Clinical manifestations and early effectiveness of methimazole in patients with graves' hyperthyroidism-related severe hepatic dysfunction.

BACKGROUND: Graves' hyperthyroidism (GH) is often accompanied by mild to moderate liver injury, but severe hepatic dysfunction (SHD) is relatively rare. Whether patients with GH-related SHD can be treated with methimazole (MMI) remains controversial. This study aimed to determine the clinical characteristics and to evaluate the role of low-dose MMI for such patients. METHODS: 33 patients with GH-related SHD were selected for this retrospective study in the Fifth Medical Center of Chinese PLA General Hospital from January 2017 to July 2022. The clinical manifestations, therapeutic responses, and effectiveness of MMI were evaluated. RESULTS: Systemic jaundice (100.0%), yellow urine (100.0%), fatigue (87.9%), and goiter (66.7%) were the main symptoms. Total bilirubin (TBIL) had no linear correlation with free triiodothyronine (FT3) (r = -0.023, p = .899), free thyroxine (FT4) (r = 0.111, p = .540), T3 (r = -0.144, p = .425), and T4 (r = 0.037, p = .837). On the 14th day after admission, FT3, FT4, T3, T4, TBIL, direct bilirubin (DBIL), alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), γ-glutamyltransferase (GGT), and international normalized ratio (INR) decreased compared with the baseline (p < .05). The decrease rates of FT3, FT4, T3, T4, TBIL, and DBIL in the MMI group were higher than those in the non-MMI group (p < .05). The improvement rate of the MMI group (77.8%) was higher than that of the non-MMI group (9.5%, p = .001). MMI treatment is an independent predictor affecting the early improvement of patients (OR = 0.022, p = .010). CONCLUSIONS: The main clinical manifestations of patients with GH-related SHD were symptoms related to liver disease. Low-dose MMI was safe and effective for them.

The diagnostic performance of ultrasound computer-aided diagnosis system for distinguishing breast masses: a prospective multicenter study.

OBJECTIVES: To evaluate the diagnostic value of computer-aided diagnosis (CAD) software on ultrasound in distinguishing benign and malignant breast masses and avoiding unnecessary biopsy. METHODS: This prospective, multicenter study included patients who were scheduled for pathological diagnosis of breast masses between April 2019 and November 2020. Ultrasound images, videos, CAD analysis, and BI-RADS were obtained. The AUC, accuracy, sensitivity, specificity, PPV, and NPV were calculated and compared with radiologists. RESULTS: Overall, 901 breast masses in 901 patients were enrolled in this study. The accuracy, sensitivity, specificity, PPV and NPV of CAD software were 89.6%, 94.2%, 87.0%, 80.4%, and 96.3, respectively, in the long-axis section; 89.0%, 91.4%, 87.7%, 80.8%, and 94.7%, respectively, in the short-axis section. With BI-RADS 4a as the cut-off value, CAD software has a higher AUC (0.906 vs 0.734 vs 0.696, all p < 0.001) than both experienced and less experienced radiologists. With BI-RADS 4b as the cut-off value, CAD software showed better AUC than less experienced radiologists (0.906 vs 0.874, p < 0.001), but not superior to experienced radiologists (0.906 vs 0.883, p = 0.057). After the application of CAD software, the unnecessary biopsy rate of BI-RADS categories 4 and 5 was significantly decreased (33.0% vs 11.9%, 37.8% vs 14.5%), and the malignant rate of biopsy in category 4a was significantly increased (11.6% vs 40.7%, 7.4% vs 34.9%, all p < 0.001). CONCLUSIONS: CAD software on ultrasound can be used as an effective auxiliary diagnostic tool for differential diagnosis of benign and malignant breast masses and reducing unnecessary biopsy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT03887598) KEY POINTS: • Prospective multicenter study showed that computer-aided diagnosis software provides greater diagnostic confidence for differentiating benign and malignant breast masses. • Computer-aided diagnosis software can help radiologists reduce unnecessary biopsy. • The management of patients with breast masses becomes more appropriate.

[Mean microvessel density of the prepuce and its relationship with the severity of hypospadias and early postoperative complications].

OBJECTIVE: To investigate the mean preputial microvessel density (mMVD) and features of hypospadias and their relationship with the severity and early postoperative complications of the disease. METHODS: Sixty children with hypospadias and another 14 age-matching ones with phimosis (the control group) underwent penile curvature correction, Snodgrass procedure or staged surgery, the excessive dorsal foreskin trimmed and retained. We determined the mMVD in the prepuce tissue of the patients by immunohistochemistry, and followed up those treated by Snodgrass procedure. RESULTS: The mMVD was significantly lower in the patients with severe hypospadias than in those with mild hypospadias and the controls (15.51 ± 3.53 vs 19.27 ± 4.42 and 22.09 ± 6.15, P < 0.05), with a median of 21.8 in the control group. The incidence of postoperative complications was obviously lower in the high mMVD (≥ 21.8) than in the low mMVD (< 21.8) group. CONCLUSIONS: The preputial mMVD is significantly lower in patients with severe hypospadias than in normal children, decreasing in a severity-dependent manner. The lower the preputial mMVD, the higher the incidence rate of postoperative complications. The preputial mMVD of 21.8 can be used as a reference index for evaluating the prognosis of surgery clinically. ?

Infection deteriorating hepatitis B virus related acute-on-chronic liver failure: a retrospective cohort study.

BACKGROUND: Infection is common in acute-on-chronic liver failure (ACLF), which may worsen the clinical condition and prognosis. However, the characteristics of infection and its influence on prognosis in hepatitis B virus related ACLF (HBV-ACLF) as defined by the European Association for the Study of the Liver (EASL) have not been clarified. We aimed to investigate the characteristics of infection and its influence on mortality in patients with HBV-ACLF defined by EASL in China. METHODS: We performed a retrospective cohort study in patients with HBV-ACLF defined by EASL in a single center from January 2015 to December 2017. These patients were divided into two groups with and without infection. The incidence, sites of infection, isolated strains, and risk factors associated with mortality were evaluated. RESULTS: A total of 289 patients were included, among them 185 (64.0%) were diagnosed with an infection. The most common type of infection was pneumonia (55.7%), followed by spontaneous bacterial peritonitis (47.6%) and others. The gram-negative bacteria were the most frequent (58.3%). Patients with one, two, and three or more infection sites had a gradually increasing incidence of sepsis (P < 0.01), septic shock (P < 0.001), and ACLF-3 (P < 0.05). Also, patients with infection isolated one, two, and three or more strains showed a growing incidence of sepsis (P < 0.01) and septic shock (P < 0.001). Patients with infection showed a significantly higher 28-day mortality than those without (P < 0.01), especially in patients with ACLF-3. Infection was identified as an independent risk factor for 28-day mortality in all HBV-ACLF patients. Pneumonia and sepsis were identified as independent predictors of 28-day mortality for patients with infection. CONCLUSIONS: Infection is associated with severe clinical course and high mortality in HBV-ACLF defined by EASL. The increased number of infection sites or isolated strains was associated with the occurrence of sepsis and septic shock. Pneumonia and sepsis were independent predictors for mortality in HBV-ACLF patients with infection.

Differential characteristics and prognosis of patients with hepatitis B virus-related acute-on-chronic liver failure defined by European Association for the Study of the Liver - Chronic Liver Failure criteria.

AIM: To determine the differential characteristics and prognosis of patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) detected using Asian Pacific Association for the Study of the Liver (APASL) criteria and then classified using European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) criteria. METHODS: We retrospectively reviewed 316 HBV-related APASL ACLF patients treated at Beijing 302 Hospital or Beijing You'An Hospital (both Beijing, China) between February 2015 and February 2016. Clinical characteristics and mortality rates were compared among patients with different EASL-CLIF ACLF severity grades (no ACLF, and ACLF grades 1-3). RESULTS: According to the EASL-CLIF criteria, 138 patients had no ACLF, 123 had ACLF at enrollment, and 55 developed ACLF during hospitalization. Both 28-day and 90-day transplant-free mortality were dramatically lower in patients without EASL-CLIF ACLF (0.7% and 5.1%, respectively) than in patients with EASL-CLIF ACLF (40.7% and 63.2%, respectively; both P < 0.001). Liver failure rates were similar in patients with and without EASL-CLIF ACLF, but extrahepatic organ failure was rare in patients without EASL-CLIF ACLF. Baseline serum creatinine, new bacterial infection and new acute kidney injury during hospitalization, maximum rising rates of CLIF-C ACLF score, and Model for End-stage Liver Disease score were independent predictors of EASL-CLIF ACLF after enrollment. CONCLUSIONS: The EASL-CLIF ACLF classification can accurately prognosticate the short-term mortality of patients with HBV-related APASL ACLF. It can also distinguish distinct clinical characteristics and prognoses in patients with and without EASL-CLIF ACLF.

The correlation between LIN28B gene potentially functional variants and Wilms tumor susceptibility in Chinese children.

BACKGROUND: Wilms tumor (WT) is the most common urologic cancer in children. However, genetic bases underlying WT remain largely unknown. Previous studies indicated that Lin28 homolog B (LIN28B) level is significantly elevated in some WTs. Enforced expression of Lin28b during kidney development could induce WT. Genetic variations in the LIN28B gene may be related to WT susceptibility. METHOD: In this study, we aimed to assess the association between LIN28B gene polymorphisms and WT susceptibility in Chinese children. Four potentially functional polymorphisms in the LIN28B gene (rs314276 C>A, rs221634 A>T, rs221635 T>C and rs9404590 T>G) were genotyped in 145 cases and 531 cancer-free controls, using Taqman method. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the associations. RESULTS: Our results showed that the rs314276 CA genotype was associated with a decreased WT risk (CA vs CC: adjusted OR=0.65, 95% CI=0.43-0.98, P=.042). Moreover, we found that carriers of the 1-3 risk genotypes had a significantly increased WT risk when compared to the non-carriers (adjusted OR=1.51, 95% CI=1.03-2.20, P=.035). The association with risk genotypes was more predominant in children 18 month old or younger and in females. CONCLUSION: In summary, these results indicated that the LIN28B gene rs314276 C>A polymorphism alone and three combined polymorphisms may be able to modify WT susceptibility in Southern Chinese children. Our findings call for further validation in large studies with different ethnicities involved.

Aspafilioside B induces G2/M cell cycle arrest and apoptosis by up-regulating H-Ras and N-Ras via ERK and p38 MAPK signaling pathways in human hepatoma HepG2 cells.

We recently establish that aspafilioside B, a steroidal saponin extracted from Asparagus filicinus, is an active cytotoxic component. However, its antitumor activity is till unknown. In this study, the anticancer effect of aspafilioside B against HCC cells and the underlying mechanisms were investigated. Our results showed that aspafilioside B inhibited the growth and proliferation of HCC cell lines. Further study revealed that aspafilioside B could significantly induce G2 phase cell cycle arrest and apoptosis, accompanying the accumulation of reactive oxygen species (ROS), but blocking ROS generation with N-acetyl-l-cysteine (NAC) could not prevent G2/M arrest and apoptosis. Additionally, treatment with aspafilioside B induced phosphorylation of extracellular signal-regulated kinase (ERK) and p38 MAP kinase. Moreover, both ERK inhibitor PD98059 and p38 inhibitor SB203580 almost abolished the G2/M phase arrest and apoptosis induced by aspafilioside B, and reversed the expression of cell cycle- and apoptosis-related proteins. We also found that aspafilioside B treatment increased both Ras and Raf activation, and transfection of cells with H-Ras and N-Ras shRNA almost attenuated aspafilioside B-induced G2 phase arrest and apoptosis as well as the ERK and p38 activation. Finally, in vivo, aspafilioside B suppressed tumor growth in mouse xenograft models, and the mechanism was the same as in vitro study. Collectively, these findings indicated that aspafilioside B may up-regulate H-Ras and N-Ras, causing c-Raf phosphorylation, and lead to ERK and p38 activation, which consequently induced the G2 phase arrest and apoptosis. This study provides the evidence that aspafilioside B is a promising therapeutic agent against HCC.

Comparison of tubularized incised plate urethroplasty combined with a meatus-based ventral dartos flap or dorsal dartos flap in hypospadias.

PURPOSE: Tubularized incised plate urethroplasty (TIPU) is the preferred surgical option for distal and mid-shaft hypospadias repair. Neourethra dartos flap coverage is routinely used as a protective layer with good results. We modified meatus-based ventral dartos flap (MBVDF) to TIPU by dissecting the proximal mid-ventral dartos attached urethra and leaving the subcutaneous fascia connecting the meatus, and retrospectively compared the outcomes of using MBVDF with single dorsal dartos flap (DDF) on the complication rates of TIPU. METHODS: We present 2 surgeons' experiences with 356 patients with distal and mid-shaft hypospadias between January 2010 and December 2014. Patients were divided into two groups. Group DDF included 185 patients (mean age 29 months) underwent TIPU with DDF rotated laterally covering the suture lines of the neourethra. Group MBVDF included 171 patients (mean age 26 months) underwent TIPU with MBVDF covering the suture lines of the neourethra. Statistical analysis of patient basic information and complications was performed by two independent sample t test and Chi square test or Fisher's exact test. RESULTS: There were no statistical differences in age, type of hypospadias, and follow-up time between the two groups. The mean operative time in the group MBVDF (68.93 ± 8.32 min) was significantly shorter than in the group DDF (73.60 ± 9.06 min). Ventral skin necrosis (2.7%) and penile rotation (3.8%) in group DDF was significantly higher than group MBVDF which did not occur. The differences in other complication rates including fistula rate (2.7 vs 2.9%) between the groups were not statistically significant. CONCLUSION: DDF and MBVDF with TIPU are similarly effective methods for decreasing fistula in hypospadias repair. MBVDF with TIPU may be an easier method and can avoid ventral skin necrosis and penile rotation.

[Relation between serum levels of high mobility group box 1 and hepatitis B virus-related acute-on-chronic liver failure].

OBJECTIVE: To evaluate the levels of high mobility group box 1 protein (HMGB1) in serum of patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF) and investigate its potential relation to the clinical features of these patients. METHODS: Sixty patients with HBV-related ACLF, 30 patients with chronic hepatitis B (CHB), and 24 healthy individuals (controls) were enrolled in the study. Markers of liver function, such as aspartate aminotransferase (AST), were measured by routine biochemical methods. Imaging studies, such as abdominal computed tomography or magnetic resonance imaging, were used for disease staging. Serum levels of HMGB1 were measured by ELISA. Deaths within the 2-month follow-up after serum collection were used for the survival analysis. Patients who developed peritonitis, pneumonia, or other bacterial and fungal infections during the 2-month follow-up after serum collection were classified as the infected group. Pairwise comparisons were carried out by t-test, and multiple comparisons were carried out by analysis of variance. RESULTS: Patients with HBV-related ACLF had significantly higher serum levels of HMGB1 than CHB patients or controls (P = 0.003). Among the patients with HBV-related ACLF, those in the late stage (n = 20) had significantly higher levels of HMGB1 than those in the early stage (n = 20) (P = 0.005). The serum levels of HMGB1 correlated well with AST level in patients with HBV-related ACLF (P = 0.006). In addition, patients with HBV-related ACLF who developed infection or died during follow-up also had significantly higher levels of HMGB1 (P = 0.028 or P = 0.017, respectively). CONCLUSION: Enhanced serum level of HMGB1 is associated with development of HBV-related ACLF in CHB patients. The strong correlation between HMGB1 and AST levels suggest that HMGB1 may be useful as a prognostic marker for development of ACLF.

[Orthogonal design based optimization of a mouse model of acute liver failure induced by D-galactosamine and lipopolysaccharide].

OBJECTIVE: To apply an orthogonal design optimization strategy to a mouse model of acute liver failure induced by D-galactosamine (D-GalN) and lipopolysaccharide (LPS) exposure. METHODS: A four-level orthogonal array design (L16(45)) was constructed to test factors with potential impact on successful establishment of the model (D-GalN and LPS dosages, and dilution rate of the D-GalN/LPS mixture). The mortality rate of mice within 24 hours of D-GalN/LPS administration was determined by the Kaplan-Meier method. The model outcome was verified by changes in serum alanine transferase level, liver histology, and hepatocyte apoptosis. RESULTS: The orthogonal array identified the optimal model technique as intraperitoneal injection of a combination of D-GalN and LPS at dosages of 350 mg/kg and 30 mug/kg, respectively, and using a dilution rate of 3. The dosages tested had no effect on survival. The typical signs of liver failure appeared at 6 hrs after administration of the D-GalN/LPS combination. CONCLUSION: The orthogonal design optimization strategy provided a procedure for establishing a mouse model of acute liver failure induced by D-GalN and LPS that showed appropriate disease outcome and survival, and which will serve to improve future experimental research of acute liver failure.

Melamine-related urinary stones in 195 infants and young children: clinical features within 2 years of follow-up.

OBJECTIVE: To summarize the clinical features and follow-up, the effects of melamine-tainted milk powder (MMP) consumption on kidney and body growth in children who suffered from melamine-related urinary stones (MUS) 2 years earlier were checked. MEASUREMENTS: Body height and weight, kidney and bladder morphology monitored by ultrasound, urinalysis and renal function were recorded. Plain abdominal radiography was performed for differential diagnosis. The first follow-up was carried out at 15 months and the second 2 years later for patients who showed any abnormality at the first follow-up. Two hundred age- and gender-matched cohorts were included. RESULTS: All cases received conservative treatment in hospital. Fifteen months of follow-up was successfully carried out in 167 cases. 91 children had residual MUS at the time of discharge, 58 MUS disappeared completely, 25 dissolved partially, 1 increased in size, and 7 did not change. At 2 years of follow-up, the residual stones all disappeared except for 1 case; the patient who showed a delayed development with regard to height caught up at 24 months of follow-up. CONCLUSIONS: Conservative treatment shows a high effectiveness in cases with residual MUS. Consumption of MMP with timely treatment did not demonstrate an evident impact on kidney and bladder although body height is slightly affected in a few cases.

[Comparison of MELD-Na versus MELDNa in the prediction of short-term prognosis for acute-on-chronic hepatitis B liver failure].

OBJECTIVE: To evaluate the short-term prognostic values for the model of end-stage liver disease-sodium (MELD-Na), end-stage liver disease sodium (MELDNa) and their dynamic changes in patients with acute-on-chronic hepatitis B liver failure (ACLF-HBV). METHODS: A total of 172 patients diagnosed with ACLF-HBV, admitted between January 2007 to February 2009 and hospitalized for over 2 weeks, were retrospectively recruited. The predictive accuracy of MELD-Na, MELDNa and their dynamic change (Δ) was compared by the method of the area under the receiver operating characteristic curve. RESULTS: The 3-month mortality rate was 43.6%. The largest concordance (c) statistic predicting 3-month mortality was MELDNa score after a 2-week treatment (0.790), followed by MELD-Na (0.728) score, ΔMELDNa (0.713) and ΔMELD-Na (0.646). The average MELD-Na, MELDNa scores after a 2-week treatment and ΔMELD-Na, ΔMELDNa of survival group were 27.7 ± 8.9, 25.9 ± 5.0, -2.1 ± 10.0 and -1.9 ± 4.2 while those of dead group 34.6 ± 8.7, 31.5 ± 5.0, 2.4 ± 10.3 and 2.4 ± 10.3. There was significant difference in MELD-Na, MELDNa, ΔMELD-Na and ΔMELDNa between two groups. The 3-month mortality of the MELD-Na scores group < 25, 25 - 30, 30 - 35 and > 35 were 18.9%, 37.8%, 57.6% and 65.3% while the MELDNa scores group 14.6%, 33.3%, 72.5% and 84.2% respectively. There was significant difference in the 3-month mortality between four groups. The 3-month mortality of the ΔMELD-Na > 0 group was 58.5% while that of the ΔMELD-Na ≤ 0 group 30%; the 3-month mortality of the ΔMELDNa > 0 group was 61.3% while that of the ΔMELDNa ≤ 0 group 29.9%. There was significant difference between two groups. CONCLUSION: MELDNa score after a 2-week treatment is a promising and useful predictor for 3-month mortality in ACLF-HBV patients. The predictive value may further improve if in conjunctions with dynamic changes.

The periscreen strip is an accurate and rapid method to diagnose spontaneous bacterial peritonitis among patients with acute-on-chronic liver failure.

BACKGROUND: Leukocyte esterase reagent strips may help diagnose spontaneous bacterial peritonitis (SBP), but their effective application among patients with acute-on-chronic liver failure (ACLF) remains unknown. AIM: This study aimed to assess the performance of periscreen strips in the rapid diagnosis of SBP among patients with ACLF. METHODS: Periscreen strips were used to test 261 ascites samples taken from 251 inpatients with ACLF between January 2014 and June 2019. The colors of the reagent strip were divided into four colorimetric graduations ('negative', 'trace', 'small', and 'large'), among which 'trace' is used as the SBP detection threshold. The polymorphonuclear neutrophils (PMN) of ascites ≥250/mm3 was used as the gold standard for SBP diagnosis. RESULTS: SBP was detected in 92 (35.2%) ascite samples. The ascites PMN count of 'negative' (32.5/mm3) was lower than those of 'trace' (248.2/mm3), 'small' (379.0/mm3), and 'large' (7426.0/mm3) (P < 0.001). The colorimetric graduations of the strips were positively correlated with ascites PMN count (r = 0.867, P < 0.001). Periscreen strips had 100% sensitivity, 91.1% specificity, 86.0% positive predictive value, 100% negative predictive value, 11.3 positive likelihood ratios, and 0 negative likelihood ratios. For patients with negative results judged by the gold standard, ascites white blood cells count [odds ratio (OR) = 1.007) and ascites PMN count (OR = 1.028) were independent predictors of false-positive cases. CONCLUSION: Liver failure did not affect the diagnostic performance of periscreen strips. Therefore, these strips can efficiently and rapidly diagnose SBP among patients with ACLF.

Substance P restores spermatogenesis in busulfan-treated mice: A new strategy for male infertility therapy.

Male infertility has become an important health problem that is primarily caused by testicular dysfunction with abnormal spermatogenesis. In this study, we demonstrated that the neuropeptide, substance P (SP), is essential for spermatogonia proliferation in a seminiferous tubule culture system. In addition, SP (5 nmol/kg) treatment markedly restored spermatogenesis, improved sperm quality, and increased the number of ZBTB16+ or LIN28+ undifferentiated spermatogonia as well as STRA8+ differentiated spermatogonia in a busulfan-induced non-obstructive azoospermic mouse model. Furthermore, 100 nM SP treatment in vitro significantly stimulated the proliferation of GC-1 spg cells (a spermatogonia cell line) via activation of the Erk1/2 signaling pathway. Moreover, the sperm quality and the number of spermatogonia were significantly reduced after treatment with RP67580, a selective NK-1 receptor antagonist, suggesting that SP-NK1R signaling plays an important role in spermatogenesis. Taken together, these results suggest that SP may be a potential therapeutic agent for male infertility by accelerating the restoration of spermatogenesis.

Assessment of different modalities for repeated tissue acquisition in diagnosing malignant biliary strictures: A two-center retrospective study.

OBJECTIVE: Various modalities are applied for pathological diagnosis of malignant biliary strictures (MBS), including brush cytology (BC), forceps biopsy (FB) and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA). We aimed to assess the value of these modalities in a repeated tissue acquisition process for biliary strictures with initially inconclusive pathological outcomes. METHODS: Patients who were suspected of having MBS and underwent a BC in two large teaching hospitals were retrospectively included. The sensitivity, specificity, positive and negative predictive values, and accuracy of the initial and repeated BC, FB and EUS-FNA were analyzed. Their performances were compared to determine which modality was superior in repeated tissue acquisition. RESULTS: In total, 476 patients were included. The sensitivity, specificity and accuracy in diagnosing MBS for the initial BC were 30.3%, 100% and 55.0%, respectively. Altogether 39, 27 and 44 patients underwent a repeat BC, FB and EUS-FNA, respectively. The sensitivity for repeated BC, FB and EUS-FNA was 41.2%, 61.1% and 44.4%, respectively, whereas their specificity all reached 100%. When comparing diagnostic accuracy, none of the modalities was superior (74.4% vs 74.1% vs 54.5%, P = 0.173). In the repeated process, one patient who underwent BC and two underwent FB developed mild pancreatitis. CONCLUSIONS: Repeated tissue acquisition achieves a conclusive diagnosis of MBS in nearly half patients who have an initially inconclusive cytological diagnosis. None of the tissue acquisition methods is significantly superior in the repeated process.

The pharmacodynamic effect of terlipressin versus high-dose octreotide in reducing hepatic venous pressure gradient: a randomized controlled trial.

BACKGROUND: Vasoactive drugs can reduce portal venous pressure and control variceal bleeding. However, few studies have explored the hemodynamic effects of terlipressin and high-dose octreotide in such patients. Our purpose was to evaluate the hemodynamic changes and safety of using terlipressin and high-dose octreotide in patients with decompensated liver cirrhosis. METHODS: A multi-center randomized controlled trial was conducted. Cirrhotic patients with a history of variceal bleeding were included. Terlipressin or high-dose octreotide was administered during the procedure of measuring hepatic venous pressure gradient (HVPG). Hemodynamic parameters and symptoms were recorded. RESULTS: A total of 88 patients were included. HVPG was significantly reduced at 10, 20, and 30 min after drug administration in the terlipressin group (16.3±6.4 vs. 14.7±5.9, 14.0±6.1, and 13.8±6.1, respectively, P<0.001) and the high-dose octreotide group (17.4±6.6 vs. 15.1±5.8, 15.3±6.2, and 16.1±6.0, respectively P<0.01). Decreased heart rate and increased mean arterial pressure were more often observed in the terlipressin group. The overall response rates were not significantly different between the groups (52.8% vs. 44.8%, P=0.524). The terlipressin group had significantly higher response rates at 30 min compared to the high-dose octreotide group in those with alcoholic liver cirrhosis [6/6 (100%) vs. 0/4 (0%), P=0.005]. The incidence of adverse drug events was rare and similar in the two groups. CONCLUSIONS: Both terlipressin and high-dose octreotide were effective and safe for reducing HVPG. The pharmacodynamic effect of terlipressin persisted longer. The terlipressin group had higher response rates in those with alcoholic cirrhosis (trial number: NCT02119884).

Mesenchymal stem cell therapy in decompensated liver cirrhosis: a long-term follow-up analysis of the randomized controlled clinical trial.

BACKGROUND: Mesenchymal stem cell (MSC) infusion was reported to improve liver function in patients with decompensated liver cirrhosis (DLC); however, whether the medication can improve outcome of these patients is poorly understood. METHODS: This prospective, open-labeled, randomized controlled study enrolled 219 patients with HBV-related DLC who were divided into control group (n = 111) and umbilical cord-derived MSC (UC-MSC)-treated group (n = 108), then all of them received a follow-up check from October 2010 to October 2017. The treated patients received three times of UC-MSC infusions at 4-week intervals plus conventional treatment that was only used for control group. The overall survival rate and HCC-free survival rate were calculated as primary endpoints and the liver function and adverse events associated with the medication were also evaluated. RESULTS: During the follow-up check period from 13 to 75th months, there was a significantly higher overall survival rate in the treated group than the control group, while the difference of the hepatocellular carcinoma event-free survival rate between the treated and control groups was not observed during the 75-month follow-up. UC-MSC treatment markedly improved liver function, as indicated by the levels of serum albumin, prothrombin activity, cholinesterase, and total bilirubin during 48 weeks of follow-up. No significant side effects or treatment-related complications were observed in the UC-MSC group. CONCLUSIONS: Therapy of UC-MSC is not only well tolerated, but also significantly improves long-term survival rate, as well as the liver function in patients with HBV-related DLC. UC-MSC medication, therefore, might present a novel therapeutic approach for the disease.

Added Value of a New Strain Elastography Technique in Conventional Ultrasound for the Diagnosis of Breast Masses: A Prospective Multicenter Study.

OBJECTIVE: This study aimed to explore the value of elasticity score (ES) and strain ratio (SR) combined with conventional ultrasound in distinguishing benign and malignant breast masses and reducing biopsy of BI-RADS (Breast Imaging Reporting and Data System) 4a lesions. METHODS: This prospective, multicenter study included 910 patients from nine different hospitals. The acquisition and analysis of conventional ultrasound and strain elastography (SE) were obtained by radiologists with more than 5 years of experience in breast ultrasound imaging. The diagnostic sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under curve (AUC) of conventional ultrasound alone and combined tests with ES and/or SR were calculated and compared. RESULTS: The optimal cutoff value of SR for differentiating benign from malignant masses was 2.27, with a sensitivity of 60.2% and a specificity of 84.8%. When combined with ES and SR, the AUC of the new BI-RADS classification increased from 0.733 to 0.824 (p < 0.001); the specificity increased from 48.1% to 68.5% (p < 0.001) without a decrease in the sensitivity (98.5% vs. 96.4%, p = 0.065); and the PPV increased from 52.2% to 63.7% (p < 0.001) without a loss in the NPV (98.2% vs. 97.1%, p = 0.327). All three combinations of conventional ultrasound, ES, and SR could reduce the biopsy rate of category 4a lesions without reducing the malignant rate of biopsy (from 100% to 68.3%, 34.9%, and 50.4%, respectively, all p < 0.001). CONCLUSIONS: SE can be used as a useful and non-invasive additional method to improve the diagnostic performance of conventional ultrasound by increasing AUC and specificity and reducing the unnecessary biopsy of BI-RADS 4a lesions.

[Clinical features and prognostic analysis of 51 drug-induced case of liver failure].

OBJECTIVE: To enhance the understanding of drug-induced liver failure by analyzing the etiology, clinical features and prognosis associated factors of patients with drug-induced liver failure. METHODS: Fifty-one cases of drug-induced liver failure admitted to our hospital from 2002 - 2007 were reviewed according to their drug history, clinical features, Laboratory tests, complications and prognosis associated factors. RESULTS: The predominant etiological drugs were the traditional Chinese medicine (54.9%) and antitubercular agent (25.5%). Two predominant types of liver failure were acute liver failure (13.7%) and subacute liver failure (78.4%). The common complications were electrolyte disturbance, ascites and hepatic encephalopathy. The total improvement rate in patients was 29.4%. The incidences of hepatic encephalopathy, electrolyte disturbance and PTA value had statistical difference between improvement group and ineffective group. CONCLUSION: The etiologies of drugs-induced liver failure are traditional Chinese medicine and antitubercular agent in China. The prognosis of drug-induced liver failure remains poor. During the therapy of these drugs treatment, liver function test should be monitored.

[The short-term efficacy of nucleoside analogue on the treatment of acute-on-chronic liver failure].

OBJECTIVE: To discuss the short-term efficacy of nucleoside analogue on the treatment of hepatitis B virus induced acute-on-chronic liver failure (HBV-ACLF). METHODS: 348 patients with HBV-ACLF in our hospital from January 2006 to June 2008 were selected. According to the stages of patient's condition and whether or not with nucleoside analogue administration, The patients were divided into early stage therapy group, early stage control group, middle stage therapy group and middle stage control group. Groups were compared on the basis of stages. The clinical data were analyzed using chisquare test and independent-Samples T Test. RESULTS: After 2 weeks of therapy no significant difference found between the therapy group and the control group. the total bilirubin (TBil) and alanine transaminase (ALT) showed no significant difference between the middle stage therapy group and the control group in 4 weeks of therapy. However significant differences existed in the HBV DNA negative rate, PTA, the model for end-stage liver disease (MELD) score and the improvement rate between the two groups (P<0.05, P<0.01). Only the 4 week survival rate and HBV DNA negative rate showed significant difference in patients who received anti-virus therapy on the early stage as compared to the control group. CONCLUSION: Anti-virus therapy with nucleoside analogue is an effective way for the treatment of those patients with HBV-ACLF and can increase the survival rate.