the clinical impact of FLT3 inhibitors on survival outcomes in patients with FLT3-ITD-positive AML, particularly when combined with HCT. FLT3 inhibitors can improve the prognosis of AML with FLT3 mutations, especially in patients who undergo HCT.