Are EPB41 and alpha-synuclein diagnostic biomarkers of sport-related concussion?Findings from the NCAA and Department of Defense CARE Consortium

Background:Current protein biomarkers are only moderately predictive at identifying individuals with mild traumatic brain injury or concussion.Therefore,more accurate diagnostic markers are needed for sport-related concussion.Methods:This was a multicenter,prospective,case-control study of athletes who provided blood samples and were diagnosed with a concussion or were a matched non-concussed control within the National Collegiate Athletic Association-Department of Defense Concussion Assessment,Research,and Education Consortium conducted between 2015 and 2019.The blood was collected within 48 h of injury to identify protein abnormalities at the acute and subacute timepoints.Athletes with concussion were divided into 6 h post-injury(0-6 h post-injury)and after 6 h postinjury(7-48 h post-injury)groups.We applied a highly multiplexed proteomic technique that used a DNA aptamers assay to target 1305proteins in plasma samples from athletes with and without sport-related concussion.Results:A total of 140 athletes with concussion(79.3%males;aged 18.71±1.10 years,mean±SD)and 21 non-concussed athletes(76.2%males;19.14±1.10 years)were included in this study.We identified 338 plasma proteins that significantly differed in abundance(319 upregulated and 19 downregulated)in concussed athletes compared to non-concussed athletes.The top 20 most differentially abundant proteins discriminated concussed athletes from non-concussed athletes with an area under the curve(AUC)of 0.954(95%confidence interval:0.922-0.986).Specifically,after 6 h of injury,the individual AUC of plasma erythrocyte membrane protein band 4.1(EPB41)and alpha-synuclein(SNCA)were 0.956 and 0.875,respectively.The combination of EPB41 and SNCA provided the best AUC(1.000),which suggests this combination of candidate plasma biomarkers is the best for diagnosing concussion in athletes after 6 h of injury.Conclusion:Our data suggest that proteomic profiling may provide novel diagnostic protein markers and that a combination of EPB41 and SNCA is the most predictive biomarker of concussion after 6 h of injury.

Relationships of hospitalization outcomes and timing to endoscopy in non-variceal upper gastrointestinal bleeding:A nationwide analysis

BACKGROUND The optimal timing of esophagogastroduodenoscopy(EGD)and the impact of clinico-demographic factors on hospitalization outcomes in non-variceal upper gastrointestinal bleeding(NVUGIB)remains an area of active research.AIM To identify independent predictors of outcomes in patients with NVUGIB,with a particular focus on EGD timing,anticoagulation(AC)status,and demographic features.METHODS A retrospective analysis of adult patients with NVUGIB from 2009 to 2014 was performed using validated ICD-9 codes from the National Inpatient Sample database.Patients were stratified by EGD timing relative to hospital admission(≤24 h,24-48 h,48-72 h,and>72 h)and then by AC status(yes/no).The primary outcome was all-cause inpatient mortality.Secondary outcomes included healthcare usage.RESULTS Of the 1082516 patients admitted for NVUGIB,553186(51.1%)underwent EGD.The mean time to EGD was 52.8 h.Early(<24 h from admission)EGD was associated with significantly decreased mortality,less frequent intensive care unit admission,shorter length of hospital stays,lower hospital costs,and an increased likelihood of discharge to home(all with P<0.001).AC status was not associated with mortality among patients who underwent early EGD(aOR 0.88,P=0.193).Male sex(OR 1.30)and Hispanic(OR 1.10)or Asian(aOR 1.38)race were also independent predictors of adverse hospitalization outcomes in NVUGIB.CONCLUSION Based on this large,nationwide study,early EGD in NVUGIB is associated with lower mortality and decreased healthcare usage,irrespective of AC status.These findings may help guide clinical management and would benefit from prospective validation.

Pre-operative visceral adipose tissue radiodensity is a potentially novel prognostic biomarker for early endoscopic post-operative recurrence in Crohn’s disease

BACKGROUND Evidence suggests inflammatory mesenteric fat is involved in post-operative recurrence(POR)of Crohn’s disease(CD).However,its prognostic value is INTRODUCTION Crohn’s disease(CD)is a debilitating chronic immune-mediated inflammatory disease(IMID)of the gastrointestinal tract that is increasing in incidence and prevalence globally[1].CD patients often undergo surgery for disease-related complic-ations and/or medically refractory disease.Unfortunately,surgery is not curative,and many patients develop post-operative recurrence(POR)of CD with a significant proportion eventually requiring additional surgeries.With advances in early detection and therapeutics,the contemporary 10-year risk of surgery has improved from 50%to 26%,but the risk of recurrent surgery has remained unchanged at 30%,suggesting a need to improve post-operative management strategies[2].Presently,there are two accepted strategies to mitigate POR,but each have potential limitations.Firstly,patients start early post-operative pharmacologic prophylaxis within 4-6 wk after surgery.This strategy can potentially overtreat a subset of patient who may not develop long-term disease recurrence off therapy.Consequently,these patients are at risk of medication-related adverse events and the direct and indirect costs associated with therapy with little or no benefit[3].The second strategy is performing early colonoscopy within 6-12 months after surgery and escalating therapy based on FOOTNOTES Author contributions:Gu P is the guarantor of the article and was involved in concept and design,data collection,statistical analysis,drafting of manuscript,and final approval of manuscript;Dube S and Choi SY were involved in statistical analysis,drafting of the manuscript,and final approval of manuscript;Gellada N,Win S,Lee YJ and Yang S were involved in the data collection,drafting of the manuscript,and final approval of manuscript;Haritunians T and Li D were involved in data analysis and interpretation,drafting of manuscript and final approval of manuscript;Melmed GY,Yarur AJ,Fleshner P,Kallman C and Devkota S were involved in study concept and design,data interpretation,drafting of manuscript and final approval of manuscript;Vasiliauskas EA,Bonthala N,Syal G,Ziring D and Targan SR were involved in data interpretation,drafting of manuscript and final approval of manuscript;Rabizadeh S was involved in study concept and design,drafting of manuscript and final approval of manuscript;McGovern DPB was involved in concept and design,statistical analysis,drafting of manuscript and final approval of manuscript.

Histone methyltransferases and demethylases:regulators in balancing osteogenic and adipogenic differentiation of mesenchymal stem cells

Mesenchymal stem cells （MSCs） are characterized by their self-renewing capacity and differentiation potential into multiple tissues. Thus, management of the differentiation capacities of MSCs is important for MSC-based regenerative medicine, such as craniofacial bone regeneration, and in new treatments for metabolic bone diseases, such as osteoporosis. In recent years, histone modification has been a growing topic in the field of MSC lineage specification, in which the Su（var）3-9, enhancer-of-zeste, trithorax （SET） domain-containing family and the Jumonji C （JmjC） domain-containing family represent the major histone lysine methyltransferases （KMTs） and histone lysine demethylases （KDMs）, respectively. In this review, we summarize the current understanding of the epigenetic mechanisms by which SET domain-containine KMTs and JmiC domain-containinlz KDMs balance the osteogenic and adipogenic differentiation of MSCs.

Management of hepatocellular carcinoma with portal vein thrombosis

Management of hepatocellular carcinoma(HCC) with portal vein thrombosis(PVT) is complex andrequires an understanding of multiple therapeutic options. PVT is present in 10%-40% of HCC at the time of diagnosis, and is an adverse prognostic factor. Management options are limited, as transplantation is generally contraindicated, and surgical resection is only rarely performed in select centers. Systemic medical therapy with sorafenib has been shown to modestly prolong survival. Transarterial chemoembolization has been performed in select cases but has shown a high incidence of complications. Emerging data on treatment of PVT with Y-90 radioembolization suggest that this modality is well-tolerated and associated with favorable overall survival. Current society guidelines do not yet specifically recommend radioembolization for patients with PVT, but this may change with the development of newer staging systems and treatment algorithms. In this comprehensive literature review, we present current and available management options with the relative advantages, disadvantages and contraindications of these treatment options with summarized data on overall survival.

Management of centrally located hepatocellular carcinoma:Update 2016

Centrally located hepatocellular carcinoma(HCC)is sited in the central part of the liver and adjacent to main hepatic vascular structures.This special location is associated with an increase in the difficulty of surgery,aggregation of the recurrence disease,and greater challenge in disease management.This review summarizes the evolution of our understanding for centrally located HCC and discusses the development of treatment strategies,surgical approaches and recurrence prevention methods.To improve patient survival,a multi-disciplinary modality is greatly needed throughout the whole treatment period.

Nationwide trends and predictors of inpatient mortality in 83884 transjugular intrahepatic portosystemic shunt

AIM: To evaluate and validate the national trends and predictors of in-patient mortality of transjugular intrahepatic portosystemic shunt(TIPS) in 15 years.METHODS: Using the National Inpatient Sample which is a part of Health Cost and Utilization Project, we identified a discharge-weighted national estimate of 83884 TIPS procedures performed in the United States from 1998 to 2012 using international classification of diseases-9 procedural code 39.1. The demographic, hospital and co-morbility data were analyzed using a multivariant analysis. Using multi-nominal logistic regression analysis, we determined predictive factors related to increases in-hospital mortality. Comorbidity measures are in accordance to the Comorbidity Software designed by the Agency for Healthcare Research and Quality.RESULTS: Overall, 12.3% of patients died during hospitalization with downward trend in-hospitalmortality with the mean length of stay of 10.8 ± 13.1 d. Notable, African American patients(OR = 1.809 vs Caucasian patients, P < 0.001), transferred patients(OR = 1.347 vs non-transferred, P < 0.001), emergency admissions(OR = 3.032 vs elective cases, P < 0.001), patients in the Northeast region(OR = 1.449 vs West, P < 0.001) had significantly higher odds of inhospital mortality. Number of diagnoses and number of procedures showed positive correlations with in-hospital death(OR = 1.249 per one increase in number of procedures). Patients diagnosed with acute respiratory failure(OR = 8.246), acute kidney failure(OR = 4.359), hepatic encephalopathy(OR = 2.217) and esophageal variceal bleeding(OR = 2.187) were at considerably higher odds of in-hospital death compared with ascites(OR = 0.136, P < 0.001). Comorbidity measures with the highest odds of in-hospital death were fluid and electrolyte disorders(OR = 2.823), coagulopathy(OR = 2.016), and lymphoma(OR = 1.842).CONCLUSION: The overall mortality of the TIPS procedure is steadily decreasing, though the length of stay has remained relatively constant. Specific patient ethnicity, location, transfer status, primary diagnosis and comorbidities correlate with increased odds of TIPS in-hospital death.

Numerical Simulation of the Impact of Vegetation Index on the Interannual Variation of Summer Precipitation in the Yellow River Basin

Two sets of numerical experiments using the coupled National Center for Environmental Prediction General Circulation Model （NCEP/GCM T42L18） and the Simplified Simple Biosphere land surface scheme （SSiB） were carried out to investigate the climate impacts of fractional vegetation cover （FVC） and leaf area index （LAI） on East Asia summer precipitation, especially in the Yellow River Basin （YRB）. One set employed prescribed FVC and LAI which have no interannual variations based on the climatology of vegetation distribution; the other with FVC and LAI derived from satellite observations of the International Satellite Land Surface Climate Project （ISLSCP） for 1987 and 1988. The simulations of the two experiments were compared to study the influence of FVC, LAI on summer precipitation interannual variation in the YRB. Compared with observations and the NCEP reanalysis data, the experiment that included both the effects of satellite-derived vegetation indexes and sea surface temperature （SST） produced better seasonal and interannual precipitation variations than the experiment with SST but no interannual variations in FVC and LAI, indicating that better representations of the vegetation index and its interannual variation may be important for climate prediction. The difference between 1987 and 1988 indicated that with the increase of FVC and LAI, especially around the YRB, surface albedo decreased, net surface radiation increased, and consequently local evaporation and precipitation intensified. Further more, surface sensible heat flux, surface temperature and its diurnal variation decreased around the YRB in response to more vegetation. The decrease of surface-emitting longwave radiation due to the cooler surface outweighed the decrease of surface solar radiation income with more cloud coverage, thus maintaining the positive anomaly of net surface radiation. Further study indicated that moisture flux variations associated with changes in the general circulation also contributed to the precipitation interannual variation.

Characterization of the osteogenic potential of mesenchymal stem cells from human periodontal ligament based on cell surface markers

Mesenchymal stem cell （MSC）-mediated therapy has been shown to be clinically effective in regenerating tissue defects. For improved regenerative therapy, it is critical to isolate homogenous populations of MSCs with high capacity to differentiate into appropriate tissues. The utilization of stem cell surface antigens provides a means to identify MSCs from various tissues. However, few surface markers that consistently isolate highly regenerative MSCs have been validated, making it challenging for routine clinical applications and making it all the more imperative to identify reliable surface markers. In this study, we used three surface marker combinations： CD51/CD140a, CD271, and STRO-1/CD146 for the isolation of homogenous populations of dental mesenchymal stem cells （DMSCs） from heterogeneous periodontal ligament cells （PDLCs）. Fluorescence-activated cell sorting analysis revealed that 24% of PDLCs were CD51＋/CD140a＋, 0.8% were CD271＋, and 2.4% were STRO-1＋/CD146＋. Sorted cell populations were further assessed for their multipotent properties by inducing osteogenic and chondrogenic differentiation. All three subsets of isolated DMSCs exhibited differentiation capacity into osteogenic and chondrogenic lineages but with varying degrees. CD271＋ DMSCs demonstrated the greatest osteogenic potential with strong induction of osteogenic markers such as DLX5, RUNX2, and BGLAP. Our study provides evidence that surface marker combinations used in this study are sufficient markers for the isolation of DMSCs from PDLCs. These results provide important insight into using specific surface markers for identifying homogenous populations of DMSCs for their improved utilization in regenerative medicine.

Central role of Yes-associated protein and WW-domain-containing transcriptional co-activator with PDZ-binding motif in pancreatic cancer development

Pancreatic ductal adenocarcinoma(PDAC) remains a deadly disease with no efficacious treatment options. PDAC incidence is projected to increase, which may be caused at least partially by the obesity epidemic. Significantly enhanced efforts to prevent or intercept this cancer are clearly warranted. Oncogenic KRAS mutations are recognized initiating events in PDAC development, however, they are not entirely sufficient for the development of fully invasive PDAC.Additional genetic alterations and/or environmental, nutritional, and metabolic signals, as present in obesity, type-2 diabetes mellitus, and inflammation, are required for full PDAC formation. We hypothesize that oncogenic KRAS increases the intensity and duration of the growth-promoting signaling network.Recent exciting studies from different laboratories indicate that the activity of the transcriptional co-activators Yes-associated protein(YAP) and WW-domaincontaining transcriptional co-activator with PDZ-binding motif(TAZ) play a critical role in the promotion and maintenance of PDAC operating as key downstream target of KRAS signaling. While initially thought to be primarily an effector of the tumor-suppressive Hippo pathway, more recent studies revealed that YAP/TAZ subcellular localization and co-transcriptional activity is regulated by multiple upstream signals. Overall, YAP has emerged as a central node of transcriptional convergence in growth-promoting signaling in PDAC cells. Indeed, YAP expression is an independent unfavorable prognostic marker for overall survival of PDAC. In what follows, we will review studies implicating YAP/TAZ in pancreatic cancer development and consider different approaches to target these transcriptional regulators.

HYPERBOLIC MEAN CURVATURE FLOW:EVOLUTION OF PLANE CURVES

In this paper we investigate the one-dimensional hyperbolic mean curvatureflow for closed plane curves. More precisely, we consider a family of closed curves F ： S1 × [0, T ） → R^2 which satisfies the following evolution equation δ^2F /δt^2 （u, t） = k（u, t）N（u, t）-▽ρ（u, t）, ∨（u, t） ∈ S^1 × [0, T ） with the initial data F （u, 0） = F0（u） and δF/δt （u, 0） = f（u）N0, where k is the mean curvature and N is the unit inner normal vector of the plane curve F （u, t）, f（u） and N0 are the initial velocity and the unit inner normal vector of the initial convex closed curve F0, respectively, and ▽ρ is given by ▽ρ Δ=（δ^2F /δsδt ,δF/δt） T , in which T stands for the unit tangent vector. The above problem is an initial value problem for a system of partial differential equations for F , it can be completely reduced to an initial value problem for a single partial differential equation for its support function. The latter equation is a hyperbolic Monge-Ampere equation. Based on this, we show that there exists a class of initial velocities such that the solution of the above initial value problem exists only at a finite time interval [0, Tmax） and when t goes to Tmax, either the solution convergesto a point or shocks and other propagating discontinuities are generated. Furthermore, we also consider the hyperbolic mean curvature flow with the dissipative terms and obtain the similar equations about the support functions and the curvature of the curve. In the end, we discuss the close relationship between the hyperbolic mean curvature flow and the equations for the evolving relativistic string in the Minkowski space-time R^1,1.

Effects of Yttrium-90 selective internal radiation therapy on non-conventional liver tumors

The liver is a common site of metastasis, with essentially all metastatic malignancies having been known to spread to the liver. Nearly half of all patients with extrahepatic primary cancer have hepatic metastases. The severe prognostic implications of hepatic metastases have made surgical resection an important first line treatment in management. However, limitations such as the presence of extrahepatic spread or poor functional hepatic reserve exclude the majority of patients as surgical candidates, leaving chemotherapy and locoregional therapies as next best options. Selective internal radiation therapy(SIRT) is a form of catheter-based locoregional cancer treatment modality for unresectable tumors, involving trans-arterial injection of microspheres embedded with a radioisotope Yttrium-90. The therapeutic radiation dose is selectively delivered as the microspheres permanently embed themselves within the tumor vascular bed. Use of SIRT has been conventionally aimed at treating primary hepatic tumors(hepatocellular carcinoma) or colorectal and neuroendocrine metastases. Numerous reviews are available for these tumor types. However, little is known or reviewed on non-colorectal or nonneuroendocrine primaries. Therefore, the aim of this paper is to systematically review the current literature to evaluate the effects of Yttrium-90 radioembolization on non-conventional liver tumors including those secondary to breast cancer, cholangiocarcinoma, ocular and percutaneous melanoma, pancreatic cancer, renal cell carcinoma, and lung cancer.

Human immunodeficiency virus and nodular regenerative hyperplasia of liver: A systematic review

AIM: To investigate the diagnosis, pathogenesis, natural history, and management of nodular regenerative hyperplasia(NRH) in patients with human immunodeficiency virus(HIV). METHODS: We performed a systematic review of the medical literature regarding NRH in patients with HIV. Inclusion criteria include reports with biopsy proven NRH. We studied the clinical features of NRH, in particular, related to its presenting manifestation and laboratory values. Combinations of the following keywords were implemented: "nodular regenerative hyperplasia", "human immunodeficiency virus", "noncirrhotic portal hypertension", "idiopathic portal hypertension", "cryptogenic liver disease", "highly active antiretroviral therapy" and "didanosine". The bibliographies of these studies were subsequently searched for any additional relevant publications.RESULTS: The clinical presentation of patients with NRH varies from patients being completely asymptomatic to the development of portal hypertension – namely esophageal variceal bleeding and ascites. Liver associated enzymes are generally normal and synthetic function well preserved. There is a strong association between the occurrence of NRH and the use of antiviral therapies such as didanosine. The management of NRH revolves around treating the manifestations of portal hypertension. The prognosis of NRH is generally good since liver function is preserved. A high index of suspicion is required to make a identify NRH. CONCLUSION: The appropriate management of HIVinfected persons with suspected NRH is yet to be outlined. However, NRH is a clinically subtle condition that is difficult to diagnose, and it is important to be able to manage it according to the best available evidence.

WJSC 6^(th) Anniversary Special Issues(2):Mesenchymal stem cells “Ins” and “Outs” of mesenchymal stem cell osteogenesis in regenerative medicine

Repair and regeneration of bone requires mesenchymal stem cells that by self-renewal,are able to generate a critical mass of cells with the ability to differentiate into osteoblasts that can produce bone protein matrix(osteoid)and enable its mineralization.The number of human mesenchymal stem cells(hMSCs)diminishes with age and ex vivo replication of hMSCs has limited potential.While propagating hMSCs under hypoxic conditions may maintain their ability to self-renew,the strategy of using human telomerase reverse transcriptase(hTERT)to allow for hMSCs to prolong their replicative lifespan is an attractive means of ensuring a critical mass of cells with the potential to differentiate into various mesodermal structural tissues including bone.However,this strategy must be tempered by the oncogenic potential of TERT-transformed cells,or their ability to enhance already established cancers,the unknown differentiating potential of high population doubling hMSCs and the source of hMSCs(e.g.,bone marrow,adipose-derived,muscle-derived,umbilical cord blood,etc.)that may provide peculiarities to self-renewal,differentiation,and physiologic function that may differ from non-transformed native cells.Tissue engineering approaches to use hMSCs to repair bone defects utilize the growth of hMSCs on three-dimensional scaffolds that can either be a base on which hMSCs can attach and grow or as a means of sequestering growth factors to assist in the chemoattraction and differentiation of native hMSCs.The use of whole native extracellular matrix(ECM)produced by hMSCs,rather than individual ECM components,appear to be advantageous in not only being utilized as a three-dimensional attachment base but also in appropriate orientation of cells and their differentiation through the growth factors that native ECM harbor or in simulating growth factor motifs.The origin of native ECM,whether from hMSCs from young or old individuals is a critical factor in"rejuvenating"hMSCs from older individuals grown on ECM from younger individuals.

Characterization of Fusobacterium nucleatum ATCC 23726 adhesins involved in strain-specific attachment to Porphyromonas gingivalis

Bacterial adherence is an essential virulence factor in pathogenesis and infection. Fusobacterium nucleatum has a central role in oral biofilm architecture by acting as a bridge between early Gram-positive and late Gram-negative colonizers that do not otherwise adhere to each other. In this study, we survey a key adherence interaction of F. nucleatum with Porphyromonas gingivalis, and present evidence that multiple fusobacterial adhesins have a role in the attachment of F. nucleatum ATCC 23726 to P. gingivalis in a highly strain-dependent manner. Interaction between these species displayed varying sensitivities to arginine, galactose and lactose. Arginine was found to hamper coaggregation by at least 62% and up to 89% with several P. gingivalis strains and galactose inhibition ranged from no inhibition up to 58% with the same P. gingivalis strains. Lactose consistently inhibited F. nucleatum interaction with these P. gingivalis strains ranging from 40% to 56% decrease in coaggregation. Among the adhesins involved are the previously described Fap2 and surprisingly, RadD, which was described in an earlier study for its function in attachment of F. nucleatum to Gram-positive species. We also provide evidence for the presence of at least one additional adhesin that is sensitive to arginine but unlike Fap2 and RadD, is not a member of the autotransporter family type of fusobacterial large outer membrane proteins. The strain-specific binding profile of multiple fusobacterial adhesins to P. gingivalis highlights the heterogeneity and complexity of interspecies interactions in the oral cavity.

The nature of near-wall convection velocity in turbulent channel flow

A novel notion of turbulent structure the local cascade structure-is introduced to study the convection phenomenon in a turbulent channel flow. A space-time cross-correlation method is used to calculate the convection velocity. It is found that there are two characteristic convection speeds near the wall, one associated with small-scale streaks of a lower speed and another with streamwise vortices and hairpin vortices of a higher speed. The new concept of turbulent structure is powerful to illustrate the dominant role of coherent structures in the near-wall convection, and to reveal also the nature of the convection-the propagation of patterns of velocity fluctuations-which is scale-dependent.

Validation and application of soil moisture active passive sea surface salinity observation over the Changjiang River Estuary

Using sea surface salinity(SSS)observation from the soil moisture active passive(SMAP)mission,we analyzed the spatial distribution and seasonal variation of SSS around Changjiang River(Yangtze River)Estuary for the period of September 2015 to August 2018.First,we found that the SSS from SMAP is more accurate than soil moisture and ocean salinity(SMOS)mission observation when comparing with the in situ observations.Then,the SSS signature of the Changjiang River freshwater was analyzed using SMAP data and the river discharge data from the Datong hydrological station.The results show that the SSS around the Changjiang River Estuary is significantly lower than that of the open ocean,and shows significant seasonal variation.The minimum value of SSS appears in July and maximum SSS in December.The root mean square difference of daily SSS between SMAP observation and in situ observation is around 3 in both summer and winter,which is much lower than the annual range of SSS variation.In summer,the diffusion direction of the Changjiang River freshwater depicted by SSS from SMAP is consistent with the path of freshwater from in situ observation,suggesting that SMAP observation may be used in coastal seas in monitoring the diffusion and advection of freshwater discharge.

RACIAL DIFFERENCES OF OPTIC DISC TOPOGRAPHY IN OCULAR HYPERTEN- SIVE EYES: RESULTS FROM THE CON- FOCAL SCANNING LASER OPHTHAL- MOSCOPY ANCILLARY STUDY TO THE OCULAR HYPERTENSION TREATMENT STUDY

Purpose: To examine racial differences in optic disc topography among ocular hypertensive participants in the Ocular Hypertension Treatment Study (OHTS). Methods: 436 participants

Noninvasive scores for the prediction of esophageal varices and risk stratification in patients with cirrhosis

The primary purpose of variceal screening in patients with cirrhosis is to detect gastroesophageal varices at high risk of hemorrhage and implement preventative intervention(s).It was previously recommended that all patients with cirrhosis undergo initial and periodic longitudinal variceal screening via upper endoscopy.However,there has been growing interest and methods to identify patients with cirrhosis who may not have clinically significant portal hypertension and therefore be unlikely to have varices requiring intervention or benefit from upper endoscopy.Because the population of patients with compensated advanced chronic liver disease continues to grow,it is neither beneficial nor cost-effective to perform endoscopic variceal screening in all patients.Therefore,there is ongoing research into the development of methods to non-invasively risk stratify patients with cirrhosis for the presence of high-risk esophageal varices and effectively limit the population that undergoes endoscopic variceal screening.This is particularly important and timely in light of increasing healthcare reform and barriers to healthcare.In this review,we discuss and compare,with respect to test characteristics and clinical applicability,the available methods used to noninvasively predict the presence of esophageal varices.

Current concepts and controversies in the treatment of alcoholic hepatitis

The treatment of alcoholic hepatitis remains one of the most debated topics in medicine and a field of continued research. In this review, we discuss the evolution of scoring systems, including the recent development of the Glasgow alcoholic hepatitis score, role of liver biopsy and current treatment interventions. Studies of treatment interventions with glucocorticoids, pentoxifylline, infliximab, s-adenosyl-methionine, and colchicine are reviewed with discussion on quality. Glucocorticoids currently remain the mainstay of treatment for severe alcoholic hepatitis.