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.

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.

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.

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.

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.

The long-term quality of life after distal and pylorus-preserving gastrectomy for stage I gastric cancer: A prospective multi-institutional study (CCOG1601).

PURPOSE: While regarded as function-preserving gastrectomy, few prospective longitudinal clinical trials have addressed the postoperative quality of life (QOL) after pylorus-preserving gastrectomy (PPG). We prospectively compared chronological changes in postoperative body weight and the QOL between PPG and distal gastrectomy (DG) for pathological Stage I gastric cancer (GC). METHODS: We conducted a multi-institutional prospective study (CCOG1601) to evaluate patients who underwent DG and PPG. The QOL was examined using the European Organization for Research and Treatment of Cancer Quality of life questionnaire-C30 (EORTC QLQ-C30) and the Post-Gastrectomy Syndrome Assessment Scale-37 (PGSAS-37). A total of 295 patients were enrolled from 15 institutions, and propensity score matching was performed to adjust for the essential variables for comparison analyses. RESULTS: After propensity score matching, 25 pairs of patients were identified. In the first postoperative month, DG achieved a superior nausea and vomiting score (EORTC QLQ-C30) and meal-related distress, indigestion, and dumping scores (PGSAS-37). No significant differences were noted between DG and PPG in the long-term QOL. Postoperative body weight loss was similar in both groups. CONCLUSIONS: This prospective observational study failed to demonstrate the superiority of PPG over DG in terms of postoperative body weight changes and the QOL.

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.

Astrocyte Ca2+ signaling is facilitated in Scn1a+/- mouse model of Dravet syndrome.

Dravet syndrome (DS) is an infantile-onset epileptic encephalopathy. More than 80% of DS patients have a heterozygous mutation in SCN1A, which encodes a subunit of the voltage-gated sodium channel, Nav1.1, in neurons. The roles played by astrocytes, the most abundant glial cell type in the brain, have been investigated in the pathogenesis of epilepsy; however, the specific involvement of astrocytes in DS has not been clarified. In this study, we evaluated Ca2+ signaling in astrocytes using genetically modified mice that have a loss-of-function mutation in Scn1a. We found that the slope of spontaneous Ca2+ spiking was increased without a change in amplitude in Scn1a+/- astrocytes. In addition, ATP-induced transient Ca2+ influx and the slope of Ca2+ spiking were also increased in Scn1a+/- astrocytes. These data indicate that perturbed Ca2+ dynamics in astrocytes may be involved in the pathogenesis of DS.

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.

Circulating Cell-Free DNA as a Biomarker for Prognosis and Response to Systemic Therapy in Patients with Unresectable Hepatocellular Carcinoma.

INTRODUCTION: Systemic therapy provides clinical benefits to a subset of patients with advanced unresectable hepatocellular carcinoma (HCC). However, few biomarkers are available for predicting prognosis and treatment response in patients with advanced HCC undergoing treatment with systemic therapies. This study aimed to examine whether circulating cell-free DNA (cfDNA) containing circulating tumor DNA can act as a therapeutic response and prognostic biomarker in patients with advanced HCC. METHODS: We analyzed longitudinally collected plasma cfDNA of patients with advanced HCC who were naïve to systemic therapy, and assessed their prognostic and predictive values to determine treatment responses. RESULTS: cfDNA concentration positively correlated with entire tumor volume on computed tomography before (p = 0.0231) and at the end (p < 0.0001) of the first-line systemic therapy. The overall survival rate was higher in patients with cfDNA concentrations lower than the median cfDNA level at baseline compared to patients with higher cfDNA concentrations (hazard ratio, 0.2765; 95% confidence interval, 0.08-0.81; p = 0.0197). The ratio of cfDNA at 4 weeks to that at baseline was predictive of radiographic disease response. In patients with progressive disease, cfDNA concentration at 4 weeks increased significantly (p = 0.0245), whereas the concentration remained unchanged in patients with other disease courses (p = 0.9375). CONCLUSION: The baseline plasma cfDNA concentration can be used as a prognostic biomarker in patients with advanced HCC. cfDNA kinetics may also predict the tumor response to therapy and disease progression.

Coincidental items in the definition of metabolic dysfunction-associated fatty liver are useful in identifying patients having significant fibrosis with fatty liver.

AIM: We aimed to establish a method that will identify patients at a high risk for progressive phenotype of fatty liver. METHODS: Patients with fatty liver who underwent liver biopsy between July 2008 and November 2019 were included as cohort 1, and those who underwent abdominal ultrasound screening examination by general physicians between August 2020 and May 2022 served as cohort 2. According to the definition of metabolic dysfunction-associated fatty liver (MAFLD), the subjects were classified by body mass index of ≥23, diabetes mellitus, and coexistence of two or more metabolic risk items. The progressive phenotype of MAFLD is defined by significant fibrosis complicated with either nonalcoholic fatty liver disease activity score ≥4 (BpMAFLD) or steatosis grade ≥2 by ultrasound examination (UpMAFLD). RESULTS: One hundred sixty-eight patients and 233 patients were enrolled in cohorts 1 and 2, respectively. In cohort 1, the prevalence of BpMAFLD was 0% in patients without a complicating factor (n = 10), 13% in those with one complicating factor (n = 67), 32% in those with two (n = 73), and 44% in those with all three complicating factors (n = 36). A logistic regression analysis revealed that factors in the MAFLD definition were significantly associated with BpMAFLD. In cohort 2, a criterion of two or more positive MAFLD definitions was found to have a 97.4% negative predictive value for the diagnosis of UpMAFLD. CONCLUSION: Patients with two or more complicating factors in the MAFLD definition should have further evaluation for liver fibrosis.

Prognostic impact of lung computed tomography density in cardiogenic shock patients with veno-arterial extracorporeal membrane oxygenation.

BACKGROUND: Pulmonary complications often occur in patients receiving veno-arterial extracorporeal membrane oxygenation (VA ECMO). However, the prognostic impact of lung damage has not been fully elucidated. METHODS: This single-center retrospective observational study targeted patients with cardiogenic shock who received VA ECMO between 2012 and 2021. This study included 65 patients who underwent chest computed tomography (CT) on VA ECMO, followed by escalation to central mechanical circulatory support (MCS) with left ventricular venting. The average density of lung CT images was measured using region-of-interest methods, and the primary endpoint was 180-day all-cause death after escalation to the central MCS. RESULTS: Twenty-two patients (34%) developed 180-day all-cause death. According to the Cox regression analysis, age (hazard ratio [HR], 1.08; 95% confidence interval [CI], 1.03-1.14; p = 0.001), ischemic etiology (HR, 5.53; 95% CI, 2.09-14.62; p < 0.001), duration of VA ECMO support (HR, 1.19; 95% CI, 1.00-1.40; p = 0.045), and lung CT density (≥ -481 Hounsfield unit [HU]) (HR, 6.33; 95% CI, 2.26-17.72; p < 0.001) were independently associated with all-cause death. Receiver operating characteristic curve analysis determined that lung CT density ≥ -481 HU is an optimal cutoff value for predicting all-cause death (area under the curve [AUC], 0.72). The 180-day overall survival rate for patients with high lung CT density (≥ -481 HU) was significantly lower than that for those with low lung CT density (< -481 HU) (44.4% vs. 81.6%, respectively, p = 0.002). CONCLUSIONS: Higher lung CT density could be a useful predictor of death in patients with VA ECMO requiring central MCS escalation.

Comparison of the clinical outcomes of intramedullary nailing between impending and completed pathological fractures caused by metastatic femoral tumors from solid cancers.

BACKGROUND: We examined the treatment outcomes following intramedullary nailing in patients with metastatic femoral tumors, excluding those from hematological malignancies. METHODS: We retrospectively evaluated treatment outcomes following intramedullary nailing between patients who underwent preventative surgery compared with those who had surgery following pathological fracture. Patients who underwent preventative surgery (Mirels' score ≥8) were allocated to the impending fracture group (n = 11) and those who underwent surgery after pathological fracture were allocated to the completed fracture group (n = 20). RESULTS: Duration of surgery was significantly shorter in the impending fracture group than in the completed fracture group. Median blood loss was significantly less, and the median duration of hospital stay was significantly shorter in the impending fracture group than in the completed fracture group. Among patients who died following surgery, the median postoperative survival duration was significantly longer in the impending fracture group than in the completed fracture group. Significantly more patients regained walking function in the impending fracture group than in the completed fracture group. Regarding complications, infection occurred in one patient in the completed fracture group. No implant damage was observed in either group. CONCLUSIONS: Patients with metastatic femoral tumors who underwent intramedullary nailing in the impending fracture group had better postoperative survival and gait function, less blood loss, and shorter durations of surgery and hospital stay than those in the completed fracture group. These findings indicate the importance of early diagnosis and treatment and value of treatment prior to fracture occurrence.

Risk Assessment of Neutropenia during Low-Dose Valganciclovir Prophylaxis for Heart Transplant Recipients.

The aim of this study was to investigate whether low-dose valganciclovir (VGCV) prophylaxis for cytomegalovirus (CMV) infection increased the risk of developing neutropenia in heart transplant recipients (HTRs). Forty-three HTRs receiving VGCV were divided into two groups: those who received VGCV prophylaxis (n = 22) and those who did not (n = 21). Neutropenia was defined as an absolute neutrophil count ˂1500/µL and was monitored for approximately one year post-transplantation. In the prophylaxis group, 77.3% (17/22) of HTRs experienced neutropenia, which was significantly higher than that in the no prophylaxis group (42.9% [9/21], p = 0.031). No significant differences in the duration of VGCV administration and cumulative dose up to the first neutropenia episode were observed between the groups. Meanwhile, the cumulative dose of mycophenolate mofetil was significantly higher in the prophylaxis group than in the no prophylaxis group (p = 0.018); the daily maintenance dose and regularly measured area under the concentration-time curve (AUC) of mycophenolic acid did not significantly differ between groups. In conclusion, the risk of developing neutropenia was higher in HTRs receiving low-dose VGCV prophylaxis than it was in those not receiving prophylaxis, probably not attributed to dosing period and cumulative dose of VGCV until the onset of neutropenia.

Impact of sleep-disordered breathing on ventricular tachyarrhythmias after left ventricular assist device implantation.

Sleep-disordered breathing (SDB) is associated with an increased risk of adverse events in patients with heart failure (HF); however, its impact in patients implanted with a left ventricular assist device (LVAD) remains unclear. We aimed to investigate the prevalence of SDB in patients with LVAD and its impact on their clinical outcomes. Fifty consecutive patients with LVAD who underwent portable sleep monitoring between September 2017 and April 2018 were prospectively enrolled, and they were followed up for 170 ± 36 days. According to their respiratory disturbance indexes (RDIs), they were categorized into the SDB group (RDI ≥ 15, n = 12) and the non-SDB group (RDI < 15, n = 38). The incidence of adverse events during the follow-up period was investigated after enrollment. Multivariate logistic regression analysis revealed significant differences in SDB in LVAD-implanted patients in terms of the logarithmic transformation brain natriuretic peptide (BNP) values (p = 0.005). The optimal BNP cut-off value for SDB prediction in LVAD-implanted patients was 300 pg/mL (sensitivity: 58.3%, specificity: 94.7%). During follow-up, ventricular tachyarrhythmias (VTas) occurred significantly more frequently in the SDB group (4 [33%] vs. 2 [5%] patients, p = 0.02); Atrial tachyarrhythmia (ATa) also tended to occur more frequently in the SDB group (2 [25%] vs. 2 [2%] patients, p = 0.07). SBD was prevalent in 24% of the LVAD-implanted patients with advanced HF. Furthermore, SDB was significantly associated with high BNP levels and was also potentially associated with subsequent incidence of VTa in patients with LVAD.

Bridge from central extracorporeal life support is a risk factor of cerebrovascular accidents after durable left ventricular assist device implantation.

A bridging strategy from extracorporeal life support (ECLS) is effective in salvage and a bridge to recovery or to a durable left ventricular assist device (LVAD) for acute refractory heart failure. However, the correlation of this strategy with adverse events after durable LVAD implantation has not been fully investigated. This study enrolled 158 consecutive patients who had either the HeartMate II or HeartMate 3 and were implanted for bridge-to-transplantation. These devices were implanted as the primary mechanical support device in 115 patients, whereas the remaining 43 underwent LVAD implantation as the bridge from central ECLS. The primary study endpoint was all-cause mortality and cerebrovascular accidents (CVAs) after durable LVAD implantation, and the secondary endpoints were adverse events. Overall survival was not significantly different between the two groups. In contrast, the probability of CVAs was significantly greater in the bridge group than in the primary group (probability of CVAs, P = 0.002; log-rank test). In Cox multivariate logistic regression analysis, a bridge from central ECLS was an independent predictive factor of CVAs (hazard ratio 4.27, 95% confidence interval 1.43-12.8; P = 0.0095). Patients who are bridged from central ECLS are more frequently complicated by CVAs compared with those who undergo primary implantation of a durable LVAD, but survival is not significantly different between the two groups. A bridge from central ECLS is an independent predictive factor of CVAs post-implantation of an LVAD.

Neuroligin3 splice isoforms shape inhibitory synaptic function in the mouse hippocampus.

Synapse formation is a dynamic process essential for the development and maturation of the neuronal circuitry in the brain. At the synaptic cleft, trans-synaptic protein-protein interactions are major biological determinants of proper synapse efficacy. The balance of excitatory and inhibitory synaptic transmission (E-I balance) stabilizes synaptic activity, and dysregulation of the E-I balance has been implicated in neurodevelopmental disorders, including autism spectrum disorders. However, the molecular mechanisms underlying the E-I balance remain to be elucidated. Here, using single-cell transcriptomics, immunohistochemistry, and electrophysiology approaches to murine CA1 pyramidal neurons obtained from organotypic hippocampal slice cultures, we investigate neuroligin (Nlgn) genes that encode a family of postsynaptic adhesion molecules known to shape excitatory and inhibitory synaptic function. We demonstrate that the NLGN3 protein differentially regulates inhibitory synaptic transmission in a splice isoform-dependent manner at hippocampal CA1 synapses. We also found that distinct subcellular localizations of the NLGN3 isoforms contribute to the functional differences observed among these isoforms. Finally, results from single-cell RNA-Seq analyses revealed that Nlgn1 and Nlgn3 are the major murine Nlgn genes and that the expression levels of the Nlgn splice isoforms are highly diverse in CA1 pyramidal neurons. Our results delineate isoform-specific effects of Nlgn genes on the E-I balance in the murine hippocampus.

The novel mitochondria activator, 10-ethyl-3-methylpyrimido[4,5-b]quinoline-2,4(3H,10H)-dione (TND1128), promotes the development of hippocampal neuronal morphology.

Adenosine triphosphate (ATP) is the most vital energy source produced mainly in the mitochondria. Age-related mitochondrial dysfunction is associated with brain diseases. Nicotinamide adenine dinucleotide (NAD+) is an essential cofactor for energy production in mitochondria. Here, we examined how the novel NAD+-assisting substance, 10-ethyl-3-methylpyrimido[4,5-b]quinoline-2,4(3H,10H)-dione (TND1128), modulates the morphological growth of cultured mouse hippocampal neurons. The morphological growth effect of TND1128 was also compared with that of ß-nicotinamide mononucleotide (ß-NMN). TND1128 induced the branching of axons and dendrites, and increased the number of excitatory synapses. This study provides new insight into TND1128 as a mitochondria-stimulating drug for improving brain function.

The Predictive Value of Changes in Body Mass Index for the Incidence of Device-Specific Infections in Patients With Implantable Left Ventricular Assist Devices.

BACKGROUND: Implantable left ventricular assist devices (LVAD) have improved quality of life and survival in patients with advanced heart failure. However, LVAD-specific infections and predicting which patients will develop infections remain challenging. This study investigated whether changes in body mass index (BMI) during hospitalization following LVAD implantation are associated with LVAD-specific infections within 1 year of implantation.Methods and Results:Patients (n=135) undergoing LVAD implantation were retrospectively divided into 2 groups based on changes in BMI from LVAD implantation to discharge: those with and without decreases in BMI. Each group was further subdivided according to baseline albumin concentrations (high [>3.7 g/dL] and low [≤3.7 g/dL]). Twenty patients developed LVAD-specific infections within 1 year. Receiver operating characteristic curve analysis resulted in a ∆BMI cut-off of less than -0.128 kg/m2. In multivariate analysis, younger patients and those with decreases in BMI had significantly higher rates of LVAD-specific infection (P=0.010 and P=0.035, respectively). LVAD-specific infection rates were significantly higher for patients with low albumin and decreases in BMI than for patients with low albumin but no decrease in BMI. CONCLUSIONS: Decreases in BMI during hospitalization after LVAD implantation and younger age were independently associated with LVAD-specific infection within 1 year. Strict patient management may be needed to avoid decreases in BMI during hospitalization after LVAD implantation, particularly in patients with low baseline albumin concentrations.