Microglia activation can cause degeneration of retinal ganglion cells (RGCs). This study aimed to investigate the potential therapeutic effect of minocycline on microglia activation-related degeneration of RGCs in both retinas after unilateral optic nerve crush (ONC) in the left eye of male adult C57BL/6 mice.

First, the primary degeneration of RGCs after unilateral ONC in the left eye and the secondary degeneration of RGCs in the contralateral eye were investigated. Second, microglia activation in both eyes was examined longitudinally at 1, 5 and 14 days post-ONC. Finally, the effects of minocycline treatment on the primary or/and secondary RGC degeneration as well as the function of both retinas (estimated by flash electroretinogram) at 5 days post-ONC were analyzed.

The results indicated that ONC induced the primary RGC degeneration, which was more severe than the secondary RGC degeneration and microglia activation in both eyes. Treatment with minocycline partially inhibited microglia activation, preserved the function of retinas in both eyes, and delayed the secondary degeneration of RGCs in the contralateral retina.

ONC caused RGC degeneration in both eyes of mice. Minocycline treatment delayed the secondary degeneration of RGCs and improved the function of both retinas post-ONC in mice, which were associated with inhibition of microglia activation.

With mortality rates of liver cancer doubling in the last 20 years, this disease is on the rise and has become the fifth most common cancer in men and the seventh most common cancer in women. Hepatocellular carcinoma (HCC) represents approximately 90% of all primary liver cancers and is a major global health concern. Patients with HCC can be managed curatively with surgical resection or with liver transplantation, if they are diagnosed at an early stage. Unfortunately, most patients with HCC present with advanced stages of the disease and have underlying liver dysfunction, which allows only 15% of patients to be eligible for curative treatment. Several different treatment modalities are available, including locoregional therapy radiofrequency ablation, microwave ablation, percutaneous ethanol injection, trans-arterial chemoembolization, transarterial radio-embolization, cryoablation, radiation therapy, stereotactic radiotherapy, systemic chemotherapy, molecularly targeted therapies, and immunotherapy. Immunotherapy has recently become a promising method for inhibiting HCC tumor progression, recurrence, and metastasis. The term “Immunotherapy” is a catch-all, encompassing a wide range of applications and targets, including HCC vaccines, adoptive cell therapy, immune checkpoint inhibitors, and use of oncolytic viruses to treat HCC. Immunotherapy in HCC is a relatively safe option for treating patients with advanced disease in the USA who are either unable to receive or failed sorafenib/lenvatinib therapy and thus may offer an additional survival benefit for these patients. The purpose of this review is to elaborate on some of the most recent advancements in immunotherapy.

The lineage of the erythroid cell has been revisited in recent years. Instead of being classified as simply inert oxygen carriers, emerging evidence has shown that they are a tightly regulated in immune potent population with potential developmental plasticity for lineage crossing. Erythroid cells have been reported to exert immune regulatory function through secreted cytokines, or cell-cell contact, depending on the conditions of the microenvironment and disease models. In this review, we explain the natural history of erythroid cells in the liver through a developmental lens, as it offers perspectives into newly recognized roles of this lineage in liver biology. Here, we review the known immune roles of erythroid cells and discuss the mechanisms in the context of disease models and stages. Then, we explore the capability of erythroid lineage as a cell source for regenerative medicine. We propose that the versatile lineage of erythroid cells provides an underappreciated and potentially promising area for basic and translational research in the field of liver disease.

This review discusses the efficiency and sensitivity of 68Ga-labelled prostate-specific membrane antigen (PSMA) positron emission tomography (PET)/computed tomography (CT) imaging in comparison to other radiotracers and imaging techniques. It also conveys its impact on the treatment or management of prostate cancer patients. PSMA, observed in almost all prostate cancer cells, is used for staging and treatment, due to its high multiplication in this cancer when compared to normal tissues. PSMA PET/magnetic resonance imaging (MRI) has applications in the management of prostate cancer. Though PSMA PET/MRI has yielded preliminary results, it is still studied as an imaging biomarker for tumor responses. PSMA-PET/CT is known for its highly sensitive resolution, as it lights up only the parts harboring prostate cancer or tumor cells and not any other kind of lesion. Therefore, 68Ga-PSMA-PET imaging is chosen over other variants of 68Ga-PSMA-11, such as 177Lu-PSMA or 225Ac-PSMA, and it is used for its greater ability to detect metastatic sites in patients with biochemical recurrence and low serum prostate-specific antigens values. The efficacy of 68Ga-PSMA PET/CT also allows for estimation of oligometastases, as it supports the design of therapeutic trials in measuring long-term effects in patients. Finally, 68Ga-PSMA PET/CT is effective in identifying recurrence localization and, hence, permits the ability to choose the best therapeutic strategy as early as possible.

In addition to liver injury, elevation of aminotransferases can be caused by strenuous exercise and use of muscle-building and weight-loss supplements. The purpose of this review is to discuss the various mechanisms of elevation of aminotransferases related to body building. A literature review was performed on clinical trials and case reports involving exercise or supplement use and their effects on aminotransferases. Normal aminotransferase levels varied according to gender, age, body mass index, and comorbidities. Strenuous exercise and weight lifting, especially in the unaccustomed, can cause elevated aminotransferases in the absence of liver damage. Supplements such as anabolic steroids, ephedra, and LipoKinetix, amongst others, have also been associated with aminotransferase elevations. The pattern of elevation of aminotransferases is not helpful in distinguishing liver from muscle injury. Other associated muscle enzymes can be useful in making that distinction. To prevent aminotransferase elevations, subjects not accustomed to moderate-high intensity workouts, are recommended to undertake gradual increase in intensity. When causes of liver injury have been ruled out, investigation into bodybuilding, extreme exercise, and supplement use is warranted.

Xia Sang Ju (XSJ) granule, a Chinese drug and herbal tea made up of Prunellae spica (Xia Ku Cao), Mori folium (Sang Ye), and Flos Chrysanthemi Indici (Ye Ju Hua), is commonly used for fever, headache, and sore throat. The underlying pharmacological mechanism of XSJ on hypertension treatment is described here, based on network pharmacology.

The compounds in XSJ were searched using the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (commonly known as TCMSP), and the active components, according to oral bioavailability and drug likeness, were screened. Compounds targets were predicted by the SwissTargetPrediction web server, while hypertension targets were collected from the Online Mendelian Inheritance in Man (commonly known as OMIM) and GeneCards databases. The interaction of targets was analyzed by STRING. The compound-compound target network was constructed by Cytoscape. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes (commonly known as KEGG) pathways were analyzed by the Database for Annotation, Visualization and Integrated Discovery (commonly known as DAVID).

Forty-five active compounds were obtained from 359 ingredients present in the XSJ decoction, corresponding to 237 targets. In addition, 189 genes were found to be related to hypertension, of which 11 overlapped with XSJ targeted by 28 compounds and were thus considered therapeutically-relevant. ESR2 was the most frequent gene targeted by the compounds, while NR3C1 showed the most interaction with other genes. These results revealed that the anti-hypertensive activity of XSJ may directly relate to the regulation of several hypertension-associated biological processes and pathways, such as cellular nitrogen compound biosynthetic process, positive regulation of the nitrogen compound metabolic process, steroid hormone biosynthesis, and aldosterone-regulated sodium reabsorption.

These findings provide a reference for further interpretation of the potential mode of action of XSJ against hypertension and serve as an example for elucidation of the Traditional Chinese Medicine concept of “multiple compounds-multiple targets-multiple effects”.

In recent years, there has been a significant increase in the incidence of peptic ulcer cases among military personnel. It is important for clinicians to identify the risk factors of peptic ulcer and then implement the appropriate prophylactic measures in a timely manner. This study aims to systematically review the risk factors of peptic ulcer in military personnel.

We searched literature from the PubMed, EMBASE, Wanfang, China National Knowledge Infrastructure, and VIP databases up to November 17, 2019. Eligible studies analyzed at least one risk factor of peptic ulcer in military personnel with descriptive or comparative data. The risk factors’ data were then extracted and tabulated.

Of the 1,008 studies initially identified, 11 were eligible for the present study. The total sample size was 29,925 (ranging from 203 to 10,046). The study population included military officers and soldiers, pilots, armed policemen, and firefighters. The most studied risk factor of peptic ulcer was history of smoking (n = 8), followed by high-intensity training (n = 5), mental stress (n = 5), family history of peptic ulcer (n = 4), history of alcohol drinking (n = 4), and use of non-steroidal anti-inflammatory drugs (n = 4).

Several major risk factors of peptic ulcer have been systematically identified, of which some are modifiable. In the future, proper intervention of these modifiable risk factors may be helpful in preventing military personnel from the development of peptic ulcer.

Acute kidney injury (AKI) occurs frequently in patients with cirrhosis, and hepatorenal syndrome (HRS) is second most common etiology of AKI after volume responsible pre-renal etiology. AKI in these patients negatively impacts pre- and post-transplant patient survival and healthcare burden. Reduced effective blood volume with consequent reduced renal blood flow, along with systemic inflammation in patients with decompensated cirrhosis, result in susceptibility to HRS. In this article, we will review updates over the last 5 years on the changing definition with diagnostic criteria and nomenclature of AKI and HRS, data on medical treatment with vasoconstrictors, and urinary biomarkers in diagnosis of etiology of AKI. We will also discuss the significance of liver transplantation evaluation once the diagnosis of HRS is established and the post-transplant immunosuppression management. We will also review one of the challenging issues that remains among transplant-eligible patients, that of allocation of simultaneous liver kidney transplant. Finally, we will review the new implemented policy from the Organ Procurement Transplant Network on simultaneous liver kidney allocation.

Background and Aims: Evaluation of significant liver fibrosis is important for treatment decision and treatment response evaluation in patients with chronic hepatitis B. Since liver biopsy is invasive and transient elastography (TE) has limited availability, various non-invasive blood parameters need evaluation for their capabilities for detection of significant fibrosis.

Methods: In this retrospective study, records of patients who had undergone liver biopsy for treatment-naïve chronic hepatitis B were evaluated to obtain various non-invasive blood parameters (aspartate aminotransferase-to-platelet ratio index [referred to as APRI], Fibrosis-4 score [referred to as FIB-4], gamma-glutamyl transpeptidase-to-platelet ratio [referred to as GPR], and gamma-glutamyl transpeptidase-to-albumin ratio [referred to as GAR]), in addition to TE, to assess significant liver fibrosis and compare these to fibrosis stage in liver biopsy.

Results: A total of 113 patients were included in the study (median age 33 [interquartile range: 11-82 years], 74% males). Most (75%) patients were HBeAg-negative. The liver biopsy revealed significant fibrosis (Ishak ≥3) in 13% of the patients and nil or mild fibrosis (Ishak <3) in 87% of the patients. TE findings were available for 85 patients, APRI and FIB-4 for 95 patients, GPR for 79 patients, and GAR for 78 patients. The median values of all the parameters were significantly higher in patients with significant fibrosis, as compared to patients with non-significant fibrosis, and all the blood parameters as well as TE were able to identify patients with significant fibrosis significantly well (p<0.05). All non-invasive parameters had low positive predictive value but negative predictive value above 92%. Compared to TE, all the non-invasive blood parameters had similar area under the curve for detecting significant fibrosis, with excellent negative predictive value (≥93%).

Conclusions: Non-invasive blood parameters (APRI, FIB-4, GPR, and GAR) with negative predictive values above 93% are excellent parameters for ruling-out significant fibrosis in patients with chronic hepatitis B. These can be used at bedside in place of TE.

The most common Gram-negative bacteria, such as enteric bacilli, Escherichia coli and Klebsiella pneumoniae, and Gram-positive bacteria, such as Streptococcus spp., are seen in patients suffering from cirrhosis and/or chronic liver diseases. The objective of this prospective observational study was to compare the efficacy and pattern of antibiotic use in patients with bacterial translocation.

This 10-month study was conducted at the Gastroenterology Department of the KIMS hospital, Telangana, India. The patients were more than 18 years of age (n = 60) and diagnosed with liver cirrhosis and/ or chronic liver diseases. All data was analyzed statistically, at a significance threshold of p < 0.05.

Among the 60 patients, the Child-Pugh-Turcotte scores were A in 30%, B in 35% and C in 14%. White blood cell count was reduced from 12,620 ± 1,266 (before treatment) to 8,385 ± 944 (after treatment with antibiotics; p < 0.05). Serum glutamic pyruvic transaminase values were reduced from 360.1 ± 87.3 (before treatment) to 141.9 ± 37.9 (after treatment with antibiotics therapy (p < 0.001), whereas serum bilirubin values were reduced from 6.064 ± 0.91 (Before treatment) to 3.514 ± 0.44 (after treatment with antibiotics therapy; p < 0.0001). The mortality rate was 6.6 %, i.e. only 4 patients died post-treatment. It was also observed that meropenem was prescribed in the majority of cases and norfloxacin was the least prescribed of all antibiotics.

Our study suggests that antibiotic treatment might be effective for patients suffering with cirrhosis or chronic liver diseases with improved life expectancy.

Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome. The spread of obesity worldwide in pandemic proportions has led to a rapid rise of NAFLD in developed and developing countries alike. There are no approved pharmacological agents to treat steatohepatitis or advanced fibrosis but obeticholic acid recently has shown some promise in phase III trial. Currently, NAFLD is the number one etiology for simultaneous liver and kidney transplantation in the USA, second most common indication for liver transplantation (LT) and projected to become number one very soon. LT for NAFLD poses unique challenges, as these patients are generally older, obese and more likely to have a number of metabolic risk factors. Bariatric surgery is an option and can be considered if a structured weight loss program does not achieve the sustained weight loss goal. Comprehensive cardiovascular risk assessment and aggressive management of comorbid conditions are crucial in the LT evaluation process to improve post-transplant survival. Recurrent nonalcoholic steatohepatitis after LT is not uncommon, and thus warrants primary and secondary prevention strategies through a multidisciplinary approach. Prevalence of NAFLD in a donor population is a unique and growing concern that limits the access to quality liver grafts.

Antiphospholipid syndrome (APS) is an autoimmune disease with autoantibodies and hypercoagulability. Although APS has a variable clinical presentation, APS commonly presents vascular thrombosis and obstetrical complications, such as repeated miscarriages in women. Here, we report an elderly male with the clinical manifestations of APS and recurrent deep venous thrombosis (referred to as DVT) in Sudan. A 52 year-old male had a chief complaint of severe left leg pain and high-grade fever for 10 days, with no history of recent surgery, trauma or prolonged immobilization but with a previous history of DVT. Doppler ultrasonography revealed left lower limb DVT, and laboratory examinations detected autoantibodies without other causes. Accordingly, he was diagnosed with APS. He was treated with Cefuroxime, Flucloxacillin and subcutaneous enoxaparin. His clinical condition markedly improved and the swelling subsided. His blood international normalized ratio reached 2.5 and he was discharged.

Globally, hepatitis B virus (HBV) infection is recognized as a major risk factor for the development of hepatocellular carcinoma, and HBV-induced liver failure is one of the leading indications for liver transplantation. Until about two decades ago, liver transplantation in patients with chronic HBV infection was a relative contraindication, due to high risk of viral replication with the use of immunosuppressants which could result in graft infection. In the 1990s, hepatitis B immunoglobulin (HBIg) use significantly reduced the risk of graft infection, improving outcomes of liver transplant in patients with chronic HBV infection. However, very high costs, especially with the need for long-term use, became a major concern. With the advent of nucleos(t)ide analogs (NAs), there was less need for high-dose, long-term HBIg use to prevent HBV recurrence. Lamivudine was initially used but resistance soon became a major issue. This was followed by more potent NAs, such as entecavir and tenofovir, emerging as the more preferred agents. Additionally, the use of these antiviral agents (HBIg and/or NAs) have made it possible to use the grafts from donors with positivity for hepatitis B core antibody, allowing for expansion of the donor pool. Nevertheless, there is no consensus on management protocols, which vary significantly amongst centers. In this review, we appraise studies on management strategies used and the role of active vaccination in the prevention of HBV recurrence in post-liver transplant patients.

Background and Aims: Acute kidney injury (AKI) is common in patients with cirrhosis but the incidence is heterogeneous among studies. We performed a meta-analysis to describe the incidence of AKI and its impact on patient mortality in patients with cirrhosis. We also evaluated the admission variables predicting development of AKI.

Methods: A systematic search of various databases was performed up to November 2018. Meta-analyses were performed using random effects models.

Results: Of 18,474 patients with cirrhosis from 30 selected studies, 5,648 developed AKI, with a pooled incidence of 29% (95% confidence interval [CI]: 28-30%, I2 of 99%). In-hospital mortality assessed in eight studies was six-fold higher among AKI patients, as compared to those without AKI (odds ratio [OR] 6.72, 95% CI: 3.47-13, p<0.0001, I2 of 70%). Three studies on patients admitted to intensive care showed about six-fold higher mortality among AKI patients (OR 5.90, 95% CI: 3.21-10.85, p>0.0001). Mortality remained significantly high, at days 30 and 90 and even at 1-year follow up after development of AKI. Of 12 admission variables analyzed, model for end-stage liver disease score, Child-Pugh-Turcotte stage C, presence of ascites, and presence of sepsis/septic shock were statistically significant risk factors for AKI.

Conclusions: AKI occurred in about 29% of patients with cirrhosis and is associated with a six-fold increased risk of in-hospital mortality. Mortality remained high even in long-term follow-up of 1 year. Patients at risk for AKI development can be recognized at admission. Prospective studies are needed to develop strategies for improving outcome of these patients.

Microbiota are thought to play a role in the development of gastric cancer (GC). Several studies have put forward putatively carcinogenic species in addition to Helicobacter pylori but are not in perfect alignment, possibly due to variable parameters in the experiments. Meta-analyses on this subject have not been published so far. Therefore, there is a lack of clinical guidance beyond H. pylori eradication therapy.

Here, we analyzed gastric mucosa samples from nine public datasets, including GC samples. We defined fine grain bacterial networks of gastric mucosa and identified the species associated with the tumor status of samples.

Despite study-specific variability, the periodontal species Fusobacterium nucleatum, Parvimonas micra and Peptostreptococcus stomatis were found in association with tumor status in several datasets. The three species were predicted to be in interaction by ecological network analysis and also formed the intersection of tumor-associated species between four GC datasets and five colorectal cancer datasets we reanalyzed. We formulated a probiotic composition putatively competing with the GC pathogen spectrum, from correlation analysis in a large superset of gut samples (n = 17,800) from clinical- and crowd-sourced studies.

The overlapping pathogen spectrum between two gastrointestinal tumor types, GC and colorectal cancer, has implications for etiology, treatment and prevention. In vitro testing results reported in the literature suggest H. pylori eradication treatment should be efficient against the GC pathogen spectrum, yet the existence of an upstream periodontal reservoir is of concern. To address this, we propose use of the formulated probiotics composition.