Clinical scenarios for the use of S100β as a marker of hepatic encephalopathy

AIM: To evaluate the association between serum concentrations of S100β in patients with cirrhosis and the presence of low grade hepatic encephalopathy(HE).METHODS: This was a cross-sectional study. The population was categorized into four groups healthy subjects, cirrhosis without HE, cirrhosis with covert hepatic encephalopathy(CHE) and cirrhosis with overt HE. Kruskal-Wallis, Mann Whitney's U with Bonferroni adjustment Spearman correlations and area under the ROC were used as appropriate.RESULTS: A total of 61 subjects were included, 46 cirrhotic patients and 15 healthy volunteers. S100β values were different among all groups, and differences remained significant between groups 1 and 2(P < 0.001), and also between groups 2 and 3(P = 0.016), but not between groups 3 and 4. In cirrhotic patients with HE S100β was higher than in patients without HE [0.18(0.14-0.28) ng/m L vs 0.11(0.06-0.14) ng/m L, P < 0.001]. There was a close correlation between serum concentrations of S100β and psychometric hepatic encephalopathy score in patients with cirrhosis without HE compared to the patients with cirrhosis with CHE(r =-0.413, P = 0.019). ROC curve analysis yielded > 0.13 ng/m L as the best cutoff value of S100β for the diagnosis of HE(sensitivity 83.3%, specificity 63.6%).CONCLUSION: Serum concentrations of S100β are higher in patients with cirrhosis than in healthy volunteers, and are further increased in the presence of hepatic encephalopathy. The results suggest that serum biomarkers such as S100β could help in the correct characterization of incipient stages of HE.

Cerium oxide nanoparticles as promising ophthalmic therapeutics for the treatment of retinal diseases

Nanotechnology offers exciting new approaches for biology and medicine. In recent years, nanoparticles,particularly those of the rare metal cerium, are showing potential for a wide range of applications in medicine.Cerium oxide nanoparticles or nanoceria are antioxidants and possess catalytic activities that mimic those of super oxide dismutase and catalase, thereby protecting cellsfrom oxidative stress. The retina is highly susceptible to oxidative stress because of its high oxygen consumption and high metabolic activity associated with exposure to light. Many retinal diseases progress through oxidative stress as a result of a chronic or acute rise in reactive oxygen species. Diseases of the retina are the leading causes of blindness throughout the world. Although some treatments may delay or slow the development of retinal diseases, there are no cures for most forms of blinding diseases. In this review is summarized evidence that cerium oxide nanoparticles can function as catalytic antioxidants in vivo in rodent models of age-related macular degeneration and inherited retinal degeneration and may represent a novel therapeutic strategy for the treatment of human eye diseases. This may shift current research and clinical practice towards the use of nanoceria, alone or in combination with other therapeutics.

Cost analysis of childhood glaucoma surgeries using the US Medicaire allowable costs

AIM: To analyze and calculate the relative cost of various childhood glaucoma surgical interventions per mm Hg intraocular pressure(IOP) reduction($/mm Hg).METHODS: Representative index studies were reviewed to quantitate the reduction of mean IOP and glaucoma medications for each surgical intervention in childhood glaucoma. A US perspective was adopted, using Medicare allowable costs to calculate cost/mm Hg IOP reduction($/mm Hg) at 1y postoperatively.RESULTS: At 1y postoperatively, the cost/mm Hg IOP reduction was $226/mm Hg for microcatheter-assisted circumferential trabeculotomy, $284/mm Hg for cyclophotocoagulation, $288/mm Hg for conventional ab-externo trabeculotomy, $338/mm Hg for Ahmed glaucoma valve, $350/mm Hg for Baerveldt glaucoma implant, $351/mm Hg for goniotomy, and $400/mm Hg for trabeculectomy.CONCLUSION: Microcatheter-assisted circumferential trabeculotomy is the most cost-efficient surgical method to lower IOP in childhood glaucoma, while trabeculectomy is the least cost-efficient surgical method.

Combined Sacral Nerve Roots Stimulation and Low Thoracic Spinal Cord Stimulation for the Treatment of Chronic Pelvic Pain

Some pelvic pain syndromes are very resistant to medical treatment. Several studies have demonstrated that sacral neuromodulation, which has been successfully used for the treatment of bladder dysfunction, incontinence, urinary retention and urinary frequency [1]-[3], can be successfully used for the treatment of chronic pelvic pain [4]-[7]. Several studies have also demonstrated significant involvement of dorsal column pathways in the transmission of visceral pelvic pain [8] and the successful use of spinal cord stimulation for the treatment of chronic pelvic pain [9]. We report three cases of severe chronic pelvic pain that failed conservative treatment modalities. Placement of a combined sacral nerve roots stimulator and a low thoracic spinal cord stimulator resulted in a significant pain relief and improvement in daily life activities. We believe that this combination may help patients suffering from chronic pelvic pain resistant to medical management.

Continuous Inferior Alveolar Nerve Block Using an Indwelling Catheter and Inferior Maxillary Artery Embolization for the Management of Atypical Trigeminal Neuralgia

A 40-years-old female patient with severe right facial pain with a throbbing component along the mandibular division of the trigeminal nerve resistant to medical management. Continuous inferior alveolar nerve block with local anesthetics using an indwelling catheter provided a complete pain resolution for the patient for 2 weeks, after which the catheter got infected and was removed. A trial of balloon occlusion of the right internal maxillary artery provided complete resolution of the throbbing component of the patient’s pain. This was followed by permanent embolization with multiple coils.

The Use of Near-Infrared Spectroscopy As a Substitute for Blood Pressure Monitoring in a Patient with Severe Osteogenesis Imperfecta

The use of near-infrared spectroscopy (NIRS) as a means of assessing regional oxygen supply is a method that has gained recent support and interest. Given the potential of NIRS, this technology was utilized in an infant patient with a case of severe osteogenesis imperfecta that precluded conventional blood pressure monitoring. Using NIRS as a monitor and titrating the anesthetic accordingly produced a good outcome, with no post-operative evidence of detrimental intra-operative hypotension or ischemia.

Reversal of the diabetic bone signature with anabolic therapies in mice

The mechanisms underlying the bone disease induced by diabetes are complex and not fully understood;and antiresorptive agents,the current standard of care,do not restore the weakened bone architecture.Herein,we reveal the diabetic bone signature in mice at the tissue,cell,and transcriptome levels and demonstrate that three FDA-approved bone-anabolic agents correct it.Diabetes decreased bone mineral density(BMD)and bone formation,damaged microarchitecture,increased porosity of cortical bone,and compromised bone strength.Teriparatide(PTH),abaloparatide(ABL),and romosozumab/anti-sclerostin antibody(Scl-Ab)all restored BMD and corrected the deteriorated bone architecture.Mechanistically,PTH and more potently ABL induced similar responses at the tissue and gene signature levels,increasing both formation and resorption with positive balance towards bone gain.In contrast,Scl-Ab increased formation but decreased resorption.All agents restored bone architecture,corrected cortical porosity,and improved mechanical properties of diabetic bone;and ABL and Scl-Ab increased toughness,a fracture resistance index.Remarkably,all agents increased bone strength over the healthy controls even in the presence of severe hyperglycemia.These findings demonstrate the therapeutic value of bone anabolic agents to treat diabetes-induced bone disease and suggest the need for revisiting the approaches for the treatment of bone fragility in diabetes.

Gut microbiome supplementation as therapy for metabolic syndrome

The gut microbiome is defined as an ecological community of commensal symbiotic and pathogenic microorganisms that exist in our body.Gut microbiome dysbiosis is a condition of dysregulated and disrupted intestinal bacterial homeostasis,and recent evidence has shown that dysbiosis is related to chronic inflammation,insulin resistance,cardiovascular diseases(CVD),type 2 diabetes mellitus(T2DM),and obesity.It is well known that obesity,T2DM and CVD are caused or worsened by multiple factors like genetic predisposition,environmental factors,unhealthy high calorie diets,and sedentary lifestyle.However,recent evidence from human and mouse models suggest that the gut microbiome is also an active player in the modulation of metabolic syndrome,a set of risk factors including obesity,hyperglycemia,and dyslipidemia that increase the risk for CVD,T2DM,and other diseases.Current research aims to identify treatments to increase the number of beneficial microbiota in the gut microbiome in order to modulate metabolic syndrome by reducing chronic inflammation and insulin resistance.There is increasing interest in supplements,classified as prebiotics,probiotics,synbiotics,or postbiotics,and their effect on the gut microbiome and metabolic syndrome.In this review article,we have summarized current research on these supplements that are available to improve the abundance of beneficial gut microbiota and to reduce the harmful ones in patients with metabolic syndrome.

Recent advances in endoscopic management of gastric neoplasms

The development and clinical application of new diagnostic endoscopic technologies such as endoscopic ultrasonography with biopsy,magnification endoscopy,and narrow-band imaging,more recently supplemented by artificial intelligence,have enabled wider recognition and detection of various gastric neoplasms including early gastric cancer(EGC)and subepithelial tumors,such as gastrointestinal stromal tumors and neuroendocrine tumors.Over the last decade,the evolution of novel advanced therapeutic endoscopic techniques,such as endoscopic mucosal resection,endoscopic submucosal dissection,endoscopic fullthickness resection,and submucosal tunneling endoscopic resection,along with the advent of a broad array of endoscopic accessories,has provided a promising and yet less invasive strategy for treating gastric neoplasms with the advantage of a reduced need for gastric surgery.Thus,the management algorithms of various gastric tumors in a defined subset of the patient population at low risk of lymph node metastasis and amenable to endoscopic resection,may require revision considering upcoming data given the high success rate of en bloc resection by experienced endoscopists.Moreover,endoscopic surveillance protocols for precancerous gastric lesions will continue to be refined by systematic reviews and meta-analyses of further research.However,the lack of familiarity with subtle endoscopic changes associated with EGC,as well as longer procedural time,evolving resection techniques and tools,a steep learning curve of such high-risk procedures,and lack of coding are issues that do not appeal to many gastroenterologists in the field.This review summarizes recent advances in the endoscopic management of gastric neoplasms,with special emphasis on diagnostic and therapeutic methods and their future prospects.

Significance of endothelial dysfunction in the pathogenesis of early and delayed radiation enteropathy

This review summarizes the current state of knowledge regarding the role of endothelial dysfunction in the pathogenesis of early and delayed intestinal radiation toxicity and discusses various endothelial-oriented interventions aimed at reducing the risk of radiation enteropathy. Studies published in the biomedical literature during the past four decades and cited in PubMed, as well as clinical and laboratory data from our own research program are reviewed. The risk of injury to normal tissues limits the cancer cure rates that can be achieved with radiation therapy. During treatment of abdominal and pelvic tumors, the intestine is frequently a major dose-limiting factor. Microvascular injury is a prominent feature of both early (inflammatory), as well as delayed (fibroproliferative) radiation injuries in the intestine and in many other normal tissues. Evidence from our and other laboratories suggests that endothelial dysfunction, notably a deficiency of endothelial thrombomodulin, plays a key role in the pathogenesis of these radiation responses. Deficient levels of thrombomodulin cause loss of vascular thromboresistance, excessive activation of cellular thrombin receptors by thrombin, and insufficient activation of protein C, a plasma protein with anticoagulant, anti-inflammatory, and cytoprotective properties. These changes are presumed to be critically involved in many aspects of early intestinal radiation toxicity and may sustain the fi broproliferative processes that lead to delayed intestinal dysfunction, fi brosis, and clinical complications. In conclusion, injury of vascular endothelium is important in the pathogenesis of the intestinal radiation response. Endothelial-oriented interventions are appealing strategies to prevent or treat normal tissue toxicity associated with radiation treatment of cancer.

Acoustic dipole radiation model for magnetoacoustic tomography with magnetic induction

An acoustic dipole radiation model for magnetoacoustic tomography with magnetic induction (MAT-MI) is pro-posed,based on the analyses of one-dimensional tissue vibration,three-dimensional acoustic dipole radiation and acoustic waveform detection with a planar piston transducer.The collected waveforms provide information about the conductiv-ity boundaries in various vibration intensities and phases due to the acoustic dipole radiation pattern.Combined with the simplified back projection algorithm,the conductivity configuration of the measured layer in terms of shape and size can be reconstructed with obvious border stripes.The numerical simulation is performed for a two-layer cylindrical phantom model and it is also verified by the experimental results of MAT-MI for a tissue-like sample phantom.The proposed model suggests a potential application of conductivity differentiation and provides a universal basis for the further study of conductivity reconstruction for MAT-MI.

Management of gastric variceal bleeding:Role of endoscopy and endoscopic ultrasound

Gastric varices(GVs)are notorious to bleed massively and often difficult to manage with conventional techniques.This mini-review addresses endoscopic management principles for gastric variceal bleeding,including limitations of ligation and sclerotherapy and merits of endoscopic variceal obliteration.The article also discusses how emerging use of endoscopic ultrasound provides optimism of better diagnosis,improved classification,innovative management strategies and confirmatory tool for eradication of GVs.

Aspirin resistance: Fact or fiction? A point of view

Aspirin is a wonder drug that has been used for well over 100 years for its analgesic and antipyretic effects. For the past three decades, it has increasingly been used for the prevention of primary and secondary cardiovascular events. Lately, it has been suggested that a significant number of individuals taking aspirin have become resistant to this drug. The phenomenon of "aspirin resistance" is based on the observation of clinical events in some patients taking aspirin, and/or a diminished platelet aggregation inhibitory response to aspirin therapy. Unfortunately, laboratory assays used to monitor the efficacy of aspirin are far from accurate and the results are not reproducible. Furthermore, results of different platelet function tests are often not congruent. In addition, platelet aggregation studies show marked interindividual and intra-individual variability. Patients with coronary heart disease take many drugs that interfere with the effect of aspirin on platelet aggregation. Besides inhibiting formation of thromboxane A2 from arachidonic acid, aspirin has a host of platelet-independent effects that complement its platelet inhibitory effects. Laboratory assays designed to measure platelet function do not take into account these pleiotropic effects of aspirin. In our view, use of the term "aspirin resistance" based on inadequate knowledge of imperfect laboratory tests does a disservice to physicians and patients.

The genetics of nicotine dependence:Relationship to Pancreatic cancer

SmoKing or tobacco products continues to De a major cause of worldwide health problems. Epidemiological studies have shown that tobacco smoking is the greatest risk factor for the development of pancreatic cancer. Smokers who are able to quit smoking can reduce their risk of pancreatic cancer by nearly 50% within two years, however, their risk of developing pancreatic cancer remains higher than that of non-smokers for 10 years. Nicotine is the major psychoactive substance in tobacco, and is responsible for tobacco dependence and addiction. Recent evidence suggests that individuals have genetically based differences in their ability to metabolize nicotine, as well as genetic differences in the psychological reward pathways that may influence individual response to smoking initiation, dependence, addiction and cessation. Numerous associations have been reported between smoking behavior and genetic polymorphisms in genes that are responsible for nicotine metabolism. In addition, polymorphisms in genes that encode neurotransmitters and transporters that function in psychological reward pathways have been implicated in differences in smoking behavior. However, there is a large degree of between-study variability that demonstrates the need for larger, well-controlled case-control studies to identify target genes and deduce mechanisms that account for the genetic basis of inter-individual differences in smoking behavior. Understanding the genetic factors that increase susceptibility to tobacco addiction may result in more effective tobacco cessation programs which will, in turn, reduce the incidence of tobacco related disease, including pancreatic cancer.

Molecular signaling mechanisms of apoptosis in hereditary non-polyposis colorectal cancer

Colorectal cancer is the second most leading cause of cancer related deaths in the western countries. One of the forms of colorectal cancer is hereditary non-polyposis colorectal cancer (HNPCC), also known as "Lynch syndrome". It is the most common hereditary form of cancer accounting for 5%-10% of all colon cancers. HNPCC is a dominant autosomal genetic disorder caused by germ line mutations in mismatch repair genes. Human mismatch repair genes play a crucial role in genetic stability of DNA, the inactivation of which results in an increased rate of mutation and often a loss of mismatch repair function. Recent studies have shown that certain mismatch repair genes are involved in the regulation of key cellular processes including apoptosis. Thus, differential expression of mismatch repair genes particularly the contributions of MLH1 and MSH2 play important roles in therapeutic resistance to certain cytotoxic drugs such as cisplatin that is used normally as chemoprevention. An understanding of the role of mismatch repair genes in molecular signaling mechanism of apoptosis and its involvement in HNPCC needs attention for further work into this important area of cancer research, and this review article is intended to accomplish that goal of linkage of apoptosis with HNPCC. The current review was not intended to provide a comprehensive enumeration of the entire body of literature in the area of HNPCC or mismatch repair system or apoptosis; it is rather intended to focus primarily on the current state of knowledge of the role of mismatch repair proteins in molecular signaling mechanism of apoptosis as it relates to understanding of HNPCC.

Utility of endoscopic ultrasound and endoscopy in diagnosis and management of hepatocellular carcinoma and its complications: What does endoscopic ultrasonography offer above and beyond conventional cross-sectional imaging?

Hepatocellular carcinoma constitutes over 90% of the primary liver tumors, the rest being cholangiocarcinoma. It has an insidious presentation, which is responsible for the delayed presentation. Hence, the management strategy relies on screening to diagnose it an early stage for curative resection and/or treatment with local ablative techniques or chemotherapy. However, even with different screening programs, more than 60% of tumors are still detected at an advanced stage, leading to an unchanged mortality rate, thereby implying a room for improvement in the screening and diagnostic process. In the last few years, there has been evolution of utility of endoscopy, specifically endoscopic ultrasonography along with Fine needle aspiration, for this purpose, which we comprehensively review in this article.

Role of cardiac CTA in estimating left ventricular volumes and ejection fraction

Left ventricular ejection fraction(LVEF)is an impor-tant predictor of cardiac outcome and helps in makingimportant diagnostic and therapeutic decisions suchas the treatment of different types of congestive heartfailure or implantation of devices like cardiac resynchro-nization therapy-defibrillator.LVEF can be measuredby various techniques such as transthoracic echo-cardiography,contrast ventriculography,radionuclidetechniques,cardiac magnetic resonance imaging andcardiac computed tomographic angiography(CTA).Thedevelopment of cardiac CTA using multi-detector rowCT(MDCT)has seen a very rapid improvement in thetechnology for identifying coronary artery stenosis andcoronary artery disease in the last decade.During theacquisition,processing and analysis of data to studycoronary anatomy,MDCT provides a unique opportunityto measure left ventricular volumes and LVEF simulta-neously with the same data set without the need foradditional contrast or radiation exposure.The develop-ment of semi-automated and automated software to measure LVEF has now added uniformity,efficiency and reproducibility of practical value in clinical practice rather than just being a research tool.This article will address the feasibility,the accuracy and the limitations of MDCT in measuring LVEF.

Nicotine as a mitogenic stimulus for pancreatic acinar cell proliferation

Cell proliferation is an important process in life for growth of normal and cancer cells. The signal transduction pathways activated during this process are strictly regulated. This editorial focuses on the role of nicotine, a mitogen, in the induction of signaling pathways resulting in proliferation of pancreatic tumor cells and compares these events with those in normal acinar cells isolated from the rat pancreas. The data shows striking similarities between these two cellular systems. In addition, the editorial reviews very recent literature of the contribution of MAPK signaling in cell lines associated with human diseases. A prospective cellular model of nicotine induced activation of MAPK cascade is presented.

Low phase angle is associated with the development of hepatic encephalopathy in patients with cirrhosis

AIM Evaluate the association between phase angle and the development of hepatic encephalopathy in the longterm follow-up of cirrhotic patients.METHODS This was a prospective cohort study. Clinical, nutritional and biochemical evaluations were performed. MannWhitney's U and χ2 tests were used as appropriate. Kaplan-Meier curves and Cox proportional Hazards analysis were used to evaluate the prediction and incidence of hepatic encephalopathy.RESULTS Two hundred and twenty were included; the most frequent etiology of cirrhosis was hepatitis C infection, 52% of the patients developed hepatic encephalopathy(18.6% covert and 33.3% overt); the main precipitating factors were infections and variceal bleeding. KaplanMeier curves showed a higher proportion of HE in the group with low phase angle(39%) compared to the normal phase angle group(13%)(P = 0.012). Furthermore, creatinine and phase angle remained independently associated to hepatic encephalopathy in the Cox regression multivariate analysis [hazard ratio = 1.80(1.07-3.03)]. CONCLUSION In our cohort of patients low phase angle was associated with an increased incidence of hepatic encephalopathy. Phase angle is a useful nutritional marker that evaluates cachexia and could be used as a part of the integral assessment in patients with cirrhosis.