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Background: Jaundice is a common clinical finding in clinical practice of hepatologists and general practitioners. It occurs when serum bilirubin levels exceed 3 mg/dL. Summary: In this review, we summarize the pathophysiological mechanism of jaundice, clinical approach to the patient with jaundice, and laboratory and imaging techniques. Clinical presentation of jaundice manifests through yellow skin and sclera coloration. Evaluation of every patient includes detailed medical history and examination. In the laboratory, evaluation of enzymes of hepatic inflammation as well as cholestatic enzymes with serum bilirubin must be included. Additional laboratory analysis and imaging modalities are needed in order to differentiate jaundice etiology. Moreover, imaging is available and needed in further evaluation, and treatment is dependent on the underlying cause. Key Messages: In this review, we will outline the pathophysiological mechanism of jaundice, clinical approach to the patient with jaundice, and diagnostic and treatment approach to these patients.

Background and Aim. Differentiating iron deficiency anemia (IDA) from anemia of chronic disease (ACD) in patients with inflammatory bowel disease (IBD) represents a clinical challenge. Hepcidin is a polypeptide synthetized in the liver, and iron levels or inflammation mostly regulate hepcidin production. Our aim was to determine serum hepcidin levels in patients with inflammatory bowel disease (IBD) as well to investigate whether hepcidin levels correlate with disease activity. Material and Methods. A case-control study was preformed among newly diagnosed IBD patients and same number age- and sex-matched healthy controls. All patients underwent a total ileocolonoscopy. Complete blood count was obtained in addition to inflammatory markers (CRP, erythrocyte sedimentation rate-ESR). Serum levels of hepcidin were determined with commercially available enzyme-linked immunosorbent assay (DRG Instruments Marburg, Germany). Serum iron, TIBC, and UIBC were assessed with an electrochemiluminesence immunoassay, and soluble transferrin receptor (sTfR) was assessed using an immunoturbidimetric method. Mayo score and CDAI, respectively, were calculated for each patient. Statistical analyses were performed using the SPSS software version 20.0 for Windows. Results. There was a high statistically significant difference between IBD patients and controls in levels of hepcidin ( P < 0.01 ). Namely, serum hepcidin levels were significantly higher in the control group. There was no statistically significant correlation of serum hepcidin with CRP, Mayo score, or CDAI, respectively ( P > 0.05 ). However, we have found a statistically significant negative correlation of sTfR and TIBC with hepcidin ( P < 0.01 ). Conclusion. Results of our study suggest that hepcidin is a reliable marker of IDA in patients with IBD, and it could be used in routine clinical practice when determining adequate therapy in these patients.

BACKGROUND Rectal cancer (RC) is one of the most common diagnosed cancers, and one of the major causes of cancer-related death nowadays. Majority of the current guidelines rely on TNM classification regarding therapy regiments, however recent studies suggest that additional histopathological findings could affect the disease course. AIM To determine whether perineural invasion alone or in combination with lymphovascular invasion have an effect on 5-years overall survival (OS) of RC patients. METHODS A prospective study included newly diagnosed stage I-III RC patients treated and followed at the Digestive Surgery Clinic, Clinical Center of Serbia, between the years of 2014–2016. All patients had their diagnosis histologically confirmed in accordance with both TMN and Dukes classification. In addition, the patient’s demographics, surgical details, postoperative pathological details, differentiation degree and their correlation with OS was investigated. RESULTS Of 245 included patients with stage I-III RC, lymphovascular invasion (LVI) was identified in 92 patients (38%), whereas perineural invasion (PNI) was present in 46 patients (19%). Using Kaplan-Meier analysis for overall survival rate, we have found that both LVI and PNI were associated with lower survival rates (P < 0.01). Moreover when Cox multiple regression model was used, LVI, PNI, older age, male gender were predictors of poor prognosis (HR = 5.49; 95%CI: 2.889-10.429; P < 0.05). CONCLUSION LVI and PNI were significant factors predicting worse prognosis in early and intermediate RC patients, hence more aggressive therapy should be reserved for these patients after curative resection.

Introduction/Objective. Due to a very high mortality risk, acute-on-chronic liver failure (ACLF) patients require early identification and intensive treatment. Precise prediction is crucial for determining the urgency degree and therapy appropriateness, considering high mortality and multitude of clinical resources. The aim of our study was to determine the exact cut-off values of various prognostic scores in the prediction of morality of ACLF. Methods. This prospective study includes chronic liver disease (CLD) patients, admitted due to decompensation, that were subsequently diagnosed with ACLF at the Emergency unit. All patients were evaluated based on various prognostic scores, including Child?Pugh, MELD Na, MELD, SOFA, APACHE II, and CLIF C, which were calculated on admission. Results. Alcoholic liver disease (ALD) was the most common underlying CLD cause (77.9%), followed by viral (8.6%), autoimmune (7.7%), and other causes (5.8%). A total of 37.5% of the patients died at the end of the first month of treatment. Average values of Child?Pugh, MELD Na, MELD, SOFA, APACHE II, and CLIF C scores were significantly higher in patients who died compared to survivors (p < 0.05). CLIF C score showed the best performance with a cut-off value of 50.5, with a sensitivity of 94.9% and specificity of 40%. Conclusion. ACLF remains a condition with a high short-term mortality. Of all of the scores examined in our study, CLIF C proved to be the best scoring system for predicting short term and end of treatment mortality in patients with ACLF.

Summary: Background: Smartphone apps might enable interventions to increase physical activity, but few randomised trials testing this hypothesis have been done. The MyHeart Counts Cardiovascular Health Study is a longitudinal smartphone-based study with the aim of elucidating the determinants of cardiovascular health. We aimed to investigate the effect of four different physical activity coaching interventions on daily step count in a substudy of the MyHeart Counts Study. Methods: In this randomised, controlled crossover trial, we recruited adults (aged ≥18 years) in the USA with access to an iPhone smartphone (Apple, Cupertino, CA, USA; version 5S or newer) who had downloaded the MyHeart Counts app (version 2.0). After completion of a 1 week baseline period of interaction with the MyHeart Counts app, participants were randomly assigned to receive one of 24 permutations (four combinations of four 7 day interventions) in a crossover design using a random number generator built into the app. Interventions consisted of either daily prompts to complete 10 000 steps, hourly prompts to stand following 1 h of sitting, instructions to read the guidelines from the American Heart Association website, or e-coaching based upon the individual's personal activity patterns from the baseline week of data collection. Participants completed the trial in a free-living setting. Due to the nature of the interventions, participants could not be masked from the intervention. Investigators were not masked to intervention allocation. The primary outcome was change in mean daily step count from baseline for each of the four interventions, assessed in the modified intention-to-treat analysis set, which included all participants who had completed 7 days of baseline monitoring and at least 1 day of one of the four interventions. This trial is registered with ClinicalTrials.gov, NCT03090321. Findings: Between Dec 12, 2016, and June 6, 2018, 2783 participants consented to enrol in the coaching study, of whom 1075 completed 7 days of baseline monitoring and at least 1 day of one of the four interventions and thus were included in the modified intention-to-treat analysis set. 493 individuals completed the full set of assigned interventions. All four interventions significantly increased mean daily step count from baseline (mean daily step count 2914 [SE 74]): mean step count increased by 319 steps (75) for participants in the American Heart Association website prompt group (p

Background: According to recent epidemiological data, annual deaths due to liver disease have increased dramatically, while predictions show that trends will continue to rise in the upcoming years. Summary: Abnormal liver blood tests are one of the most common challenges encountered in the primary care setting. The prevalence of mildly elevated transaminase levels is around 10–20% in the general population. The most common causes for the rising burden of liver disease are nonalcoholic fatty liver disease (NAFLD), alcohol-related liver disease (ARLD), and viral hepatitis. With improvements in the management of viral hepatitis over the last decades, the causes for the rising burden of liver disease are shifting toward ARLD and NAFLD. It is well-known that liver disease usually progresses silently for years or decades until the complications of cirrhosis occur. The majority of patients will not require referral to a specialist but will need further assessment in primary care. They should be evaluated for the etiology of liver disease irrespective of the duration of abnormal liver blood tests or unmarked clinical presentation. The evaluation should include a history of alcohol use, a history of medicines or herbal supplements, testing for viral hepatitis, and assessment for NAFLD, especially in obese patients and patients with type 2 diabetes. Abdominal ultrasound should be performed. Key Messages: The general practitioner may contribute significantly by identifying and screening patients at risk for chronic liver disease, as well as prioritize individuals with symptoms or signs of advanced liver disease to the specialist clinic.

Background: Cancer is the second leading cause of death worldwide next to cardiovascular diseases. Despite the advancement in screening, early diagnosis, and development in treatment technology in last several decades, cancer incidence overall, particularly that of gastrointestinal (GI) cancers, is far from being controlled, and is expected to increase worldwide. Summary: Although numerous preclinical and population-based clinical studies have already made important progress in restraining the overall cancer incidence and mortality, the full potential of preventive strategy is still far from being realized, and remains at an early stage. There are several major challenges regarding this issue, and one of the crucial challenges is to maintain the balance between risks and benefits. As a result of past investments, primary prevention nowadays include the integration of various activities such as lifestyle changes to reduce risk, screening to detect early lesions, vaccines and preventive therapies aimed to actively interrupt the carcinogenic pathway. Long-term aspirin use seems to have the largest potential effect on the general population on cancer incidence and mortality overall, especially GI cancers. Helicobacter pylori eradication reduces the risk for gastric cancer and is advocated regardless of the symptoms and stage of disease. Metformin and statins are promising in cancer prevention in patients with type 2 diabetes. Vitamin D supplementation is promising in the prevention of colorectal adenoma recurrence. Key Message: However, additional studies are warranted to establish the potential of various agents and to identify more specific and highly targeted new agents for chemoprevention in digestive oncology.

Background: The increasing incidence of duodenal neoplasm has underlined different methods of resection depending on the clinical presentation, endoscopic features and histopathology. In this comprehensive review, we systematically describe the current knowledge concerning the diagnosis and management of duodenal adenomas (DAs) and discuss data considering all possible therapeutic approaches. Summary: Among a variety of duodenal lesions, including neuroendocrine tumors and gastrointestinal stromal tumors, DAs present precancerous lesions of the duodenal papilla or non-ampullary region necessitating removal. DAs can occur sporadically (SDA) as rare lesions or relatively common in polyposis syndromes. The endoscopic resections of DA are associated with an increased degree of complexity due to distinctive anatomical properties of the duodenal wall, luminal diameter and the presence of ampulla with pancreatic and biliary drainage. The endoscopic techniques including cold snare polypectomy (CSP), endoscopic mucosal resection (EMR), and argon plasma coagulation ablation are suggested to be less invasive than surgical treatment, associated with shorter hospital stay and lower cost. According to the current clinical practice, surgery has been accepted as standard therapeutic approach in familial adenomatous polyposis patients with severe polyposis or DA not amenable to endoscopic resection. Key Messages: The strategy for endoscopic resection of DAs depends on the lesion size, morphology, location, and histopathology findings. Small adenomas are most frequently diagnosed and removed by standard CSP techniques, while large laterally spreading lesions and ampullary adenoma are referred for EMR or endoscopic papillectomy respectively. Screening colonoscopy is indicated in patients with SDA. Additional studies for new endoscopic strategies and techniques for curative therapy of DAs are needed to refine future management decisions. Complete resection of DA is considered curative, but nevertheless, long-term endoscopic follow-up is still required to detect and treat any recurrent arising lesions.

Background/Aim. In recent years, many studies have demonstrated a proximal shift in the distribution of adenomas and colorectal cancers. The aim of this study was to investigate whether there are differences in the incidence and anatomical distribution of adenomas and colorectal cancers spanning a 20 year time gap. Methods. We performed a retrospective observational study of colorectal adenomas and cancers diagnosed during total colonoscopy in a high volume tertiary care facility in two 1-year periods of time ? 1990 and 2010. Results. During the analyzed period, 4,048 colonoscopies were performed, 1,148 were performed in 1990 and 2,900 were done in 2010. The study included 466 patients with adenomas and 121 patients with colorectal cancers. Frequency of proximal adenoma changed from 16.5% to 32.7% (p < 0.001). By analyzing colonoscopies in 2010, an increase in the incidence of adenomas compared to 1990 was noticed. The number of adenomas sized 0?5 mm rose from 32.8% to 56.9% (p < 0.001). Frequency of colon carcinoma changed from 5.3% to 2.0% (p < 0.001). Incidence of cancers in the proximal colon rose from 21.3% to 48.4% (p = 0.002). A higher incidence of cancers in the proximal colon and a lower incidence of distal cancers were observed, while no difference was observed in the incidence of rectal cancers. Conclusion. Presence of proximal colon adenoma and cancer is higher, while the overall incidence of colon cancer is lower. This finding should be taken into account when planning the screening for colorectal cancer.

Background and Objectives. Determination of inflammatory bowel disease activity determines further therapeutic approach and follow-up. The aim of our study was to investigate correlation between patients’ reported symptoms and endoscopic and histological disease activity. Methods. A cross-sectional study was conducted in consecutive newly diagnosed patients with inflammatory bowel disease in a tertiary care referral center. The initial evaluation included patient-reported outcome for stool frequency subscore and rectal bleeding. Endoscopic activity was determined using the Mayo scoring system for ulcerative colitis and the Simple Endoscopic Score for Crohn’s disease. Histopathological activity was assessed using a validated numeric scoring system. Results. We included 159 patients (63 Crohn’s disease with colonic involvement and 96 with ulcerative colitis). We found significant correlation between the Mayo endoscopic subscoring system and histology activity in ulcerative colitis, while no correlation was found in patients with Crohn’s disease. Patient-reported outcome showed inverse correlation with endoscopic and histological activity in Crohn’s disease (rs=−0.67; rs=−0.72), while positive correlation was found in ulcerative colitis (rs=0.84; rs=0.75). Interpretation and Conclusions. Patient-reported outcome is a practical and noninvasive tool for assessment of disease activity in ulcerative colitis patients but not in Crohn’s disease.

Introduction. Cerebral small vessel disease is a neurological con- dition characterized by motor, cognitive and affective disorders, often found on brain magnetic resonance imaging scans in patients with vascular risk factors. Affective disorders may have a major impact on patients’ quality of life, although they are often ignored as an entity in cerebrovascular pathology. Material and Methods. This prospective study included 80 patients with the diagnosis of cerebral small vessel disease admitted at the Clinic of Neurology, Clinical Center of Serbia in the period from January 1, 2017 to January 1, 2019. Baseline demographic data and brain magnetic resonance findings were obtained along with the results of cogni- tive function and affective status tests. Data were analyzed using standard statistical tests. Results. Standard screening tests revealed that 51.25% and 33.75% of our patients with cerebral small vessel disease suffer from apathy and depression, respectively. A sig- nificant correlation was found between the severity of white mat- ter changes on magnetic resonance scans and apathy (p = 0.0092). Additionally, white matter changes were also significantly associ- ated with depression (p = 0.021). Conclusion. Affective disorders are not uncommon in cerebral small vessel disease and apathy was the leading phenomenon among our patients. Since a strong cor- relation was detected between affective disorders and severity of vascular changes on magnetic resonance scans, we may conclude that both apathy and depression are key features of an underlying brain injury, rather than just comorbidity. Uvod. Bolest malih krvnih sudova mozga je neurološko stanje za koje su karakteristični motorni, kognitivni i afektivni poremećaji i koje se često dijagnostikuje na snimcima mozga magnetnom rezo- nancijom kod pacijenata sa vaskularnim faktorima rizika. Promene u afektivnom statusu imaju veliki uticaj na kvalitet života pacijena- ta iako su neretko bile zanemaren fenomen u cerebrovaskularnoj patologiji. Materijal i metode. U prospektivnoj studiji obuhvaćeno je 80 pacijenata sa dijagnozom bolest malih krvnih sudova mozga lečenih i ispitivanih na Klinici za neurologiju Kliničkog centra Sr- bije, u periodu od 1. januara 2017. godine do 1. januara 2019. godine. Analizirani su osnovni demografski podaci, nalaz na magnetnoj rezonanciji mozga i rezultati testova kognitivnih funkcija i afektiv- nog statusa, upotrebom standardnih statističkih metoda. Rezultati. Rezultati testova za apatiju i depresiju ukazali su da je 51,25% bo- lesnika sa ovom bolešću pokazivalo prisustvo apatije, a 33,75% prisustvo depresivnog poremećaja. Dokazana je statistički značajna povezanost između težine lezija bele mase mozga na magnetnore- zonantnim snimcima mozga i apatije (p = 0,0092), odnosno težine lezija bele mase i depresije (p = 0,021). Zaključak. Izmene afektiv- nog statusa nisu retka manifestacija cerebralne bolesti malih krvnih sudova mozga, a najčešći fenomen u našoj grupi bolesnika bila je apatija. Budući da je detektovana značajna povezanost između afek- tivnih poremaćaja i težine vaskularnih lezija na magnetno-rezonan- tnim snimcima mozga, smatramo da su apatija i depresivnost najpre deo kliničke slike ove bolesti a ne jedan od komorbiditeta.

Background. Systemic inflammation in colorectal cancer (CRC) may be reflected by neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and mean platelet volume (MPV). This study was designed to investigate the efficiency of preoperative NLR, PLR, and MVP as a tool for the assessment of tumor characteristics in newly diagnosed patients with CRC. Patients and Methods. For 300 patients and 300 healthy volunteers, complete blood counts with automated differential counts were performed. The NLR was calculated by dividing the absolute neutrophil count by the absolute lymphocyte count; PLR was calculated by dividing the absolute platelet count by the absolute lymphocyte count. The diagnostic performance of NLR, PLR, and MVP was estimated by ROC curve. Results. ROC curve analysis showed high diagnostic efficacy of NLR and PLR in CRC patients with cut-off values of 2.15 (AUC=0.790, 95% CI 0.736-0.884, Se=74.1%, and Sp=73%) and 123 (AUC=0.846, 95% CI 0.801-0.891, Se=73.5%, and Sp=80%) compared to healthy controls, respectively. The diagnostic efficacy of three combined markers was superior compared with individual markers (AUC=0.904, 95% CI 0.812-0.989, Se=96%, and Sp=70%). Conclusion. NRL, PLR, and MPV may be useful markers in diagnostic and early recognition of different stages of CRC; additionally combined all together have stronger diagnostic efficacy.

Background: Smartphone applications may enable interventions to increase physical activity but this has limited evidence in randomized trials. Objectives: The MyHeart Counts Cardiovascular Health study (MHC) is a smartphone-based longitudinal research study aimed at elucidating the determinants of cardiovascular health. Among MHC participants, we performed a randomized controlled trial to investigate the response to four different physical activity coaching interventions on the primary outcome of change in daily step count. Secondary outcomes included life satisfaction, 6-minute walk distance, and sleep quality. Methods: The trial was completed entirely using personal smartphones: participants were digitally consented, the interventions were delivered via the device, and measurements of the primary and secondary outcomes were collected from smartphone sensors. Participants were enrolled from December 12, 2016 to June 6, 2018 and followed for up to 5 weeks. Participants completed the trial through the MyHeart Counts phone app in a free-living setting. All adults over 18 years of age with access to a smartphone (Apple iPhone, version 5S or later) were eligible to participate. After one week of baseline measurements, participants (n=2783) were randomized to a sequence of four, week-long interventions delivered in random order. Interventions consisted of either daily prompts to complete 10,000 steps (completed by n=853); hourly prompts to stand following a full hour of sitting (completed by n=879); instructions to read the guidelines from the American Heart Association website (completed by n=868); and e-coaching based upon the individual's personal activity patterns from the baseline week of data collection (completed by n=896). Results: 2783 participants consented to enroll in the coaching study, of whom 1075 completed the baseline week of data collection and at least one of the four interventions. 493 individuals completed the full set of assigned interventions. All four interventions were found effective at modestly increasing daily step count by a mean of 266 ±75 steps from a baseline mean of 2958±69 steps (p=0.003). Intervention-specific step increases were: 319±74 steps (p

Uvod: Bolest malih krvnih sudova (BMKS) mozga je čest nalaz kod pacijenata sa klasičnim vaskularnim faktorima rizika i povezana je sa motornim, kognitivnim i afektivnim poremećajima. Neuroradiološki, BMKS mozga se manifestuje lakunarnim infarktima i/ ili hiperintenzitetima bele mase (HBM), a moguća je i pojava mikrokrvarenja. Pored retkih naslednih oblika BMKS mozga, pacijenti sa glavoboljom, posebno migrenskog tipa, nalaze se u povećanom riziku za nastanak ovih lezija, mada je povezanost kompleksna i nedovoljno razjašnjena. Cilj: Cilj rada je identifikacija učestalosti i tipa glavobolja kod pacijenata sa sporadičnom BMKS mozga. Materijal i metode: Retrospektivnom studijom obuhvaćeno je 115 pacijenata sa dijagnozom BMKS mozga, lečenih i ispitivanih hospitalno na Odeljenju za cerebrovaskularne bolesti i rezistentne glavobolje Klinike za neurologiju Kliničkog centra Srbije, u periodu od 1. januara 2015. godine do 31. decembra 2017. godine. Analizirani su osnovni demografski podaci, tip glavobolje i nalaz na nuklearnoj magnetnoj rezonanci (NMR) mozga (prisustvo lakunarnih ishemija, HBM i ukupna težina lezija) standardnim statističkim testovima. Rezultati: Od ukupnog broja pacijenata uključenih u studiju, 44% je patilo od glavobolje. Lakunarni infarkti su uočeni kod 86,1% pacijenata, a HBM kod 46,1% pacijenta. Povezanost glavobolje i prisustva lakunarnih ishemija je bila na nivou statističkog trenda (p = 0,072), dok su pacijenti bez glavobolje imali tendenciju češće pojave HBM u odnosu na one sa glavoboljom (p = 0,065). Zaključak: Veliki broj pacijenata sa sporadičnom, arterioloskleroznom BMKS mozga se ujedno žali na glavobolju. Na NMR snimcima mozga prisustvo lakunarnih infarkta je vezano sa glavobolju kao simptom, a postojanje HBM je češće kod pacijenata bez glavobolje u anamnezi. Introduction: Cerebral small vessel disease (CSVD), a common finding in patients with vascular risk factors, is associated with motor, cognitive and affective disorders. Magnetic resonance imaging (MRI) brain scans of patients with CSVD include lacunar infarcts and/or white matter hyperintensities (WMH) and microhemorrhages. Aside from rare familiar forms of CSVD, patients with headaches, especially migraineurs, have an increased risk to develop these lesions, although this relationship is rather complex and yet to be fully elucidated. Aim: The aim of the study was to determine the frequency and type of headache in patients with CSVD. Material and methods: This retrospective study included 115 patients with CSVD diagnosis admitted at the Clinic of Neurology, Clinical Center of Serbia in the period January 1st, 2015 - December 31st, 2017. Baseline demographic data, headache type and MRI findings (ischemic lacunar infarctions, WMH, and overall lesion severity) were obtained. Data were compared between CSVD patients with headache and headache-free CSVD cases, with the use of standard statistical methods. Results: Among all patients included in this study, 44% had headaches. Lacunar infarcts were present in 86,1% and WMH in 46,1% cases. Correlation between headache symptoms and lacunar infarcts showed a trend towards statistical significance (p = 0.072) whereas headache-free patients more frequently had WMH, also approaching statistical significance (p = 0.065). Conclusion: A large number of arteriolosclerotic CSVD patients complain of different types of headaches. Based on MRI findings, lacunar infarcts are related to headache symptoms, and WMHs are more frequently present in patients with a negative history of headache.

Background The genetic determinants of heart failure (HF) and response to medical therapy remain unknown. We hypothesized that identifying genetic variants of HF that associate with response to medical therapy would elucidate the genetic basis of cardiac function. Objectives This study sought to identify genetic variations associated with response to HF therapy. Methods This study compared extremes of response to medical therapy in 866 HF patients using a genome-wide approach that informed the systems-based design of a customized single nucleotide variant array. The effect of genotype on gene expression was measured using allele-specific luciferase reporter assays. Candidate gene transcription-deficient mice underwent echocardiography and treadmill exercise. The ability of the target gene agonist to rescue mice from chemically-induced HF was assessed with echocardiography. Results Of 866 HF patients, 136 had an ejection fraction improvement of 20% attributed to resynchronization (n = 83), revascularization (n = 7), tachycardia resolution (n = 2), alcohol cessation (n = 1), or medications (n = 43). Those with the minor allele for rs7767652, upstream of hypocretin (orexin) receptor-2 (HCRTR2), were less likely to have improved left ventricular function (odds ratio: 0.40 per minor allele; p = 3.29 × 10−5). In a replication cohort of 798 patients, those with a minor allele for rs7767652 had a lower prevalence of ejection fraction >35% (odds ratio: 0.769 per minor allele; p = 0.021). In an HF model, HCRTR2-deficient mice exhibited poorer cardiac function, worse treadmill exercise capacity, and greater myocardial scarring. Orexin, an HCRTR2 agonist, rescued function in this HF mouse model. Conclusions A systems approach identified a novel genetic contribution to human HF and a promising therapeutic agent efficacious in an HF model.

OBJECTIVES Colorectal cancer (CRC) is one of the most common malignancies worldwide. The aim of this study was to compare the outcomes of two different screening approaches in a small country (Montenegro, 650,000 inhabitants) with a CRC incidence lower than the European average. METHODS Two structured invitation programs were compared with respect to compliance and neoplasia yield: (i) program A focused on first-degree relatives of CRC patients diagnosed in two hospitals (n=206), inviting them for colonoscopy; (ii) program B was an invitation program for fecal occult blood testing, followed by colonoscopy if positive, conducted in University Hospital, Podgorica, Montenegro, on 2760 randomly selected average-risk persons, age 50-74 years, living in a single municipality. RESULTS Of 710 first-degree relatives of 206 CRC patients approached, 540 presented for colonoscopy (76.05% uptake). Overall, 31 were diagnosed with a cancer, 58 with advanced adenoma, and 151 with adenoma in general. In the general screening program, of 2760 individuals invited, 920 underwent fecal immunochemical test (33.3% uptake) and colonoscopy was performed in all 95 positive cases (10.3%); six cancers was found in five patients (one patient had two cancers), 19 patients were diagnosed with advanced adenoma, and 26 with any adenomas. The risk-targeted screening program had a significantly higher yield for cancers in both per invited (31/710 vs. 5/2760, P

Objectives This study sought to discover the key determinants of exercise capacity, maximal oxygen consumption (oxygen uptake [Vo2]), and ventilatory efficiency (ventilation/carbon dioxide output [VE/Vco2] slope) and assess the prognostic potential of metabolic exercise testing in hypertrophic cardiomyopathy (HCM). Background The intrinsic mechanisms leading to reduced functional tolerance in HCM are unclear. Methods The study sample included 156 HCM patients consecutively enrolled from January 1, 2007 to January 1, 2012 with a complete clinical assessment, including rest and stress echocardiography and cardiopulmonary exercise test (CPET) with impedance cardiography. Patients were also followed for the composite outcome of cardiac-related death, heart transplant, and functional deterioration leading to septal reduction therapy (myectomy or septal alcohol ablation). Results Abnormalities in CPET responses were frequent, with 39% (n = 61) of the sample showing a reduced exercise tolerance (Vo2 max 34). The variables most strongly associated with exercise capacity (expressed in metabolic equivalents), were peak cardiac index (r = 0.51, p 34 (hazard ratio: 3.14; 95% CI: 1.26 to 7.87; p = 0.014), and LAVI >40 ml/m2 (hazard ratio: 3.32; 95% CI: 1.08 to 10.16; p = 0.036). Conclusions In HCM, peak cardiac index is the main determinant of exercise capacity, but it is not significantly related to ventilatory efficiency. Peak Vo2, ventilatory inefficiency, and LAVI are associated with an increased risk of major events in the short-term follow-up.

Backgrund/Aim. In recent decades noninvasive methods for the assessment and monitoring of liver fibrosis have been developed and evaluated in numerous chronic liver diseases. The aim of this study was to evaluate the diagnostic accuracy of noninvasive markers for fibrosis assessment transient elastography (TE) and biochemical markers using liver biopsy as reference in patients with primary biliary cirrhosis (PBC). Methods. One hundred and twenty-two patients underwent both liver biopsy and blood tests on the same day and TE in a month following the biopsy and the tests. Liver biopsies were reviewed by a single pathologist using the METAVIR scoring system for assessment of liver fibrosis. Aspartate aminotransferase (AST), platelet ratio index (APRI), Forns scores, AST and alanine transaminase (ALT) ratio and TE were compared with liver fibrosis stage in order to determine the best noninvasive marker of liver fibrosis. Results. There was a statistically significant difference (p < 0.05) for the APRI score, Forns index and TE according to stages of liver fibrosis. TE showed superior diagnostic performance when compared to other surrogate markers of liver fibrosis that were investigated. Optimal cut-off for TE were 4.25 and 5.9 kPa for diagnosing the presence of fibrosis and distinguishing mild/moderate and advanced stages of fibrosis respectively. The areas under the receiver operating characteristic (AUROC) of TE were 0.963 and 0.865, respectively. Conclusion. Based on our investigation the APRI score, Forns index and TE adequately predict fibrosis stage in patients with primary biliary cirrhosis, but the most sensitive and specific parameter appears to be TE. Using noninvasive markers and methods in the evaluation of patients in daily clinical practice may reduce, but not eliminate, the need for invasive diagnostic procedures.

Purpose We tested whether providing a genetic risk score (GRS) for coronary artery disease (CAD) would serve as a motivator to improve adherence to risk-reducing strategies. Methods We randomized 94 participants with at least moderate risk of CAD to receive standard-of-care with (N = 49) or without (N = 45) their GRS at a subsequent 3-month follow-up visit. Our primary outcome was change in low density lipoprotein cholesterol (LDL-C) between the 3- and 6-month follow-up visits (ΔLDL-C). Secondary outcomes included other CAD risk factors, weight loss, diet, physical activity, risk perceptions, and psychological outcomes. In pre-specified analyses, we examined whether there was a greater motivational effect in participants with a higher GRS. Results Sixty-five participants completed the protocol including 30 participants in the GRS arm. We found no change in the primary outcome between participants receiving their GRS and standard-of-care participants (ΔLDL-C: −13 vs. −9 mg/dl). Among participants with a higher GRS, we observed modest effects on weight loss and physical activity. All other secondary outcomes were not significantly different, including anxiety and worry. Conclusion Adding GRS to standard-of-care did not change lipids, adherence, or psychological outcomes. Potential modest benefits in weight loss and physical activity for participants with high GRS need to be validated in larger trials.

Vitamin A is essential for the early development and normal functioning of the brain throughout life. A deficiency of vitamin A is one of the leading causes of morbidity and mortality in developing countries, and subclinical deficiency is probably present worldwide. The main active molecule in vitamin A is retinoic acid, which is involved in vision, the immune system, skin health, olfaction and cognition (learning, memory, spatial functions, olfaction, etc.) through processes of neuroplasticity and neurogenesis. Vitamin A is involved in the regulation of about one-sixth of the human genome. It has non-genomic actions in protein translation and paracrine actions. Retinal vitamin A aldehyde is crucial for day and night vision. The best-known manifestation of hypovitaminosis A is night blindness but in more severe cases, it causes blindness. In the hypothalamus, vitamin A, with information from the retina, acts in circadian and seasonal regulation. Increased retinoic acid levels in the blood are associated with increased risk of depression, and lower levels have been connected with Alzheimer’s disease, Parkinson’s disease, cerebral ischemia, autistic spectrum disorders and schizophrenia. Higher doses and longer periods of treatment pose the threat of hypervitaminosis A. Vitamin A and its analogs are a promising new class of therapeutic agents in a wide spectrum of disorders, albeit with a narrow therapeutic window. [Projekat Ministarstva nauke Republike Srbije, br. 175033 i br. 175022]

Introduction. Primary biliary cirrhosis (PBC) is an immunemediated chronic progressive inflammatory liver disease leading to destruction of small interlobular bile ducts. Sarcoidosis is a chronic disorder of unknown etiology characterized by non-caseous granulomas. Case report. We reported a 69-year-old female patient with abdominal pain, malaise, vertigo, headaches, hands tremor and partial loss of hearing. Initial laboratory findings revealed elevated liver function tests and cholesterol with positive antimytochondrial and antinuclear antibodies. Liver biopsy revealed granuloma typical for PBC and granulomatous lesions typical for sarcoidosis. Elevated serum angiotensin-converting enzyme and granulomatous lesion on the brain magnetic resonance imaging (MRI) were detected and the patient was diagnosed with overlap of PBC and liver sarcoidosis and neurosarcoidosis. The patient was treated with ursodeoxicholic acid (UDCA) and prednisolone. Six months later the patient was symptom-free with laboratory findings within normal range. Conclusion. In PBC patients it is important to consider coexisting granulomatous liver diseases if elevated liver function tests persist despite UDCA therapy.

Objective. Keeping in mind the rising prevalence of nonalcoholic fatty liver disease (NAFLD) and the need to establish noninvasive tests for its detection, the aim of our study was to investigate whether platelet count (PC), mean platelet volume (MPV), and platelet distribution width (PDW) can predict the presence of liver fibrosis in this group of patients. Methods. In 98 patients with NAFLD and 60 healthy volunteers, complete blood counts with automated differential counts were performed and values of PC, PDW, MPV, and PCT were analyzed. Results. Patients with NAFLD had lower PC and higher MPV, PCT, and PDW compared to the controls (P < 0.05). When NAFLD group was stratified according to severity of liver fibrosis, there was a statistically significant difference in the average values of PDW and PC between the groups (P < 0.05). Conclusion. Patients with NAFLD have significantly higher values of PCT, PDW, and MPV when compared to the healthy controls. Further studies are needed to establish their potential use for prediction of the degree of liver steatosis and fibrosis in NAFLD patients.

Importance: Studies have established the importance of physical activity and fitness, yet limited data exist on the associations between objective, real-world physical activity patterns, fitness, sleep, and cardiovascular health. Objectives: To assess the feasibility of obtaining measures of physical activity, fitness, and sleep from smartphones and to gain insights into activity patterns associated with life satisfaction and self-reported disease. Design, Setting, and Participants: The MyHeart Counts smartphone app was made available in March 2015, and prospective participants downloaded the free app between March and October 2015. In this smartphone-based study of cardiovascular health, participants recorded physical activity, filled out health questionnaires, and completed a 6-minute walk test. The app was available to download within the United States. Main Outcomes and Measures: The feasibility of consent and data collection entirely on a smartphone, the use of machine learning to cluster participants, and the associations between activity patterns, life satisfaction, and self-reported disease. Results: From the launch to the time of the data freeze for this study (March to October 2015), the number of individuals (self-selected) who consented to participate was 48 968, representing all 50 states and the District of Columbia. Their median age was 36 years (interquartile range, 27-50 years), and 82.2% (30 338 male, 6556 female, 10 other, and 3115 unknown) were male. In total, 40 017 (81.7% of those who consented) uploaded data. Among those who consented, 20 345 individuals (41.5%) completed 4 of the 7 days of motion data collection, and 4552 individuals (9.3%) completed all 7 days. Among those who consented, 40 017 (81.7%) filled out some portion of the questionnaires, and 4990 (10.2%) completed the 6-minute walk test, made available only at the end of 7 days. The Heart Age Questionnaire, also available after 7 days, required entering lipid values and age 40 to 79 years (among 17 245 individuals, 43.1% of participants). Consequently, 1334 (2.7%) of those who consented completed all fields needed to compute heart age and a 10-year risk score. Physical activity was detected for a mean (SD) of 14.5% (8.0%) of individuals’ total recorded time. Physical activity patterns were identified by cluster analysis. A pattern of lower overall activity but more frequent transitions between active and inactive states was associated with equivalent self-reported cardiovascular disease as a pattern of higher overall activity with fewer transitions. Individuals’ perception of their activity and risk bore little relation to sensor-estimated activity or calculated cardiovascular risk. Conclusions and Relevance: A smartphone-based study of cardiovascular health is feasible, and improvements in participant diversity and engagement will maximize yield from consented participants. Large-scale, real-world assessment of physical activity, fitness, and sleep using mobile devices may be a useful addition to future population health studies.

The most frequent benign gallbladder polyps are cholesterol polyps. Next in frequency were adenomas, which may have malignant potential. The aim of this study was to assess the possibility of ultrasonography in the diagnosis and differential diagnosis of cholesterol polyps compared to adenomas. Patients were examined during the period from October 2006. to December 2008. In Department of Ultrasound, Clinic for Gastroenterology and Hepatology, Belgrade. The group of 54 patients analyzed consisted of 30 women (56%) and 24 men (44%). Most (59%) had solitary polyps. In 92.6% of patients the size of polyps was below 10 mm. 74% of respondents were over 50 years. Ultrasonography is the method of choice and gold standard in diagnosis of gallbladder polyps. Based on echoic properties cholesterol polyps can not be distinguished from adenomas. Malignant alteration of polyps also could not be detected. Appropriate ultrasonographic characteristics such as size of polyps, appearance of a broad base that sits on the wall, concomitant lithiasis findings and patient age may be indicative for malignancy.

Background/Aim. Transient global amnesia (TGA) could be related to acute ischemic disturbances in mesial parts of temporal lobes, which are important for memory. Incompetence of internal jugular vein (IJV) valve with venous congestion causes venous microthrombosis of hippocampus. The aim of this study was to investigate the frequency of IJV valve incompetence, as well as other hemodynamic and structural properties of cerebral circulation in TGA patients. Methods. IJV valve competence was investigated in 40 TGA patients and 30 persons of the control group (matched by age and sex), as well as detection of microembolic signals and detection of right to left cardiopulmonal shunt, cerebral vasomotor reactivity and echocardiography by color triplex ultrasonography and transcranial doppler. Results. A significant difference in frequency of IJV valve incompetence was found between the TGA patients and the control persons (55% TGA vs 30% controls; p < 0.001). We did not find a significant structural (plaques frequency) or hemodynamic (flow velocity, pulsatility index) differences on arteries of the neck and cerebral arteries between the TGA patients and the controls, except for the increased pulsatility index on the basilar artery (40% TGA vs 16.6% controls; p < 0.01) and decreased vasomotor reactivity in TGA patients (50% TGA vs 26.6% controls; p < 0.001). Microembolic signals were detected very rarely (17.5% TGA patients vs 13.3% controls; p > 0.05), as well as right to left cardiopulmonal shunt (15% TGA vs 16.6% controls; p > 0.05), indicating that embolism was not important for pathogenesis of TGA. Transesophageal echocardiography confirmed it, because only one TGA patient had a potent foramen ovale. Conclusion. We found a significantly increased frequency of IJV incompetence in the TGA patients, which confirmed the role of vein drainage disturbances in pathogenesis of TGA.

Uvod: Ehinokokoza predstavlja znacajan zdravstveni problem u endemskim podrucjima, ali zbog migracije ljudi, ovo postaje briga citavog covecanstva. Ehinokokoza najcesce zahvata jetru. Na osnovu ultrasonografskog izgleda, ehinokokusne ciste su klasifikovane u pet tipova. Međutim, razlicite ciste imaju razlicit klinicki tok, sa razlicitim terapijskim implikacijama. Stoga je Svetska zdravstvena organizacija 2003, dala novu podelu uzimajuci u obzir i morfoloske i klinicke karakteristike ehinokokusnih cisti, sa preporukom da naucnici sirom sveta koriste ove podelu u cilju da se njihovi podaci mogu upoređivati. Cilj: Cilj ove deskriptivne studije je prezentacija rezultat pregleda pacijenata pregledanih zbog ehinokokoze jetre tokom jedne godine. Metod: Ova studija je ukljucila 52 pacijenta ispitivanih i lecenih zbog ehinokokusne ciste jetre u Klinici za digestivnu hirurgiju, Klinickog centra Srbije u Beogradu podvrgnutih ehosonografskom pregledu abdomena. Analizirani su podaci o polu i uzrastu pacijenata, njihovi simptomi (abdominalni bol, mucnina, povracanje, povisena telesna tempretaura) i prisustvo solitarnih ili multiplih cista jetre. Prikazani su podaci o segmentnoj lokalizaciji i tipu ehinokokusnih cista jetre. Rezultati: U studiju je ukljuceno 16 muskaraca i 36 žena prosecne starosti 53,15+/-17,51 godina (najmanje 17; najvise 78). Bol u trbuhu je imalo 69,2% pacijenata, mucninu 23,1%, povracanje 15,4% i povisenu telesnu temperaturu 3,8% pacijenata. Solitarna ehinokokoza jetre je nađena kod 69,2% pacijenata. Kod 19,2% pacijenata je identifikovana Gharbi I cista, kod 29,8% Gharbi II, Gharbi III kod 33,7%, Gharbi IV kod 15,4%, a Gharbi V tip ciste je identifikovana kod 1,9% pacijenata. Vecina cisti je identifikovano u IV, VII i III segmentu jetre (34,6%, 23,1% i 11,5%). Zakljucak: Ova deskriprivna studija je analizirala, pored demografskih karakteristika i tipa i ucestalosti tegoba, rezultate ehosonografskog ispitivanja i primenu standardizovane klasifikacije ehinokokusnih cisti jetre radi doprinosa znanju o karakteristikama ehinokokusnih cisti jetre u nasem podrucju. Ovo je, takodje, koristan prikaz dijagnostickih standarda za ovo oboljenje.

Introduction: Available literature states that the incidence of colorectal adenomas and cancer is more common in men, however, lately has been observed increasing number of patients among women. Aim: to analyze the frequency and clinical characteristics of colorectal adenomas and cancer in women. Materials and Methods: We performed a retrospective study in which data of 695 patients with colorectal adenomas and carcinomas have been analyzed from a total of 10,659 patients who underwent colonoscopy. Results: Colonoscopy and colorectal neoplasms were more frequently diagnosed in man (71.88%/67.4%) than women (28.12%/32.65%), so the results must be interpreted with caution. Conclusion: The increase in the number of women who suffer from colorectal adenoma and carcinoma can be explained by balancing lifestyle and increasing the number of women who are examined, given up the initial resistance that women had to colonoscopy, which is a potentially painful and embarrassing.

Myeloid sarcoma (MS) is a rare disease that presents as an extramedullary tumor of myeloid cells. Most patients subsequently develop acute myelogenous leukemia (AML), and their prognosis is poor. Here, we report the case of a 28-year-old woman with a primary isolated myeloid sarcoma which originated in the gastrointestinal (GI) tract. Two months after initial presentation, bone marrow tests led to a diagnosis of AML. This case is noteworthy because GI tract infiltration with leukemic cells is very rare, and it is even more rare as an occurrence preceding the development of systemic leukemia.

BACKGROUND AND AIMS: Both myectomy and alcohol septal ablation (ASA) can substantially reduce left ventricular (LV) outflow obstruction, relieve symptoms, and improve outcomes in hypertrophic cardiomyopathy (HCM). It is unclear whether septal reduction decreases left atrial (LA) size and improves diastolic function. The aim of this study was to analyze the consequences of septal reduction on LA size and diastolic function in a cohort of patients with HCM. METHODS: Forty patients (mean age: 50 ± 14, male sex 64%) with HCM who underwent septal reduction (myectomy or alcohol septal ablation) were studied. Retrospective analyses of echocardiograms preprocedure, postprocedure, and at 1 year of follow-up were performed. RESULTS: Thirty-one patients had septal myectomy and 9 ASA. The degree of reduction in rest peak LV outflow tract gradient was significant (57 ± 32 vs. 23 ± 20 mmHg at 1 year, P < 0.001). Maximal interventricular septal thickness decreased from 22 ± 6 mm preprocedure to 19 ± 4 mm postprocedure (P < 0.001); moderate-to-severe mitral regurgitation (MR) was initially present in 34% of the sample and only 2% after the procedure. Average LA volume index (LAVI) decreased from 63 ± 20 to 55 ± 20 mL/m(2) at the 1-year follow-up (P < 0.001). We did not observe a significant improvement in diastolic function at Doppler (E/A 1.2 ± 0.4 vs. 1.1 ± 0.5, P = 0.07; E' 7.6 ± 3.6 vs. 6.9 ± 3.0, P = 0.4) pre- and postprocedure, respectively). At 1 year, only 5% of the patients were severely symptomatic (NYHA III). On multivariate analysis, a significant change in the LVOT gradient during stress (Δ gradient ≥30 mmHg) was the only variable independently associated with LAVI reverse remodeling >10 mL/m(2) [OR = 6.4 (CI 95% 1.12-36.44), P = 0.04]. CONCLUSIONS: Septal reduction is effective in the relief of LV obstruction and symptoms in patients with HCM. The hemodynamic changes result in a significant LA reverse remodeling, but not in an improvement of diastolic function in these patients.

Introduction. Bleeding from esophageal varices is a serious medical problem because of the risk of recurrent bleeding and high mortality rate (17-54%). Gastroesophageal varices develop in 50% of cirrhotic patients with portal hypertension, but can also develop in other pre- or post-hepatic causes of portal hypertension. Case report. We reported a 48-year-old female patient with portal hypertension caused by mesenterial vein thrombosis due to congenital thrombophilia. The patient was hospitalized several times because of recurrent gastroesophageal bleeding. Thrombosis of portal, lienal and mesenteric veins was diagnosed using multislice computed tomography (MSCT) angiography. Sclerotherapy and/or variceal ligation could not be used due to variceal size and distribution. Beta blockers were ineffective. Balloon tamponade and octreotide were used in each massive bleeding episode. Carvedilol therapy was introduced but rebleeding occured. Surgical treatment was considered a high risk procedure due to massive thrombosis of mesenterial veins, patient's general condition and high risk of postoperative thrombotic events. Thus, long-acting somatostatin analogue - Sandostatin® LAR was initiated at a dose of 30 mg im/month. The patient responded to the therapy well and variceal bleeding did not occur for the following 3 months. After 3 months another episode of gastric variceal hemorrhage occurred and surgical treatment was reconsidered. Total gastrectomy was performed in order to prevent repeated bleeding from large gastric varices and the patient recovered successfully, and after 1 year is symptom-free. Conclusion. Long-lasting somatostatin analogue was used for the first time in treatment of gastroesophageal variceal hemorrhage in the patient with prehepatic portal hyperten-sion. It was effective as temporary therapeutic option allowing the improvement of the patients general condition and adequate planning of elective surgical procedure. Futher reports are needed in order to compare efficacy in treatment of patients with variceal bleeding, where poor outcome is expected. [Projekat Ministarstva nauke Republike Srbije, br. III41004]

BACKGROUND: Results of phase III clinical studies comparing efficacy of Xeloda vs. standard 5-FU/FA protocols as first line therapy of metastatic colorectal carcinoma (MCRC), have shown better efficacy of Xeloda, with less toxic adverse effects, apart from handfoot syndrome. METHODS: From January 2000 to May 2001 the study enrolled 54 patients with MCRC, 38 males and 16 females, aged 30-78 years. All patients had metastatic diseases. In 33 the primary tumor was in colon, in 21 in rectum. All patients received Xeloda 2500 mg/m2/day in two daily doses, during 14 days followed by 7 days of pause. Dose intensity was 88,79% +/- 9,2. For efficacy evaluation the WHO criteria and tumor markers CEA and CA 19-9 were used. RESULTS: Overall response rate was 47%, with 13% complete responses, 34% partial responses 38% stable disease and 15% disease progression. No significant difference was found between patients with regard to localization of primary tumor (colon or rectum). There was no significant difference in response rate when compared 27 patients with adverse events of capecitabine ('hand and foot' syndrome and diarrhea) and those without them. Response rate in a subgroup of 21 evaluable (out of 29) patients with initial signs of liver dysfunction was worse (p

Hypertrophic cardiomyopathy (HCM) is a leading cause of sudden cardiac death among athletes in the United States [(1)][1]. The electrocardiogram (ECG) can be used for screening athletes to identify HCM [(2–4)][2]; however, its routine use remains controversial due to false positives [(5)][3]. We

To determine predictors of clinically relevant pancreatic fistulas (CRPF) by measuring drain fluid amylase (DFA) in the early postoperative period.This prospective clinical study included 382 patients with periampullary tumors that were surgically resected at our department between March 2005 and October 2012. A cephalic duodenopancreatectomy (DP) was performed on all patients. Two closed suction drains were placed at the end of the surgery. The highest postoperative DFA value was recorded and analyzed during the first three postoperative days and on subsequent days if the drains were kept longer. Pancreatic fistula (PF) was classified according to the International Study Group of Pancreatic Fistula (ISGPF) criteria. Postoperative complications were defined according to the Dindo-Clavien classification. All data were statistically analyzed. The optimal thresholds of DFA levels on the first, second and third postoperative days were estimated by constructing receiver operating curves, generated by calculating the sensitivities and specificities of the DFA levels. The DFA level limits were used to differentiate between the group without PF and the groups with biochemical pancreatic fistula (BPF) and CRPF.Pylorus-preserving duodenopancreatectomy was performed on 289 (75.6%) patients, while the remaining patients underwent a classic Whipple procedure (CW). The total incidence of PF was 37.7% (grade A 22.8%, grade B 11.0% and grade C 3.9%). Soft pancreatic texture (SPT) was present in 58.3% of patients who developed PF. Mortality was 4.2%. The median DFA value on the first postoperative day (DFA1) in patients who developed PF was 4520 U/L (range 350-99000 U/L) for grade A fistula (BPF) with a SPT and a diameter of the main pancreatic duct (MPD) of ≤ 3 mm. For grade B/C (CRPF), the median DFA1 value was 8501 U/L (range 377-92060 U/L) with a SPT and MPD of ≤ 3 mm. These values were significantly higher when compared to the patients who did not have PF (122; range 5-37875 U/L). The upper limit of DFA values for the first 3 postoperative days in the examined stages of PF were: DFA1 1200 U/L for the BPF and CRPF; DFA3 350 U/L for BPF and DFA3 800 U/L for CRPF. The determined values were highly significant and demonstrated a reliable diagnostic test for both BPF and CRPF.DFA1 ≥ 1200 U/L is an important predictive factor for PF of any degree. The trend of DFA3 (decrease of50%) compared to DFA1 is a significant factor in the differentiation of CRPF from transient BPF.

Hypertrophic cardiomyopathy (HC) is a disease that mainly affects the left ventricle (LV), however recent studies have suggested that it can also be associated with right ventricular (RV) dysfunction. The objective of this study was to determine the prevalence of RV dysfunction in patients with HC and its relation with LV function and outcome. A total of 324 consecutive patients with HC who received care at Stanford Hospital from 1999 to 2012 were included in the study. A group of 99 prospectively recruited age- and gender-matched healthy volunteers were used as controls. RV function was quantified using the RV fractional area change, tricuspid annular plane systolic excursion (TAPSE), and RV myocardial performance index (RVMPI). Compared with the controls, the patients with HC had a higher RVMPI (0.51 ± 0.18 vs 0.25 ± 0.06, p 0.4 and TAPSE

Background Exercise echocardiography is a reliable tool to assess left ventricular (LV) dynamic obstruction in hypertrophic cardiomyopathy (HCM). The aim of this study was to determine the role of exercise echocardiography in the evaluation of latent obstruction and in predicting clinical deterioration in HCM patients. Methods and Results We considered 283 HCM patients studied with exercise echocardiography. The end point was clinical deterioration leading to septal reduction (myectomy or alcohol septal ablation). LV latent obstruction was present at enrollment in 67 patients (24%). During a mean follow-up of 42 ± 31 months, 42 patients had clinical deterioration leading to septal reduction therapy: in 12/67 (22%) patients with a latent obstruction at enrollment, in 28/84 (33%) patients with obstruction at rest, and in 2/132 (1.5%) with obstruction neither at rest or during stress. Multivariate analysis identified the following variables as independently associated with the end point: LV gradient >30 mm Hg at rest (hazard ratio [HR] 2.56, 95% CI 1.27–5.14; P = .009), LV gradient >30 mm Hg during stress (HR 4.96, 95% CI 1.81–13.61; P = .002), and indexed left atrial volume (LAVi ) >40 mL/m 2 (HR 2.86, 95% CI 1.47–5.55; P = .002). In patients with a latent obstruction, the strongest independent predictor of outcome was LAVi >40 mL/m 2 (HR 3.75, 95% CI 1.12–12.51; P = .032). Conclusions Assessment of LV gradient during stress with exercise echocardiography is an important tool for the evaluation of latent obstruction in HCM and may have a role in risk stratification of these patients.

In this article, we describe a double-chambered left ventricle (LV) associated with a functional right ventricular (RV) aneurysm and right atrial (RA) enlargement in an asymptomatic 24-year-old woman with a family history of sudden cardiac death. We will discuss the differential diagnosis, genetic testing and possible prognostic implications.

Objectives: It is unclear if morphology impacts on diastole in hypertrophic cardiomyopathy (HCM). We sought to determine the relationship between various parameters of diastolic function and morphology in a large HCM cohort. Setting: Tertiary referral centre from Stanford, California, USA. Partecipants: 383 patients with HCM and normal systolic function between 1999 and 2011. A group of 100 prospectively recruited age-matched and sexmatched healthy participants were used as controls. Primary and secondary outcome measures: Echocardiograms were assessed by two blinded boardcertified cardiologists. HCM morphology was classified as described in the literature (reverse, sigmoid, symmetric, apical and undefined). Results: Reverse curvature morphology was most commonly observed (218 (57%). Lateral mitral annular E′40 mL/m2 was present in 47% in reverse curvature, 33% in sigmoid, 32% in symmetric, 37% in apical and 32% in undefined, p=0.09. Each morphology showed altered parameters of diastolic function when compared with the control population. Left ventricular (LV) obstruction was independently associated with all three diastolic parameters considered, in particular with LAVi>40 mL/ m2 (OR 2.04 (95% CI 1.23 to 3.39), p=0.005), E/E′>15 (OR 4.66 (95% CI 2.51 to 8.64), p

Background Surgical myectomy and alcohol septal ablation (ASA) aim to decrease left ventricular outflow tract (LVOT) gradient in hypertrophic cardiomyopathy (HCM). Outcome of myectomy beyond 10 years has rarely been described. We describe 20 years of follow-up of surgical myectomy and 5 years of follow-up for ASA performed for obstructive HCM. Methods We studied 171 patients who underwent myectomy for symptomatic LVOT obstruction between 1972 and 2006. In addition, we studied 52 patients who underwent ASA for the same indication and who declined surgery. Follow-up of New York Heart Association (NYHA) functional class, echocardiographic data, and vital status were obtained from patient records. Mortality rates were compared with expected mortality rates of age- and sex-matched populations. Results Surgical myectomy improved NYHA class (2.74 ± 0.65 to 1.54 ± 0.74, p

Purpose Previous studies have shown that hypertrophic cardiomyopathy (HCM) can also affect the right ventricle (RV), but there are not univoque data about it. The aim of this study is to describe RV dysfunction in patients with HCM using the myocardial performance index (MPI), tricuspid annular plane systolic excursion (TAPSE) and RV fractional area change (RVFAC) and their association with clinical outcome. Methods and Materials Consecutive patients with HCM followed at Stanford Hospital from 1999 to 2012 were included in the study. A total of 324 patients with HCM were included in the study. A group of 99 age and sex matched healthy volunteers were used as controls. Multivariable regression analysis was used to determine independent correlates of RV function. Results Compared to matched controls, patients with HCM had higher RVMPI (0.51±0.18 vs. 0.25±0.06, p 0.4 (HR 3.13 per 0.3, CI 95% 1.63 to 6.0, p Conclusions RV dysfunction based on RVMPI is common in patients with HCM and is more frequently observed among patients with LV dysfunction and pulmonary hypertension. RV dysfunction based on RVMPI was associated with a history of syncope, defibrillator discharge or lower maximal VO2.

Characterized by ventricular dilatation, systolic dysfunction, and progressive heart failure, dilated cardiomyopathy (DCM) is the most common form of cardiomyopathy in patients. DCM is the most common diagnosis leading to heart transplantation and places a significant burden on healthcare worldwide. The advent of induced pluripotent stem cells (iPSCs) offers an exceptional opportunity for creating disease-specific cellular models, investigating underlying mechanisms, and optimizing therapy. Here, we generated cardiomyocytes from iPSCs derived from patients in a DCM family carrying a point mutation (R173W) in the gene encoding sarcomeric protein cardiac troponin T. Compared to control healthy individuals in the same family cohort, cardiomyocytes derived from iPSCs from DCM patients exhibited altered regulation of calcium ion (Ca(2+)), decreased contractility, and abnormal distribution of sarcomeric α-actinin. When stimulated with a β-adrenergic agonist, DCM iPSC-derived cardiomyocytes showed characteristics of cellular stress such as reduced beating rates, compromised contraction, and a greater number of cells with abnormal sarcomeric α-actinin distribution. Treatment with β-adrenergic blockers or overexpression of sarcoplasmic reticulum Ca(2+) adenosine triphosphatase (Serca2a) improved the function of iPSC-derived cardiomyocytes from DCM patients. Thus, iPSC-derived cardiomyocytes from DCM patients recapitulate to some extent the morphological and functional phenotypes of DCM and may serve as a useful platform for exploring disease mechanisms and for drug screening.

Primary biliary cirrhosis (PBC) is a chronic, progressive liver disease with elevated serum lipids. It remains unclear if hyperlipidemia increases the risk for atherosclerosis in PBC patients. Metabolic syndrome (MS) promotes the development of atherosclerotic cardiovascular disease due to abdominal obesity and insulin resistance. The aim of this study was to assess incidence and parameters of MS, as well as subcutaneous and visceral fat using noninvasive ultrasonographic measurement in patients with PBC in our population. We included 55 patients with PBC and 44 age- and sex-matched healthy controls (CG-control group). Anthropometric measurements (weight, height, and waist circumference), age, sex, and body mass index were recorded for patients and controls. Laboratory tests for assessing MS and liver function tests were analyzed. We used ultrasonography to determine subcutaneous and visceral fat diameter and area (SF, VF and SA, VA, respectively), as well as perirenal fat diameter (PF). Patients with PBC had significantly higher levels of cholesterol and liver function tests. There were no statistically significant difference in serum insulin and HOMA levels, as well as incidence of MS was diagnosed in 30.9 % (17/55) PBC patients and 43.2 % (19/44) controls. We registered lower amount of VF (PBC:10.92 +/- 3.63 mm, CG:16.84 +/- 5.51 mm, lt 0.001), VA (PBC:403.64 +/- 166.97 mm(2), CG:720.57 +/- 272.50 mm(2), lt 0.001), and PF (PBC:7.03 +/- 1.82 mm, CG 10.49 +/- 2.70 mm, lt 0.001) in patients with PBC. MS is not more frequent in patients with PBC compared with healthy volunteers in our population. Lower amount of VF could be related to lower risk for cardiovascular events in PBC patients.

About one third of ischaemic cerebrovascular diseases have embolic properties. Because of that, transcranial Doppler (TCD) test for detection of microembolic signals (MES), as the only one method for detection of microemboli, is a very important test for the evaluation of cerebral artery embolism. Cerebral emboli are particles of thrombus or atheromatous plaque, platelet aggregates, lipid or air particles in cerebral circulation, which can occlude arterioles and cause ischemic transient attack (TIA) or stroke. Most frequently, they derive from exulcerated plaques of the carotid bifurcation or the aortic arch, from the atrial thrombus, prosthetic heart valves, as well as during carotid endarterectomy, arterial stent, aortocoronary by-pass. For MES detection, bilateral monitoring of a. cerebri mediae (ACM) is performed with each probe held in place over a temporal bone. MES are represented as brightly coloured embolic tracks as they pass through the insonated arteries. A computer hard disk provides continuous recording that is replayed for counting embolic signals. Colour intensity or acoustic range indicate the size and structure of MES. MES in the range of one ACM indicate the source of embolism on the ipsilateral carotid artery, while the bilateral detection of MES suggests a cardiogenic source. Indications for TCD detection of MES are the evaluation of pathogenesis and risk for embolic stroke or TIA and assessing the source of embolism. We started applying this method at the Institute of Neurology in Belgrade 2 years ago. We have investigated 78 patients till today and detected MES in 23 patients (28.7%). The Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology, 2004, considers that TCD is probably useful for detection of cerebral MES in various cardiovascular and cerebrovascular disorders and procedures.

Aims Structural valve deterioration (SVD) limits the long-term durability of homograft aortic valve replacement (AVR). Valves are implanted predominantly using two techniques, the free-hand sub-coronary (SC) technique or aortic root replacement (RR). Our objective was to identify risk factors associated with the development of SVD or ascending aortic dilatation. In particular we strived to determine whether the mode of implantation had an independent effect. Methods and results Demographic and pre-operative clinical data were obtained retrospectively through case-note review. All operations were performed by a single surgeon. Actuarial freedom from ≥2+ AR (aortic regurgitation), elevated trans-valvular gradient (TVG) (≥25 mmHg) and ascending aortic dilatation (≥4.0 cm) were assessed using Kaplan–Meier curves and multivariable Cox proportional hazards regression. A propensity analysis was carried out using a non-parsimonius logistic regression model for implantation with SC vs. RR. Between 1 January 1991 and 1 January 2001, 215 patients underwent AVR with a homograft. The SC technique was used in 131 (61%) patients and 84 (39%) patients underwent RR. Technique was not an independent predictor for ≥2+ AR (adjusted hazard ratio 1.9; 95% CI 0.56–6.16, P = 0.31), elevated TVG (adjusted hazard ratio; 0.99; 95% CI 0.15–6.71, P = 0.99) or ascending aortic dilatation (adjusted hazard ratio 2.01; 95% CI 0.50–8.25, P = 0.33). One and 5 year actuarial freedom from ≥2+ AR (log-rank – P = 0.09) and ascending aortic dilatation (log-rank – P = 0.88) were not significantly different between groups. Conclusion The incidence of SVD and ascending aortic dilatation is not affected by the method of implantation of the aortic homograft. All homografts are prone to SVD which is responsible for a progressive increase in the prevalence of these changes over time.