Mapping of Purkinje-related ventricular arrhythmias by a multispline catheter with small and close-paired electrodes: Comparison with conventional catheters.

BACKGROUND: Precise mapping of the Purkinje fiber network is essential in catheter ablation of Purkinje-related ventricular arrhythmias (PrVAs). We sought to evaluate the mapping ability of a multi-spline duodecapolar catheter (PentaRay) for PrVAs. METHODS: Mappings of Purkinje fibers by PentaRay catheters were compared with those by conventional mapping catheters in consecutive patients undergoing catheter ablation of PrVAs from 2015 to 2022. RESULTS: Sixteen PrVAs (7 premature ventricular contractions or non-reentrant fascicular tachycardias [PVCs/NRFTs] and 9 fascicular ventricular tachycardias [FVTs]) were retrospectively studied. In PVCs/NRFTs, earliest preceding Purkinje potentials (PPs) could be recorded by the PentaRay catheters but not by the mapping and ablation catheters in 5 cases. At the earliest PP sites, the precedence from the QRS onset was greater, and the amplitude of the preceding potentials was higher in the PentaRay catheter compared with those in the mapping and ablation catheter (-62.0 ± 42.8 vs. -29.4 ± 34.2 ms, P = 0.02; 0.45 ± 0.43 vs. 0.09 ± 0.08 mV, P = 0.02). In FVTs, late diastolic potentials (P1) were recorded by the PentaRay catheters but not by the mapping and ablation catheters or the linear duodecapolar catheter in 2 cases. The amplitude of P1 was higher in the PentaRay catheter compared with that in the linear duodecapolar catheter and the mapping and ablation catheters (0.72 ± 0.49 vs. 0.17 ± 0.18 vs. 0.27 ± 0.21 mV, P = 0.0006, P = 0.002). The localized critical PPs, defined as the earliest preceding potentials in PVCs/NRFTs and P1 in FVTs, could be recorded in all the patients by the PentaRay catheter. The mapping ability of critical PPs of PrVAs was better with the PentaRay catheter than with the conventional mapping catheters (16/16 vs. 9/16, P = 0.004 by McNemar exact test). CONCLUSIONS: The PentaRay catheter has clinical advantages in mapping of the Purkinje fiber network to reveal critical PPs as ablation targets of PrVAs.

Preoperative zinc status predicts the occurrence and healing time of pancreatic fistula after distal pancreatectomy.

BACKGROUND: There are few studies that examined the relationship between preoperative zinc (Zn) concentrations and postoperative pancreatic fistula (POPF) after distal pancreatectomy (DP). METHODS: Data from 98 patients who underwent DP between January 2016 and April 2022 were retrospectively reviewed. Patients' clinicopathological and surgical outcomes were analyzed, and we examined the relationship between Zn and clinically relevant POPF (CR-POPF) after DP. RESULTS: In this series, 41 (41.8%) patients had POPF and 31 (31.8%) patients had CR-POPF. The cut-off value for the preoperative Zn concentration was 74 µg/dL for POPF and CR-POPF. Patients with low Zn concentrations were significantly related with high age, low albumin concentrations, higher CRP concentrations, higher NLR, lower PNI, higher rates of POPF and CR-POPF, longer POPF healing time, longer hospital stay, and postoperative complications than patients with high Zn concentrations. The healing time of POPF after DP was significantly negatively correlated with serum Zn concentrations. A multivariate logistic regression analysis showed that preoperative lower Zn concentrations and a prolonged operation time were independent predictors of CR-POPF and the healing time of POPF after DP. The POPF healing time in patients with high Zn was significantly shorter than that in patients with low Zn concentrations. CONCLUSIONS: This retrospective study showed the association between the preoperative Zn concentrations and the occurrence of POPF and the healing time after DP. Zn is a simple biomarker for malnutrition, which may lead to POPF after DP.

Impact of the serum creatinine and cystatin C ratio for prediction of sarcopenia and prognosis in biliary tract cancer.

BACKGROUND: Sarcopenia is a poor prognostic factor in cancer patients. In recent years, there have been reports that serum creatinine and cystatin C (Cr/CysC) ratio is associated with sarcopenia. However, the prognostic value of the Cr/CysC ratio in biliary tract cancer is unclear. We evaluated the impact of the Cr/CysC ratio on sarcopenia and prognosis in biliary tract cancer. METHODS: We retrospectively reviewed the records of 190 patients with biliary tract cancer who had undergone surgical resection from January 2017 to March 2023. Frozen serum samples collected at the time of surgery were used to measure CysC. We calculated the Cr/CysC ratio and investigated the relationship with sarcopenia and the prognostic significance. RESULTS: We calculated the cutoff value of the Cr/CysC ratio for low skeletal muscle index (SMI) (< 42 cm2/m2 for males and < 38 cm2/m2 for females). The optimal cutoff value of the Cr/CysC ratio was 0.848. The low Cr/CysC ratio group was significantly associated with higher preoperative CRP and lower albumin, lower SMI, lower handgrip strength, and higher intramuscular adipose tissue content. In multivariate analysis, patients with a low Cr/CysC ratio showed poorer overall survival (hazard ratio 2.60, 95% confidence interval 1.07-6.29, p = 0.033), which was significantly worse than in those with a high Cr/CysC ratio. CONCLUSIONS: In patients with biliary tract cancer, the Cr/CysC ratio showed weak correlation with sarcopenic indicators. However, the Cr/CysC ratio could be strong prognostic factor in biliary tract cancer.

New predictors of microvascular invasion for small hepatocellular carcinoma ≤ 3 cm.

BACKGROUND: Microvascular invasion (MVI) is a risk factor for postoperative recurrence of hepatocellular carcinoma (HCC), even in early-stage HCC. In small HCC ≤ 3 cm, treatment options include anatomical resection or non-anatomical resection, and MVI has a major effect on treatment decisions. We aimed to identify the predictors of MVI in small HCC ≤ 3 cm. METHODS: We retrospectively studied 129 patients with very early or early-stage HCC ≤ 3 cm who had undergone 18F-fluorodeoxyglucose positron emission tomography/computed tomography and subsequent hepatic resection from January 2016 to August 2023. These patients were divided into the derivation cohort (n = 86) and validation cohort (n = 43). We examined the risk factors for MVI using logistic regression analysis, and established a predictive scoring system in the derivation cohort. We evaluated the accuracy of our scoring system in the validation cohort. RESULTS: In the derivation cohort, a Lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3), prothrombin induced by vitamin K deficiency or antagonist-II (PIVKA-II), and metabolic tumor volume (MTV) were independent predictors of MVI. We established the scoring system using these three factors. In the validation test, there were no MVI-positive cases with a score of 0 and 1, and all cases were MVI-positive with a score of 4. Moreover, with a score ≥ 2, the sensitivity, specificity, and accuracy of our scoring system were 100%, 71.4%, and 81.4%, respectively. CONCLUSIONS: Our scoring system can accurately predict MVI in small HCC ≤ 3 cm, and could contribute to establishing an appropriate treatment strategy.

An attempt to consider cooperativity in helical-sense preferences induced in fused macrocycles.

We synthesized bis and tris(macrocycle)s in which a two- or three-fold macrocycle was fused and each adopted twisted forms with M- or P-helicity. According to the sense of twisting in each element, diverse conformations can be generated in a molecule. We present two types of conformational preferences. One is the innate preference for a helical form with an identical sense of twisting throughout the entire molecule. The other is the helical-sense preference for a particular sense of twisting. We were interested in the relationship between Kn and (K1)n, where Kn is an equilibrium constant for the conformational interconversion between two helical forms (MM and PP, MMM and PPP) and n is the number of elements, since we considered that the relationship could be a metric to see the interinfluence among these macrocyclic elements in a single molecule. Through VT measurements in 1H NMR and CD spectroscopy, we attempted to quantify the helical-sense preferences induced in the fused macrocycles (n = 2 and 3) to compare Kn and (K1)n.

Wider Dissemination of Simplified Chest Compression-Only Cardiopulmonary Resuscitation Training Combined With Conventional Cardiopulmonary Resuscitation Training and 10-Year Trends in Cardiopulmonary Resuscitation Performed by Bystanders in a City.

BACKGROUND: Little is known about how to effectively increase bystander cardiopulmonary resuscitation (CPR), so we evaluated the 10-year trend of the proportion of bystander CPR in an area with wide dissemination of chest compression-only CPR (CCCPR) training combined with conventional CPR training.Methods and Results: We conducted a descriptive study after a community intervention, using a prospective cohort from September 2010 to December 2019. The intervention consisted of disseminating CCCPR training combined with conventional CPR training in Toyonaka City since 2010. We analyzed all non-traumatic out-of-hospital cardiac arrest (OHCA) patients resuscitated by emergency medical service personnel. The primary outcome was the trend of the proportion of bystander CPR. We conducted multivariate logistic regression models and assessed the adjusted odds ratio (AOR) using a 95% confidence interval (CI) to determine bystander CPR trends. Since 2010, we have trained 168,053 inhabitants (41.9% of the total population of Toyonaka City). A total of 1,508 OHCA patients were included in the analysis. The proportion of bystander CPR did not change from 2010 (43.3%) to 2019 (40.0%; 1-year incremental AOR 1.02 [95% CI: 0.98-1.05]). CONCLUSIONS: The proportion of bystander CPR did not increase even after wider dissemination of CPR training. In addition to continuing wider dissemination of CPR training, other strategies such as the use of technology are necessary to increase bystander CPR.

In-hospital extracorporeal cardiopulmonary resuscitation for patients with out-of-hospital cardiac arrest: an analysis by time-dependent propensity score matching using a nationwide database in Japan.

BACKGROUND: Extracorporeal cardiopulmonary resuscitation (ECPR) has been proposed as a rescue therapy for patients with refractory cardiac arrest. This study aimed to evaluate the association between ECPR and clinical outcomes among patients with out-of-hospital cardiac arrest (OHCA) using risk-set matching with a time-dependent propensity score. METHODS: This was a secondary analysis of the JAAM-OHCA registry data, a nationwide multicenter prospective study of patients with OHCA, from June 2014 and December 2019, that included adults (≥ 18 years) with OHCA. Initial cardiac rhythm was classified as shockable and non-shockable. Patients who received ECPR were sequentially matched with the control, within the same time (minutes) based on time-dependent propensity scores calculated from potential confounders. The odds ratios with 95% confidence intervals (CI) for 30-day survival and 30-day favorable neurological outcomes were estimated for ECPR cases using a conditional logistic model. RESULTS: Of 57,754 patients in the JAAM-OHCA registry, we selected 1826 patients with an initial shockable rhythm (treated with ECPR, n = 913 and control, n = 913) and a cohort of 740 patients with an initial non-shockable rhythm (treated with ECPR, n = 370 and control, n = 370). In these matched cohorts, the odds ratio for 30-day survival in the ECPR group was 1.76 [95%CI 1.38-2.25] for shockable rhythm and 5.37 [95%CI 2.53-11.43] for non-shockable rhythm, compared to controls. For favorable neurological outcomes, the odds ratio in the ECPR group was 1.11 [95%CI 0.82-1.49] for shockable rhythm and 4.25 [95%CI 1.43-12.63] for non-shockable rhythm, compared to controls. CONCLUSION: ECPR was associated with increased 30-day survival in patients with OHCA with initial shockable and even non-shockable rhythms. Further research is warranted to investigate the reproducibility of the results and who is the best candidate for ECPR.

Significance of malnutrition defined with Global Leadership Initiative on Malnutrition criteria in patients with hepatocellular carcinoma after hepatic resection.

AIM: A recent study reported the utility of the definition of malnutrition according to the Global Leadership Initiative on Malnutrition (GLIM) criteria in many types of cancers and chronic inflammatory disease. The present retrospective study aimed to investigate the significance of malnutrition defined with GLIM criteria in patients with hepatic resection for hepatocellular carcinoma (HCC) and also to compare malnutrition using handgrip strength. METHODS: We retrospectively reviewed data from 174 patients who had undergone curative hepatic resection for HCC including both skeletal muscle area and handgrip strength. Patients were divided according to malnutrition defined by GLIM or modified GLIM and clinicopathologic and short- and long-term outcomes were analyzed. The modified GLIM criteria was defined using both handgrip strength and skeletal muscle area. RESULTS: Malnutrition defined by GLIM criteria was diagnosed in 47 patients (26.7%) and malnutrition defined by modified GLIM criteria was diagnosed in 21 patients (11.9%). Malnutrition defined by GLIM or modified GLIM criteria was associated with poorer liver function and malignant tumor behavior, but modified GLIM criteria predicted the postoperative complication and recurrence-free survival outcome independently. In patients with poor liver function, malnutrition defined by modified GLIM criteria predicted postoperative complication and overall and recurrence-free survival. CONCLUSIONS: Malnutrition defined by modified GLIM criteria using both handgrip strength and skeletal muscle area can more accurately predict short- and long-term outcomes compared to malnutrition defined by the GLIM criteria. Nutritional and exercise therapy could become more important in patients with malnutrition and poor liver function.

Location and coupling interval of an ectopic excitation determine the initiation of atrial fibrillation from the pulmonary veins.

INTRODUCTION: Ectopic beats originating from the pulmonary vein (PV) trigger atrial fibrillation (AF). The purpose of this study was to clarify the electrophysiological determinant of AF initiation from the PVs. METHODS: Pacing studies were performed with a single extra stimulus mimicking an ectopic beat in the left superior PVs (LSPVs) in 62 patients undergoing AF ablation. Inducibility of AF, effective refractory period (ERP), and conduction properties within the PVs were analyzed. RESULTS: A single extra stimulus in LSPV induced AF in 20 patients (32% of all patients) at the mean coupling interval (CI) of 172 ms. A CI-dependent anisotropic conduction at the AF onset was visualized in a three-dimensional mapping. Onset of AF was site-specific with reproducibility in each individual. Mean ERP in LSPV in the AF-inducible group was shorter than that in the AF-noninducible group (182 ± 55 vs. 254 ± 51 ms, p < .0001). LSPV ERP dispersion was greater in the AF-inducible group than in the AF-noninducible group (45 ± 28 vs. 27 ± 19 ms, p < .01). Circumferential intra-PV conduction time (IPVCT) exhibited decremental properties in response to shortening of CI and the prolongation of IPVCT in the AF-inducible site was greater than that in the AF-noninducible site (p < .05) in each individual. CONCLUSIONS: Location and CI of an ectopic excitation ultimately determine the initiation of AF from the PVs. ERP dispersion and circumferential conduction delay may lead to anisotropic conduction and reentry within the PVs that initiate AF.

Early prognostic impact of serum sodium level among out-of-hospital cardiac arrest patients: a nationwide multicentre observational study in Japan (the JAAM-OHCA registry).

Dysnatremia is an electrolytic disorder commonly associated with mortality in various diseases. However, little is known about dysnatremia in out-of-hospital cardiac arrest (OHCA) cases. Here, we investigated the association between serum sodium level on hospital arrival and neurological outcomes after OHCA. This nationwide hospital-based observational study (The Japanese Association for Acute Medicine Out-of-Hospital Cardiac Arrest registry) enrolled patients with OHCA between 2014 and 2017. We included adult patients aged ≥ 18 years with non-traumatic OHCA who achieved return of spontaneous circulation (ROSC) and whose serum sodium level on hospital arrival was available. Based on the serum sodium level, patients were divided into three levels: hyponatremia (Na < 135 mEq/L), normal sodium level (Na ≥ 135 or ≤ 145 mEq/L), and hypernatremia (Na > 145 mEq/L). The primary outcome was 1-month survival with favourable neurological outcomes. Altogether, 34 754 patients with OHCA were documented, and 5160 patients with non-traumatic OHCA and who achieved ROSC were eligible for our analyses. The proportion of favourable neurological outcomes was highest in patients with normal sodium levels at 17.6% (677/3854), followed by patients with hyponatremia at 8.2% (57/696) and patients with hypernatremia at 5.7% (35/610). Moreover, hyponatremia and hypernatremia were associated with a decreased probability of favourable neurological outcomes compared with normal sodium level (vs. hyponatremia, adjusted odds ratio [AOR] 0.97, 95% confidence interval [CI] 0.95-0.99; vs. hypernatremia, AOR 0.96, 95% CI 0.94-0.98). Hypo- and hypernatremia on hospital arrival were associated with a decreased probability of favourable neurological outcomes in patients with non-traumatic OHCA who achieved ROSC.

Association between initial body temperature on hospital arrival and neurological outcome among patients with out-of-hospital cardiac arrest: a multicenter cohort study (the CRITICAL study in Osaka, Japan).

BACKGROUND: The association between spontaneous initial body temperature on hospital arrival and neurological outcomes has not been sufficiently studied in patients after out-of-hospital cardiac arrest (OHCA). METHODS: From the prospective database of the Comprehensive Registry of Intensive Care for OHCA Survival (CRITICAL) study in Osaka, Japan, we enrolled all patients with OHCA of medical origin aged > 18 years for whom resuscitation was attempted and who were transported to participating hospitals between 2012 and 2019. We excluded patients who were not witnessed by bystanders and treated by a doctor car or helicopter, which is a car/helicopter with a physician. The patients were categorized into three groups according to their temperature on hospital arrival: ≤35.9 °C, 36.0-36.9 °C (normothermia), and ≥ 37.0 °C. The primary outcome was 1-month survival, with a cerebral performance category of 1 or 2. Multivariable logistic regression analyses were performed to evaluate the association between temperature and outcomes (normothermia was used as the reference). We also assessed this association using cubic spline regression analysis. RESULTS: Of the 18,379 patients in our database, 5014 witnessed adult OHCA patients of medical origin from 16 hospitals were included. When analyzing 3318 patients, OHCA patients with an initial body temperature of ≥37.0 °C upon hospital arrival were associated with decreased favorable neurological outcomes (6.6% [19/286] odds ratio, 0.51; 95% confidence interval, 0.27-0.95) compared to patients with normothermia (16.4% [180/1100]), whereas those with an initial body temperature of ≤35.9 °C were not associated with decreased favorable neurological outcomes (11.1% [214/1932]; odds ratio, 0.78; 95% confidence interval, 0.56-1.07). The cubic regression splines demonstrated that a higher body temperature on arrival was associated with decreased favorable neurological outcomes, and a lower body temperature was not associated with decreased favorable neurological outcomes. CONCLUSIONS: In adult patients with OHCA of medical origin, a higher body temperature on arrival was associated with decreased favorable neurologic outcomes.

Bi-allelic loss of function variants of TBX6 causes a spectrum of malformation of spine and rib including congenital scoliosis and spondylocostal dysostosis.

BACKGROUND: Congenital scoliosis (CS) is a common vertebral malformation. Spondylocostal dysostosis (SCD) is a rare skeletal dysplasia characterised by multiple vertebral malformations and rib anomalies. In a previous study, a compound heterozygosity for a null mutation and a risk haplotype composed by three single-nucleotide polymorphisms in TBX6 have been reported as a disease-causing model of CS. Another study identified bi-allelic missense variants in a SCD patient. The purpose of our study is to identify TBX6 variants in CS and SCD and examine their pathogenicity. METHODS: We recruited 200 patients with CS or SCD and investigated TBX6 variants. We evaluated the pathogenicity of the variants by in silico prediction and in vitro experiments. RESULTS: We identified five 16p11.2 deletions, one splice-site variant and five missense variants in 10 patients. In vitro functional assays for missense variants identified in the previous and present studies demonstrated that most of the variants caused abnormal localisation of TBX6 proteins. We confirmed mislocalisation of TBX6 proteins in presomitic mesoderm cells induced from SCD patient-derived iPS cells. In induced cells, we found decreased mRNA expressions of TBX6 and its downstream genes were involved in somite formation. All CS patients with missense variants had the risk haplotype in the opposite allele, while a SCD patient with bi-allelic missense variants did not have the haplotype. CONCLUSIONS: Our study suggests that bi-allelic loss of function variants of TBX6 cause a spectrum of phenotypes including CS and SCD, depending on the severity of the loss of TBX6 function.

[Gastric Neuroendocrine Carcinoma(NEC)Treated with CDDP plus CPT-11 Chemotherapy].

A 69-year-old man with chronic gastritis, reflux esophagitis, esophageal hiatal hernia, and history of appendicitis surgery complained of difficulty swallowing. Upper gastrointestinal endoscopy revealed a 10 cm sized Type 3 gastric cancer. Immunostaining was positive for chromogranin A(2+), synaptophysin(3+), CD56(-), and Ki-67>70%. Contrast computed tomography(CT)showed upper gastric wall thickening, and #1, #3, #7, #8a, and #11p enlarged lymph nodes but no distant metastasis. We diagnosed gastric cancer, UM, Less, Type 3, gastric neuroendocrine carcinoma, cT4aN3M0P0CY0, Stage ⅢC. We administered 2 courses of CDDP plus CPT-11 chemotherapy, and a partial response was obtained for the primary gastric lesion and lymph node metastases. We subsequently performed open distal gastrectomy, D2 lymph node dissection, and splenectomy. Pathological examination confirmed that the lesion was gastric cancer, U, Less, Type 3, gastric neuroendocrine carcinoma, MP, Ul-Ⅱ(+), int, INF b, ly2, v0, PM0, DM0, R0, ypT2N2, Stage ⅡB, with a therapeutic value of Grade 2. The patient was discharged on day 15 after the surgery and received 2 courses of adjuvant chemotherapy with CDDP plus CPT-11. Nine months after the surgery, metastasis of the left adrenal grand was found. We performed open left adrenal gland resection and administered adjuvant S-1 chemotherapy.

Chiroptical molecular propellers based on hexakis(phenylethynyl)benzene through the complexation-induced intramolecular transmission of local point chirality.

We designed hexakis(phenylethynyl)benzene derivatives with a tertiary amide group on each blade to achieve a helically biased propeller arrangement through the complexation-induced intramolecular transmission of point chirality. A hydrogen-bonding ditopic guest was captured at two amide groups, and thus could pair two neighboring blades to form a supramolecular cyclic structure, in which an auxiliary chiral group associated with a blade acted as a chiral handle to control the helical bias, while the chiral auxiliary did not exert any helical influence on the dynamic helicity in the absence of a guest due to the high flexibility of each blade.

Total lesion glycolysis by 18F-fluorodeoxyglucose positron emission tomography predicts tumor aggressiveness in patients with extrahepatic bile duct carcinoma.

BACKGROUND: 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT) parameters are prognostic factors in multiple malignancies. However, the prognostic value in bile duct carcinoma is unclear. We evaluated the impact of metabolic parameters of 18F-FDG-PET/CT in resectable extrahepatic bile duct carcinoma. METHODS: We retrospectively reviewed the records of 100 patients with extrahepatic bile duct carcinoma who had undergone 18F-FDG-PET/CT and subsequent surgical resection between January 2017 and January 2023. We calculated maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) and investigated their prognostic significance. RESULTS: The optimal cutoff values of SUVmax, MTV, and TLG for predicting overall survival (OS) after surgery were 3.88, 3.55 and 7.55, respectively. In multivariate analysis, each metabolic parameter influenced both OS and recurrence-free survival (RFS). TLG showed the lowest Akaike information criteria statistic value, indicating that it had the best ability to predict OS and RFS. High TLG was significantly associated with the number of lymph node metastases and poorly differentiated type. Patients with high TLG showed poorer RFS and OS, which were significantly worse than in those with low TLG. CONCLUSIONS: Tumor TLG predicted tumor malignancy potential and could be a useful prognostic predictor for extrahepatic bile duct carcinoma.

Advantages of laparoscopic segmentectomy of the liver using ICG fluorescent navigation by the negative staining method: A comparison with open procedure.

Aim: Laparoscopic segmentectomy (LS) using indocyanine green (ICG) fluorescence navigation with negative staining method has potential for performing accurate and safe anatomical excision. This study aimed to evaluate the significance of LS using ICG fluorescence navigation compared with open segmentectomy (OS). Methods: Eighty-seven patients who underwent anatomical segmentectomies were evaluated for OS (n = 44) and LS (n = 43). The Glissonean pedicle approach was performed using either extra- or intrahepatic method, depending on the location of segment in LS. After clamping pedicle, negative staining method was performed. Liver transection was done along intersegmental plane visualizing by overlay mode of ICG camera. Surgical outcomes were compared between two groups. Correlation between predicted resecting liver volume (PRLV) calculated using volumetry and actual resected liver volume (ARLV) was assessed in two groups. Results: Patients who underwent LS showed better outcomes in operative time, blood loss, and length of hospital stay. There were significantly fewer Grade II and Grade III or higher postoperative complications in LS group. Both values of AST (p < 0.001) and ALT (p < 0.001) on postoperative day 1 were significantly lower in LS group than in OS group. PRLV and ARLV were more strongly correlated in LS (r = 0.896) than in OS (r = 0.773). The difference between PRLV and ARLV was significantly lower in LS group than in OS group (p = 0.022), and this trend was particularly noticeable in posterosuperior segment (p = 0.008) than in anterolateral segment (p = 0.811). Conclusion: LS using ICG navigation allows precise resection and may contribute to safer short-term outcomes than OS, particularly in posterosuperior segment.

Lower Geriatric Nutritional Risk Index and Prognostic Nutritional Index Predict Postoperative Prognosis in Patients with Hepatocellular Carcinoma.

Increasing evidence suggests that nutritional indices, including the geriatric nutritional risk index (GNRI) and prognostic nutritional index (PNI), are predictors of poor prognosis in patients with hepatocellular carcinoma (HCC). Hence, this study aimed to explore the value of the GNRI and PNI in evaluating postoperative prognosis in patients with HCC, particularly regarding its recurrence patterns. We performed a retrospective analysis of 203 patients with HCC who underwent initial hepatic resection. Patients were divided into two groups according to the GNRI (cutoff: 98) and PNI (cutoff: 45). The GNRI and PNI were significantly associated with body composition (body mass index and skeletal muscle mass index), hepatic function (Child-Pugh Score), tumor factors (tumor size and microvascular invasion), and perioperative factors (blood loss and postoperative hospitalization). Patients with a low PNI or low GNRI had significantly worse overall survival (OS) and recurrence-free survival. Patients with early recurrence had lower PNI and GNRI scores than those without early recurrence. Patients with extrahepatic recurrence had lower PNI and GNRI scores than those without extrahepatic recurrence. The PNI and GNRI might be useful in predicting the prognosis and recurrence patterns of patients with HCC after hepatic resection.

Oxidative phosphorylation is a pivotal therapeutic target of fibrodysplasia ossificans progressiva.

Heterotopic ossification (HO) is a non-physiological bone formation where soft tissue progenitor cells differentiate into chondrogenic cells. In fibrodysplasia ossificans progressiva (FOP), a rare genetic disease characterized by progressive and systemic HO, the Activin A/mutated ACVR1/mTORC1 cascade induces HO in progenitors in muscle tissues. The relevant biological processes aberrantly regulated by activated mTORC1 remain unclear, however. RNA-sequencing analyses revealed the enrichment of genes involved in oxidative phosphorylation (OXPHOS) during Activin A-induced chondrogenesis of mesenchymal stem cells derived from FOP patient-specific induced pluripotent stem cells. Functional analyses showed a metabolic transition from glycolysis to OXPHOS during chondrogenesis, along with increased mitochondrial biogenesis. mTORC1 inhibition by rapamycin suppressed OXPHOS, whereas OXPHOS inhibitor IACS-010759 inhibited cartilage matrix formation in vitro, indicating that OXPHOS is principally involved in mTORC1-induced chondrogenesis. Furthermore, IACS-010759 inhibited the muscle injury-induced enrichment of fibro/adipogenic progenitor genes and HO in transgenic mice carrying the mutated human ACVR1. These data indicated that OXPHOS is a critical downstream mediator of mTORC1 signaling in chondrogenesis and therefore is a potential FOP therapeutic target.

External Validation of Updated Prediction Models for Neurological Outcomes at 90 Days in Patients With Out-of-Hospital Cardiac Arrest.

BACKGROUND: Few prediction models for individuals with early-stage out-of-hospital cardiac arrest (OHCA) have undergone external validation. This study aimed to externally validate updated prediction models for OHCA outcomes using a large nationwide dataset. METHODS AND RESULTS: We performed a secondary analysis of the JAAM-OHCA (Comprehensive Registry of In-Hospital Intensive Care for Out-of-Hospital Cardiac Arrest Survival and the Japanese Association for Acute Medicine Out-of-Hospital Cardiac Arrest) registry. Previously developed prediction models for patients with cardiac arrest who achieved the return of spontaneous circulation were updated. External validation was conducted using data from 56 institutions from the JAAM-OHCA registry. The primary outcome was a dichotomized 90-day cerebral performance category score. Two models were updated using the derivation set (n=3337). Model 1 included patient demographics, prehospital information, and the initial rhythm upon hospital admission; Model 2 included information obtained in the hospital immediately after the return of spontaneous circulation. In the validation set (n=4250), Models 1 and 2 exhibited a C-statistic of 0.945 (95% CI, 0.935-0.955) and 0.958 (95% CI, 0.951-0.960), respectively. Both models were well-calibrated to the observed outcomes. The decision curve analysis showed that Model 2 demonstrated higher net benefits at all risk thresholds than Model 1. A web-based calculator was developed to estimate the probability of poor outcomes (https://pcas-prediction.shinyapps.io/90d_lasso/). CONCLUSIONS: The updated models offer valuable information to medical professionals in the prediction of long-term neurological outcomes for patients with OHCA, potentially playing a vital role in clinical decision-making processes.

Non-linear association between the time required to reaching temperature targets and the neurological outcome in patients undergoing targeted temperature management after out-of-hospital cardiac arrest: Observational multicentre cohort study.

Purpose: We evaluated associations between outcomes and time to achieving temperature targets during targeted temperature management of out-of-hospital cardiac arrest. Methods: Using Comprehensive Registry of Intensive Care for out-of-hospital cardiac arrest Survival (CRITICAL) study, we enrolled all patients transported to participating hospitals from 1 July 2012 through 31 December 2017 aged ≥ 18 years with out-of-hospital cardiac arrest of cardiac aetiology and who received targeted temperature management in Osaka, Japan. Primary outcome was Cerebral Performance Category scale of 1 or 2 one month after cardiac arrest, designated as "one-month favourable neurological outcome". Non-linear multivariable logistic regression analyses assessed the primary outcome based on time to reaching temperature targets. In patients subdivided into quintiles based on time to achieving temperature targets, multivariable logistic regression calculated adjusted odds ratios and 95% confidence intervals. Results: We analysed 473 patients. In non-linear multivariable logistic regression analysis, p value for non-linearity was < 0.01. In the first quintile (< 26.7 minutes), second quintile (26.8-89.9 minutes), third quintile (90.0-175.1 minutes), fourth quintile (175.2-352.1 minutes), and fifth quintile (≥ 352.2 minutes), one-month favourable neurological outcome was 32.6% (31/95), 40.0% (36/90), 53.5% (53/99), 57.4% (54/94), and 37.9% (36/95), respectively. Adjusted odds ratios with 95% confidence intervals for one-month favourable neurological outcome in the first, second, third, and fifth quintiles compared with the fourth quintile were 0.38 (0.20 to 0.72), 0.43 (0.23 to 0.81), 0.77 (0.41 to 1.44), and 0.46 (0.25 to 0.87), respectively. Conclusion: Non-linear multivariable logistic regression analysis could clearly describe the association between neurological outcome in patients with out-of-hospital cardiac arrest and the time from the introduction of targeted temperature management to reaching the temperature targets.