Low liver reserve is a risk factor for acute pancreatitis in patients with acute liver failure.

AIM: Acute pancreatitis is a complication of acute liver failure (ALF). This study aimed to investigate the prevalence of and clinical features associated with acute pancreatitis in patients with ALF. METHODS: We retrospectively analyzed a cohort of ALF patients without hepatic encephalopathy diagnosed during a period 2011-2018, and compared clinical features between patients with acute pancreatitis and those without. Acute pancreatitis was diagnosed according to the Acute Pancreatitis Clinical Practice Guidelines 2021. A multivariate analysis was carried out to identify factors associated with acute pancreatitis. RESULTS: There were 83 ALF patients without hepatic encephalopathy (34 men; 11 deaths; 6 liver transplants; median age, 63 years). Acute pancreatitis occurred in nine patients (10.8%). The median time duration from ALF to the onset of acute pancreatitis was 8 days. The survival rate was lower in patients with than those without acute pancreatitis (22% vs. 86%). The model for end-stage liver disease score (hazard ratio 1.10, 95% confidence interval 1.03-1.18) was found to be a significant factor associated with acute pancreatitis, whereas triglyceride, age, and sex were not. CONCLUSIONS: A high model for end-stage liver disease score may be a marker to stratify patients with ALF at a risk of acute pancreatitis.

Grip strength complements performance status in assessing general condition in patients with unresectable hepatocellular carcinoma treated with atezolizumab and bevacizumab.

AIM: An accurate assessment of the general condition of patients with hepatocellular carcinoma (HCC) is essential. We evaluated the impact of grip strength (GS) and Eastern Cooperative Oncology Group Performance Status (ECOG-PS) on the clinical outcomes of patients with unresectable HCC (u-HCC) treated with atezolizumab plus bevacizumab. METHODS: This observational cohort study analyzed 89 patients with u-HCC treated with atezolizumab plus bevacizumab between October, 2020 and October, 2023. A Cox proportional hazards model and Kaplan-Meier curve were used to identify the prognostic factors associated with survival outcomes. RESULTS: There were 33 patients who had low GS and 16 had an ECOG-PS ≥1. The frequency of patients with low GS increased as the ECOG-PS score increased. The overall survival of the normal GS group was significantly higher than that of the low GS group (p < 0.01). There was no significant difference in progression-free survival between the normal GS group and low-GS group (p = 0.28). Among the patients in the ECOG-PS 0 groups, the overall survival in the normal GS group was significantly higher than that in the low GS group (p < 0.01). A multivariate analysis revealed that modified albumin-bilirubin 2b (HR 2.24; 95% confidence interval [CI] 1.06-4.73), α-fetoprotein ≥100 ng/mL (HR 2.35; 95% CI 1.20-4.58), and low GS (HR 2.87; 95% CI 1.31-6.27) were independently associated with a poor overall survival. CONCLUSIONS: The present study demonstrated that GS is a sensitive marker for detecting a subclinical decline in the general condition and is therefore a potential predictor of the outcome of u-HCC patients treated with atezolizumab plus bevacizumab.

Airway stent intervention in a high-volume center: safe procedures and educational perspectives.

Background: Airway intervention, including stenting, can rapidly improve a patient's respiratory condition, but the procedure requires highly specialized techniques and expertise. Therefore, educating young endoscopists and passing on the techniques are major issues. However, the best way to educate new doctors on these techniques remains unclear. This study analyzed our educational system for airway intervention and its outcomes. Methods: Patients who underwent airway intervention regarding airway stents under general anesthesia in our department between January 2010 and September 2023 were included. The outcomes of interventions related to airway stents in our hospital were evaluated retrospectively, including from an educational perspective. Results: A total of 96 patients (76 undergoing stenting for airway stenosis, 8 stenting for airway-esophageal fistula, and 12 stent removal) were analyzed. The median experience level of the main physician was 5 (range, 1-17) years, and that of the supervising physician was 18 (range, 5-23) years. The median number of physicians who participated in the interventions was four. A rigid bronchoscope was used in 86.5% of cases. The procedure success rate was 95.8%. Intraoperative complications occurred in 8.3% and postoperative complications in 10.5% of cases, and there was 1 procedure-related death (1.3%). In the analysis of factors related to the development of complications, the years of experience of the main physician had no influence. Conclusions: These findings indicate that our method of airway intervention is safe. Young endoscopists were able to master the technique by gaining experience under the supervision of experts.

Shoulder Movement-Centered Measurement and Estimation Scheme for Underarm-Throwing Motions.

Underarm throwing motions are crucial in various sports, including boccia. Unlike healthy players, people with profound weakness, spasticity, athetosis, or deformity in the upper limbs may struggle or find it difficult to control their hands to hold or release a ball using their fingers at the proper timing. To help them, our study aims to understand underarm throwing motions. We start by defining the throwing intention in terms of the launch angle of a ball, which goes hand-in-hand with the timing for releasing the ball. Then, an appropriate part of the body is determined in order to estimate ball-throwing intention based on the swinging motion. Furthermore, the geometric relationship between the movements of the body part and the release angle is investigated by involving multiple subjects. Based on the confirmed correlation, a calibration-and-estimation model that considers individual differences is proposed. The proposed model consists of calibration and estimation modules. To begin, as the calibration module is performed, individual prediction states for each subject are updated online. Then, in the estimation module, the throwing intention is estimated employing the updated prediction. To verify the effectiveness of the model, extensive experiments were conducted with seven subjects. In detail, two evaluation directions were set: (1) how many balls need to be thrown in advance to achieve sufficient accuracy; and (2) whether the model can reach sufficient accuracy despite individual differences. From the evaluation tests, by throwing 20 balls in advance, the model could account for individual differences in the throwing estimation. Consequently, the effectiveness of the model was confirmed when focusing on the movements of the shoulder in the human body during underarm throwing. In the near future, we expect the model to expand the means of supporting disabled people with ball-throwing disabilities.

Positive impact of obesity on the prognosis of liver cirrhosis.

BACKGROUND AND AIM: The study aims to determine the prognostic impact of obesity, sarcopenic obesity, and dynapenic obesity in patients with chronic liver disease. METHODS: This retrospective observational study enrolled patients with chronic hepatitis (n = 746) and liver cirrhosis (n = 434) without hepatocellular carcinoma at entry. The patients were evaluated for sarcopenia and obesity between April 2016 and April 2022. Obesity was defined as a body mass index of ≥ 25 kg/m2. Sarcopenic obesity was defined as low skeletal muscle mass (pre-sarcopenia) with obesity and dynapenic obesity was defined as low muscle strength (dynapenia) with obesity. The effects of obesity on survival were evaluated retrospectively. RESULTS: The mean observation period was 2.5 years. Obesity, sarcopenic obesity, and dynapenic obesity were found in 271 (45.5%), 17 (2.9%), and 21 (3.5%) men, and 261 (44.7%), 59 (10.1%), and 53 (9.1%) women, respectively. A multivariate Cox proportional hazards model revealed that Child-Pugh class, dynapenia (hazard ratio [HR] 3.89), elderly (≥ 65 years old) (HR 2.11), and obesity (HR 0.58) were independently associated with overall survival (OS). However, neither sarcopenic nor dynapenic obesity were associated with OS. In patients with cirrhosis, the OS of the obese group was significantly higher than that of the non-obese group. The effect of obesity on OS was significant in elderly patients, but not in younger patients. CONCLUSIONS: Sarcopenic and dynapenic obesity seem unrelated to the prognosis of patients with chronic liver disease. Obesity has a positive effect on the prognosis of elderly patients with cirrhosis.

Location analysis of presynaptically active and silent synapses in single-cultured hippocampal neurons.

A morphologically present but non-functioning synapse is termed a silent synapse. Silent synapses are categorized into "postsynaptically silent synapses," where AMPA receptors are either absent or non-functional, and "presynaptically silent synapses," where neurotransmitters cannot be released from nerve terminals. The presence of presynaptically silent synapses remains enigmatic, and their physiological significance is highly intriguing. In this study, we examined the distribution and developmental changes of presynaptically active and silent synapses in individual neurons. Our findings show a gradual increase in the number of excitatory synapses, along with a corresponding decrease in the percentage of presynaptically silent synapses during neuronal development. To pinpoint the distribution of presynaptically active and silent synapses, i.e., their positional information, we employed Sholl analysis. Our results indicate that the distribution of presynaptically silent synapses within a single neuron does not exhibit a distinct pattern during synapse development in different distance from the cell body. However, irrespective of neuronal development, the proportion of presynaptically silent synapses tends to rise as the projection site moves farther from the cell body, suggesting that synapses near the cell body may exhibit higher synaptic transmission efficiency. This study represents the first observation of changes in the distribution of presynaptically active and silent synapses within a single neuron.

Identifying physiological determinants of 800 m running performance using post-exercise blood lactate kinetics.

PURPOSE: The aims of the present study were to investigate blood lactate kinetics following high intensity exercise and identify the physiological determinants of 800 m running performance. METHODS: Fourteen competitive 800 m runners performed two running tests. First, participants performed a multistage graded exercise test to determine physiological indicators related to endurance performance. Second, participants performed four to six 30-s high intensity running bouts to determine post-exercise blood lactate kinetics. Using a biexponential time function, lactate exchange ability (γ1), lactate removal ability (γ2), and the quantity of lactate accumulated (QLaA) were calculated from individual blood lactate recovery data. RESULTS: 800 m running performance was significantly correlated with peak oxygen consumption (r = -0.794), γ1 and γ2 at 800 m race pace (r = -0.604 and -0.845, respectively), and QLaA at maximal running speed (r = -0.657). V ˙ O2peak and γ2 at 800 m race pace explained 83% of the variance in 800 m running performance. CONCLUSION: Our results indicate that (1) a high capacity to exchange and remove lactate, (2) a high capacity for short-term lactate accumulation and, (3) peak oxygen consumption, are critical elements of 800 m running performance. Accordingly, while lactate has primarily been utilized as a performance indicator for long-distance running, post-exercise lactate kinetics may also prove valuable as a performance determinant in middle-distance running.

CORRIGENDUM: Impact of Different Therapeutic Strategies With Left Ventricular Assist Devices on Health-Related Quality of Life During Prolonged Device-Based Support.

[This corrects the article DOI: 10.1253/circrep.CR-22-0126.].

Evaluation of the risk factors for the failure of a single prophylactic dose of anticholinergic drugs for irinotecan-induced cholinergic symptoms.

OBJECTIVE: Irinotecan (IRI) is an anticancer drug that is frequently used to treat colorectal, gastric, and pancreatic cancers. Its side effects include cholinergic symptoms, such as diarrhea, abdominal pain, nausea, and hyperhidrosis. Anticholinergic medicines are frequently used for treatment or prophylaxis; however, the risk factors for the failure of a single prophylactic anticholinergic administration remain unclear. Moreover, an appropriate anticholinergic drug for prophylaxis remains unknown. Thus, we aimed to identify the risk factors associated with the failure of a single prophylactic dose of anticholinergic drugs for IRI-induced cholinergic symptoms and to evaluate the usefulness of multiple prophylactic doses of anticholinergic drugs. MATERIALS AND METHODS: Patients who underwent IRI treatment for colorectal, gastric, or pancreatic cancer and received prophylactic anticholinergic drugs for IRI-induced cholinergic symptoms (n = 135) were retrospectively evaluated. Univariate and multivariate logistic regression analyses were performed to identify the risk factors for failure of a single prophylactic dose of anticholinergic drugs. We also evaluated the efficacy of multiple prophylactic anticholinergic drug administration. RESULTS: Based on univariate and multivariate analyses, colorectal cancer, female sex, and prophylactic use of scopolamine butyl bromide were identified as risk factors for failure of a single prophylactic dose of anticholinergic drugs. The efficacy of multiple prophylactic doses was confirmed to be 95% of the patients who had a single prophylactic failure due to temporary effect but symptom appearance after a certain period of time (wearing-off). CONCLUSION: We determined that colorectal cancer, female sex, and prophylactic use of scopolamine butyl bromide were risk factors associated with the failure of a single prophylactic dose of anticholinergic drugs, and that multiple prophylactic doses for wearing-off can be a promising method.

A multi-institutional prospective observational study to compare postoperative quality of life of patients who undergo total or proximal gastrectomy for early gastric cancer (CCOG1602).

BACKGROUND: Proximal gastrectomy (PG) has become an increasingly preferred procedure for treating early cancer in the upper third of the stomach. However, advantages of PG in postoperative quality of life (QOL) over total gastrectomy (TG) has not fully proven. METHODS: We conducted a multi-institutional prospective observational study (CCOG1602) of patients who undergo TG or PG for cStage I gastric cancer. We used the PGSAS-37 and EORTC-QLQ-C30 to evaluate the changes in body weight and QOL over a 3-year postoperative period. The primary endpoint was the weight loss rate 3 years after surgery. RESULTS: We enrolled 109 patients from 18 institutions and selected 65 and 19 patients for inclusion in the TG and PG groups, respectively. Mean postoperative weight loss rates were 16.0% and 11.7% for the TG and PG groups, respectively (p = 0.056, Cohen's d 0.656) during postoperative year 1% and 15.0% and 10.8% for TG and PG (p = 0.068, Cohen's d 0.543), respectively, during postoperative year 3, indicating that the PG group achieved a better trend with a moderate effect size. According to the PGSAS-37, the PG group experienced a better trend in the indigestion subscale (p < 0.001, Cohen's d -1.085) and total symptom score (p = 0.050, Cohen's d -0.59) during postoperative year 3 compared with the TG group. In contrast, the EORTC-QLQ-C30 detected no difference between the groups at any time point during 3-year postoperative period. CONCLUSIONS: This prospective study demonstrates that PG tended to be more favorable compared with TG with respect to postoperative weight loss and QOL, particularly regarding indigestion.

Case report: Recovery from refractory myasthenic crisis to minimal symptom expression after add-on treatment with efgartigimod.

Myasthenic crisis, a life-threatening exacerbation of myasthenia gravis, is a significant clinical challenge, particularly when refractory to standard therapies. Here, we described a case of myasthenic crisis in which the patient transitioned from refractory myasthenic crisis to minimal symptom expression after receiving add-on treatment with efgartigimod, a novel neonatal Fc receptor antagonist. A 54 years-old woman who was diagnosed with anti-acetylcholine receptor antibody-positive myasthenia gravis experienced respiratory failure necessitating mechanical ventilation. Despite aggressive treatment with plasmapheresis, intravenous immunoglobulins, and high-dose corticosteroids, her condition continued to deteriorate, culminating in persistent myasthenic crisis. Efgartigimod was administered as salvage therapy. Remarkable improvement in neuromuscular function was observed within days, allowing for successful weaning from mechanical ventilation. Over the subsequent weeks, the patient's symptoms continued to ameliorate, ultimately reaching a state of minimal symptom expression. Serial assessments of her serum anti-acetylcholine receptor antibody titer showed a consistent decline in parallel with this clinical improvement. This case highlights efgartigimod's potential as an effective therapeutic option for refractory myasthenic crisis, offering new hope for patients facing this life-threatening condition.

Kamikihito reduces ß-amyloid25-35-induced axon damage via neurotrophic factors.

The Japanese herbal medicine kamikihito (KKT) is widely used for insomnia, anorexia, anemia, and depression. Recently, the efficacy of KKT against Alzheimer's disease (AD) has been demonstrated in clinical and non-clinical studies. To address the mechanism underlying the effect of KKT on AD, we examined the effects of KKT in ß-amyloid (Aß)25-35-exposed primary cultured neurons. The effects of KKT on Aß25-35-induced neurotoxicity were assessed by immunocytochemical assays and Sholl analysis of neurites, and the influence of KKT on neurotrophic factor (NF) gene expression was examined using RT-PCR analysis. As a result, Aß25-35 exposure attenuated the arborization of neurites of single cultured hippocampal neurons, and KKT treatment for 3 days ameliorated the Aß25-35-induced impairment of tau-positive axon outgrowth. This ameliorative effect of KKT was largely abolished by the Trk inhibitor K252a, and expression of NFs, nerve growth factor (Ngf), brain-derived neurotrophic factor (Bdnf), neurotrophin-3 (NT-3) was significantly increased by KKT. These results indicate that KKT ameliorates axonal atrophy via NFs signaling, providing a mechanistic basis for treatment of AD with KKT.

Acute cerebellitis following COVID-19 infection associated with autoantibodies to glutamate receptors: a case report.

While COVID-19 infection by the SARS-CoV-2 virus was initially identified as a respiratory disease, mounting evidence suggests its association with various neurological issues as well. Notably, COVID-19 has been linked to acute cerebellitis (AC) and post-infectious cerebellar ataxia. The precise underlying mechanisms behind these neurological effects remain unclear. Our case report describes AC following COVID-19 infection, associated with autoantibodies to glutamate receptors (GluRs), hinting at immunological involvement. The case is a 56-year-old woman who experienced fever and fatigue due to COVID-19 infection. About 2 weeks after these symptoms improved, she showed cerebellar symptoms such as ocular overshoot and ataxia when presenting to our hospital. Her cerebrospinal fluid (CSF) findings were normal. Brain MRI revealed cerebellar abnormalities. Treatment with methylprednisolone led to symptom improvement. Later tests of CSF yielded positive results for autoantibodies to GluRs. Our findings suggest a possible immune-mediated mechanism in the onset of AC following COVID-19 infection. Clinicians should consider the possibility of immunological pathogenesis when diagnosing cerebellar symptoms after COVID-19 infection.

High Expression of Fas-Associated Factor 1 Indicates a Poor Prognosis in Non-Small-Cell Lung Cancer.

Fas-associated factor 1 (FAF1) is a death-promoting protein identified as an interaction partner of the death receptor Fas. The downregulation and mutation of FAF1 have been reported in a variety of human tumors, but there have been few studies on lung cancer. Here, we investigated the prognostic significance of FAF1 expression in non-small-cell lung cancer (NSCLC), and whether aberrant FAF1 expression may be involved in the pathogenesis and prognosis of NSCLC. FAF1 expression was examined in NSCLC specimens as well as human lung cancer cell lines. In addition, changes in cell viability and apoptosis upon regulating FAF1 expression were investigated in lung cancer cell lines. As a result, high FAF1 expression was significantly associated with a poor prognosis in NSCLC. In lung cancer cell lines, FAF1 downregulation hindered cell viability and tended to promote early apoptosis. In conclusion, this is the first study of the clinical significance of FAF1 in NSCLC, showing that FAF1 overexpression is associated with a poor prognosis in NSCLC and that FAF1 acts as a dangerous factor rather than an apoptosis promoter in NSCLC.

Successful echocardiography-guided medical management of severe early post-implant right ventricular failure in a patient with left ventricular assist device support: a case report.

BACKGROUND: Post-implant right heart failure (RHF) has been recognized as a crucial prognostic factor in patients receiving left ventricular assist devices (LVADs), and its management has long attracted attention from cardiologists and surgeons. CASE PRESENTATION: This report described an 18-year-old female with acutely deteriorating heart failure due to dilated cardiomyopathy who underwent paracorporeal pulsatile-flow LVAD and developed early post-implant RHF. At postoperative day (POD) six, she was almost asymptomatic at rest on 2.5 mg/kg/min of dobutamine; however, the echocardiogram, performed as part of the daily postoperative care, revealed a severely enlarged right ventricle with a decompressed left ventricle, implying the development of post-implant RHF. Bolus infusion of saline and reduction of pump flow (6.0 L/min to 3.0 L/min) led to normalization of both ventricular shapes in 30 s, suggesting that RHF could be managed without surgical interventions. Milrinone was started on POD six, followed by sildenafil administration on POD seven. Fluid balance was strictly adjusted under the close observation of daily echocardiograms. Milrinone and dobutamine were discontinued on PODs 18 and 21, respectively. The patient was listed for a heart transplant on POD 40. Despite reduced right ventricular function (right ventricular stroke work index of 182.34 mmHg*ml/m- 2, body surface area 1.5 m2), she was successfully converted to implantable LVAD on POD 44 with no recurrence of post-implant RHF thereafter for four years. CONCLUSIONS: In post-implant RHF management, early detection, together with proper and prompt medical management, is crucial to avoiding any surgical intervention. Close observation of daily echocardiograms might be helpful in detecting subclinical RHF and is useful for post-implant medical management.

Glioblastoma/high-grade glioma with a primitive neuronal component including rhabdoid differentiation that was difficult to diagnose: A case report.

Glioblastoma with a primitive neuronal component (GBM-PNC) is a rare subtype. In this case, GBM-PNC was difficult to diagnose conclusively because the specimen consisted of only a few high-grade glioma components. A 73-year-old woman presented with sensory aphasia and minor right-sided hemiplegia. Imaging revealed a neoplastic lesion with a maximum diameter of approximately 5 cm in the left frontal lobe for which surgery was performed. Histologically, most atypical cells were immature components with high nuclear-cytoplasmic ratios and immunopositive for neuroendocrine markers. Minor components of atypical glial cells were found at tumor margins. Rhabdoid cells were observed in undifferentiated components. Immunostaining was positive for glial fibrillary acidic protein (GFAP), nestin, and Olig2 in both undifferentiated and atypical glial cells. The major undifferentiated components showed significantly low GFAP, nestin, and Olig2 expression levels within the foci of the undifferentiated components, in contrast to the atypical glial component, neurofilaments and synaptophysin were immunopositive for undifferentiated components. Rhabdoid cells were immunopositive for myogenin, desmin, and HHF35, suggesting their differentiation into striated muscles. This was a particularly rare case because rhabdoid differentiation was observed in PNC.

The Effects of Ninjinyoeito on Impaired Spatial Memory and Prefrontal Cortical Synaptic Plasticity through α-Amino-3-hydroxy-5-4-isoxazole Propionic Acid Receptor Subunit in a Rat Model with Cerebral Ischemia and ß-Amyloid Injection.

Ninjinyoeito (NYT), a traditional Japanese medicine, is effective for improving physical strength and treating fatigue and anorexia. Recently, a clinical report revealed that NYT ameliorates cognitive dysfunction in Alzheimer's disease (AD) patients, although the mechanisms remain unclear. AD is a neurodegenerative disorder accompanied by a progressive deficit in memory. Current therapeutic agents are largely ineffective in treating cognitive dysfunction in AD patients. In this study, we investigated the effects of NYT on spatial memory impairment in a rat model of dementia. Rats were prepared with transient cerebral ischemia and intraventricular injection of ß-amyloid1-42 for 7 days (CI + Aß). NYT was orally administered for 7 days after cerebral ischemia. We evaluated spatial memory using the Morris water maze and investigated the expression of α-amino-3-hydroxy-5-4-isoxazole propionic acid receptor subunits, the phosphorylation level of glutamate receptor A (GluA)1 at serine sites S831 and S845, and the Ca2+/calmodulin-dependent protein kinase II (CaMKII) in the hippocampus and prefrontal cortex of CI + Aß rats. In the CI + Aß rats, NYT treatment shortened the extended time to reach the platform. However, NYT did not restore the decrease in the hippocampal GluA1, GluA2, or CaMKII expression but increased prefrontal cortical phosphorylation levels of S845-GluA1 and CaMKII. Therefore, NYT may alleviate spatial memory impairment by promoting glutamatergic transmission involved in the phosphorylation of S845-GluA1 and CaMKII in the prefrontal cortex of CI + Aß rats. Our results suggest that NYT is a valuable treatment for AD patients.