Background: Acute kidney injury (AKI) is a common condition in severely ill patients associated with poor outcomes. We assessed the associations between urinary neutrophil gelatinase-associated lipocalin (uNGAL), urinary liver-type fatty acid-binding protein (uLFABP), and urinary cystatin C (uCysC) concentrations and patient outcomes. Methods: We assessed the predictive performances of uNGAL, uLFABP, and uCysC measured in the early phase of intensive care unit (ICU) management and at discharge from the ICU in severely ill patients for short- and long-term outcomes. The primary outcome was the occurrence of AKI during ICU stay; secondary outcomes were 28-day and 1-yr allcause mortality. Results: In total, 1,759 patients were admitted to the ICU, and 728 (41.4%) developed AKI. Median (interquartile range, IQR) uNGAL, uLFABP, and uCysC concentrations on admission were 147.6 (39.9–827.7) ng/mL, 32.4 (10.5–96.0) ng/mL, and 0.33 (0.12–2.05) mg/L, respectively. Biomarker concentrations on admission were higher in patients who developed AKI and associated with AKI severity. Three hundred fifty-six (20.3%) and 647 (37.9%) patients had died by 28 days and 1-yr, respectively. Urinary biomarker concentrations at ICU discharge were higher in non-survivors than in survivors. The areas under the ROC curve (95% confidence interval) of uLFABP for the prediction of AKI, 28-day mortality, and 1-yr mortality (0.70 [0.67–0.72], 0.63 [0.59–0.66], and 0.57 [0.51–0.63], respectively) were inferior to those of the other biomarkers. Conclusions uNGAL, uLFABP, and uCysC concentrations on admission were associated with poor outcomes. However, their predictive performance, individually and in combination, was limited. Further studies are required to confirm our results.

Background/Aims: Immune checkpoint blockade has recently been reported to be effective in treating microsatellite instability (MSI)-high tumors. Therefore, sufficient sampling of histological specimens is necessary in cases of unresectable pancreatic cancer (UR-PC). This multicenter study investigated the efficacy of endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) using a Franseen needle for MSI evaluation in patients with UR-PC. Methods: A total of 89 patients with UR-PC who underwent endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) or EUS-FNB using 22-G needles at three hospitals in Japan (2018–2021) were enrolled. Fifty-six of these patients (FNB 23 and FNA 33) were followed up or evaluated for MSI. Patient characteristics, UR-PC data, and procedural outcomes were compared between patients who underwent EUS-FNB and those who underwent EUS-FNA. Results: No significant difference in terms of sufficient tissue acquisition for histology was observed between patients who underwent EUS-FNB and those who underwent EUS-FNA. MSI evaluation was possible significantly more with tissue samples obtained using EUS-FNB than with tissue samples obtained using EUS-FNA (82.6% [19/23] vs. 45.5% [15/33], respectively; p<0.01). In the multivariate analysis, EUS-FNB was the only significant factor influencing the possibility of MSI evaluation. Conclusions EUS-FNB using a Franseen needle is desirable for ensuring sufficient tissue acquisition for MSI evaluation.

Objective: Acute mechanical thrombectomy (AMT) in patients with acute ischemic stroke from large vessel occlusion (LVO) is performed without directly identifying the occluded vessels. In this study, we evaluated whether 1.5 T magnetic resonance imaging (MRI) with 3D-fast imaging employing steady-state acquisition (FIESTA) could visualize the occluded intracranial middle cerebral artery (MCA) and internal carotid artery (ICA) before AMT. Methods: This retrospective study included 21 consecutive patients who underwent time-of-flight magnetic resonance angiography (TOF MRA) and 3D-FIESTA MRI immediately before AMT. The patients also underwent TOF MRA after AMT and achieved TICI 2b or 3 by AMT at our hospital between February 2018 and April 2019. When LVO in the anterior circulation was detected by TOF MRA, 3D-FIESTA MRI was additionally performed. Then, the occluded intracranial MCA and ICA, including their branches, were constructed on the workstation with volume rendering. The obtained images were fused with the TOF MRA images to create combined 3D images. Results: The length and top-to-bottom distance of the affected M1 segment (calculated by the ipsilateral-to-contralateral ratio) were 1.29 and 1.17, respectively, on 3D-FIESTA MRI before AMT and 1.34 and 1.24, respectively, on TOF MRA after AMT. We assessed the number of M2 segments branching from the affected M1/M2 junction and visualized the affected anterior temporal artery. The 3D-FIESTA MRI before AMT and TOF MRA after AMT were consistent in all patients, except for two who moved vigorously during imaging. Conclusions Images acquired by 1.5T 3D-FIESTA MRI can visualize to predict the existing path of the occluded MCA and ICA before AMT in patients with LVO of the anterior circulation.

Objective: Acute mechanical thrombectomy (AMT) in patients with acute ischemic stroke from large vessel occlusion (LVO) is performed without directly identifying the occluded vessels. In this study, we evaluated whether 1.5 T magnetic resonance imaging (MRI) with 3D-fast imaging employing steady-state acquisition (FIESTA) could visualize the occluded intracranial middle cerebral artery (MCA) and internal carotid artery (ICA) before AMT. Methods: This retrospective study included 21 consecutive patients who underwent time-of-flight magnetic resonance angiography (TOF MRA) and 3D-FIESTA MRI immediately before AMT. The patients also underwent TOF MRA after AMT and achieved TICI 2b or 3 by AMT at our hospital between February 2018 and April 2019. When LVO in the anterior circulation was detected by TOF MRA, 3D-FIESTA MRI was additionally performed. Then, the occluded intracranial MCA and ICA, including their branches, were constructed on the workstation with volume rendering. The obtained images were fused with the TOF MRA images to create combined 3D images. Results: The length and top-to-bottom distance of the affected M1 segment (calculated by the ipsilateral-to-contralateral ratio) were 1.29 and 1.17, respectively, on 3D-FIESTA MRI before AMT and 1.34 and 1.24, respectively, on TOF MRA after AMT. We assessed the number of M2 segments branching from the affected M1/M2 junction and visualized the affected anterior temporal artery. The 3D-FIESTA MRI before AMT and TOF MRA after AMT were consistent in all patients, except for two who moved vigorously during imaging. Conclusions Images acquired by 1.5T 3D-FIESTA MRI can visualize to predict the existing path of the occluded MCA and ICA before AMT in patients with LVO of the anterior circulation.

Objective: The antitumor effects of anti-PD-1 antibody against mismatch repair deficiency (MMR-D)-associated cancers have been reported. MMR-D is found in approximately 20%–30% of endometrial carcinomas (ECs) and frequently occurs due to MLH1 promoter hypermethylation (MLH1-PHM). ECs with MLH1-PHM are classified according to the molecular screening of Lynch syndrome (LS), but few detailed reports are available. The purpose of this study was to clarify the clinical features of EC with MLH1-PHM. Methods: Immunohistochemistry of MMR proteins (MLH1, MSH2, MSH6, and PMS2) was performed on specimens from 527 ECs treated at our university hospital from 2003 to 2018. MLH1 methylation analysis was added to cases with MLH1/PMS2 loss. ECs were classified as follows: cases that retained MMR proteins as “MMR-proficient;” cases with MLH1/PMS2 loss and MLH1-PHM as “met-EC;” and cases with other MMR protein loss and MLH1/PMS2 loss without MLH1-PHM as “suspected-LS.” The clinical features, including long-term prognosis, of each group, were analyzed. Results: Accordingly, 419 (79.5%), 65 (12.3%), and 43 (8.2%) cases were categorized as “MMR-proficient,” “suspected-LS,” and “met-EC,” respectively. Significantly, “met-EC” had a lower proportion of grade 1 tumors (37.5%) and a higher proportion of stage III/IV tumors (37.2%) than the other groups. The overall and progression-free survival of “met-EC” were significantly worse than those of “suspected-LS” in all cases. Conclusion In ECs with MMR-D, “met-ECs” were a subgroup with a poorer prognosis than “suspected-LS.” “Met-ECs” would be the main target for anti-PD-1 antibody treatment, and its clinical susceptibility should be verified individually.

Objective: Combination therapy with glecaprevir and pibrentasvir (G/P) has been shown to provide a sustained virologic response (SVR) rate of >97% in patients with chronic hepatitis C virus (HCV) infection in the first published real-world Japanese data. However, a recently published study showed that the treatment was often discontinued in patients ≥75 years old, resulting in low SVR in intention-to-treat (ITT) analysis. Thus, our aim was to evaluate real-world data for G/P therapy in patients ≥75 years of age, the population density of which is high in “rural” regions.Patients and Methods: We conducted a multicenter study to assess the efficacy and safety of G/P therapy for chronic HCV infection, in the North Kanto area in Japan.Results: Of the 308 patients enrolled, 294 (95.5%) completed the treatment according to the protocol. In ITT and per-protocol analyses, the overall SVR12 rate was 97.1% and 99.7%, respectively. The old-aged patients group consisted of 59 participants, 56 of whom (94.9%) completed the scheduled protocol. Although old-aged patients tended to have non-SVR factors such as liver cirrhosis, history of HCC, and prior DAA therapies, the SVR12 rates in old-aged patients were 98.3% and 100% in the ITT and PP analyses, respectively. Of 308 patients enrolled, adverse events were observed in 74 patients (24.0%), with grade ≥3 events in 8 patients (2.6%). There was no significant difference in any grade and grade ≥3 adverse events between the old-aged group and the rest of the study participants. Only one patient discontinued the treatment because of adverse events.Conclusion: G/P therapy is effective and safe for old-aged patients.

Morphine is the only opioid that has been found effective for the relief of dyspnea in cancer patients. However, efficacy has not been fully demonstrated for other opioids such as fentanyl. Here, we report a case of lung cancer in which the use of fentanyl was effective for the relief of dyspnea. The patient was an 88-year-old man who had cT4N2M0, cStage IIIB lung cancer with right bronchial involvement and mediastinal lymph node metastases. Although the patient complained of dyspnea, he was not given morphine due to underlying renal dysfunction. He instead received oxygen therapy, and treatment with oral steroids and oxycodone. As oral administration became more difficult with subsequent lung cancer progression, the patient underwent opioid switching from oxycodone to subcutaneous injections of fentanyl. Dyspnea was not exacerbated following the switching, and was thereafter effectively managed by increasing the fentanyl dose and using rescue medication. Fentanyl is suggested to be a possible therapeutic option for dyspnea in cases where the use of morphine is difficult.

BACKGROUND: Leukotriene receptor antagonists have been used to prevent virus-induced asthma exacerbations in autumn. Its efficacy, however, might differ with age and sex. OBJECTIVE: This study aimed to investigate whether pranlukast added to usual asthma therapy in Japanese children during autumn, season associated with the peak of asthma, reduces asthma exacerbations. It was also evaluated the effect of age and sex on pranlukast's efficacy. METHODS: A total of 121 asthmatic children aged 1 to 14 years were randomly assigned to receive regular pranlukast or not according to sex, and were divided in 2 age groups, 1–5 years and 6–14 years. The primary outcome was total asthma score calculated during 8 weeks by using a sticker calendar related to the days in which a child experienced a worsening of asthma symptoms. This open study lasted 60 days from September 15 to November 14, 2007. RESULTS: Significant differences in pranlukast efficacy were observed between sex and age groups. Boys aged 1 to 5 years had the lower total asthma score at 8 weeks (p = 0.002), and experienced fewer cold episodes (p = 0.007). There were no significant differences between pranlukast and control group in total asthma score at 8 weeks (p = 0.35), and in the days in which a child experienced a worsening of asthma symptoms (p = 0.67). CONCLUSION: There was a substantial benefit of adding pranlukast to usual therapy in asthmatic children, especially in boys aged 1 to 5 years, during autumn season.
Asian Continental Ancestry Group ; Asthma ; Child ; Child, Preschool ; Humans ; Leukotriene Antagonists ; Seasons

BACKGROUND/AIMS: Small intestinal bacterial overgrowth (SIBO) is considered to be involved in the pathogenesis of functional gastrointestinal disorders (FGID). However, the prevalence and clinical conditions of SIBO in patients with FGID remain to be fully elucidated. Here, we examined the frequency of SIBO in patients with refractory FGID. METHODS: We prospectively enrolled patients with refractory FGID based on Rome III criteria. A glucose hydrogen breath test (GHBT) was performed using a gas analyzer after an overnight fast, with breath hydrogen concentration measured at baseline and every 15 minutes after administration of glucose for a total of 3 hours. A peak hydrogen value > or = 10 ppm above the basal value between 60 and 120 minutes after administration of glucose was diagnosed as SIBO. RESULTS: A total of 38 FGID patients, including 11 with functional dyspepsia (FD), 10 with irritable bowel syndrome (IBS), and 17 with overlapping with FD and IBS, were enrolled. Of those, 2 (5.3%) were diagnosed with SIBO (one patient diagnosed with FD; the other with overlapping FD and IBS). Their symptoms were clearly improved and breath hydrogen levels decreased to normal following levofloxacin administration for 7 days. CONCLUSIONS: Two patients initially diagnosed with FD and IBS were also diagnosed with SIBO as assessed by GHBT. Although the frequency of SIBO is low among patients with FGID, it may be important to be aware of SIBO as differential diagnosis when examining patients with refractory gastrointestinal symptoms, especially bloating, as a part of routine clinical care.
Adult ; Blind Loop Syndrome ; Breath Tests ; Diagnosis, Differential ; Dyspepsia ; Gastrointestinal Diseases* ; Glucose ; Humans ; Hydrogen ; Irritable Bowel Syndrome ; Levofloxacin ; Prevalence ; Prospective Studies