Preoperative prediction of microvascular invasion classification in hepatocellular carcinoma based on clinical features and MRI parameters.

Microvascular invasion (MVI) in hepatocellular carcinoma (HCC) is a critical pathological factor and the degree of MVI influences treatment decisions and patient prognosis. The present study aimed to predict the MVI classification based on preoperative MRI features and clinical parameters. The present retrospective cohort study included 150 patients (training cohort, n=108; validation cohort, n=42) with pathologically confirmed HCC. Clinical and imaging characteristics data were collected from Shengli Oilfield Central Hospital (Dongying, China). Univariate and multivariate logistic regression analyses were conducted to assess the association of clinical variables and MRI parameters with MVI (grade M1 and M2) and the M2 classification. Nomograms were developed based on the predictive factors of MVI and the M2 classification. The discrimination capability, calibration and clinical usefulness of the nomograms were evaluated. Multivariate analysis revealed an association between the Lens culinaris agglutinin-reactive fraction of α-fetoprotein, protein induced by vitamin K absence-II and tumor margin and MVI-positive status, while peritumoral enhancement and tumor size were demonstrated to be marginal predictors, but were also included in the nomogram. However, among MVI-positive patients, only peritumoral hypointensity and tumor size were demonstrated to be risk factors for the M2 classification. The nomograms, incorporating these variables, exhibited a strong ability to discriminate between MVI-positive and MVI-negative patients with HCC in both the training and validation cohort [area under the curve (AUC), 0.877 and 0.914, respectively] and good performance in predicting the M2 classification in the training and validation cohorts (AUC, 0.720 and 0.782, respectively). Nomograms incorporating clinical parameters and preoperative MRI features demonstrated promising potential as straightforward and effective tools for predicting MVI and the M2 classification in patients with HCC. Such predictive tools could aid in the judicious selection of optimal clinical treatments.

Role of the Clinical Features and MRI Parameters on Ki-67 Expression in Hepatocellular Carcinoma Patients: Development of a Predictive Nomogram.

PURPOSE: To develop a nomogram using clinical features and the MRI parameters for preoperatively predicting the expression of Ki-67 in patients with hepatocellular carcinoma (HCC). METHODS: One hundred and forty patients (training cohorts: n = 108; validation cohorts: n = 32) with confirmed HCC were investigated. Mann-Whitney U test, independent sample t-test, and chi-squared test were used to analyze the continuous and categorical variables. Univariate and multivariate logistic regression analyses were performed to examine the clinical variables and parameters from MRI associated with Ki-67 expression. As a result, a nomogram was developed based on these associations in patients with HCC. The performance of the nomogram was evaluated using the area under the receiver operating characteristic curve (AUC) and calibration curves. RESULTS: In the training set, multivariable logistic regression analysis revealed that lens culinaris agglutinin-reactive fraction of alpha-fetoprotein (AFP-L3) levels, protein induced by vitamin K absence or antagonist-II (PIVKA-II) levels, and tumor shape were independent predictors for Ki-67 expression (p < 0.05). These three variables and the apparent diffusion coefficient (ADC) value were used to establish a nomogram, while the ADC value was found to be a marginal significant predictor. The model demonstrated a strong ability to discriminate Ki-67 expression in both the training and validation cohorts (AUC = 0.862, 0.877). CONCLUSION: A non-invasive preoperative prediction method, which incorporates MRI variables and clinical features was developed, and showed effectiveness in evaluating Ki-67 expression in HCC patients.

Risk of Severe COVID-19 in Prevalent Users of Alpha-1 Adrenergic Receptor Antagonists: A National Case-Control Study of Medicare Beneficiaries.

BACKGROUND: Alpha-1 adrenergic receptor antagonists prevent cytokine storm in mouse sepsis models. This led to the hypothesis that alpha-1 blockers may prevent severe coronavirus disease 2019 (COVID-19), which is characterized by hypercytokinemia and progressive respiratory failure. METHODS: We performed an observational case-control study in male Medicare beneficiaries aged 65 years or older, with or without benign prostatic hyperplasia (BPH), and treated with alpha-1 receptor blockers or 5-alpha reductase inhibitors. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were estimated for outcomes of uncomplicated and severe COVID-19 hospitalization (intensive care unit admission, invasive mechanical ventilation, or death). RESULTS: There were 20,963 cases of hospitalized COVID-19 matched to 101,161 controls on calendar date and neighborhood of residence. In the primary analysis (males with BPH), there was no difference in risk of uncomplicated COVID-19 hospitalization (aOR 1.08, 95% CI 0.996-1.17) or hospitalization with severe complications (aOR 0.97, 95% CI 0.88-1.08). In the secondary analysis (males with or without BPH), the corresponding aORs were 1.02 (95% CI, 0.96-1.09) (uncomplicated) and 0.99 (95% CI, 0.91-1.07) (complicated), respectively. Subgroup and sensitivity analyses yielded similar results. Of note, there was no difference in risk of severe COVID-19 hospitalization when comparing non-selective vs selective alpha-1 blocker use (aOR 0.98, 95% CI 0.86-1.10), higher- vs lower-dose alpha-1 blocker use (aOR 0.96, 95% CI 0.86-1.08), or current vs remote alpha-1 blocker use (aOR 1.04, 95% CI 0.91-1.18). CONCLUSIONS: Prevalent use of alpha-1 receptor blockers was not associated with a protective or harmful effect on risk of uncomplicated or severe hospitalized COVID-19.

Pedigree-based study to identify GOLGB1 as a risk gene for bipolar disorder.

Bipolar disorder (BD) is a complex psychiatric disorder with strong heritability. Identification of new BD risk genes will help determine the mechanism underlying disease pathogenesis. In the present study, we carried out whole genome sequencing for a Chinese BD family with three affected members and three unaffected members, and identified multiple candidate causal variations, including a frameshift mutation in the GOLGB1 gene. Since a GOLGB1 missense mutation was also found in another BD pedigree, we carried out functional studies by downregulating Golgb1 expression in the brain of neonatal mice. Golgb1 deficiency had no effect on anxiety, memory, and social behaviors in young adult mice. However, we found that young adult mice with Golgb1 deficiency exhibited elevated locomotor activity and decreased depressive behaviors in the tail suspension test and the sucrose preference test, but increased depressive behaviors in the forced swim test, resembling the dual character of BD patients with both mania and depression. Moreover, Golgb1 downregulation reduced PSD93 levels and Akt phosphorylation in the brain. Together, our results indicate that GOLGB1 is a strong BD risk gene candidate whose deficiency may result in BD phenotypes possibly through affecting PSD93 and PI3K/Akt signaling.

Noninvasive tools based on immune biomarkers for the diagnosis of central nervous system graft-vs-host disease: Two case reports and a review of the literature.

BACKGROUND: Central nervous system graft-vs-host disease (CNS-GVHD) is a rare cause of CNS disorders after allogeneic hematopoietic stem cell transplantation. Currently, establishing a diagnosis of CNS-GVHD is challenging because the diagnostic criteria and diagnostic methods are not well defined and many confounding factors need to be ruled out. CASE SUMMARY: Here, we present two patients with CNS-GVHD. Both patients with a history of acute GVHD or chronic GVHD developed neurological symptoms that could not be explained by other causes, and had abnormal cerebrospinal fluid (CSF) studies as determined by CSF and blood immune biomarker examinations, suggestive of suspected CNS-GVHD. Due to the lack of specific magnetic resonance imaging abnormalities and the rapid clinical deterioration of the patients, we did not attempt to perform a brain biopsy, but prompted the initiation of empirical immunosuppressive therapy. In view of the rapid and favorable response to local and systematic immunosuppressive treatment and the aforementioned neurologic manifestations together with CSF abnormalities and other negative findings, a final diagnosis of CNS-GVHD was made. CONCLUSION: CSF and blood immune biomarker examinations facilitated the diagnosis of CNS-GVHD, which are particularly suitable for patients who are critically ill and require urgent treatment and for those who are unsuitable for invasive diagnostic procedures.

Differentiation between pancreatic metastases from clear cell renal cell carcinoma and pancreatic neuroendocrine tumor using double-echo chemical shift imaging.

PURPOSE: The purpose of the study was to retrospectively analyze whether double-echo gradient-echo (GRE) chemical shift imaging (CSI) can differentiate between pancreatic metastases from clear cell renal cell carcinoma (PM-ccRCC) and pancreatic neuroendocrine tumor (pNET). METHODS: Institutional review board approval and informed consent were waived. CSI, T2WI, DWI, and DCE magnetic resonance imaging (MRI) were performed in patients with PM-ccRCC and pNET. Eleven patients with PM-ccRCC and 24 patients with pNET were enrolled into this retrospective study. The signal intensity was measured in the pancreatic tumor and spleen on in-phase and opposed-phase images. The signal intensity index (SII) and tumor-to-spleen ratio (TSR) in PM-ccRCC and pNET were calculated and compared. Receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic accuracy of SII and TSR in the differentiation between PM-ccRCC and pNET. RESULTS: The SII between PM-ccRCC and pNET (20.3% ± 16.8% vs. - 3.2% ± 11.4%) was significantly different (P < 0.001), as was the TSR (- 19.2% ± 16.6% vs. 6.0% ± 13.8%) (P < 0.001). The area under the ROC curve was 0.917 for the SII and 0.902 for the TSR. Additionally, an SII threshold value of 8.1% permitted the differentiation of PM-ccRCC from pNET with a sensitivity of 90.9%, a specificity of 91.7%, a positive predictive value of 90.1%, a negative predictive value of 91.7%, and an accuracy of 91.4%. A TSR cut-off value of - 4.7% enabled the differentiation of the two groups with a sensitivity of 79.2%, a specificity of 90.9%, a positive predictive value of 90.9%, a negative predictive value of 79.2% and an accuracy of 82.9%. CONCLUSION: Double-echo GRE chemical shift MR imaging can accurately differentiate between PM-ccRCC and pNET.

[A clinical research on renal protective effect of Xuebijing injection in patients with sepsis].

OBJECTIVE: To evaluate the protective effect of Xuebijing injection against renal injury in patients with sepsis, and to explore its possible mechanism. METHODS: A prospective randomized controlled trial (RCT) was conducted in which 62 severe patients with sepsis and septic shock admitted in Department of Critical Care Medicine of Jiangsu Province Traditional Chinese Medicine Hospital from June 2013 to December 2013 were randomly divided into control group and Xuebijing group, with 31 patients in each group. The patients in both groups received basic treatment for sepsis, and the patients in Xuebijing group were additionally given intravenous injection of Xuebijing 100 mL once a day for 7 days. In both groups, the changes in acute physiology and chronic health evaluation II (APACHE II) score were observed before treatment and 1, 3, 7 days after treatment, and the changes in the levels of interleukins (IL-6, IL-10), prothrombin time (PT), fibrinogen (Fib), activated partial thromboplastin time (APTT), serum creatinine (SCr), and Cystain C (Cys C) were determined before treatment and 1 day and 3 days after treatment. RESULTS: There was no statistically significant difference in APACHE II score before treatment between two groups, however, the APACHE II scores were significantly decreased in both groups 3 days and 7 days after treatment compared with those before treatment, and the degree of decrease in Xuebijing group was more obvious 7 days after treatment (13.61±7.62 vs. 16.34±8.70, P < 0.05). Serum concentrations of Cys C, SCr, IL-6, IL-10, PT, APTT, and Fib showed no difference between two groups before treatment (all P > 0.05), while after treatment the degrees of improvement of above indexes in Xuebijing group were obviously superior to those in control group, especially 3 days after treatment[Cys C (mg/L): 1.12±0.11 vs. 1.35±0.14, SCr (µmol/L): 115.0±31.0 vs. 135.0±24.0, IL-6 (ng/L): 54.27±28.79 vs. 73.35±31.01, PT (s): 13.50±0.11 vs. 15.71±0.11, APTT (s): 43.66±0.31 vs. 48.03±0.55, Fib (g/L): 1.91±0.51 vs. 1.51±0.52, P < 0.05 or P < 0.01]. CONCLUSIONS: Xuebijing injection has certain renal protective effect in patients with sepsis, and its mechanism is possibly related to the regulation and improvement of uncontrolled inflammatory response and coagulation function in sepsis.

[Experimental study of the influence of Sini decoction on the inflammatory response and the immune function in septic rats].

OBJECTIVE: To observe the effect of Sini decoction on inflammatory response and immune function in septic rats and to discuss its possible mechanism. METHODS: 66 Sprague-Dawley (SD) rats were randomly divided into normal control group (n=6), model group (n=30), and Sini decoction group (n=30). Septic model was reproduced by intraperitoneal injection of lipopolysaccharide (LPS, 5 mg/kg). After the reproduction of sepsis, rats in Sini decoction group received Sini decoction (5 g/kg) by gavage, while those in model group were given equal dose of normal saline in the same way. Rats in normal control group did not receive any treatment. Blood was collected via eye sockets at 2, 12, 24, 48, 72 hours after LPS administration, then the rats were sacrificed. The concentrations of inflammatory mediators, such as interleukin (IL-1, IL-6, IL-10), tumor necrosis factor-α (TNF-α), and the expression level of monocyte human leukocyte antigen-DR (HLA-DR) were determined with enzyme linked immunosorbent assay (ELISA), and the pathological changes in intestinal mucosa were observed under electron microscope. RESULTS: The concentration of IL-1 at 2 hours in model group was gradually increased and peaked at 48 hours (4.07±0.10 ng/L), and then gradually decreased, while the IL-1 level in Sini decoction group peaked at 12 hours (2.98±0.12 ng/L) followed by a gradual decrease. IL-6 in model and Sini decoction groups peaked twice at 12 hours (91.39±1.55 ng/L, 73.00±2.38 ng/L) and 48 hours (82.51±1.49 ng/L, 64.68±1.68 ng/L) respectively. IL-10 in model group gradually decreased after peaking at 2 hours (86.66±6.12 ng/L), and that in Sini decoction decreased at 12 hours (71.61±2.35 ng/L) followed by an increasing tendency, and approached normal level at 48 hours (109.09±4.77 ng/L vs. 124.01±7.89 ng/L, P>0.05). TNF-α in model group was gradually increased and peaked at 48 hours (83.37±3.79 ng/L), and that in Sini decoction peaked at 12 hours (48.52±1.21 ng/L), and decreased to normal level at 72 hours (18.59±1.97 ng/L vs. 15.50±2.68 ng/L, P>0.05). During the course of the experiment, as compared with those of the model group, level of IL-1, IL-6, and TNF-α were significantly lower at all time points in Sini decoction group, and IL-10 was significantly higher. The expression level of HLA-DR in model and Sini decoction groups peaked at 2 hours (4.86±0.15 µg/L, 4.85±0.17 µg/L), and then gradually lowered. HLA-DR expression at 48 hours and 72 hours in Sini decoction group was significantly lower than that in model group (48 hours: 4.21±0.12 µg/L vs. 2.74±0.16 µg/L, 72 hours: 3.80±0.09 µg/L vs. 2.27±0.12 µg/L, both P<0.01). Pathological study of intestinal mucosa showed that the intestinal mucosa were infiltrated significantly by inflammatory cells, and villi were damaged severely in both model group and Sini decoction group at 2 hours after LPS challenge. Infiltration of inflammatory cells in Sini decoction group was less intense after 12 hours, and the intestine villi repair was more obvious compared with model group. CONCLUSIONS: Sini decoction could regulate systemic inflammatory response, and promote the repair of intestinal mucosa, the intestinal function and the immune status of septic rats.