Outcomes of endoscopic submucosal dissection in cirrhotic patients: First American cohort

BACKGROUND Among patients with cirrhosis and pre-malignant or early malignant mucosal lesions,surgical intervention carries a much higher bleeding risk.When such lesions are discovered,endoscopic submucosal dissection(ESD)may offer curative therapy with lower risks than surgery and improved outcomes compared to traditional endoscopic resection.AIM To evaluate the outcomes of ESD in patients with cirrhosis.METHODS Patients with cirrhosis undergoing ESD between July 2015 and August 2022 were retrospectively matched in 1:2 fashion to controls based on lesion location,size,and anticoagulation use.Procedural outcomes were compared between groups.RESULTS A total of 64 Lesions from 59 patients were included(16 cirrhosis,43 control).There were no differences in patient or lesion characteristics between groups.En bloc and curative resection was achieved in 84.21%,78.94%of the cirrhosis group and 88.89%,68.89%of controls,respectively,with no significant differences.Cirrhotic patients had significantly higher rates of intra-procedural coagulation grasper use for control of bleeding(47.37%vs 20%;P=0.02).There were otherwise no significant differences in adverse event rates.In the 29 patients with follow up,we found higher rates of recurrence in the cirrhosis group compared to controls(40%vs 5.26%;P=0.019),however this effect did not persist on multivariable analysis controlling for known confounders.CONCLUSION ESD may be safe and effective in patients with cirrhosis.Most procedure related outcomes were not significantly different between groups.Intra-procedural bleeding requiring use of the coagulation grasper use was expectedly higher in the cirrhosis group given the known effects of liver disease on hemostasis.

Evaluation of Hemoglobin and Serum Erythropoietin Levels in Patients with Polycythemia Vera and Secondary Polycythemia

Objective: This study compares hemoglobin and erythropoietin levels in patients with polycythemia vera and secondary polycythemia. Study Design: A retrospective cross-sectional study evaluating the serum erythropoietin and hemoglobin levels in patients with polycythemia vera and secondary polycythemia. This study was performed simultaneously in Texas state of the U.S. and Fars Province in Iran. Methods: Hemoglobin, hematocrit and erythropoietin test results were collected from patients aged 19 to 75 years who were diagnosed with polycythemia vera and secondary polycythemia. Patients records with history of thrombocythemia, congestive heart failure, dyspnea, anemia and pregnant woman were excluded from study. Patients in each decade of life were examined in separate groups, so that changes in hemoglobin related to aging did not affect the research results. Results: 75% of the patients were men, and 25% were women. A total of 1580 patients were analyzed in this study. 57.3% of patients in UTMB and 38.8 patients in Iran have hemoglobin level above 17 mg/dl. 74% of patients in UTMB and 88% of patients in Iran have erythropoietin below 10 IU/mL. Polycythemia in UTMB was more common in people over 50 and in Iran in patients under 50 years old. The serum hemoglobin and erythropoietin levels in patients with polycythemia vera were not significantly different in compare to secondary polycythemia patients. Data showed that there were 84 polycythemia patients per 100,000 people. The results of this study in UTMB and Iran showed that 4.5% and 7%, respectively, of patients with polycythemia had a positive JAK2 test. Conclusion: Low erythropoietin levels may not be helpful in differentiating polycythemia vera from secondary polycythemia. .

The Combination Effect of Daphne Extract and Imatinib on the Antiproliferative Activity of the K562 Cell Line

Background: Herbal medicine is well-known among the ancient medical sciences. Healing properties have been observed in some species of Daphne plant. The effect of Daphne plant extract on the K562 cell line has been previously studied, and Gleevec is a well-known and effective medicine for the treatment of chronic myelogenous leukemia. Material and Methods: In this study, the simultaneous effects of using herbal medicine and a target therapy medicine on the K562 cell line were investigated. The presence of some species of Daphne in Iran motivated us to evaluate the cytotoxic effect of Daphne mucronata on human leukemia cancer cells. The antiproliferative activity of the dichloromethane extract of Daphne mucronate (Thymelaeaceae), a new anticancer medicinal plant, was evaluated. Cell viability was quantitated by MTT assay. Apoptotic and necrotic changes in the cell membrane were examined using flow cytometry. Changes in Bax and Bcl2 gene expression were investigated using real-time PCR. The MIC and the IC50 of the crude extract were calculated, and the MIC and IC50 of the Daphne extract in combination of imatinib were tested in the K-562 cell line. Results: K-562 cells responded to the extract treatments in a dose-dependent manner, and the increase in the expression of Bcl2 and decrease in the expression of the Bax gene intensified with increasing extract concentration. Flow cytometry revealed that most of the cells underwent necrosis. Conclusion: Daphne extract effectively decreased the viability of the K562 cell line. The necrotic effect of the Daphne extract was evaluated, and an increase in the gene expression of Bcl2 was observed in cells exposed to the Daphne extract. The combination of Daphne extracts with imatinib enhances the cytotoxic effect of imatinib.

Insights into renal and urological complications of inflammatory bowel disease

Inflammatory bowel disease(IBD)is a chronic condition characterized by immune-mediated inflammation in the gastrointestinal tract,which follows a relapsing and remitting course.Apart from affecting the gastrointestinal tract,IBD also has extra-intestinal manifestations(EIMs).While the etiology of extraintestinal manifestation remains unclear,it is theorized to be based on immunological responses influenced by genetic factors.Renal involvement is one of the EIMs observed in ulcerative colitis and Crohn’s disease.The renal manifes-tations in IBD patients encompass a range of conditions including nephrolithiasis,amyloidosis,tubulointerstitial nephritis,glomerulonephritis(GN),obstructive pathologies,and chronic kidney disease(CKD).The incidence of CKD in IBD patients varies from 5%-15%.The decline in renal function can stem from various factors such as direct inflammatory damage to the kidneys leading to glomerular or tubular injury,or from complications like recurrent stones,amyloidosis,or GN.Additionally,nephrotoxic medications used in treating IBD,such as TNF-αinhibitors,calcineurin inhibitors,and aminosalicylates,can exacerbate the decline in renal function.Currently,there is a lack of consensus regarding these patients'screening and renal function monitoring.This review aims to assess the existing literature on the different renal complications among individuals with IBD,shedding light on their pathophysiology and management.

Transperineal laser ablation of the prostate as a treatment for benign prostatic hyperplasia and prostate cancer: The results of a Delphi consensus project

Objective: To evaluate transperineal laser ablation (TPLA) with Echolaser® (Echolaser® TPLA, Elesta S.p.A., Calenzano, Italy) as a treatment for benign prostatic hyperplasia (BPH) and prostate cancer (PCa) using the Delphi consensus method.Methods: Italian and international experts on BPH and PCa participated in a collaborative consensus project. During two rounds, they expressed their opinions on Echolaser® TPLA for the treatment of BPH and PCa answering online questionnaires on indications, methodology, and potential complications of this technology. Level of agreement or disagreement to reach consensus was set at 75%. If the consensus was not achieved, questions were modified after each round. A final round was performed during an online meeting, in which results were discussed and finalized.Results: Thirty-two out of forty invited experts participated and consensus was reached on all topics. Agreement was achieved on recommending Echolaser® TPLA as a treatment of BPH in patients with ample range of prostate volume, from <40 mL (80%) to >80 mL (80%), comorbidities (100%), antiplatelet or anticoagulant treatment (96%), indwelling catheter (77%), and strong will of preserving ejaculatory function (100%). Majority of respondents agreed that Echolaser® TPLA is a potential option for the treatment of localized PCa (78%) and recommended it for low-risk PCa (90%). During the final round, experts concluded that it can be used for intermediate-risk PCa and it should be proposed as an effective alternative to radical prostatectomy for patients with strong will of avoiding urinary incontinence and sexual dysfunction. Almost all participants agreed that the transperineal approach of this organ-sparing technique is safer than transrectal and transurethral approaches typical of other techniques (97% of agreement among experts). Pre-procedural assessment, technical aspects, post-procedural catheterization, pharmacological therapy, and expected outcomes were discussed, leading to statements and recommendations.Conclusion: Echolaser® TPLA is a safe and effective procedure that treats BPH and localized PCa with satisfactory functional and sexual outcomes.

Recent and currently emerging medical treatment options for the treatment of alcoholic hepatitis

Patients with severe alcoholic hepatitis (AH) need to be treated with specific treatment for better outcome.Currently available specific treatment modalities are use of corticosteroids or pentoxifylline.However,the response rate to these drugs is only about 50%-60%.Hence,there is an urgent need for better and more effective treatment options.Tumor necrosis factor plays an important role in the pathogenesis of AH.However,agents blocking the action of tumor necrosis factor have not been found to be effective.Rather the randomized studies evaluating these agents showed an adverse effect and more infections in treated patients.Critical role of tumor necrosis factor in hepatic regen-eration explaining this contrast is discussed.Oxidative stress and inflammation derived from gut bacteria ate two main components in the pathogenesis of AH laying foundation for the role of antioxidants,probiotics,and antibiotics in the management of AH.This article reviews the current data and status of these newer agents for the treatment of AH.Of the various options available,Vitamin E and N-acetylcysteine (NAC) have shown great promise for clinical use as adjunct to corticosteroids.With these encouraging data,future well designed studies are suggested to assess Vitamin E and NAC before their routine use in clinical practice in the management of AH.

The complicated life of a physician-soldier: Medical readiness training exercises &the problem of dual loyalties

While physicians are generally understood as owing moral obligation to the health and well being of their individual patients, military health professionals can face ethical tensions between responsibilities to individual patients and responsibilities to the military mission. The conflicting obligations of the two roles held by the physician-soldier are often referred to as the problem of dual loyalties and have long been a topic of debate. This paper seeks to enrich the dualloyalties debate by examining the embedded case study of medical civilian assistance programs. These programs represent the use of medicine within the military for strategic goals. Thus, a physician is expected to meet his obligation to his role as a soldier while also practicing medicine. These programs involve obligations inherent in both roles of the physician-soldier and thusly they serve as excellent exemplars for the problem of dual loyalties at an institutional level. This paper focuses on Medical Readiness Training Exercises (MEDRETEs). These programs are short-term, generally taking place in low-income nations in order to accomplish strategic goals including training opportunities for military medical professionals that are not possible on the home front. This form of temporary program raises ethical concerns regarding the exploitation of vulnerable populations and the value of what is termed “parachute medicine”. The short-term nature of these interventions makes long-term treatment and follow-up impossible, begging the question as to whether this peak and trough approach to foreign civilian aid is of any use. Physicians are generally understood as having obligations towards the well being of the patient, which these programs do not necessarily prioritize. Rather, the programmatic intent is military, with political and strategic aims of furthering international relations, increasing US military global presence and providing austere and tropical training opportunities for military healthcare providers. This can be morally problematic for the physician-soldier.

Disparate outcomes in Hispanic patients with metabolic dysfunctionassociated steatotic liver disease/steatohepatitis and type 2 diabetes: Large cohort study

BACKGROUND Metabolic dysfunction-associated steatotic liver disease(MASLD)and metabolic dysfunction-associated steatohepatitis(MASH)are a growing health burden across a significant portion of the global patient population.However,these conditions seem to have disparate rates and outcomes between different ethnic populations.The combination of MASLD/MASH and type 2 diabetes increases the risk of hepatocellular carcinoma(HCC),and Hispanic patients experience the greatest burden,particularly those in South Texas.AIM To compare outcomes between Hispanic and non-Hispanic patients in the United States,while further focusing on the Hispanic population within Southeast Texas to determine whether the documented disparity in outcomes is a function of geographical circumstance or if there is a more widespread reason that all clinicians must account for in prognostic consideration.METHODS This cohort analysis was conducted with data obtained from TriNetX,LLC(“TriNetX”),a global federated health research network that provides access to deidentified medical records from healthcare organizations worldwide.Two cohort networks were used:University of Texas Medical Branch(UTMB)hospital and the United States national database collective to determine whether disparities were related to geographic regions,like Southeast Texas.RESULTS This study findings revealed Hispanics/Latinos have a statistically significant higher occurrence of HCC,type 2 diabetes mellitus,and liver fibrosis/cirrhosis in both the United States and the UTMB Hispanic/Latino groups.Allcause mortality in Hispanics/Latinos was lower within the United States group and not statistically elevated in the UTMB cohort.CONCLUSION This would appear to support that Hispanic patients in Southeast Texas are not uniquely affected compared to the national Hispanic population.

Epidemiology of hepatitis C virus infection

Globally, hepatitis C virus (HCV) has infected an estimated 130 million people, most of whom are chronically infected. HCV-infected people serve as a reservoir for transmission to others and are at risk for developing chronic liver disease, cirrhosis, and primary hepatocellular carcinoma (HCC). It has been estimated that HCV accounts for 27% of cirrhosis and 25% of HCC worldwide. HCV infection has likely been endemic in many populations for centuries. However, the wave of increased HCV-related morbidity and mortality that we are now facing is the result of an unprecedented increase in the spread of HCV during the 20th century. Two 20th century events appear to be responsible for this increase; the widespread availability of injectable therapies and the illicit use of injectable drugs.

Effect of Helicobacter pylori on gastric epithelial cells

The gastrointestinal epithelium has cells with features that make them a powerful line of defense in innate mucosal immunity. Features that allow gastrointestinal epithelial cells to contribute in innate defense include cell barrier integrity, cell turnover, autophagy, and innate immune responses. Helicobacter pylori (H. pylori) is a spiral shape gram negative bacterium that selectively colonizes the gastric epithelium of more than half of the world&#x02019;s population. The infection invariably becomes persistent due to highly specialized mechanisms that facilitate H. pylori&#x02019;s avoidance of this initial line of host defense as well as adaptive immune mechanisms. The host response is thus unsuccessful in clearing the infection and as a result becomes established as a persistent infection promoting chronic inflammation. In some individuals the associated inflammation contributes to ulcerogenesis or neoplasia. H. pylori has an array of different strategies to interact intimately with epithelial cells and manipulate their cellular processes and functions. Among the multiple aspects that H. pylori affects in gastric epithelial cells are their distribution of epithelial junctions, DNA damage, apoptosis, proliferation, stimulation of cytokine production, and cell transformation. Some of these processes are initiated as a result of the activation of signaling mechanisms activated on binding of H. pylori to cell surface receptors or via soluble virulence factors that gain access to the epithelium. The multiple responses by the epithelium to the infection contribute to pathogenesis associated with H. pylori.

Low-dose metformin treatment in the subacute phase improves the locomotor function of a mouse model of spinal cord injury

Metformin,a first-line drug for type-2 diabetes,has been shown to improve locomotor recovery after spinal cord injury.However,there are studies reporting no beneficial effect.Recently,we found that high dose of metformin(200 mg/kg,intraperitoneal)and acute phase administration(immediately after injury)led to increased mortality and limited locomotor function recovery.Consequently,we used a lower dose(100 mg/kg,i.p.)metformin in mice,and compared the effect of immediate administration after spinal cord injury(acute phase)with that of administration at 3 days post-injury(subacute phase).Our data showed that metformin treatment starting at the subacute phase significantly improved mouse locomotor function evaluated by Basso Mouse Scale(BMS)scoring.Immunohistochemical studies also revealed significant inhibitions of microglia/macrophage activation and astrogliosis at the lesion site.Furthermore,metformin treatment at the subacute phase reduced neutrophil infiltration.These changes were in parallel with the increased survival rate of spinal neurons in animals treated with metformin.These findings suggest that low-dose metformin treatment for subacute spinal cord injury can effectively improve the functional recovery possibly through anti-inflammation and neuroprotection.This study was approved by the Institute Animal Care and Use Committee at the University of Texas Medical Branch(approval No.1008041C)in 2010.

CD74 in antigen presentation,inflammation,and cancers of the gastrointestinal tract

CD74 is a protein whose initial role in antigen presentation was recognized two decades ago. Recent studies have revealed that it has additional functions as a receptor for macrophage migration inhibitory factor and as a receptor for an important human pathogen, Helicobacter pylori （H pylon）. The role of CD74 as a receptor is important because after binding of migration inhibitory factor or H pylori, NF-κB and Erkl/2 activation occurs, along with the induction of proinflammatory cytokine secretion. This review provides an up-to-date account of the functions of CD74 and how it might be involved in inflammation and cancer within the gastrointestinal tract.

Evaluation and management of acute pancreatitis

Acute pancreatitis(AP) is one of the most common gastrointestinal causes for hospi-talization in the United States. In 2015, AP accounted for approximately390000 hospitalizations. The burden of AP is only expected to increase over time.Despite recent advances in medicine, pancreatitis continues to be associated with a substantial morbidity and mortality. The most common cause of AP is gallstones, followed closely by alcohol use. The diagnosis of pancreatitis is established with any two of three following criteria:(1) Abdominal pain consistent with that of AP;(2) Serum amylase and/or lipase greater than three times the upper limit of normal; and(3) Characteristics findings seen in crosssectional abdominal imaging. Multiple criteria and scoring systems have been established for assessing severity of AP. The cornerstones of management include aggressive intravenous hydration, appropriate nutrition and pain management.Endoscopic retrograde cholangiopancreatography and surgery are important aspects in management of acute gallstone pancreatitis. We provide a comprehensive review of evaluation and management of AP.

Management of hepatitis C virus infection in HIV/HCV co-infected patients: Clinical review

Nearly one fourth of individuals with human immunodeficiency virus (HIV) infection have hepatitis C virus (HCV) infection in the US and Western Europe. With the availability of highly active antiretroviral therapy and the consequent reduction in opportunistic infections, resulting in the prolongation of the life span of HIV-infected patients, HCV co-infection has emerged as a signif icant factor influencing the survival of HIV patients. Patients with HIV/HCV co-infection have a faster rate of fibrosis progression resulting in more frequent occurrences of cirrhosis, end-stage liver disease, and hepatocellular carcinoma. However, the mechanism of interaction between the two viruses is not completely understood. The treatment for HCV in co-infected patients is similar to that of HCV monoinfection; i.e., a combination of pegylated interferon and ribavirin. The presence of any barriers to antiHCV therapy should be identified and eliminated in order to recruit all eligible patients. The response to treatment in co-infected patients is inferior compared to the response in patients with HCV mono-infection. The sustained virologic response rate is only 38% for genotype-1 and 75% for genotype-2 and -3 infections. Liver transplantation is no longer considered a contraindication for end-stage liver disease in coinfected patients. However, the 5 year survival rate is lower in co-infected patients compared to patients with HCV mono-infection (33% vs 72%, P = 0.07). A better understanding of liver disease in co-infected patients is needed to derive new strategies for improving outcome and survival.

Definition,epidemiology and magnitude of alcoholic hepatitis

Alcoholic liver disease(ALD) is a major cause of alcoholrelated morbidity and mortality.Its presentation ranges from fatty liver to alcoholic hepatitis(AH),cirrhosis,and hepatocellular carcinoma.Although the amount and pattern of alcohol consumption is a well recognized predisposing factor for the development of serious liver pathology,environmental factors and the host's genetic makeup may also play significant roles that have not yet been entirely explored.Continuing alcohol consumption is a major factor that influences the survival of patients with AH.The presence of cirrhosis at presentation or its development on follow up is a major factor determining the outcome in the long run.This chapter deals with the epidemiology and magnitude of ALD in general and AH in particular.

Operative complications and economic outcomes of cholecystectomy for acute cholecystitis

BACKGROUND Recent management of acute cholecystitis favors same admission(SA)or emergent cholecystectomy based on overall shorter hospital stay and therefore cost savings.We adopted the practice of SA cholecystectomy for the treatment of acute cholecystitis at our tertiary care center and wanted to evaluate the economic benefit of this practice.We hypothesized that the existence of complications,particularly among patients with a higher degree of disease severity,during SA cholecystectomy could negate the cost savings.AIM To compare complication rates and hospital costs between SA vs delayed cholecystectomy among patients admitted emergently for acute cholecystitis.METHODS Under an IRB-approved protocol,complications and charges for were obtained for SA,later after conservative management(Delayed),or elective cholecystectomies over an 8.5-year period.Patients were identified using the acute care surgery registry and billing database.Data was retrieved via EMR,operative logs,and Revenue Cycle Operations.The severity of acute cholecystitis was graded according to the Tokyo Guidelines.TG18 categorizes acute cholecystitis by Grades 1,2,and 3 representing mild,moderate,and severe,respectively.Comparisons were analyzed withχ2,Fisher’s exact test,ANOVA,ttests,and logistic regression;significance was set at P<0.05.RESULTS Four hundred eighty-six(87.7%)underwent a SA while 68 patients(12.3%)received Delayed cholecystectomy.Complication rates were increased after SA compared to Delayed cholecystectomy(18.5%vs 4.4%,P=0.004).The complication rates of patients undergoing delayed cholecystectomy was similar to the rate for elective cholecystectomy(7.4%,P=0.35).Mortality rates were 0.6%vs 0%for SA vs Delayed.Patients with moderate disease(Tokyo 2)suffered more complications among SA while none who were delayed experienced a complication(16.1%vs 0.0%,P<0.001).Total hospital charges for SA cholecystectomy were increased compared to a Delayed approach($44500±$59000 vs$35300±$16700,P=0.019).The relative risk of developing a complication was 4.2x[95%confidence interval(CI):1.4-12.9]in the SA vs Delayed groups.Among eight patients(95%CI:5.0-12.3)with acute cholecystitis undergoing SA cholecystectomy,one patient will suffer a complication.CONCLUSION Patients with Tokyo Grade 2 acute cholecystitis had more complications and increased hospital charges when undergoing SA cholecystectomy.This data supports a selective approach to SA cholecystectomy for acute cholecystitis.

Differential effects of glutamate receptor antagonists on dorsal horn neurons responding to colorectal distension in a neonatal colon irritation rat model

AIM: To investigate and compare the effects of spinal D-(-)-2-amino-7-phosphonoheptanoic acid (AP-7) and 6-cyano-7-nitroquinoxaline-2,3-dione disodium (CNQX),two glutamate receptor antagonists, on the responses of dorsal horn neurons to colorectal distension (CRD) in adult rats exposed to neonatal colon irritation (CI).METHODS: Hypersensitive SD rats were generated by CI during postnatal days 8, 10 and 12. Experiments on adult rats were performed using extracellular single-unit recording. The effects of spinal application of AP-7 (0.001,0.01, 0.1, 1 mmoL) were tested on the CRD-evoked neuronal responses in 16 controls and 17 CI rats. The effects of CNQX (0.2, 2, 5, 10 μmoL) were also tested on the CRD-evoked responses of 17 controls and 18 CI neurons.RESULTS: (1) The average responses of lumbosacral neurons to all intensities of CRD in CI rats were significantly higher than those in control rats; (2) In control rats, AP-7 (0.01 mmoL) had no significant effect on the neuronal response to all intensities of CRD (20,40, 60, 80 mmHg); while AP-7 (0.1 mmoL) inhibited the neuronal response to 80-mmHg CRD. By contrast, in CI rats, AP-7 (0.01-1 mmoL) attenuated the CRD-evoked neuronal responses to all distention pressures in a dosedependent manner; (3) In control rats, CNQX (2 μmoL)had no significantly effect on the neuronal response to all intensities of CRD; however, CNQX (5 μmoL) significantly attenuated the responses to CRD in the 40-80 mmHg range. By contrast, CNQX (2-10 μmoL)significantly decreased the neuronal responses in CI rats to non-noxious and noxious CRD in a dose-dependent manner.CONCLUSION: Our results suggest that spinal N-methyl-D-aspartate (NMDA) and non-NMDA receptors may contribute to the processing of central sensitivity in a neonatal CI rat model, but they may play different roles in it.

Extrapancreatic malignancies and intraductal papillary mucinous neoplasms of the pancreas

Over the last two decades multiple studies have demonstrated an increased incidence of additional malignancies in patients with intraductal papillary mucinous neoplasms(IPMNs).Additional malignancies have been identified in 10%-52% of patients with IPMNs.The majority of these additional cancers occur before or concurrent with the diagnosis of IPMN.The gastrointestinal tract is most commonly involved in secondary malignancies,with benign colon polyps and colon cancer commonly seen in western countries and gastric cancer commonly seen in Asian countries.Other extrapancreatic malignancies associated with IPMNs include benign and malignant esophageal neoplasms,gastrointestinal stromal tumors,carcinoid tumors,hepatobiliary cancers,breast cancers,prostate cancers,and lung cancers.There is no clear etiology for the development of secondary malignancies in patients with IPMN.Although population-based studies have shown different results from single institution studies regarding the exact incidence of additional primary cancers in IPMN patients,both have reached the same conclusion:there is a higher incidence of extrapancreatic malignancies in patients with IPMNs than in the general population.This f inding has signif icant clinical implications for both the initial evaluation and the subsequent long-term followup of patients with IPMNs.If a patient has not had recent colonoscopy,this should be performed during the evaluation of a newly diagnosed IPMN.Upper endoscopy should be performed in patients from Asian countries or for those who present with symptoms suggestive of upper gastrointestinal disease.Routine screening studies(breast and prostate) should be carried out as currently recommended for patient's age both before and after the diagnosis of IPMN.

Topical application of platelet-rich plasma for diabetic foot ulcers: a systematic review

AIM To determine if topical application of platelet-rich plasma(PRP) to diabetic foot ulcers(DFUs) results in superior healing rates. METHODS A systematic review was registered with PROSPERO and performed using PRISMA guidelines. Level Ⅰ-Ⅳ investigations of topical PRP application in DFUs were sought in multiple databases including: MEDLINE, Web of Science, and Cochrane Central Register of Controlled Trials. The search terms used were "platelet rich plasma", "diabetes", "ulcers", and "wound". The Modified Coleman Methodology Score(MCMS) was used to analyze study methodological quality. Study heterogeneity and a mostly non-comparative nature of evidence precluded meta-analysis. Only the outcome measurements used by more than 50% of the studies were included in the data synthesis to increase power of the measurement over that of individual studies. A weighted mean of healing rate per week between PRP group vs controls were compared using two-sample z-tests using P-value of less than 0.05 for significance.RESULTS One thousand two hundred and seventeen articles were screened. Eleven articles(322 PRP subjects, 126 controls, PRP subject mean age 58.4 ± 7.2 years, control mean age 58.7 ± 5.9 years) were analyzed. Six articles were level Ⅱ evidence, four were level Ⅲ, and one article was level Ⅳ. The mean MCMS was 61.8 ± 7.3. Healing rate was significantly faster with PRP application compared to controls(0.68 ± 0.56 cm2/wk vs 0.39 ± 0.09 cm2/wk; P < 0.001). Mean heal time to > 90% of the original ulcer area was 7.8 ± 2.7 wk and 8.3 ± 3.7 wk for patients in the PRP group and control groups, respectively(P = 0.115). There were significantly lower adverse effects reported with PRP application compared to controls(7 wound infections, 1 contact dermatitis vs 14 wound infections, 1 maceration; P < 0.001).CONCLUSION The topical application of PRP for DFUs results in statistically superior healing rates and lower complication rates compared to controls.

Effect of HIV-1 Tat on Secretion of TNF-α and IL-1β by U87 Cells in AIDS Patients with or without AIDS Dementia Complex

Objective To explore the role of HIV-1 tat gene variations in AIDS dementia complex （ADC） pathogenesis. Methods HIV-1 tat genes derived from peripheral spleen and central basal ganglia of an AIDS patient with ADC and an AIDS patient without ADC were cloned for sequence analysis. HIV-1 tat gene sequence alignment was performed by using CLUSTAL W and the phylogentic analysis was conducted by using Neighbor-joining with MEGA4 software. All tat genes were used to construct recombinant retroviral expressing vector MSCV-IRES-GFP/tat. The MSCV-IRES-GFP/tat was cotransfected into 293T cells with pCMV-VSV-G and pUMVC vectors to assemble the recombinant retrovirus. After infection of gliomas U87 cells with equal amount of the recombinant retrovirus, TNF-α, and IL-1β concentrations in the supernatant of U87 cells were determined with ELISA. Results HIV-1 tat genes derived from peripheral spleen and central basal ganglia of the AIDS patient with ADC and the other one without ADC exhibited genetic variations. Tat variations and amino acid mutation sites existed mainly at Tat protein core functional area （38-47aa）. All Tat proteins could induce ug7 cells to produce TNF-α and IL-1β, but the level of IL-1β production was different among Tat proteins derived from the ADC patient＇s spleen, basal ganglia, and the non-ADC patient＇s spleen. The level of Tat proteins derived from the ADC patient＇s spleen, basal ganglia, and the non-ADC patient＇s spleen were obviously higher than that from the non-ADC patient＇s basal ganglia. Conclusion Tat protein core functional area （38-47aa） may serve as the key area of enhancing the secretion of IL-1β. This may be related with the neurotoxicity of HIV-1 Tat.