Additional Risk Factor For Development Research Articles

Clinicopathological and Prognostic Value of Plasma CD24 Level in Hepatocellular Carcinoma

Abstract Background Hepatocellular carcinoma (HCC) is the sixth most common form of cancer worldwide and the second most common cause of cancer-related deaths. HCC often occurs in the background of a cirrhotic liver. there is an increased incidence of HCC due to the rise of Hepatitis B Virus, HCV infections and chronic alcohol use. Western’s HCC usually developed in cirrhotic liver while over 50% of Asian countries developed in noncirrhotic liver. More recent studies suggest metabolic syndrome, such as type II diabetes and obesity, is an additional risk factor for development of HCC. Aim of the Work The aim of this work is to determine the clinicopathological and prognostic value of plasma CD24 Level in hepatocellular carcinoma to help in choose best treatment, recurrence rate and metastasis. Patients and Methods This case control study was carried out in Ain Shams University on 60 patients divided into two groups, Group (A) that included 20 patients liver cirrhosis without hepatocellular carcinoma and Group (B) that included 40 patients liver cirrhosis with HCC. Results The current study demonstrated that CD24 protein expression was detectable in plasma of HCC patients and the controls, and plasma CD24 level was significantly higher in HCC patients over the controls. Furthermore, plasma CD24 level was associated with tumor differentiation however, it wasnot correlated with other clinic- pathologic parameters including gender, age, tumor size, tumor number, capsulation status, TNM stage, HBsAg status, ALT, AFP and GGT level. The present study showed that plasma CD24 level is higher in HCC patients and it is a valuable biomarker for prognosis of HCC patients. Therefore, CD24 might be used as a potential biomarker for evaluation of postoperative survival. Conclusion It is concluded that plasma CD24 level is higher in HCC patients and it is a valuable biomarker for prognosis of HCC patients. Therefore, CD24 might be used as a potential biomarker for evaluation of postoperative survival of HCC patients.

Early Gestational Diabetes Screening Based on ACOG Guidelines.

A recent randomized controlled trial suggested that early gestational diabetes mellitus (GDM) screening in patients with obesity (body mass index [BMI] ≥30 kg/m2) does not improve perinatal outcomes. The American College of Obstetrics and Gynecology currently recommends early screening for gestational diabetes in patients who are overweight with one or more additional risk factors. We evaluated the effect of screening based on the number of additional risk factors for development of gestational diabetes. This was a secondary analysis of a multicenter randomized controlled trial of obese patients with singleton nonanomalous fetuses comparing early (14-20 weeks' gestation) with routine (24-28 weeks' gestation) GDM screening. Exclusion criteria were pregestational diabetes, major medical illnesses, bariatric surgery, chronic steroid use, and prior cesarean. Early versus routine GDM screening groups were compared and stratified by the number of additional risk factors for GDM (0, 1, 2, and ≥3). The primary outcome was an adverse perinatal composite outcome composed of: macrosomia, primary cesarean delivery, hypertensive disorders of pregnancy, shoulder dystocia, neonatal hyperbilirubinemia, and neonatal hypoglycemia. Analyses examined effects of early versus routine screening by the number of additional risk factors and their possible interaction on the incidences of the primary outcome and GDM. Of 913 patients, 5% had 0, 52% had 1, 33% had 2, and 10% had ≥3 additional risk factors. Baseline characteristics, including the number and type of risk factors, were similar between early and routine screening groups. Breslow-Day test for interaction between early versus routine screening and the number of additional risk factors was not significant for either the primary outcome (p = 0.37) or the diagnosis of GDM (p = 0.28). The incidence of GDM and the adverse perinatal composite outcome increased as the number of risk factors increased (p < 0.001). In patients with BMI ≥30 kg/m2 and additional risk factors, early GDM screening does not prevent adverse outcomes. · The ACOG currently recommends early screening for gestational diabetes if patients have risk factors.. · Even in patients with multiple risk factors, early screening for GDM does not improve outcomes.. · Patients with three or more risk factors may have worse outcomes if they undergo early screening..

Evaluation of formulation-associated ifosfamide neurotoxicity.

e23562 Background: Ifosfamide, an alkylating agent used commonly in both hematologic and solid tumor malignancies, carries a notable risk for neurotoxicity/encephalopathy. Ifosfamide is available as both a reconstituted powder formulation and a solution for injection. Literature has shown that there may be higher rates of ifosfamide neurotoxicity/encephalopathy (INT/E) with the solution compared to the reconstituted powder. The primary objective of this study was to compare the rates of neurotoxicity/encephalopathy in association with the two available pharmaceutical formulations of ifosfamide. Methods: We performed a retrospective study of adult patients receiving at least one dose of either available pharmaceutical formulation of ifosfamide. The primary outcome was the incidence of formulation-associated INT/E. Secondary outcomes included additional risk factors for development of INT/E. Results: Of 218 patients evaluated, 212 were included in the study with 56 patients receiving the reconstituted powder formulation and 156 patients receiving the solution for injection formulation of ifosfamide. Baseline characteristics were similar between the two groups, including dose of ifosfamide received, use of INT/E prophylaxis, and renal and hepatic function. INT/E occurred in 4 patients (7.1%) receiving the reconstituted powder formulation vs 32 patients (20.5%) receiving the solution for injection (p = 0.022) Evaluation and analysis of additional risk factors for development of INT/E are ongoing, including the impact of baseline demographics, ifosfamide dosing, renal and hepatic function, and concomitant medications. Conclusions: In this study, hematology/oncology patients who were treated with ifosfamide had significantly lower rates of INT/E with the reconstituted powder formulation compared to the solution for injection. Further analysis regarding additional risk factors for INT/E development is ongoing.[Table: see text]

Empagliflozin in patients post myocardial infarction rationale and design of the EMPACT-MI trial

Patients with acute myocardial infarction (MI) are at risk for developing heart failure (HF) and subsequently are at an increased risk of mortality. Sodium-glucose cotransporter-2 inhibitors have been proven to improve outcomes in patients with HF with reduced ejection fraction, and, in the case of empagliflozin, in HF with preserved ejection fraction even without diabetes, but their efficacy and safety in the post-MI population has not yet been evaluated. The EMPACT-MI trial will evaluate the safety and efficacy of empagliflozin compared with placebo in patients hospitalized for MI with or at high risk of new onset HF, in addition to standard care. EMPACT-MI is a streamlined, multinational, randomized, double-blind, placebo-controlled trial randomizing 5,000 participants at approximately 480 centers in 22 countries. Eligible patients presenting with spontaneous MI must have new signs or symptoms of pulmonary congestion requiring treatment or new left ventricular dysfunction (LVEF<45%), and at least 1 additional risk factor for development of future HF. Eligible and consenting patients are randomized to empagliflozin 10mg or placebo daily in addition to standard of care within 14 days of hospital admission for MI. The primary composite end point is time to first hospitalization for HF or all-cause mortality. EMPACT-MI will inform clinical practice regarding the role of empagliflozin in patients after an MI with high-risk for the development of future HF and mortality.

S0804 Risk Factors and Outcomes in Inflammatory Bowel Disease Patients With Anti-Tumor Necrosis Factor Alpha-Induced Dermatologic Conditions

INTRODUCTION: Anti-tumor necrosis factor alpha agents (anti-TNFs) have been widely used for the treatment of inflammatory bowel disease (IBD). There is a paradoxical risk of skin reactions for patients (pts) on anti-TNFs. Here, we describe our experience with IBD pts who developed dermatologic (derm) adverse events (AEs) on anti-TNFs. METHODS: We retrospectively reviewed 746 charts in an established database of IBD pts to identify pts with anti-TNF induced psoriasis (PsO) or eczema between 11/1/2016 and 2/28/2019. Medical records were reviewed to obtain the following information: baseline demographics, medication use including anti-TNFs and immunomodulators, treatment of derm conditions, and whether pts were continued on anti-TNFs. RESULTS: 520 pts (58% female, median age was 23 years [range 2-77]) were exposed to anti-TNF therapy, and 14 pts (2.6%) with derm AEs were identified. Among the 14 pts with skin reactions 13/14 had PsO and 1/14 had eczema. Please see Table 1 for additional baseline demographics. The average time from anti-TNF initiation to derm AEs was 17.1 months. Eleven pts (78.6%) received treatment such as topical or systemic steroids for their skin reaction. Six pts developed a skin reaction on infliximab (IFX) and 8 pts on adalimumab (ADA). Five pts continued on the same therapy and 8 pts stopped the current therapy or switched to a different class of therapy. Interestingly, 1 pt changed to another anti-TNF therapy and did not develop dermatologic AEs. Six pts were current smokers or had a history of smoking. None had family history of psoriasis. IFX use (OR = 0.34 [95% CI 0.10-1.13], P = 0.04) was associated with a decreased likelihood of derm AEs. ADA use (OR = 0.79 [95% CI 0.24-2.80], P = 0.66) and history of or current smoking (OR = 1.27 [95% CI 0.36-4.24], P = 0.66) were not associated with increased risk of anti-TNF induced psoriasis (Table 2). Seven out of 14 (50%) of pts had anti-TNF level drawn and all were detectable; 1 out of 7 pts had antibodies to anti-TNF. CONCLUSION: In our cohort, there was a low frequency of derm AEs associated with anti-TNFs. Eight out of 14 pts (57%) who developed derm AEs were switched to a different class of IBD medications. Neither use of ADA nor smoking history increased risk for adverse skin reactions while IFX use was less likely to be associated with derm AEs. Future directions include identifying additional risk factors for development of adverse skin reactions and to assess whether there is any correlation with drug levels.Table 1Table 2

An investigation of the relationship between autonomic dysreflexia and intrathecal baclofen in patients with spinal cord injury

Objective: To study the relationship between autonomic dysreflexia and intrathecal baclofen in patients with spinal cord injury.Design: Retrospective chart review.Setting: Inpatient and outpatient acute rehabilitation facility.Participants: Thirty-four subjects.Interventions: We reviewed patients’ medical records to ascertain the presence of symptomatic autonomic dysreflexia (AD) prior to and after implantation of an intrathecal baclofen (ITB) pump for spasticity in spinal cord injury patients. We recorded risk factors for autonomic dysreflexia including kidney and bladder stones, heterotopic ossification (HO), and ischial / sacral pressure ulcers.Outcome Measures: Presence of autonomic dysreflexia pre and post-intrathecal baclofen pump placement, presence of risk factors associated with autonomic dysreflexia including (1) kidney or bladder stones, (2) heterotopic ossification, and (3) pressure ulcers.Results: Of the 34 subjects, 25 (73.5%) experienced AD prior to ITB pump placement and only 2 (5.9%) after placement. Four subjects (11.8%) had kidney or bladder stones, of which, all had AD prior to placement and none had AD afterwards. Twenty-six subjects (76.5%) had pressure ulcers, of which, all experienced AD prior to placement and only one (0.02%) afterwards. Six patients (17.6%) had HO, of which 5 (83%) had AD prior to placement and none afterwards. Additionally, three patients (8.8%) had at least 2 of the above risk factors, of which, all had AD prior to ITB placement and none afterwards.Conclusion: This study showed a significant reduction of symptomatic episodes of autonomic dysreflexia after spinal cord injury, even in those with additional risk factors for development of autonomic dysreflexia.

Glomerular filtration rate in bronchial asthma: effects of adipokines

The aim of the study was to analyze a relationship between key adipokines expression and the glomerular filtration rate (GFR) in different clinical variants of bronchial asthma (BA). Methods. We examined 178 patients with different clinical variants of BA. The glomerular filtration rate (eGFR) was estimated using CKD-EPI. Plasma concentrations of leptin, adiponectin, resistin, and apelin were measured using the ELISA method. Correlation and factor analyses were performed using the SPSS program for Windows, version 13.0. Results. A relationship between eGFR, key adipokines expression and pSTAT3 transcription factor expression, which is involved in proinflammatory adipokines effect transduction in BA, was found. Moreover, a reverse relationship between eGFR and adipokines (leptin, resistin, adiponectin) expression was mainly typical for allergic BA. Conclusion. Additional risk factors for development and progress of chronic renal disease are probably present in patients with BA even without obesity.

The combined risks of reduced or increased function variants in cell death pathway genes differentially influence cervical cancer risk and herpes simplex virus type 2 infection among black Africans and the Mixed Ancestry population of South Africa.

BackgroundCervical cancer is one of the most important cancers worldwide with a high incident and mortality rate and is caused by the human papilloma virus (HPV). Among sexually active women who get infected with human papillomavirus (HPV), a small fraction progresses to cervical cancer disease pointing to possible roles of additional risk factors in development of the disease which include host genetic factors and other infections such as HSV-2. Since cellular apoptosis plays a role in controlling the spread of virus-infections in cells, gene variants altering the function of proteins involved in cell death pathways might be associated with the clearing of virus infections. Activity altering polymorphisms in FasR (−1377G > A and -670A > G), FasL (−844 T > C) and CASP8 (−652 6 N ins/del) genes have been shown to alter the mechanism of apoptosis by modifying the level of expression of their correspondent proteins.In the present study, we set out to investigate the combined risks of CASP8, FasR, and FasL polymorphisms in cervical cancer, pre-cancerous lesions, HPV infection and HSV-2 infection.MethodsParticipants were 442 South African women of black African and mixed-ancestry origin with invasive cervical cancer and 278 control women matched by age, ethnicity and domicile status. FasR and FasL polymorphisms were genotyped by TaqMan and CASP8 polymorphism by PCR-RFLP. The results were analysed with R using haplo.stats software version 1.5.2.ResultsCASP8 -652 6 N del + FasR-670A was associated with a reduced risk (P = 0.019, Combined Polymorphism Score (CPS) = −2.34) and CASP8 -652 6 N ins + FasR-1377G was associated with a marginal increased risk (P = 0.047, CPS = 1.99) of cervical cancer among black Africans. When compared within the control group, CASP8 -652 6 N ins + FasR-1377A showed a reduced risk (P = 0.023, CPS = −2.28) of HSV-2 infection in both black African and mixed-ancestry population.ConclusionsOur results show that the combined risks of variants in cell death pathway genes are associated with the cervical cancer as well as the HSV-2 infection in the black African and mixed-ancestry population.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1678-y) contains supplementary material, which is available to authorized users.

Gastroprotective efficacy and safety of single-tablet ibuprofen/famotidine vs ibuprofen in older persons

Objectives: A combination tablet of ibuprofen 800 mg and famotidine 26.6 mg given three times daily is effective for the treatment of rheumatoid arthritis and osteoarthritis and decreases the risk of developing upper gastrointestinal (GI) ulcers. This analysis evaluated the gastroprotective efficacy and safety of the single-tablet combination of ibuprofen/famotidine compared with ibuprofen alone on the basis of age and the presence of one or more risk factors for development of upper GI ulcer. Methods: Pooled data from the 24-week, randomized, double-blind, parallel-group REDUCE-1 and REDUCE-2 trials were used. Endoscopies were performed in patients aged 40–80 years. The proportion of patients who developed ≥1 upper GI ulcer during treatment with ibuprofen/famotidine versus ibuprofen alone stratified on the basis of age (<60 or ≥60 years) was evaluated. Further, analyses were performed on additional risk factors for ulcer development. Results: Gastroprotective efficacy of the combination was not affected by age. Pooled results demonstrated statistically significantly fewer upper GI (10.0 vs 19.5%, p < 0.0001), gastric (8.9 vs 16.8%, p = 0.0004), and duodenal ulcers (1.1 vs 5.4%, p < 0.0001) in patients <60 years treated with ibuprofen/famotidine versus ibuprofen alone compared with 12.9 vs 26.6% (p = 0.0002), 11.9 vs 23.4% (p = 0.0011), and 1.0 vs 4.5% (p = 0.0096), respectively, in patients ≥60 years. The ibuprofen/famotidine combination provided nearly 51 and 59% reduction in the risk of developing a GI ulcer in patients <60 years and ≥60 of age, respectively. Efficacy was maintained in the presence of additional risk factors, as well. Conclusions: These results indicate that the fixed-combination of ibuprofen/famotidine provides gastroprotection in those of older age, with or without additional risk factors for the development of upper GI ulcers, as compared with ibuprofen alone. US National Institutes of Health registry, http://www.clinicaltrials.gov, NCT00450658 and NCT00450216.

Relationship between vaccination and atopy

Background. The rising prevalence of atopic diseases during last decades brings concern for the “Western life-style” countries. Although there is general consensus on the importance of the genetic predisposition for atopic disorders (asthma, allergic rhinitis, atopic dermatitis), only changes in environmental factors can explain the rise of allergic diseases during the last forty years. Vaccinations in infancy have been incriminated as an additional risk factor for development of atopic diseases. A potential relationship between vaccination and atopy could be analysed by two directions: either by activation of the Th2 network in the vaccine-specific memory response, or exposition to (attenuated or inactivated) pathogens or their components at a very young age of vaccinated children and possible promotion of Th1 proliferation. Materials and methods. The major electronic databases (Medline, Cochrane Library) were searched using key words: vaccination, atopy, relationship and children. Recent studies analysing a relationship between atopic disorders and vaccination in infancy were reviewed. Moreover, possible mechanisms of immune response to vaccines in atopic children were analysed. Results. Available evidence is rather convincing that the current regular childhood vaccination does not increase the risk of atopic disorders. Large epidemiological, prospective, cohort and multi-central studies all over the world published in last 10 years with quite large proportions of unvaccinated children included showed that vaccination in infancy was not related to development of atopic conditions starting from the first year of life up to the middle age. Even conversely, some studies detected that vaccinated children had a moderately reduced rate of atopic diseases. It was also denoted that atopy could be suppressed due to high vaccination coverage. Conclusions. Allergic or atopic children just like non-atopic children require routine immunization to be protected from serious life and health threatening viral and bacterial infections. The risks of infection by vaccine avoidance outweigh by far the possible minimal risks of immunization, moreover, anti-infectious treatment or natural infection (like pertussis) per se could be potential triggers of atopic disorders.

THE INFLUENCE OF GLYCEMIC STATUS OF PATIENTS WITH TRAUMA OF THE PANCREAS ON THE DEVELOPMENT OF THE POSTTRAUMATIC PANCREATITIS

It was analyzed the results of treatment of 100 patients with trauma of the pancreas. It was defined the dynamic characteristics of glycemia and insulin resistance in patients with post-traumatic pancreatitis or its absence. It was proved that hyperglycemia and insulin resistance in the early stages of traumatic disease are not only diagnostic markers, but also additional risk factors for development of post-traumatic pancreatitis in patients with trauma of the pancreas.

Incidence of Hyperglycemia by 3 Years in Patients (Pts) with Newly Diagnosed Chronic Myeloid Leukemia in Chronic Phase (CML-CP) Treated with Nilotinib (NIL) or Imatinib (IM) in ENESTnd

Abstract Abstract 1686 Background: ENESTnd established the superior efficacy of frontline NIL vs IM in pts with CML-CP. An association between NIL treatment and hyperglycemia has been previously reported. NIL-mediated increases in fasting plasma glucose levels (FGLs) have been shown to be reversible, with levels returning to normal on treatment discontinuation; in contrast, IM has been shown to decrease FGLs in pts with diabetes (Breccia M, Alimena G. Leuk Res. 2009;33:871–875). Here, we report the incidence of hyperglycemia and related glycemic outcomes with NIL and IM by 3 y in ENESTnd. Methods: Pts were randomized to receive NIL 300 mg twice daily (BID; n = 282), NIL 400 mg BID (n = 281), or IM 400 mg once daily (QD; n = 283). This analysis included randomized pts who had ≥1 dose of study drug and no drug treatment for diabetes mellitus /prediabetes at baseline (BL; 264, 262, and 267 pts in the NIL 300 mg BID, NIL 400 mg BID, and IM arms, respectively); pts with treated diabetes at BL (15, 15, and 13 pts, respectively) were excluded. Hyperglycemia was defined as FGL ≥1.1 g/L, prediabetes as FGL ≥1.1 g/L to &lt; 1.26 g/L or glycated hemoglobin (HbA1C) ≥5.7% to &lt; 6.5%, and diabetes as FGL ≥1.26 g/L or HbA1C ≥6.5%. These criteria represent a combination of World Health Organization and American Diabetes Association guidelines. Results: At BL, median age and mean body mass index (BMI) were similar across the 3 arms (Table). In the NIL 300 mg BID, NIL 400 mg BID, and IM arms, respectively, 34.9%, 35.5%, and 37.8% of pts had untreated prediabetes at BL, and 6.1%, 6.1%, and 3.4% of pts had untreated diabetes at BL. Median time on treatment in the 3 arms was similar (≈ 3 y). Cumulative incidence of hyperglycemia by 3 y was higher with NIL vs IM (Table). By 3 y, grade 3/4 hyperglycemia was reported in 6 (2.3%), 7 (2.7%), and 0 pts on NIL 300 mg BID, NIL 400 mg BID, and IM, respectively; no pt discontinued due to hyperglycemia. Median time to hyperglycemia was longer with NIL 300 mg BID than with NIL 400 mg BID. From BL to 3 y, there were minimal changes in mean BMI and mean HbA1C in all 3 arms; greater increases in mean fasting insulin were observed with NIL vs IM. Excluding pts with diabetes at BL, 20.1%, 22.8%, and 8.9% of pts developed diabetes by 3 y, and 48.8%, 51.6%, and 50.0% developed prediabetes by 3 y (NIL 300 mg BID, NIL 400 mg BID, and IM, respectively). Relatively few pts required antidiabetic medication by 3 y. Based on a multivariate analysis, prediabetes at BL was a risk factor for development of hyperglycemia in all 3 treatment arms (P =.0252.0004, and.0296 [NIL 300 mg BID, NIL 400 mg BID, and IM arms, respectively]). Age &gt; 60 y at BL was a risk factor for NIL 300 mg BID (P =.0183) and IM (P =.0010) but was not a risk factor for NIL 400 mg BID (P =.6001). Dyslipidemia (P =.0455) at BL was identified as an additional risk factor for development of hyperglycemia on IM in the multivariate analysis. Conclusions: In ENESTnd, the incidence of hyperglycemia by 3 y was higher with NIL vs IM. However, most events were low grade, HbA1C levels remained stable over time, and few pts required antidiabetic medication. The underlying mechanism of action driving NIL-mediated hyperglycemia is unknown, but the increases in fasting insulin observed suggest NIL therapy is associated with insulin resistance. NIL-treated pts with CML-CP and BL risk factors for diabetes should be monitored closely. Disclosures: Delphine: Novartis: Honoraria; BMS: Honoraria; Teva: Honoraria. Gautier:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees. Breccia:Novartis: Honoraria; BMS: Honoraria; Celgene: Honoraria. Saglio:Novartis: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau; Pfizer: Consultancy. Hughes:Novartis: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; Ariad: Consultancy, Honoraria; CSL: Research Funding. Kantarjian:Novartis Pharmaceuticals Corp: Consultancy, Research Funding; BMS: Research Funding; Pfizer: Research Funding. Kemp:Novartis Pharmaceuticals Corp: Employment. Gao:Novartis: Employment. Piccolo:Novartis Pharma AG: Employment. Larson:Novartis: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Research Funding; Pfizer: Consultancy; Ariad: Consultancy, Research Funding. Hochhaus:BMS: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Ariad: Consultancy, Honoraria, Research Funding.

A study on serum advanced glycation end products and its association with oxidative stress and paraoxonase activity in type 2 diabetic patients with vascular complications

ObjectivesEnhanced formation of advanced glycation end products (AGEs) formed secondary to hyperglycemic conditions has been linked to diabetes mellitus (DM) associated complications. We investigated the clinical relevance of estimating AGEs and their relationship with oxidative stress (OS) and paraoxonase (PON1) activity in type 2 DM (T2DM) in relation to development of vascular complications. Design and MethodsSerum AGEs along with PON1 activity, protein carbonyl (PCO), advanced oxidation protein products (AOPP), lipid peroxidation (MDA), and total thiol (T-SH) were determined in 157 T2DM patients (DM without complications n=57, DM micro-vascular complications n=53, DM macro-vascular complications n=47) and 40 healthy controls. ResultsSerum AGE level increased significantly in various study groups in following manner: healthy control<DM without complications<DM-macro<DM-micro. Logistic regression analysis using diabetic complications as dependent variable showed significant association with AGE level and PON1 activity even after adjustment for confounding factors. Receiver-operating-characteristics curve analysis showed that 2-fold increased in glycation and 50% decrease in PON1 activity may lead to development of vascular complications in diabetic subjects. PCO, AOPP and MDA were higher and PON1 activity was lower in T2DM with complications than those without complications. Among diabetic patients AGEs showed significant positive correlation with HbA1C, MDA, AOPP, and negative correlation with PON1 activity and T-SH. ConclusionHigh serum AGE concentration and low PON1 activity may be considered as additional risk factor for development of vascular complications in T2DM. AGE formation plays significant role in induction of OS in diabetes.

Interaction Between Endothelial Nitric Oxide Synthase Gene Polymorphisms (−786T>C, 894G>T and Intron 4 a/b) and Cardiovascular Risk Factors in Acute Coronary Syndromes

Endothelial rupture of coronary plaque can represent the pathomorphological substratum of acute coronary syndrome (ACS). Polymorphisms in the NOS3 gene (eNOS) -786T>C, 894G>T and intron 4 a/b VNTR can be associated with a higher susceptibility for ACS. The present study is focused on the investigation of the interaction of these polymorphisms and cardiovascular risk factors in 135 patients with ACS and 115 control subjects. Case-control study where the allele and genotype frequencies of the polymorphisms -786T> C, 894G> T and intron 4 VNTR of the gene encoding eNOS were determined by PCR-RFLP associated with cardiovascular risk factors. An association of the 894TT genotype and 894GT+GG (OR 1.4; 95% CI 1.0-1.8) in ACS has been observed. Subjects without dyslipidemia and intron 4 a/b genotype present a lower chance for ACS development, whereas subjects without diabetes and 894TT genotype show a higher risk for ACS (OR 1.7; 95% CI 1.2-2.3). In patients without dyslipidemia, the 894GG genotype presented a tendency to behave as a protector factor against ACS. Also, the 894GG genotype has been a protective factor for ACS in females (OR 0.5; CI 95% 0.2-0.9). Our results suggest that eNOS polymorphisms may be an additional risk factor in development of ACS.

104 POST-OPERATIVE COMPLICATIONS OF THE EXAGGERATED LITHOTOMY POSITION

You have accessJournal of UrologyTrauma/Reconstruction: Trauma & Reconstructive Surgery1 Apr 2011104 POST-OPERATIVE COMPLICATIONS OF THE EXAGGERATED LITHOTOMY POSITION Paul D. McAdams, Britt E. Tisdale, Mary F. Henderson, Gerald H. Jordan, and Kurt A. McCammon Paul D. McAdamsPaul D. McAdams Norfolk, VA More articles by this author , Britt E. TisdaleBritt E. Tisdale Norfolk, VA More articles by this author , Mary F. HendersonMary F. Henderson Norfolk, VA More articles by this author , Gerald H. JordanGerald H. Jordan Norfolk, VA More articles by this author , and Kurt A. McCammonKurt A. McCammon Norfolk, VA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.169AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Open surgery through a perineal incision is required to visualize the urethra and other structures of the perineum during complex surgical repairs. The exaggerated lithotomy position provides excellent access to the perineum for mobilization of the entire urethra and enables two surgeons to work side-by-side with relative freedom of movement around a small incision. Recent studies have reported a high complication rate for this position and suggested that its use should be limited. We present a review of our experience with the exaggerated lithotomy position. METHODS Data was retrospectively reviewed on 105 patients who underwent surgery in the exaggerated lithotomy position at a single institution. All patients underwent surgery on a Skytron Elite 6000 operating room table with legs positioned in Allen stirrups. Positioning related complications, time spent in exaggerated lithotomy position and other data were collected on this cohort of patients. RESULTS All patients except one underwent urethral reconstruction. Average age was 42.6 years (range, 14 to 77 years). Follow-up ranged from 1 to 22 months (with a median of 6 months.) Average time in the exaggerated lithotomy position was 172 minutes (range, 105–230 minutes). Twenty three patients (21.9%) had complications felt to be positioning related, the majority of which were minor and resolved without additional treatment or sequelae. The most common findings were peripheral neuritis manifesting as paresthesias or hypoesthesias in the dorsum of the foot or toes from compression of peroneal nerve branches seen in 20 patients (19.0%) and musculoskeletal low back pain in 4 patients (3.8%). Two patients (1.9%) had manifestations of both. All but 3 of these patients (87%) had spontaneous resolution of these symptoms prior to discharge. Average time to resolution was 2.3 days. The symptoms in the remaining 3 patients were nearly resolved by the time they met all other discharge criteria and did not warrant further hospital monitoring. A single patient (0.9%) had a significant complication – a pulmonary embolus. Medical work-up revealed the presence of lupus anticoagulants, an additional risk factor for development of thrombosis. No patients had neurapraxia, rhabdomyolysis or compartment syndrome. CONCLUSIONS The exaggerated lithotomy position provides unequaled access to the perineum for urethral reconstruction. With appropriate equipment and attention to proper positioning, there is a relatively low risk of even minor, self-limited complications and is therefore our position of choice. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e44 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Paul D. McAdams Norfolk, VA More articles by this author Britt E. Tisdale Norfolk, VA More articles by this author Mary F. Henderson Norfolk, VA More articles by this author Gerald H. Jordan Norfolk, VA More articles by this author Kurt A. McCammon Norfolk, VA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Vertebral osteolysis originating from subchondral cyst end plate defects in transforaminal lumbar interbody fusion using rhBMP-2. Report of two cases

Background Context Vertebral osteolysis has been reported as a complication of off-label recombinant human bone morphogenetic protein-2 (rhBMP-2) use in transforaminal lumbar interbody fusion (TLIF). It has been postulated that end plate violation during disc space preparation, rhBMP-2 overdosing, or a combination thereof can contribute to the development of vertebral osteolysis when rhBMP-2 is used in the lumbar interspace. Purpose To present two cases of vertebral osteolysis that occurred after TLIF in which rhBMP-2 was used. In each case, the osteolysis originated from subchondral cysts that were present on preoperative computed tomographic (CT) scans. Study Design Case report. Methods Two patients underwent instrumented TLIF using INFUSE (Medtronic, Inc., Littleton, MA, USA) on an absorbable collagen sponge carrier. In each patient, approximately 4 mg of rhBMP-2 was placed anteriorly in the disc space with 0.1 mg of rhBMP-2 being placed inside a polyetheretherketone interbody cage. Morcellized allograft bone mixed with demineralized bone matrix was also placed in the disc space and cage. The remaining rhBMP-2 was placed posterolaterally on the contralateral side. Each patient presented with worsening back pain approximately 3 to 4 months postoperatively and CT scans revealed osteolysis affecting the L4 and L5 vertebral bodies. The osteolysis appeared to originate from preoperative vertebral defects caused by subchondral cysts. Results One patient underwent removal of the interbody cage at the L4–L5 level and revision of the fusion with iliac crest autograft. At 15-month follow-up, he had no complaints of back pain, and CT scanning revealed solid fusion across the L4–L5 disc space. The other patient was offered revision of his fusion but declined any further surgery. At 2-year follow-up, that patient had persistent back pain but still declined any further surgery. A CT scan revealed unchanged osteolysis at the L4 and L5 levels. Conclusions It has been proposed that rhBMP-2-induced vertebral osteolysis occurring in TLIF procedures may be secondary to end plate violation during disc preparation or overdosing of rhBMP-2. Although overdosing may have also contributed to vertebral osteolysis in our two cases, the end plate violation from subchondral cyst formation that was present on preoperative CT scans seemed to be the origin of the osteolysis suggesting that the presence of preoperative subchondral cysts may be an additional risk factor for development of osteolysis in these patients.

Liver TX for hepatitis C cirrhosis in a low prevalence population: Risk factors and status at evaluation

Objective. Hepatitis C virus (HCV) cirrhosis is the most common indication for liver transplantation (LTX) world-wide. The prevalence of HCV infections is much lower in Norway than in most other countries from which data on HCV infection and liver transplantation have been published. Material and methods. Patients with HCV infection referred for evaluation of a possible LTX between 1990 and 2005 were included in the study. Their clinical status, biochemical parameters and risk factors were recorded. All patients were followed until 1 January 2005 irrespective of transplantation status. Results. Fifty-one patients were included; 80% were males and 18% were non-Caucasians. Previous intravenous drug abuse (28%) and exposure to contaminated IgG products (15%) were the most common routes of infection. In 45/51 (88%) of the evaluated patients at least one risk factor for rapid progression of HCV disease was identified. Twenty-seven patients were accepted on the waiting list. The MELD (model for endstage liver disease) score for the accepted patients was significantly higher than that for the patients who were not listed because they were found to be too healthy (18.4 versus 12.1, p<0.01). Twenty-four patients (89% of those listed) received a liver allograft; their 1-, 3- and 5-year survival rates following LTX were 81%, 68% and 68%, respectively. Two patients needed a second transplantation. Conclusions. A low number of HCV-infected patients have so far been evaluated for LTX in Norway. The present study demonstrates that almost all of the HCV patients progressing to cirrhosis and being evaluated for LTX in Norway have additional risk factors for development of cirrhosis.

Weight Gain After Living-Related Renal Transplantation Affects Long-Term Graft Function

Weight gain is a common problem in renal transplant recipients. This study investigated whether weight gain after living-related renal transplantation affects long-term graft function. The cohort included 93 patients (28 females, 65 males of mean age, 33.78 ± 9.78 years who were recipients of kidneys from living-related donors. The data set related risk factors to occurrence of chronic allograft nephropathy (CAN): namely, number of HLA mismatches, PRA levels, delayed graft function, acute rejection, suboptimal immunosuppression, hypertension, hyperlipidemia, and size mismatch. Patients with a 10% increase in body mass index sustained throughout at least 2 years posttransplantation were categorized as group 1 (abnormal weight gain; n = 65) and the others were categorized as group 2 (no or normal weight gain; n = 28). Chronic allograft nephropathy was more frequent among group 1 ( P < .03). The mean times to CAN diagnosis in groups 1 and 2 were 1053.41 ± 461.86 days and 1128.57 ± 416.09 days, respectively ( P > .05). Of all the risk factors for CAN, occurrence of acute rejection was the most important (OR = 5.39, 95% CI: 2.07 to 14.03, P < .001). When this factor was excluded, weight gain emerged as the most important risk factor (OR = 3.04, 95% CI: 1.01 to 9.69, P < .04). There were no significant differences between the groups with respect to the frequencies of immunologic and nonimmunologic risk factors ( P > .05 for all). The results suggest that excessive weight gain after living-related renal transplantation may be an additional risk factor for development of CAN. Patients should pay attention to diet and control weight gain after transplantation.

WEIGHT GAIN AFTER LIVING-RELATED RENAL TRANSPLANTATION AFFECTS LONG-TERM GRAFT FUNCTIONS

P314 Aim: Weight gain is a common problem in renal transplant recipients. This study investigated whether weight gain after living-related renal transplantation affects long-term graft functions. Methods: Ninety three recipients of kidneys from living-related donors (28 females, 65 males; mean age, 33.78±9.78 years) were studied. Data related to risk factors for chronic allograft nephropathy (CAN) were recorded, including number of HLA missmatch, PRA levels, delayed graft function, acute rejection, suboptimal immunosupression, hypertension, hyperlipidemia and transplant size-match. CAN was diagnosed when there was a progressive rise in serum creatinine and/or characteristic histopathology was observed in renal biopsy. Patients with sustained 10% increase in body mass index within the first 2 years after renal transplantation were categorized as Group I (n=65) and the others as Group II (n=28). Results: CAN was more frequent in Group I (p<0.03) and mean times to CAN diagnosis in Groups I and II were 1053.41±461.86 and 1128.57±416.09 days (p>0.05). Of all the risk factors for CAN, analysis identified occurrence of acute rejection as the most important one (OR=5.39, 95% CI: 2.07-14.03, p<0.001). When this factor was excluded, weight gain emerged as the most important risk factor (OR=3.04, 95% CI: 1.01-9.69, p<0.04). There were no statistical differences between the groups with respect to immunological and non-immunological risk factors (p>0.05). Conclusion: The results suggest that weight gain after living-related renal transplantation may be an additional risk factor for development of CAN. Patients should pay attention to diet and take care to control weight gain after transplantation, and physicians must strictly monitor patient body weight.

Disturbances of haemostasis in diabetes mellitus.

Diabetes mellitus is associated with disturbances in haemostasis that could contribute to the development of thrombotic complications.The present study was undertaken to determine the behavior of coagulation variables and fibrinolytic system in diabetes mellitus. Forty five diabetic patients and forty five matched controls were evaluated by doing the following haemostatic parameter, prothrombin time, partial thromboplastin time, thrombin time, coagulation factors assay II, VII, IX, & plasma fibrinogen, ADP-induced platelet aggregation, protein C, a2- antiplasmin, PAI and FDPs. Generally diabetic patients have high levels of fibrinogen, a2- antiplasmin, & PAI and lower level of protein C. Other haemostatic parameters did not show statistically significant difference between diabetic patients and control group. Significantally elevated levels of PAI, a2- antiplasmin together with low protein C level in diabetic patients may result in the disturbance of haemostatic balance favoring thrombotic events. Conclusion: High levels of plasma fibrinogen, a2A- antiplasmin with low plasma protein C activity could lead to a prothrombotic tendency in insulin dependent diabetic patients. Moreover, in non-insulin dependent diabetic patients, the above mentioned parameters together with high levels of ADP-induced platelet aggregation and plasminogen activator inhibitor may increase the risk of thrombotic complications. Obesity can be considered as an additional risk factor for development of thrombosis in diabetic patients.