Annular and supra-annular structure assessments for transcatheter aortic valve replacement in patients with bicuspid aortic stenosis.

The clinical use indications for transcatheter aortic valve replacement (TAVR) for the treatment of severe symptomatic aortic stenosis (AS) have expanded from patients at high surgical risk to those at low risk based on the results of multiple large-scale randomized trials. However, patients with bicuspid AS have traditionally been excluded from clinical trials due to their unfavorable morphological characteristics. Bicuspid aortic valve (BAV) is the most frequent congenital heart disease, occurring in 1% to 2% of the total population and affects more than 20% of octogenarians undergoing isolated aortic valve replacement for AS. In recent years, TAVR in patients with bicuspid AS has been the focus of research, especially with respect to the standard of prosthesis size selection. Annulus-based prosthesis size selection using computed tomography (CT) is the standard sizing strategy for tricuspid AS, but no standard sizing for bicuspid AS has been developed thus far. According to Western TAVR experiences, transcatheter heart valve (THV) size selection for BAV patients should be based on the annular structure assessment by CT measurement, whereas Chinese experiences favor adopting the supra-annulus structure assessment for THV size selection. This article will review annular and supra-annular sizing for prosthesis size selection in patients with bicuspid AS before TAVR and discuss which has more favorable clinical outcomes.

Asymmetric Construction of Axially Chiral 2-Arylpyrroles by Chirality Transfer of Atropisomeric Alkenes.

Axially chiral 2-arylpyrrole frameworks are efficiently accessed through a direct chirality transfer strategy by rapid cyclization of enantioenriched atropisomeric alkenes, which are generated by organocatalytic asymmetric N-alkylation reactions. This approach accommodates a broad scope of substrates with remarkably high chirality transfer efficiency, affording novel atropisomers with a fully substituted pyrrole moiety and high enantiopurities. Given the enantioenriched atropisomeric alkenes, novel heterocyclic 2-arylazepine atropisomers were realized through a rationally designed ene reaction.

Evaluating segmental liver function using T1 mapping on Gd-EOB-DTPA-enhanced MRI with a 3.0 Tesla.

BACKGROUND: Assessing the liver function provides valuable information to evaluate surgical risk and plan accordingly. Current studies focus on whole liver function evaluation. However, assessment of segmental liver function is equally important in the clinical practice. The purpose of this study was to investigate whether Gd-EOB-DTPA-enhanced MRI can evaluate the liver function of each segment by using T1 mapping at 3 Tesla MRI. METHODS: One hundred three patients were classified into one of 4 groups: a normal liver function (NLF) group (n = 38), a liver cirrhosis with Child-Pugh A (LCA) group (n = 33), a liver cirrhosis with Child-Pugh B (LCB) group (n = 21), and a liver cirrhosis with Child-Pugh C (LCC) group (n = 11). All patients underwent Gd-EOB-DTPA-enhanced MRI scans. T1 relaxation times were measured on the liver superimposing T1 mapping images. Reduction rate (△%) of T1 relaxation time of the liver parenchyma were calculated. RESULTS: After 20 min of Gd-EOB-DTPA enhancement, the T1 relaxation time of all liver segments in the LCC group were different from those in all the other groups, and more liver segments from the LCB and LCA groups different from the NLF group (p < 0.05). For the LCB group, the areas under the receiver operating characteristic curves (AUCs) of different liver segments for hepatobiliary phase (HBP) were 0.654-0.904 on T1 relaxation time, and 0.709-0.905 on △%. For the LCC group, the AUCs of different liver segments for HBP were 0.842-0.997 on T1 relaxation time, and 0.887-0.990 on △%. CONCLUSIONS: For LCB patients, segmental liver function evaluation is possible using Gd-EOB-DTPA-enhanced MRI T1 mapping. For LCC patients, all liver segments can be used to evaluate liver function and both T1 relaxation time and the △% of T1 relaxation time have good diagnostic performance.

Gd-EOB-DTPA-enhanced MRI T1 mapping for assessment of liver function in rabbit fibrosis model: comparison of hepatobiliary phase images obtained at 10 and 20 min.

OBJECTIVES: To compare hepatobiliary phase (HBP) images obtained at 10 and 20 min after Gd-EOB-DTPA-enhanced MRI for assessment of liver function in rabbit fibrosis model on 3.0 T MR imaging. METHODS: 34 animals were separated into three groups: 5 for a control group, 14 for a mild fibrosis group, and 15 for a severe fibrosis group based on pathological proof. T1 relaxation times (T1rt) were measured on T1 mapping and reduction rates of T1rt (rrT1rt) were calculated. HBP images were obtained at 10 and 20 min after Gd-EOB-DTPA enhancement. Indocyanine green retention rates at 15 min (ICG R15) were performed for all animals. RESULTS: T1rt on pre-enhancement imaging showed no significant difference (p > 0.05) among all groups. T1rt on 10 min HBP and 20 min HBP showed significant difference (p < 0.05) among all groups. T1rt and rrT1rt in three groups showed no-significant difference (p > 0.05) between 10 min HBP and 20 min HBP. T1rt on both 10 and 20 min HBP showed significant correlation with ICG R15 (p < 0.05); rrT1rt on both 10 min HBP and 20 min HBP showed significant inverse correlation with ICG R15 (p < 0.05). CONCLUSIONS: Comparing 10 min HBP and 20 min HBP T1 mapping after Gd-EOB-DTPA enhancement, our results suggest that 10 min HBP T1 mapping is feasible for quantitatively assessing liver function.

Reduced Nicotinamide Adenine Dinucleotide Phosphate, a Pentose Phosphate Pathway Product, Might Be a Novel Drug Candidate for Ischemic Stroke.

BACKGROUND AND PURPOSE: Our previous study has defined a role of TP53-induced glycolysis and apoptosis regulator in neuroprotection against ischemic injury through increasing the flow of pentose phosphate pathway. We hypothesized that the pentose phosphate pathway product nicotinamide adenine dinucleotide phosphate (NADPH) could be a novel drug for treatment of ischemic stroke. METHODS: The NADPH was given before, at the onset, or after stroke onset with single or repeated intravenous (mice and rats) or intraperitoneal injections (monkey). The short- and long-term therapeutic effects of NADPH were evaluated in male adult ICR mice (total=614) with transient middle cerebral artery occlusion, in male adult Sprague-Dawley rats (total=114) with permanent middle cerebral artery occlusion, and in male adult rhesus monkey (total=12) with thrombotic middle cerebral artery occlusion. RESULTS: Administration of NADPH led to a dramatic increase in the levels of ATP and reduced form of glutathione, whereas it decreased the levels of reactive oxygen species. NADPH significantly reduced infarct volume, improved poststroke survival, and recovery of neurological functions in mouse and rat models of stroke. Robust neuroprotection of a single dose of NADPH was seen when it was administered within 5 hours after reperfusion; however, repeat administration of NADPH twice a day for 7 days starting 24 hours after the onset of stroke also offered therapeutic effects. Pretreatment with NADPH also significantly improved the outcome of stroke insult. CONCLUSIONS: Administration of exogenous NADPH significantly protected neurons against ischemia/reperfusion-induced injury in 2 rodent stroke models. Thus, NADPH might be a promising drug candidate for treatment of ischemic stroke.

A TIGAR-regulated metabolic pathway is critical for protection of brain ischemia.

TP53-induced glycolysis and apoptosis regulator (TIGAR) inhibits glycolysis and increases the flow of pentose phosphate pathway (PPP), which generates NADPH and pentose. We hypothesized that TIGAR plays a neuroprotective role in brain ischemia as neurons do not rely on glycolysis but are vulnerable to oxidative stress. We found that TIGAR was highly expressed in brain neurons and was rapidly upregulated in response to ischemia/reperfusion insult in a TP53-independent manner. Overexpression of TIGAR in normal mice with lentivirus reduced ischemic neuronal injury, whereas lentivirus-mediated TIGAR knockdown aggravated it. In cultured primary neurons, increasing TIGAR expression reduced oxygen and glucose deprivation (OGD)/reoxygenation-induced injury, whereas decreasing its expression worsened the injury. The glucose 6-phosphate dehydrogenase was upregulated in mouse and cellular models of stroke, and its upregulation was further enhanced by overexpression of TIGAR. Supplementation of NADPH also reduced ischemia/reperfusion brain injury and alleviated TIGAR knockdown-induced aggravation of ischemic injury. In animal and cellular stroke models, ischemia/reperfusion increased mitochondrial localization of TIGAR. OGD/reoxygenation-induced elevation of ROS, reduction of GSH, dysfunction of mitochondria, and activation of caspase-3 were rescued by overexpression of TIGAR or supplementation of NADPH, while knockdown of TIGAR aggravated these changes. Together, our results show that TIGAR protects ischemic brain injury via enhancing PPP flux and preserving mitochondria function, and thus may be a valuable therapeutic target for ischemic brain injury.

TNF-α, HGF and macrophage in peritumoural liver tissue relate to major risk factors of HCC Recurrence.

BACKGROUND/AIMS: Hepatocyte growth factor (HGF) responds to tumor necrosis factor- α (TNF- α) secreted by macrophages and has been suggested to function in malignant metastasis. This study was performed to shed a light on the complicated relation between intrahepatic macrophages, TNF- α, HGF and hepatocellular carcinoma (HCC) microvascular invasion (MVI) and pathological grade. METHODOLOGY: Forty-eight HCC cases were divided into three groups according to pathological grade: poorly-differentiated (PD), moderately-differentiated (MD) and well-differentiated (WD) groups. Each group was divided into subgroups based on the condition of MVI. Macrophages were counted, and TNF- α and HGF were tested in all specimens by immunohistochemical analysis and RT-PCR. RESULTS: In peritumoural liver tissue, MVI had more HGF (t=8.22, p<0.05) and less TNF- α (t=4.20, p<0.05) than non-MVI. With MVI, PD and MD had more TNF- α (t=3.30, p<0.05and t=2.82, p<0.05) than WD in peritumoural tissue. CONCLUSIONS: Overexpressed TNF- α and HGF in microenvironment were related to poor differentiation and microvascular invasion of HCC. We suggest that inflammation of hepatic microenvironment promote pathological degradation and microvascular invasion of HCC.

Effectiveness of early heparin therapy on outcomes in critically ill patients with sepsis-induced coagulopathy.

Background: This study aimed to investigate whether early unfractionated heparin (UFH) administration provides a survival advantage for patients with sepsis-induced coagulopathy (SIC). Methods: Patients hospitalized with sepsis-induced coagulopathy from the Medical Information Mart for Intensive Care (MIMIC)-IV database were identified. Patients were divided into two groups, who received unfractionated heparin (UFH) subcutaneously within 24 h after intensive care unit (ICU) admission, and the control group, who received not. The primary endpoint was intensive care unit mortality, the secondary outcomes were 7, 14, and 28-day and hospital mortality. Propensity score matching (PSM) the marginal structural Cox model (MSCM) and E-value analysis were used to account for baseline differences, time-varying and unmeasured confounding factors. Results: A total of 3,377 patients with sepsis-induced coagulopathy were enrolled in the study, of which 815 in unfractionated heparin group and 2,562 in control group. There was significant effect on primary and secondary outcomes with unfractionated heparin after propensity score matching (intensive care unit mortality, hazard ratio [HR] 0.69, 95% confidence interval [CI] 0.52-0.92; 7-day, HR 0.70, 95% CI 0.49-0.99; 14-day, HR 0.68.95% CI 0.50-0.92; 28-day, HR 0.72, 95% CI 0.54-0.96; hospital mortality, HR 0.74, 95% CI 0.57-0.96), marginal structural Cox model manifested unfractionated heparin associated with decreased intensive care unit mortality in all populations (HR 0.64, 95% CI 0.49-0.84), and stratification with the marginal structural Cox model indicated analysis further indicated the survival advantage only among patients with an sepsis-induced coagulopathy score of 4 (HR 0.56, 95% CI 0.38-0.81). Further analysis showed that treatment with 6,250-13750 IU/day of unfractionated heparin associated with a decreased risk of intensive care unit mortality. Similar results were replicated in subgroup analysis with propensity score matching only for patients with an sepsis-induced coagulopathy score of 4 (intensive care unit mortality, HR 0.51, 95% CI 0.34-0.76). Conclusion: This study found early unfractionated heparin therapy to patients with sepsis-induced coagulopathy appears to be associated with improved outcomes. Subgroup analysis further demonstrates heparin therapy decreased intensive care unit mortality primarily in patients only with SIC score of 4.

Impact of early heparin therapy on mortality in critically ill patients with sepsis associated acute kidney injury: a retrospective study from the MIMIC-IV database.

Background: Inflammatory-coagulation dysfunction plays an increasingly important role in sepsis associated acute kidney injury (SAKI). This study aimed to investigate whether early heparin therapy improves survival in patients with SAKI. Methods: Patients with SAKI were identified from the Medical Information Mart for Intensive Care-IV database. The patients were divided into two groups: those who received heparin subcutaneously within 48 h after intensive care unit (ICU) admission and the control group, who received no heparin. The primary endpoint was ICU mortality, the secondary outcomes were 7-day, 14-day, 28-day, and hospital mortality. Propensity score matching (PSM), marginal structural Cox model (MSCM), and E-value analyses were performed. Results: The study included 5623 individuals with SAKI, 2410 of whom received heparin and 3213 of whom did not. There were significant effects on ICU and 28-day mortality in the overall population with PSM. MSCM further reinforces the efficacy of heparin administration reduces ICU mortality in the general population. Stratification analysis with MSCM showed that heparin administration was associated with decreased ICU mortality at various AKI stages. Heparin use was also associated with reduced 28-day mortality in patients with only female, age >60 years, and AKI stage 3, with HRs of 0.79, 0.77, and 0.60, respectively (p < 0.05). E-value analysis suggests robustness to unmeasured confounding. Conclusion: Early heparin therapy for patients with SAKI decreased ICU mortality. Further analysis demonstrated that heparin therapy was associated with reduced 28-day mortality rate in patients only among female, age > 60 years and AKI stage 3.

Impact of early heparin therapy on outcomes in patients with solid malignancy associated sepsis: a marginal structural model causal analyse.

Background: Previous studies documented that heparin can inhibit the invasion and metastasis of tumors, but its role on outcomes in patients with solid malignancy complicated sepsis remains unclear. Methods: A retrospective cohort study was conducted in critically ill patients with solid malignancy associated sepsis from the Medical Information Mart for Intensive Care (MIMIC)-IV database. The primary endpoint was intensive care unit (ICU) mortality, secondary outcomes were thrombosis and hospital mortality. Propensity score matching (PSM), marginal structural Cox model (MSCM), cox proportional hazards model, stratification analysis and E-value were used to account for baseline differences, time-varying confounding and unmeasured variables. Results: A total of 1,512 patients with solid malignancy complicated sepsis were enrolled, of which 683 in the heparin group with intensive care unit mortality, thrombosis rate and hospital mortality were 9.7%, 5.4%, 16.1%, and 829 in the non-heparin group with ICU mortality, thrombosis rate and hospital mortality were 14.6%, 12.5%, 22.6%. Similar results were observed on outcomes for patients with PSM (ICU mortality hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.41-0.92), thrombosis rate (HR 0.42, 95% confidence interval 0.26-0.68); hospital mortality HR 0.70, 95% CI 0.50-0.99). marginal structural Cox model further reinforced the efficacy of heparin in reducing ICU mortality (HR 0.48, 95% CI 0.34-0.68). Logistic regression and Cox regression model showed heparin use also markedly reduced thrombosis (HR 0.42; 95% CI 0.26-0.68; p < 0.001) and hospital mortality (HR 0.70; 95% CI 0.50-0.99; p = 0.043). Stratification analysis with the MSCM showed an effect only those with digestive system cancer (HR 0.33, 95% CI 0.16-0.69). Conclusion: Early heparin therapy improved outcomes in critically ill patients with solid malignancy complicated sepsis. These results are evident especially in those with digestive system cancer. A prospective randomized controlled study should be designed to further assess the relevant findings.

Beneficial effects of high-density lipoprotein (HDL) on stent biocompatibility and the potential value of HDL infusion therapy following percutaneous coronary intervention.

Several epidemiological studies have shown a clear inverse relationship between serum levels of high-density lipoprotein cholesterol (HDL-C) and the risk of atherosclerotic cardiovascular disease (ASCVD), even at low-density lipoprotein cholesterol levels below 70 mg/dL. There is much evidence from basic and clinical studies that higher HDL-C levels are beneficial, whereas lower HDL-C levels are detrimental. Thus, HDL is widely recognized as an essential anti-atherogenic factor that plays a protective role against the development of ASCVD. Percutaneous coronary intervention is an increasingly common treatment choice to improve myocardial perfusion in patients with ASCVD. Although drug-eluting stents have substantially overcome the limitations of conventional bare-metal stents, there are still problems with stent biocompatibility, including delayed re-endothelialization and neoatherosclerosis, which cause stent thrombosis and in-stent restenosis. According to numerous studies, HDL not only protects against the development of atherosclerosis, but also has many anti-inflammatory and vasoprotective properties. Therefore, the use of HDL as a therapeutic target has been met with great interest. Although oral medications have not shown promise, the developed HDL infusions have been tested in clinical trials and have demonstrated viability and reproducibility in increasing the cholesterol efflux capacity and decreasing plasma markers of inflammation. The aim of the present study was to review the effect of HDL on stent biocompatibility in ASCVD patients following implantation and discuss a novel therapeutic direction of HDL infusion therapy that may be a promising candidate as an adjunctive therapy to improve stent biocompatibility following percutaneous coronary intervention.

Early prophylactic anticoagulation with heparin alleviates mortality in critically ill patients with sepsis: a retrospective analysis from the MIMIC-IV database.

Background: Minimal data exist on anticoagulation use and timing and the dose of heparin in patients with sepsis, and whether heparin use improves sepsis survival remains largely unclear. This study was performed to assess whether heparin administration would provide a survival advantage in critically ill patients with sepsis. Methods: A retrospective cohort study of patients with sepsis in the Medical Information Mart for Intensive Care (MIMIC)-IV database was conducted. Cox proportional hazards model and propensity score matching (PSM) were used to evaluate the outcomes of prophylactic anticoagulation with heparin administered by subcutaneous injection within 48 h of intensive care unit (ICU) admission. The primary outcome was in-hospital mortality. Secondary outcomes included 60-day mortality, length of ICU stay, length of hospital stay and incidence of acute kidney injury (AKI) on day 7. E-Value analysis were used for unmeasured confounding. Results: A total of 6646 adult septic patients were included and divided into an early prophylactic heparin group (n = 3211) and a nonheparin group (n = 3435). In-hospital mortality in the heparin therapy group was significantly lower than that in the nonheparin group (prematched 14.7 vs 20.0%, hazard ratio (HR) 0.77, 95% confidence interval (CI) [0.68-0.87], p < 0.001, and postmatched 14.9 vs 18.3%, HR 0.78, 95% CI [0.68-0.89], p < 0.001). Secondary endpoints, including 60-day mortality and length of ICU stay, differed between the heparin and nonheparin groups (p < 0.01). Early prophylactic heparin administration was associated with in-hospital mortality among septic patients in different adjusted covariates (HR 0.71-0.78, p < 0.001), and only administration of five doses of heparin was associated with decreased in-hospital mortality after PSM (HR 0.70, 95% CI 0.56-0.87, p < 0.001). Subgroup analysis showed that heparin use was significantly associated with reduced in-hospital mortality in patients with sepsis-induced coagulopathy, septic shock, sequential organ failure assessment score ≥ 10, AKI, mechanical ventilation, gram-positive bacterial infection and gram-negative bacterial infection, with HRs of 0.74, 0.70, 0.58, 0.74, 0.73, 0.64 and 0.72, respectively (p <0.001). E-Value analysis suggested robustness to unmeasured confounding. Conclusions: This study found an association between early administration prophylactic heparin provided to patients with sepsis and reduced risk-adjusted mortality. A prospective randomized-controlled study should be designed to further assess the relevant findings.

Early Combination of Albumin With Crystalloid Administration Might Reduce Mortality in Patients With Cardiogenic Shock: An Over 10-Year Intensive Care Survey.

Background: In updated international guidelines, combined albumin resuscitation is recommended for septic shock patients who receive large volumes of crystalloids, but minimal data exist on albumin use and the optimal timing in those with cardiogenic shock (CS). The objective of this study was to evaluate the relationship between resuscitation with a combination of albumin within 24 h and 30-day mortality in CS patients. Methods: We screened patients with CS from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Multivariable Cox proportional hazards models and propensity score matching (PSM) were employed to explore associations between combined albumin resuscitation within 24 h and 30-day mortality in CS. Models adjusted for CS considered potential confounders. E-value analysis suggested for unmeasured confounding. Results: We categorized 1,332 and 254 patients into crystalloid-only and early albumin combination groups, respectively. Patients who received the albumin combination had decreased 30-day and 60-day mortality (21.7 vs. 32.4% and 25.2 vs. 34.2%, respectively, P < 0.001), and the results were robust after PSM (21.3 vs. 44.7% and 24.9 vs. 47.0%, respectively, P < 0.001) and following E-value. Stratified analysis showed that only ≥ 60 years old patients benefited from administration early albumin. In the early albumin combination group, the hazard ratios (HRs) of different adjusted covariates remained significant (HRs of 0.45-0.64, P < 0.05). Subgroup analysis showed that resuscitation with combination albumin was significantly associated with reduced 30-day mortality in patients with maximum sequential organ failure assessment score≥10, with acute myocardial infarction, without an Impella or intra-aortic balloon pump, and with or without furosemide and mechanical ventilation (HRs of 0.49, 0.58, 0.65, 0.40, 0.65 and 0.48, respectively; P < 0.001). Conclusion: This study found, compared with those given crystalloid-only, resuscitation with combination albumin within 24 h is associated with lower 30-day mortality of CS patients aged≥60. The results should be conducted to further assess in randomized controlled trials.

Radiomics and nomogram of magnetic resonance imaging for preoperative prediction of microvascular invasion in small hepatocellular carcinoma.

BACKGROUND: Microvascular invasion (MVI) of small hepatocellular carcinoma (sHCC) (≤ 3.0 cm) is an independent prognostic factor for poor progression-free and overall survival. Radiomics can help extract imaging information associated with tumor pathophysiology. AIM: To develop and validate radiomics scores and a nomogram of gadolinium ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) for preoperative prediction of MVI in sHCC. METHODS: In total, 415 patients were diagnosed with sHCC by postoperative pathology. A total of 221 patients were retrospectively included from our hospital. In addition, we recruited 94 and 100 participants as independent external validation sets from two other hospitals. Radiomics models of Gd-EOB-DTPA-enhanced MRI and diffusion-weighted imaging (DWI) were constructed and validated using machine learning. As presented in the radiomics nomogram, a prediction model was developed using multivariable logistic regression analysis, which included radiomics scores, radiologic features, and clinical features, such as the alpha-fetoprotein (AFP) level. The calibration, decision-making curve, and clinical usefulness of the radiomics nomogram were analyzed. The radiomic nomogram was validated using independent external cohort data. The areas under the receiver operating curve (AUC) were used to assess the predictive capability. RESULTS: Pathological examination confirmed MVI in 64 (28.9%), 22 (23.4%), and 16 (16.0%) of the 221, 94, and 100 patients, respectively. AFP, tumor size, non-smooth tumor margin, incomplete capsule, and peritumoral hypointensity in hepatobiliary phase (HBP) images had poor diagnostic value for MVI of sHCC. Quantitative radiomic features (1409) of MRI scans) were extracted. The classifier of logistic regression (LR) was the best machine learning method, and the radiomics scores of HBP and DWI had great diagnostic efficiency for the prediction of MVI in both the testing set (hospital A) and validation set (hospital B, C). The AUC of HBP was 0.979, 0.970, and 0.803, respectively, and the AUC of DWI was 0.971, 0.816, and 0.801 (P < 0.05), respectively. Good calibration and discrimination of the radiomics and clinical combined nomogram model were exhibited in the testing and two external validation cohorts (C-index of HBP and DWI were 0.971, 0.912, 0.808, and 0.970, 0.843, 0.869, respectively). The clinical usefulness of the nomogram was further confirmed using decision curve analysis. CONCLUSION: AFP and conventional Gd-EOB-DTPA-enhanced MRI features have poor diagnostic accuracies for MVI in patients with sHCC. Machine learning with an LR classifier yielded the best radiomics score for HBP and DWI. The radiomics nomogram developed as a noninvasive preoperative prediction method showed favorable predictive accuracy for evaluating MVI in sHCC.

Impact of early empirical antifungal therapy on prognosis of sepsis patients with positive yeast culture: A retrospective study from the MIMIC-IV database.

Background: Mortality and other clinical outcomes of culture-negative and culture-positive among patients with fungal sepsis have not been documented, and whether antifungal therapy prior to fungal culture reports is related to decreased mortality among patients remains largely controversial. This study aimed to determine the mortality and other clinical outcomes of patients with positive yeast cultures and further investigate the effects of initial empiric antifungal therapy. Methods: A retrospective study was conducted among septic patients using the Medical Information Mart for Intensive Care (MIMIC)-IV database. Patients with sepsis were divided into two groups based on first fungal culture status during intensive care unit (ICU) stay, and initial empirical antifungal therapy was prescribed based on physician's experience prior to fungal culture reports within 48 h. The primary outcome was in-hospital all-cause mortality. The secondary outcomes were 30-day all-cause mortality, 60-day all-cause mortality, length of ICU stay and length of hospital stay. Multivariate logistic regression, propensity score matching (PSM), subgroup analyses and survival curve analyses were performed. Results: This study included 18,496 sepsis patients, of whom 3,477 (18.8%) had positive yeast cultures. Patients with positive yeast cultures had higher in-hospital all-cause mortality, 60-day all-cause mortality, and longer lengths of ICU stay and hospital stay than those with negative yeast cultures after PSM (all p < 0.01). Multivariate logistic regression analysis revealed that positive yeast culture was a risk factor for in-hospital mortality in the extended model. Subgroup analyses showed that the results were robust among the respiratory infection, urinary tract infection, gram-positive bacterial infection and bacteria-free culture subgroups. Interestingly, empiric antifungal therapy was not associated with lower in-hospital mortality among patients with positive yeast cultures, mainly manifested in stratification analysis, which showed that antifungal treatment did not improve outcomes in the bloodstream infection (odds ratio, OR 2.12, 95% CI: 1.16-3.91, p = 0.015) or urinary tract infection groups (OR 3.24, 95% CI: 1.48-7.11, p = 0.003). Conclusion: Culture positivity for yeast among sepsis patients was associated with worse clinical outcomes, and empiric antifungal therapy did not lower in-hospital all-cause mortality in the bloodstream infection or urinary tract infection groups in the ICU.

Gut microbiota-derived indole 3-propionic acid partially activates aryl hydrocarbon receptor to promote macrophage phagocytosis and attenuate septic injury.

Sepsis is associated with a high risk of death, and the crosstalk between gut microbiota and sepsis is gradually revealed. Indole 3-propionic acid (IPA) is a gut microbiota-derived metabolite that exerts immune regulation and organ protective effects. However, the role of IPA in sepsis is not clear. In this study, the role of IPA in sepsis-related survival, clinical scores, bacterial burden, and organ injury was assessed in a murine model of cecal ligation and puncture-induced polymicrobial sepsis. Aryl hydrocarbon receptor (AhR) highly specific inhibitor (CH223191) was used to observe the role of AhR in the protection of IPA against sepsis. The effects of IPA on bacterial phagocytosis by macrophages were investigated in vivo and vitro. The levels of IPA in feces were measured and analyzed in human sepsis patients and patient controls. First, we found that gut microbiota-derived IPA was associated with the survival of septic mice. Then, in animal model, IPA administration protected against sepsis-related mortality and alleviated sepsis-induced bacterial burden and organ injury, which was blunted by AhR inhibitor. Next, in vivo and vitro, IPA enhanced the macrophage phagocytosis through AhR. Depletion of macrophages reversed the protective effects of IPA on sepsis. Finally, on the day of ICU admission (day 0), septic patients had significantly lower IPA level in feces than patient controls. Also, septic patients with bacteremia had significantly lower IPA levels in feces compared with those with non-bacteremia. Furthermore, in septic patients, reduced IPA was associated with worse clinical outcomes, and IPA in feces had similar prediction ability of 28-day mortality with SOFA score, and increased the predictive ability of SOFA score. These findings indicate that gut microbiota-derived IPA can protect against sepsis through host control of infection by promoting macrophages phagocytosis and suggest that IPA may be a new strategy for sepsis treatment.

Radioactive 125I seed implantation for pancreatic cancer with unexpected liver metastasis: A preliminary experience with 26 patients.

BACKGROUND: Preoperative diagnosis rate of pancreatic cancer has increased year by year. The prognosis of pancreatic cancer patients with unexpected liver metastasis found by intraoperative exploration is very poor, and there is no effective and unified treatment strategy. AIM: To evaluate the therapeutic effect of radioactive 125I seed implantation for pancreatic cancer patients with unexpected liver metastasis. METHODS: The demographics and perioperative outcomes of patients who underwent 125I seed implantation to treat pancreatic cancer with unexpected liver metastasis between January 1, 2017 and June 1, 2019 were retrospectively analyzed. During the operation, 125I seeds were implanted into the pancreatic tumor under the guidance of intraoperative ultrasound, with a spacing of 1.5 cm and a row spacing of 1.5 cm. For patients with obstructive jaundice and digestive tract obstruction, choledochojejunostomy and gastroenterostomy were performed simultaneously. After operation, the patients were divided into a non-chemotherapy group and a chemotherapy group that received gemcitabine combined with albumin-bound paclitaxel treatment. RESULTS: Preoperative imaging evaluation of all patients in this study showed that the tumor was resectable without liver metastasis. There were 26 patients in this study, including 18 males and 8 females, aged 60.5 ± 9.7 years. The most common tumor site was the pancreatic head (17, 65.4%), followed by the pancreatic neck and body (6, 23.2%) and pancreatic tail (3, 11.4%). Fourteen patients (53.8%) underwent palliative surgery and postoperative pain relief occurred in 22 patients (84.6%). The estimated blood loss in operation was 148.3 ± 282.1 mL and one patient received blood transfusion. The postoperative hospital stay was 7.6 ± 2.8 d. One patient had biliary fistula, one had pancreatic fistula, and all recovered after conservative treatment. After operation, 7 patients received chemotherapy and 19 did not. The 1-year survival rate was significantly higher in patients who received chemotherapy than in those who did not (68.6% vs 15.8%, P = 0.012). The mean overall survival of patients in the chemotherapy group and non-chemotherapy group was 16.3 mo and 10 mo, respectively (χ 2 = 7.083, P = 0.008). CONCLUSION: Radioactive 125I seed implantation combined with postoperative chemotherapy can prolong the survival time and relieve pain of pancreatic cancer patients with unexpected liver metastasis.

Robotic resection of duodenal gastrointestinal stromal tumour: Preliminary experience from a single centre.

BACKGROUND: Experience in minimally invasive surgery in the treatment of duodenal gastrointestinal stromal tumors (DGISTs) is accumulating, but there is no consensus on the choice of surgical method. AIM: To summarize the technique and feasibility of robotic resection of DGISTs. METHODS: The perioperative and demographic outcomes of a consecutive series of patients who underwent robotic resection and open resection of DGISTs between May 1, 2010 and May 1, 2020 were retrospectively analyzed. The patients were divided into the open surgery group and the robotic surgery group. Pancreatoduodenectomy (PD) or limited resection was performed based on the location of the tumour and the distance between the tumour and duodenal papilla. Age, sex, tumour location, tumour size, operation time (OT), estimated blood loss (EBL), postoperative hospital stay (PHS), tumour mitosis, postoperative risk classification, postoperative recurrence and recurrence-free survival were compared between the two groups. RESULTS: Of the 28 patients included, 19 were male and 9 were female aged 51.3 ± 13.1 years. Limited resection was performed in 17 patients, and PD was performed in 11 patients. Eleven patients underwent open surgery, and 17 patients underwent robotic surgery. Two patients in the robotic surgery group underwent conversion to open surgery. All the tumours were R0 resected, and there was no significant difference in age, sex, tumour size, operation mode, PHS, tumour mitosis, incidence of postoperative complications, risk classification, postoperative targeted drug therapy or postoperative recurrence between the two groups (P > 0.05). OT and EBL in the robotic group were significantly different to those in the open surgery group (P < 0.05). All the patients survived during the follow-up period, and 4 patients had recurrence and metastasis. No significant difference in recurrence-free survival was noted between the open surgery group and the robotic surgery group (P > 0.05). CONCLUSION: Robotic resection is safe and feasible for patients with DGISTs, and its therapeutic effect is equivalent to open surgery.

Clinical Characteristics and Risk Factors for Critically Ill Patients with Carbapenem-Resistant Klebsiella pneumonia e (CrKP): A Cohort Study from Developing Country.

BACKGROUND: Increasing evidence indicates carbapenem-resistant Klebsiella pneumoniae (CrKP) is increasingly prevalent in intensive care unit (ICU), but its clinical characteristics and risk factors remain unknown. AIM: The aim of the present study was to evaluate clinical characteristics, risk factors in critically ill patients with CrKP infection. METHODS: A retrospective study was included in patients from January 2013 to October 2019. Clinical data were collected from CrKP patients on the day of specimen collection admitted to ICU. Multivariable logistic regression was used for risk factors. Receiver operating curve (ROC) and the area under the curve (AUC) with DeLong method of MedCalc software were used. Two-way repeated-measures ANOVA analysis was used to analyze the characteristics of independent risk factors over time. FINDINGS: A total of 147 adult patients with CrKP were screened, among them, 89 (median age 64.0 years, 66 (74.15%) males) patients with CrKP were finally included, of which 38 patients (42.7%) were non-survival group. Multivariate logistic regression analysis indicated that lactic acid (OR3.04 95% CI 1.38-6.68, P = 0.006), APACHE II score (OR 1.20, 95% CI 1.09-1.33, P < 0.001), tigecycline combined with fosfomycin treatment (OR0.15, 95% CI 0.04-0.65, P = 0.011) are independent risk factors for 28-day mortality in patients with CRKP infection (P<0.05). Combined lactic acid with APACHE II score could predict 28-day mortality, of which AUC value was 0.916 (95% CI, 0.847-0.985), with sensitivity 0.76 and specificity 0.98. ANOVA analysis showed that APACHE II score and lactic acid between the two groups at three-time points were statistically significant, which interactive with time and showed an upward and downward trend with time (P < 0.05). CONCLUSION: Therapeutic strategy based on improving lactic acid and APACHE II would contribute to the outcome in patients with CrKP infection. Tigecycline combined with fosfomycin could reduce the 28-day mortality in patients with CrKP infection in developing country.

Perineural invasion of hilar cholangiocarcinoma in Chinese population: One center's experience.

BACKGROUND: Hilar cholangiocarcinoma (HCCA) often produces perineural invasion (PNI) extending to extra-biliary sites, while significant confusion in the incidence of PNI in HCCA has occurred in the literature, and the mechanism of that procedure remains unclear. AIM: To summarize the incidence of PNI in HCCA and to provide the distribution of nerve plexuses around hepatic portal to clinical surgeons. METHODS: Reported series with PNI in HCCA since 1996 were reviewed. A clinicopathological study was conducted on sections from 75 patients with HCCA to summarize the incidence and modes of PNI. Immunohistochemical stains for CD34 and D2-40 in the cancer tissue were performed to clarify the association of PNI with microvessel and lymph duct. Sections of the hepatoduodenal ligament from autopsy cases were scanned and handled by computer to display the distribution of nerve plexuses around the hepatic portal. RESULTS: The overall incidence of PNI in this study was 92% (69 of 75 patients), while the rate of PNI in HCCA in the literature ranging from 38% to 100%. The incidence of PNI did not show any remarkable differences among various differentiated groups and Bismuth-Corlette classification groups. Logistic regression analysis identified the depth of tumor invasion was the only factor that correlated significantly with PNI (P < 0.01). In spite of finding tumor cells that could invade microvessels and lymph ducts in HCCA, we did not find tumor cells invaded nerves via microvessels or lymph ducts. Three nerve plexuses in the hepatoduodenal ligament and Glisson's sheath were classified, and they all surrounded the great vessels very closely. CONCLUSION: The incidence of PNI of HCCA in Chinese population is around 92% and correlated significantly with a depth of tumor invasion. It also should be considered when stratifying HCCA patients for further treatment.