Mycobacterium tuberculosis sepsis with multiple intermuscular abscesses and respiratory failure as the main manifestations: a case report.

BACKGROUND: Tuberculous sepsis is uncommon in individuals without human immunodeficiency virus (HIV) infection, and some patients may not exhibit clinical signs and symptoms of suspected sepsis upon admission, leading to delayed diagnosis and treatment. CASE PRESENTATION: This report present the case of a 60-year-old female patient who presented with erythema, edema, and pain in her right upper limb accompanied by fever and chills. Further evaluation revealed multiple intermuscular abscesses caused by suspected gram-positive bacteria. Despite receiving anti-infection treatment, the patient rapidly progressed to septic shock and respiratory failure. Metagenomic next-generation sequencing (mNGS) analysis of blood samples detected Mycobacterium tuberculosis complex groups (11 reads). Additionally, mNGS analysis of fluid obtained from puncture of the abscess in the right upper extremity also suggested Mycobacterium tuberculosis complex groups (221 981 reads). Consequently, the patient was diagnosed with tuberculous sepsis resulting from hematogenous dissemination of Mycobacterium tuberculosis. Following the administration of anti-tuberculosis treatment, a gradual recovery was observed during the subsequent follow-up period. CONCLUSION: It is noteworthy that atypical hematogenous disseminated tuberculosis can be prone to misdiagnosis or oversight, potentially leading to septic shock. This case illustrates the importance of early diagnosis and treatment of tuberculosis sepsis. Advanced diagnostic techniques such as mNGS can aid clinicians in the early identification of pathogens for definitive diagnosis.

LHX3 is an advanced-stage prognostic biomarker and metastatic oncogene in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a common cancer and exhibits high morbidity and mortality in the world. We recently identified LHX3 as a preferentially expressed gene with a possible involvement in HCC. OBJECTIVE: To determine the expression, clinical relevance, prognostic significance and functions of LHX3 in HCC. MATERIALS AND METHODS: LHX3 expression was assessed in 190 cancerous and 40 adjacent non-cancerous tissues by PCR, western blot and immunohistochemistry. Associations between LHX3 expression and clinicopathological characteristics of patients were investigated. Correlations between LHX3 expression and overall survival of patients were analyzed by Kaplan-Meier and Cox-regression methods. Functional roles of LHX3 were evaluated by transwell assays. RESULTS: LHX3 expression is significantly increased in carcinoma tissues, and associated with clinical stage and metastasis of patients. LHX3 expression is much higher in the advanced-stage patients than the early-stage patients, and is sharply increased in metastasic patients. High LHX3 expression is associated with unfavorable overall survival, and is an independent prognostic factor of patients. Moreover, LHX3 is an unfavorable and independent prognostic factor unique to advanced-stage patients. Knockdown expression of LHX3 obviously inhibits tumor cell migration and invasion. CONCLUSION: LHX3 is an advanced-stage prognostic biomarker, and acts as a new potential metastatic oncogene in HCC.

Pretreatment microRNA levels can predict HBsAg clearance in CHB patients treated with pegylated interferon α-2a.

BACKGROUND: To investigate the predictive capability of microRNAs (miRNAs) prior treatment for HBsAg clearance in chronic hepatitis B (CHB) treated with pegylated interferon α-2a (PEG-IFNα-2a). METHODS: The treatment effect was determined by HBsAg clearance and subjects were classified into HBsAg clearance group and non HBsAg clearance group. Differential miRNAs expression in peripheral blood mononuclear cells (PBMC) was screened using microarrays in an identification cohort (n = 20) and validated by quantitative reverse-transcription polymerase chain reaction (qRT-PCR) in a confirmation cohort (n = 47). Receiver operating characteristic curve (ROC), logistic regression and gene ontology (GO)/Pathway analyses were used to evaluate the predictive capability of selected miRNAs for HBsAg clearance and determine their mechanistic roles. RESULTS: Twenty-seven subjects (40.3%) acquired HBsAg clearance, ten in the identification cohort and seventeen in the confirmation cohort. Four miRNAs out of twelve (miR-3960, miR-126-3p, miR-335-5p, miR-23a-3p) were verified to be differential expressed by qRT-PCR in the confirmation cohort. Their expression patterns were consistent with the microarray results. Their levels were lower in the response group compared with the nonresponse group (p < 0.05). The areas under curve (AUC) were 0.8333 (p = 0.001), 0.751 (p = 0.01), 0.7294 (p = 0.013), 0.6275 (p = 0.094) and positive predict values (PPV) were 84.62, 60.00, 70.00, 28.57% for miR-3960, miR-126-3p, miR-335-5p, and miR-23a-3p respectively. The AUC and PPV of the combination of miR-3960 and miR-126-3p were 0.8529 and 92.31%, which were better than using miR-3960 alone, but the differences were not statistically significance (p > 0.05). CONCLUSIONS: We identified differential expressed miRNAs between response and nonresponse groups of PEG-IFNα-2a treatment and demonstrated that miR-3960 was the optimal predictor for HBsAg clearance compared with other miRNAs, but it requires to be further comfired in larger cohort studies. TRIAL REGISTRATION: ChiCTR ChiCTR-ROC-16008735, registered retrospectively on 28 June, 2016.

Effect of entecavir on CD4+ T-cell subpopulations in patients with chronic hepatitis B.

UNLABELLED:  Background and aims. CD4+ T cells play an important role in response to hepatitis B virus (HBV) infection. We investigated the change in CD4+ T-cell subpopulations and viral load in patients with chronic HBV infection who were treated with entecavir. MATERIAL AND METHODS: Thirty patients with chronic HBV infection were enrolled according to the criteria recommended by the Chinese Society of Infectious Diseases and the Chinese Society of Hepatology. The expressions of signature transcription factors and cytokines of CD4+ T-cell subpopulations were measured in chronic hepatitis B (CHB) patients treated with entecavir treatment. RESULTS: Entecavir treatment significantly attenuated hepatitis B virus DNA load and affected the CD4+ T-cell subsets in CHB patients. A dramatic decrease in the Th17 and Treg cell frequencies and expressions of their related cytokines were found in CHB patients with entecavir treatment. In contrast, entecavir treatment caused a remarkable increase in the Th2 cell frequencies and expressions of their related cytokines. CONCLUSION: Our results suggested that Th17 and Treg cells were the more sensitive subtypes to entecavir- induced inhibition of HBV replication compared to Th1 and Th2 cells in chronic HBV patients.

The thalamus in cirrhotic patients with and without hepatic encephalopathy: a volumetric MRI study.

BACKGROUND & AIMS: The thalamus is a major relay and filter station in the central neural system. Some previous studies have suggested that the thalamus maybe implicated in the pathogenesis of hepatic encephalopathy. The aim of our study was to investigate changing thalamic volumes in cirrhotic patients with and without hepatic encephalopathy. METHODS: Neuropsychological tests and structural MR scanning were performed on 24 cirrhotic patients, 23 cirrhotic patients with minimal hepatic encephalopathy, 24 cirrhotic patients during their first episode of overt hepatic encephalopathy, and 33 healthy controls. Voxel-based morphometry analysis was performed to detect gray matter morphological changes. The thalamus and whole brain volume were extrapolated. A receiver operating characteristic curve analysis of thalamic volumes was used to discriminate patients with minimal hepatic encephalopathy from those with hepatic cirrhosis. RESULTS: Thalamic volume increased in a stepwise manner in patients with progressively worse stages of hepatic encephalopathy compared to healthy subjects. Additionally, a comparison of gray matter morphometry between patients with Child-Pugh grades A, B, or C and controls revealed a progression in thalamic volumes in parallel with the degree of liver failure. Moreover, thalamic volume was significantly correlated with the number connection test A time and digit-symbol test score in cirrhotic patients with minimal hepatic encephalopathy (r=0.659, P=0.001; r=-0.577, P=0.004; respectively). The area under the receiver operating characteristic curve was 0.827 (P=0.001). CONCLUSIONS: A significantly increased thalamic volume may be provide an objective imaging measure for predicting seizures due to minimal hepatic encephalopathy in cirrhotic patients.

Gamna-Gandy bodies of the spleen detected with susceptibility weighted imaging: maybe a new potential non-invasive marker of esophageal varices.

BACKGROUND/OBJECTIVES: Portal hypertension (PH) is a clinical sequelae of liver cirrhosis, and bleeding from esophageal varices (EV) is a serious complication of PH with significant morbidity and mortality. The aims of this study were to assess the ability of 2D multislice breath-hold susceptibility weighted imaging (SWI) to detect Gamna-Gandy bodies (GGBs) in the spleens of patients with PH and to evaluate the potential role of GGB number as a non-invasive marker of PH and EV. MATERIALS AND METHODS: T1-, T2- and T2(*)-weighted imaging and SWI were performed on 135 patients with PH and on 37 control individuals. Platelet counts were collected from all PH patients. Two radiologists analyzed all magnetic resonance imaging (MRI) data, and measured the portal vein diameter, splenic index (SI), and platelet count/spleen diameter ratio. The numbers of patients with GGBs in the spleen were determined, and the numbers of GGB were counted in the four MRI sequences in GGB-positive patients. The portal vein diameter, SI, platelet count, and platelet count/spleen diameter ratio of control individuals were compared with those of GGB-negative and GGB-positive patients on SWI images. The correlations among GGB numbers, the portal vein diameter, the SI, the platelet count, and the platelet count/spleen diameter ratio were analyzed. RESULTS: The GGB detection rate and the detected GGB number by using SWI were significantly greater than those by using T1-, T2-, and T2*-weighted images. The number of GGBs in the SWI images correlated positively with the portal vein diameter and SI and correlated negatively with the platelet count and platelet count/spleen diameter ratio. CONCLUSION: SWI provided more accurate information of GGBs in patients with PH. The number of GGB may be a non-invasive predictor of improving the selection for endoscopic screening of PH patients at risk of EV.

An in vitro and in vivo analysis of the correlation between susceptibility-weighted imaging phase values and R2* in cirrhotic livers.

OBJECTIVE: To establish a baseline of susceptibility-weighted imaging (SWI) phase value as a means of detecting iron abnormalities in cirrhotic liver and to analyze its relationship with R2*. MATERIALS AND METHODS: Sixteen MnCl(2) phantoms, thirty-seven healthy individuals and 87 cirrhotic patients were performed SWI and multi-echo T2*-weighted imaging, and the signal processing in NMR (SPIN) software was used to measure the radian on SWI phase images and the R2* on T2* maps. The mean minus two times standard deviation (SD) of Siemens Phase Unit (SPU) in healthy individuals was designated as a threshold to separate the regions of interest (ROIs) into high- and low-iron areas in healthy participants and cirrhotic patients. The SWI phase values of high-iron areas were calculated. The R2* values was measured in the same ROI in both healthy participants and patients. RESULTS: SWI phase values correlated linearly with R2* values in cases of MnCl(2) concentrations lower than 2.3 mM in vitro (r = -0.996, P<0.001). The mean value and SD of 37 healthy participants were 2003 and 15 (SPU), respectively. A threshold of 1973 SPU (-0.115 radians) was determined. The SWI phase value and R2* values had a negative correlation in the cirrhotic patients (r = -0.742, P<0.001). However, no similar relationship was found in the healthy individuals (r = 0.096, P = 0.576). Both SWI phase values and R2* values were found to have significant correlations with serum ferritin concentrations in 42 patients with blood samples (r = -0.512, P = 0.001 and r = 0.641, P<0.001, respectively). CONCLUSION: SWI phase values had significant correlations with R2* after the establishment of a baseline on the phase image. SWI phase images may be used for non-invasive quantitative measurement of mild and moderate iron deposition in hepatic cirrhosis in vivo.

Detection of siderotic nodules in the liver with susceptibility weighted imaging: correlations to serum ferritin, Child-Pugh grade and hyaluronic acid levels.

BACKGROUND: Chronic liver disease causes aberrant formation of fibrous tissue that impedes normal liver function, ultimately resulting in liver cirrhosis. Iron uptake can occur within the hepatic parenchyma or within the various nodules that form in a cirrhotic liver, termed siderotic nodules (SN). We aimed to investigate the diagnostic performance of susceptibility weighted imaging (SWI) for detection of SN in patients with liver cirrhosis, and to evaluate the potential of SN numbers for assessing the degree of hepatic iron deposition, liver function, and liver fibrosis stage. METHODS: Ninety-one patients with chronic liver cirrhosis, who underwent megnetic resonance imagine (MRI) scanning in our department between November 2010 and April 2011, were included in the study. A 3.0T MRI scanner was used to acquire T1WI, T2WI, T2WI, and SWI images. The number of nodules, signal intensity ratio (SIR), and contrast noise ratio (CNR) were recorded and analyzed by chi-square and ANOVA statistical tests. Correlation analysis was performed to evaluate the correlations between the number of SN and Child-Pugh classification, ferritin and hyaluronic acid levels. RESULTS: The sensitivity of SWI, T1WI, T2WI, and T2 WI for detecting SN was 62.5%, 12.1%, 24.2% and 41.8%, respectively. SWI detected significantly more nodules than routine T1WI, T2WI, and T2 WI procedures (P < 0.05). The SIR was the lowest in SWI (0.361 ± 0.209), as compared to T1WI (0.852 ± 0.163), T2WI (0.584 ± 0.172), and T2 WI (0.497 ± 0.196). The CNR was the highest in SWI (13.932 ± 5.637), as compared to T1WI (9.147 ± 5.785), T2WI (9.771 ± 5.490), and T2 WI (11.491 ± 4.573). The correlation coefficients of the number of SN with ferritin, Child-Pugh classification, and hyaluronic acid levels were 0.672, -0.055, and 0.163, respectively. CONCLUSIONS: The sensitivity and contrast of SWI for detecting SN in patients with liver cirrhosis are higher than conventional MRI. The number of SN can help to assess the degree of iron deposition in patients with liver cirrhosis.

Association of TBX21 promoter polymorphisms with type 1 autoimmune hepatitis in a Chinese population.

The T-box transcription factor T-bet is a key regulator for the lineage commitment in CD4 Th1 cells and CD8 T cells by activating the hallmark production of interferon-γ, and its expression level is linked to autoimmune diseases. T-1993C and T-1514C polymorphisms in the TBX21 gene (encoding T-bet) promoter can affect transcription activity. We investigated the distributions of these functional polymorphisms in 84 adult patients with type 1 autoimmune hepatitis (AIH-1) and 318 healthy controls. Intracellular T-bet staining of polarized CD4 Th1 cells from healthy controls corresponding to T-1993C genotypes were analyzed by flow cytometry. The -1993C allele frequency was 3.0% in AIH-1 and 11.8% in controls (p = 0.000 25). Individuals carrying the -1993C allele had a decreased risk to AIH-1 compared with those without the -1993C allele (p = 0.0016, odds ratio [OR] = 0.22, 95% confidence interval = 0.09-0.56). No association was found between the T-1514C polymorphism and AIH-1. The onset age of AIH-1 was also accelerated among -1993TT homozygotic individuals (p = 0.013). The fractions of T-bet positive Th1 cells in the -1993TT homozygotes were 2.2-fold higher than those in -1993CC homozygotes (p = 0.002). Our results suggest that the T-1993C polymorphism in the TBX21 promoter influences susceptibility to AIH-1 in a Chinese population.