European Journal of Internal Medicine - Articles in Press

Time to change the glomerular filtration rate estimating formula in primary care? - Corrected Proof

Päivi E. Korhonen, Hannu Kautiainen, Salme Järvenpää, Sirkka-Liisa Kivelä — 2012-01-30

Abstract: Background: The most commonly used equation for estimated glomerular filtration rate (eGFR) is nowadays the four-variable Modification of Diet in Renal Disease (MDRD) equation. This formula was derived from patients with non-diabetic chronic kidney disease (CKD) with mean GFR 40ml/min.Methods: We compared the MDRD study equation and the recently developed Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation by applying the two formulas in 1747 middle-aged cardiovascular risk persons in primary care.Results: The prevalence of renal insufficiency defined as eGFR<60ml/min was 6.7% (95% CI 5.6–8.0) according to the MDRD formula, and 3.6% (95% CI 2.8–4.6) according to the CKD-EPI formula. The subjects who were classified as having CKD according to the MDRD equation, but no-CKD according to the CKD-EPI formula, were mostly women (86%) and slightly younger than the subjects having CKD according to both formulas.Conclusion: The characteristics of the subjects commonly treated in primary care resemble more closely the population from which the CKD-EPI than the MDRD study equation was derived from. Thus, we suppose that in general practice, the CKD-EPI equation is more suitable for estimating renal function than the MDRD equation.

Contribution of Hla-B51 in the susceptibility and specific clinical features of Behcet's disease in Tunisian patients - Corrected Proof

2012-01-30

Abstract: Background: Many researchers have tried to investigate the association of HLA-B51 with the severity and the clinical features of BD with conflicting results.Methods: We aimed at investigating the association of HLA-B51 with demographical and clinical manifestations as well as the severity of BD, by studying 178 native Tunisian BD patients, fulfilling the International Study group criteria for the BD classification recruited from the Department of Internal Medicine, Rabta Hospital in Tunis and compared with 125 native Tunisian healthy age and sex matching volunteers.Results: According to our findings, the frequency of HLAB 51 was significantly higher in BD patients than in controls (p<0.001). Positive pathergy test (PPT) (p=0.01) and retinal vasculitis (p=0.045), were significantly more frequent in HLA B51(+) patients, while the frequency of arterial aneurysms (p=0.009) and neurological involvement, especially the parenchymal involvement (p<0.001), were significantly and clearly higher in HLA B51(−) patients. The patients without HLA B51 had a significantly less severe disease (p=0.001).Discussion/conclusionWe conclude that HLA B51 is a predisposing marker for BD in our population as in most ethnic groups. It seems to be associated with a subgroup of BD patients characterized by a higher frequency of ocular involvement and PPT, but a lower frequency of arterial aneurysm and neurological involvement, and a less severe disease course.

Changes in body mass index on a gluten-free diet in coeliac disease: A nationwide study - Corrected Proof

2012-01-30

Abstract: Objective: The clinical presentation of coeliac disease has changed and patients are often overweight at diagnosis. There is concern that patients might gain further weight while on a gluten-free diet (GFD). The aim of the study was to evaluate the impact of a GFD on the body mass index (BMI) in a nationwide cohort of coeliac patients and to determine variables predictive of favourable or unfavourable BMI changes.Methods: We prospectively investigated weight and disease-related issues in 698 newly detected adults diagnosed due to classical or extraintestinal symptoms or by screening. BMI at diagnosis and after one year on a GFD were assessed and compared with that in the general population.Results: At diagnosis, 4% of subjects were underweight, 57% normal, 28% overweight and 11% obese. On a GFD, 69% of underweight patients gained and 18% of overweight and 42% of obese lost weight; in the rest BMI remained stable. Changes were similar in both symptom- and screen-detected patients. The coeliac group had a more favourable BMI pattern than the general population. Favourable BMI changes were associated with subjects' self-rated expertise on GFD and young age at diagnosis, but not dietary counselling received.Conclusions: BMI improved similarly in screen- and symptom-detected coeliac disease patients on a GFD.

Fibrates: Therapeutic potential for diabetic nephropathy? - Corrected Proof

2012-01-19

Abstract: Despite intensive glucose-lowering treatment and advanced therapies for cardiovascular risk factors, such as hypertension and dyslipidaemia, diabetes mellitus with its macro- and microvascular complications remains a major health problem. Especially diabetic nephropathy is a leading cause of morbidity and mortality, and its prevalence is increasing. Peroxisome proliferator-activated receptor-α (PPAR-α), a member of a large nuclear receptor superfamily, is expressed in several tissues including the kidney. Recently, experimental data have suggested that PPAR-α activation plays a pivotal role in the regulation of fatty acid oxidation, lipid metabolism, inflammatory and vascular responses, and might regulate various metabolic and intracellular signalling pathways that lead to diabetic microvascular complications. This review examines the role of PPAR-α activation in diabetic nephropathy and summarises data from experimental and clinical studies on the emerging therapeutic potential of fibrates in diabetic nephropathy.

Evaluation of transient hyperglycemia in non-diabetic patients with febrile neutropenia - Corrected Proof

2012-01-19

Abstract: Background: We aimed to examine the effect of transient hyperglycemia in non-diabetic patients with febrile neutropenia.Methods: A total of 86 patients with febrile neutropenia were evaluated between June 2006 and December 2009. After measuring random blood glucose level at admission, cases with stress hyperglycemia were included in the study. Stress hyperglycemia was defined as documented random blood glucose level of 140mg/dl and above without known diabetes mellitus, impaired glucose tolerance and impaired fasting glucose. A Multinational Association for Supportive Care in Cancer (MASCC) scoring system was used for the prediction of low and high risk patients according to medical complications at the onset of the febrile episode.Results: There were more patients with stress hyperglycemia than the patients with normoglycemia in the high risk group (p=0.001). The growth of gram negative bacteria and fungi was higher in patients with stress hyperglycemia than with normoglycemia (p=0.001). The patients receiving antifungal therapy had a higher rate of stress hyperglycemia than the patients without receiving antifungal therapy (p=0.009). The patients with stress hyperglycemia had higher mortality rates than the patients with normoglycemia (p=0.007). According to the MASCC risk-index, stress hyperglycemia increased 3.35 fold in the high risk patients compared to the low risk patients (p=0.046) and 4.14 fold in the patients treated with antibacterial and antifungal agents compared to the patients treated with only antibacterial agents (p=0.038).Conclusion: Patients with stress hyperglycemia had more adverse clinical outcomes than patients with normoglycemia. We think further studies are needed to evaluate the relationship between stress hyperglycemia and febrile neutropenia.

Clinical trial data provides hope for attenuation of mucosal injury in coeliac disease - Corrected Proof

Laura Crespo Pérez, Francisco León — 2012-01-18

Our review article on therapeutic clinical trials in coeliac disease , published on-line in EJIM in September 2011, is partially obsolete even before its publication in print. We have been made aware of the preparation of two manuscripts reporting on histological benefit of experimental medicines for coeliac disease.

Limitations of gammaglutamyl transaminase as an indicator of biliary obstruction - Corrected Proof

Oscar M.P. Jolobe — 2012-01-18

When levels of serum alkaline phosphatase(ALP), serum bilirubin, and serum gamma glutamyly transaminase(GGT) fluctuate in a patient in whom suspected choledocholithiasis(CDL) is associated with non-diagnostic ultrasonographic images, it would be useful to know which of the above parameters is indicative of persistent retention of common bile duct(CBD) calculi and, hence, need for interventional endoscopic retrograde cholangiopancreatography(ERCP) in order to implement CBD clearance. On the one hand, if two or more of the parameters spontaneously revert to the normal range, this might signify spontaneous expulsion of CBD calculi and, hence, no need for interventional ERCP. On the other hand, this might merely signify disimpaction of retained CBD calculi and, hence, the need for interventional ERCP, not only to validate the diagnosis of CDL, but, also to implement bile duct clearance. This was the dilemma in a subgroup of 16 patients with suspected CDL in whom serum ALP as well as serum bilirubin spontaneously reverted to the normal range in the interval between ultrasonographic evaluation of the biliary system and ERCP. In all but three of the 16 patients who demonstrated this phenomenon, ultrasonography had failed to identify CBD calculi. In these 16 patients, prior to the fall in blood levels of these parameters, the mean value for peak serum ALP was 244.3iu/l, with concurrent mean serum bilirubin 39.4mcmol/l, and concurrent mean GGT 470.9iu/l. Serum ALP subsequently reverted to the normal range, characterised by nadir levels averaging 86.3iu/l (reference range 25–125), with concurrent normalisation of all serum bilirubin levels . Concurrent nadir levels of serum GGT, however, averaged 103.6iu/l (reference range 0–50), with only six instances of restoration of levels to the normal range. Among the six patients in whom all three parameters, namely, serum ALP, serum bilirubin, and serum GGT reverted to the normal range despite subsequent ERCP documentation of retained CBD calculi, only one had previous validation of CBD calculi by ultrasonography. The following were the characteristics of some of the patients in whom all three biochemical parameters reverted to the normal range despite continuing retention of CBD calculi:-In one patient diagnostic quality of ultrasonography was impaired by pneumobilia. In that patient blood cultures revealed E. coli septicaemia, and, at ERCP, there was a purulent discharge from the CBD. In the other patient with E. coli septicaemia, ultrasonography revealed calculi only in the gallbladder, and there was no dilatation of the CBD. The most remarkable feature of the one and only patient with prior ultrasonographic documentation of CBD calculi was that all three biochemical parameters were within the normal range during the entire period he was under clinical observation. In that patient the original indication for ultrasonography (which showed calculi in the CBD and in the gallbladder) had been his presentation with anorexia, weight loss, and hepatomegaly. Concurrent serum levels of ALP, bilirubin, and GGT were 44iu/l, 9.5mcmol/l, and 34iu/l, respectively. In spite of the fact that these parameters remained within the normal range even on repeat testing, subsequent ERCP validated the original ultrasonographic diagnosis of CBD calculi. The 16 patients documented here were a subgroup of a series comprising 88 consecutive patients aged 57–99 with a final diagnosis of CBD obstruction, attributable, in 86 instances, to calculi in the CBD, and, in two other instances, to Mirizzzi's syndrome. Seventy one of those 88 patients had liver function tests on two occasions or more before final verification of the diagnosis. Given the fact that, among the 16 patients who spontaneously reverted to normal levels of both serum ALP and serum bilirubin, there were ten who had persistently elevated serum GGT, the observation that elevated GGT is a more significant predictor of the presence of CBD stones than elevated serum ALP , can be paraphrased to say that there should be a high index of suspicion for choledocholithiasis even when an elevated serum GGT is the only derangement in the liver function tests. The caveat, however, is that, in some instances(as in six of the patients reported here), even though CBD calculi remain in situ, this state of affairs may not be associated with elevation in either serum ALP, serum bilirubin, or serum GGT. Accordingly, in the context of clinically suspicious spontaneous passage of bile duct stones, and also in the event that biochemical and ultrasonographic parameters fall short of predictions for the probability of CDL magnetic resonance imaging should be utilised to determine whether or not there is continuing retention of CBD calculi . This was certainly the case in a patient who experienced a spontaneous fall in ALP, serum bilirubin, and GGT to levels amounting to 69iu/l, 5.4mcmol/l, and 19iu/l, respectively, from previous levels of 316iu/l, 15.5mcmol/l, and 259iu/l, respectively. In that patient ultrasonography had previously documented CBD dilatation, calculi in the gallbladder, but no CBD calculi. One hundred and eleven days following the resolution of abnormal liver function tests, magnetic resonance cholangiopancreatography documented calculous obstruction of the CBD.

High prevalence of polymorphism and low activity of thiopurine methyltransferase in patients with inflammatory bowel disease - Corrected Proof

2012-01-09

Abstract: Background: Gene polymorphism of thiopurine methyltransferase (TPMT) correlates with decreased enzyme activity which determines a significant risk of adverse effect reactions (ADR) in patients treated with thiopurines. The aim of this study was to investigate TPMT genotype and phenotype status in patients with inflammatory bowel diseases (IBD).Methods: Fifty-one consecutive out-patients with IBD were genotyped for the following allelic variants: rs1800462 (referred as TPMT*2 allele), rs1800460 (referred as TPMT *3B allele), and 1142345 (referred as TPMT *3C allele). Red blood cell TPMT activity was measured using a competitive micro-well immunoassay for the semi-quantitative determination of TPMT activity in red blood cells (RBC) by means of a 6-MP substrate.Results: Polymorphism of TPMT was found in 5 out of 51 patients (10%; 95% CI 2%–18%), three heterozygous and two homozygous carriers. Six patients (11.8%; 95% CI 2.4%–19.5%) displayed very low, 12 (23.5%; 95% CI 11.4%–34.5%) intermediate, and 33 (64.7%; 95% CI 52%–78%) normal/high TPMT activity. There were no differences between TPMT genotype and phenotype groups according to age, type of disease, smoking, and chronic medications. A 71% (95% CI 61%–81%; κ=0.45) concordance rate was found between genotype and phenotype status. Six out of 27 (22%) current or past users of azathioprine developed ADR, with three (50%) displaying TPMT genotype and/or phenotype alterations.Conclusion: Compared to the general population, IBD patients may have significantly higher prevalence of TPMT polymorphism and, even more, low activity. Phenotypic more than genotypic TPMT analysis could be useful to better manage IBD therapy with thiopurines.

Did British Royal Navy actually report scurvy in 1747? - Corrected Proof

Apostolos I. Beloukas, Aristidis Diamantis, Emmanouil Magiorkinis — 2012-01-09

We read with interest Baron's letter commenting on our review article on the history of scurvy . We hereby reply to the comments made by Baron and we would like to thank the author for the opportunity to clarify and discuss some aspects of our work.

Limitations of gammaglutamyl transaminase as an indicator of biliary obstruction. Reply by the authors - Corrected Proof

Predrag Jovanovic, Nermin Salkic, Enver Zerem, Farid Ljuca — 2012-01-09

We read with interest the comments made by Jolobe OMP: “Limitations of gammaglutamyl transaminase as an indicator of biliary obstruction” . The author raised some interesting points and I would like to address some of those. There is no doubt that the isolated elevation of serum gammaglutamyl transaminase (GGT) is not a firm predictive factor for choledocholithiasis (CDL) in itself , but what we learned was that the combination of an elevated GGT, common bile duct (CBD) diameter and the presence of a hyperechoic structure in CBD on ultrasound (US) could be used to construct a predictive model for the presence of CBD stones on ERCP . That predictive model is a clinical decision tool which provides sufficient diagnostic accuracy to help us classify patients with high and low probabilities for the presence of CBD stones on ERCP. It was intended for this predictive model to be used as a quantitative measure of probability for the presence of CBD stones on ERCP.

Seasonal variations of systemic lupus erythematosus flares in southern France - Corrected Proof

2012-01-09

Abstract: Objective: Exposure to sunlight is one of the environmental factors involved in the pathogenesis of systemic lupus erythematosus. We investigated whether there is seasonal variation in the incidence of cutaneous and noncutaneous severe lupus flares in southern France.Methods: We retrospectively reviewed clinical and biological data from all SLE patients hospitalized for a flare of the disease during a two year period in our centre and collected corresponding meteorological data from the official website of MeteoFrance.Results: Forty one patients, mean age 36.7±13.8years, were included. Twenty-six patients (63.4%) had kidney biopsy performed, showing in all cases proliferative nephritis, associated with membranous nephritis in 9 (22%). We found a clear seasonal pattern for overall lupus flares with 39% of flares occurred in Spring. Among patients without any cutaneous involvement, this seasonal pattern was still observed (p=0.024). Patients under antimalarials presented flares significantly later in the sunny season than those without (respectively median in July versus May, p=0.044). There were strong positive correlations between occurrence of lupus flares and maximum temperature increase (ρ=0.87, p<0.001), minimum temperature increase (ρ=0.87, p<0.001), and duration of sunshine increase (ρ=0.78, p=0.003). These correlations were also observed in patients with renal flares.Conclusion: We confirmed a seasonal pattern for lupus flares among patients living in Southern France, with most flares in spring, in correlation with an increase in temperature and duration of sunshine. A similar seasonal pattern was observed in patients with no cutaneous involvement and with visceral involvement.

Clinical remission or mucosal healing: A therapeutic dilemma of ulcerative colitis - Corrected Proof

Levent Filik — 2012-01-05

I read with great interest the recent article by Lopez-Palacios et al. . I appreciate the authors for the important results of their study. There are some issues to be considered. The authors pointed out persistence of endoscopic activity in patients with long-term clinical remission with monotherapy with azatioprine or mercaptopurine. So, this fact gives rise to the question of whether clinical relief or mucosal healing should be the treatment goal in ulcerative colitis. If only clinical relief is sought, this study means that current indexes especially C-reactive protein (CRP) should be reevaluated. Because, approximately half of the study patients have normal CRP although they have high Mayo endoscopic score. However, there are some exceptions. For example, 308GG homozygosity that may lead to normal CRP levels inspite of persistence of endoscopic disease could be remembered . Could the authors consider such genetic variations? On the other hand if mucosal healing is the ideal objective, this study means that mucosal healing is unattainable with azatioprine or mercaptopurine treatment.

The physiological significance and potential clinical applications of ghrelin - Corrected Proof

Takashi Akamizu, Kenji Kangawa — 2012-01-03

Abstract: Ghrelin, a natural ligand for the growth hormone (GH)-secretagogue receptor (GHS-R), is now known to play a role in a number of different physiological processes. For example, ghrelin increases GH secretion, feeding, and body weight when administered centrally or peripherally. These unique effects of ghrelin should be invaluable for the development of novel treatments and disease diagnostic techniques. Clinical trials have already been performed to assess the utility of ghrelin for the treatment of several disorders including anorexia, cachexia, and GH-related disorders. This review summarizes the recent advances in this area of research.

From stress to functional syndromes: An internist's point of view - Corrected Proof

Daniela Lucini, Massimo Pagani — 2011-12-26

Abstract: In this brief review we address schematically the relationship between two emerging issues in clinical medicine: stress and functional syndromes. It is becoming increasingly clear that they demand a multidimensional approach, considering simultaneously elements of behavioral therapy with traditional pharmacological treatment, guided by a better physiopathological understanding including autonomic assessment. New techniques, based on innovative analysis of continuous segments of electrocardiogram and non invasive arterial pressure recordings capable to extract hidden oscillations, provide quantitative indices of sympathetic and vagal modulation of the cardiovascular system. This more complete diagnostic process facilitates explanation of symptoms and reassurance of patients, based on functional evidence. The described clinical approach implies in addition an active collaboration of patients requiring the implementation of a creative alliance. Physical exercise, eating habits and muscular–mental relaxation are combined with pharmacological tools as needed.

Chloride: The queen of electrolytes? - Corrected Proof

Kenrick Berend, Leonard Hendrik van Hulsteijn, Rijk O.B. Gans — 2011-12-23

Abstract: Background: Channelopathies, defined as diseases that are caused by mutations in genes encoding ion channels, are associated with a wide variety of symptoms and have been documented extensively over the past decade. In contrast, despite the important role of chloride in serum, textbooks in general do not allocate chapters exclusively on hypochloremia or hyperchloremia and information on chloride other than channelopathies is scattered in the literature.Study design: To systematically review the function of chloride in man, data for this review include searches of MEDLINE, PubMed, and references from relevant articles including the search terms “chloride,” “HCl,” “chloride channel” “acid-base,” “acidosis,” “alkalosis,” “anion gap” “strong anion gap” “Stewart,” “base excess” and “lactate.” In addition, internal medicine, critical care, nephrology and gastroenterology textbooks were evaluated on topics pertaining the assessment and management of acid-base disorders, including reference lists from journals or textbooks.Conclusion: Chloride is, after sodium, the most abundant electrolyte in serum, with a key role in the regulation of body fluids, electrolyte balance, the preservation of electrical neutrality, acid-base status and it is an essential component for the assessment of many pathological conditions. When assessing serum electrolytes, abnormal chloride levels alone usually signify a more serious underlying metabolic disorder, such as metabolic acidosis or alkalosis. Chloride is an important component of diagnostic tests in a wide array of clinical situations. In these cases, chloride can be tested in sweat, serum, urine and feces. Abnormalities in chloride channel expression and function in many organs can cause a range of disorders.

Infectious complications of chemotherapy in clinically aggressive mature B and T cell lymphomas - Corrected Proof

Juan José Alonso, Araceli Cánovas, José Guillermo Barreiro, Ciriaco Aguirre — 2011-12-23

Abstract: Background: Scientific literature on infectious complications of chemotherapy in lymphomas is often based on retrospective studies or clinical trials performed with selected patients. This population may not be representative of the routine clinical practice. We aimed to analyse the incidence and type of infections associated to standard chemotherapy in clinically aggressive mature B and T cell lymphomas (AMBTL) and to detect baseline variables predictive of the risk of infection in a cohort of unselected patients.Methods: A prospective observational study of all the patients treated with first line chemotherapy for AMBTL in our Lymphoma Unit, in the setting of a community based teaching hospital, was performed. The statistical methods were univariate and multivariate analyses.Results: 183 infectious episodes were registered in 97 (49%) of the 198 patients. Seventy-nine of them (43%) were associated to febrile neutropenia (27% of the patients). Microbiological documentation was obtained in 46% and only clinical documentation in 15%; 39% were classified as fever of unknown origin. Gram negative bacilli were the predominant aetiology. There were several variables related to risk of infection, but in multivariate analysis only a poor initial performance status was predictive of the risk of febrile neutropenia and infection during the first line chemotherapy.Conclusions: In our cohort of AMBTL patients treated with first line chemotherapy, more than half of the relevant infections occurred without febrile neutropenia. A poor performance status was the only independent variable associated with the risk of febrile neutropenia or infection in the course of first line chemotherapy.

Venous thromboembolism prophylaxis of acutely ill hospitalized medical patients. Are we over-treating our patients? - Corrected Proof

Moshe Vardi, Michal Haran — 2011-12-19

Abstract: Venous thromboembolism (VTE) is prevalent and is associated with dire consequences. Many VTE events are related to medical hospitalization, and some of these events are avoidable when appropriate measures are taken. Despite the current knowledge of the prevalence and burden of this disease, many internists are reluctant to prescribe pharmacological prophylaxis to “at-risk” medical inpatients. The purpose of this review is to analyze the reasons for deferring such treatment, in view of the facts as presented in the medical literature. We believe that while the literature supports further emphasis on education and support systems, Internists are deficient of validated tools to decide upon their patient's true risk of clinically overt disease.

Pseudo-myelofibrosis: A new clinical entity - Corrected Proof

Ettore Bartoli, Daniele Sola, Pier Paolo Sainaghi, Luca Rossi, Renzo Boldorini — 2011-12-19

Primary myelofibrosis (MF) is an established clinical entity due to a clonal disorder of myeloid stem cells. The major diagnostic demonstration rests on the presence of fibrosis of the bone marrow, megakaryocyte and platelet alterations, and of extramedullary erythro-myelopoiesis, mainly in the liver and spleen. Reactive MF has been described in a number of conditions, like the human immunodeficiency syndrome , tuberculosis , toxic exposure to x-rays and chemicals, repeated bacterial infections , and treatment with thrombopoietic agents . We herein report two patients exhibiting features of a new entity that we call pseudo-myelofibrosis (PMLF), to be distinguished from both true and reactive MF.

The effects of low-dose fluvastatin and valsartan combination on arterial function: A randomized clinical trial - Corrected Proof

Mojca Lunder, Miodrag Janić, Borut Jug, Mišo Šabovič — 2011-12-14

Abstract: Background: Ageing progressively diminishes arterial functions, even in the absence of traditional risk factors. Our aim was to explore whether age-related arterial changes in middle-aged males could be reversed using short-term, low-dose fluvastatin/valsartan combination intervention.Methods: Forty apparently healthy, middle-aged males (43.3±5.8years) were recruited in a double-blind, randomised intervention. Individuals received either 10mg fluvastatin/20mg valsartan daily or placebo over 30days. The brachial artery flow mediated dilation (FMD), pulse wave velocity (PWV) and common carotid artery β-stiffness were assessed at baseline and after 30days, and again 5–10months after therapy discontinuation.Results: Arterial function variables significantly improved after 30days of intervention; FMD improved by 167.7% (P<0.001), PWV by 10.9% (P<0.05) and β-stiffness by 18.8% (P<0.01), whereas no changes were obtained in the placebo group. The favourable outcomes in the intervention group were accompanied by a significant decrease of high sensitivity-C reactive protein levels (1.8-fold; P<0.05). In contrast, lipids and blood pressure remained unchanged. Surprisingly, the beneficial arterial effects were still present to a substantial degree 7months after completing intervention (remaining % of initial improvement: FMD 82.1%, PWV 69.5% and β-stiffness 68.5%), but declined substantially after 10months.Conclusion: Our results indicate that age-related arterial changes, at least in middle-aged males, can be reversed. Short-term treatment with a low-dose fluvastatin/valsartan combination resulted in a large and long lasting improvement of arterial function.

Can we consider the right hepatic lobe size/albumin ratio a noninvasive predictor of oesophageal varices in hepatitis C virus-related liver cirrhotic Egyptian patients? - Corrected Proof

Serag Esmat, Dalia Omarn, Laila Rashid — 2011-12-12

Abstract: Background: The current guidelines recommend the screening of all cirrhotic patients by endoscopy, but repeated endoscopic examinations are unpleasant for patients and have a high cost impact and burden on endoscopic units. The aim of this study is to evaluate the optimal liver lobe size/albumin ratio and to compare this ratio with spleen size, platelet count and platelet count/spleen diameter ratio as potential noninvasive predictors of oesophageal varices in hepatitis C virus (HCV)-related liver cirrhosis in Egyptian patients.Methods: This prospective study included one hundred patients with HCV-related liver cirrhosis. All studied subjects underwent a detailed clinical examination, biochemical workup, upper gastrointestinal endoscopy and abdominal ultrasound. The platelet count/spleen diameter ratio and the right liver lobe/albumin concentration ratio for all patients were calculated.Results: The 4 predictors demonstrated a high statistically significant correlation with the presence and grade of oesophageal varices (P values<0.001). The platelet count/spleen diameter ratio had the highest accuracy, followed by the right liver lobe/albumin concentration ratio, spleen size and then platelet count.Conclusion: The use of the studied noninvasive predictors, especially the platelet count/spleen diameter ratio and the right liver lobe/albumin concentration ratio, can help physicians by restricting the use of endoscopic screening only to patients presenting a high probability of oesophageal varices. This is especially useful in clinical settings where resources are limited and endoscopic facilities are not present in all areas. Such is the case in Egypt, where there is a large number of patients who require oesophageal screening for oesophageal varices.

Venous thromboembolism prophylaxis of acutely ill hospitalized medical patients. Are we under-treating our patients? - Corrected Proof

Batia Roth-Yelinek — 2011-12-08

Abstract: Venous thromboembolism (VTE) is frequent in patients hospitalized in Internal Medicine wards. It carries a considerable morbidity and mortality. Recommendations for use of anticoagulation are graded 1A in leading evidence-based consensus guidelines. Implementation of these guidelines is suboptimal.Lack of awareness seems to be an important factor for the low implementation rate of thromboprophylaxis in Internal Medicine wards, but other factors may be equally important: some clinicians find the data favoring thromboprophylaxis unconvincing or believe that pharmacological prevention is too risky for the average medical inpatient. The following review will show that although there is a dispute about the clinical importance of some manifestations of thromboembolic disease, anticoagulation significantly reduces the risk for clinically relevant VTE. The bleeding risk in most patients is low and does not outweigh the benefit of treatment. Pharmacological or mechanical thromboprophylaxis is cost-effective when administered to at-risk patients. Better awareness and judicious use of risk assessment models should help the attending physician to balance the risk of VTE against the potential bleeding risk.

Respiratory High-Dependency Care Units for the burden of acute respiratory failure - Corrected Proof

Raffaele Scala — 2011-12-02

Abstract: The burden of acute respiratory failure (ARF) has become one of the greatest epidemiological challenges for the modern health systems. Consistently, the imbalance between the increasing prevalence of acutely de-compensated respiratory diseases and the shortage of high-daily cost ICU beds has stimulated new health cost-effective solutions.Respiratory High-Dependency Care Units (RHDCU) provide a specialised environment for patients who require an “intermediate” level of care between the ICU and the ward, where non-invasive monitoring and assisted ventilation techniques are preferentially applied. Since they are dedicated to the management of “mono-organ” decompensations, treatment of ARF patients in RHDCU avoids the dangerous “under-assistance” in the ward and unnecessary “over-assistance” in ICU. RHDCUs provide a specialised quality of care for ARF with health resources optimisation and their spread throughout health systems has been driven by their high-level of expertise in non-invasive ventilation (NIV), weaning from invasive ventilation, tracheostomy care, and discharging planning for ventilator-dependent patients.

KCNJ11 gene E23K variant and therapeutic response to sulfonylureas - Corrected Proof

2011-11-28

Abstract: Aims: Potassium inwardly rectifier 6.2 subunit (Kir6.2) of the ATP-sensitive potassium (KATP) channel encoded by KCNJ11 gene is a therapeutical target for sulfonylureas. KCNJ11 E23K polymorphism was associated with type 2 diabetes in genetic association studies. The aim of the present pharmacogenetic study was to examine the effect of sulfonylurea treatment on glycemic control in relationship to KCNJ11 E23K variant.Patients and methods: One hundred and one patients with type 2 diabetes who failed to achieve HbA1c<7% on previous metformin monotherapy were included to the study. Sulfonylurea drug was given in addition to metformin. The main outcome of the study was reduction in HbA1c level (ΔHbA1c) after 6-month sulfonylurea therapy. KCNJ11 genotypes were determined by real-time PCR with melting curve analysis.Results: After 6-month treatment, KCNJ11 K-allele carriers had higher decrease in HbA1c compared with EE homozygotes in the dominant genetic model (1.04±0.10 vs. 0.79±0.12%, p=0.036). In the log-additive model, greater mean reduction in HbA1c by 0.16% (95% CI 0.01–0.32, p=0.038) per each K-allele was observed. The relationship of treatment response with KCNJ11 genotype was also significant in the biggest subgroup of patients treated with gliclazide (n=55).Conclusions: Carriers of the KCNJ11 K-allele have better therapeutic response to gliclazide. This observation might help to identify patients who will have the highest benefit from sulfonylurea treatment.

Lupus: Novel therapies in clinical development - Corrected Proof

Preeta Kaur Chugh — 2011-11-28

Abstract: There have been significant advancements in understanding the immunopathogenesis of systemic lupus erythematosus. However, the developments in therapeutics have been rather slow. Belimumab, a B lymphocyte stimulator (BLyS) inhibitor has been approved for the treatment of this disease after more than 50years. Numerous biological agents are being developed which target the B cells, T cells, and various cytokines. Among anti-B cell therapy, drugs target CD20+ cells (ocrelizumab, SBI-087), CD22+ cells (epratuzumab) \or the receptors of tumor necrosis factor (TNF) superfamily (atacicept, LY2127399, A-623). Monoclonal antibodies targeting interferon alpha (IFN-α) and gamma (IFN-γ) and interleukins (IL-6, 10) are being investigated for SLE. Novel targets include toll like receptors, phosphodiesterases, CD40 ligand and retinoid receptors. This review discusses various drugs which are in different phases of clinical trials and hold promise for patients suffering from this chronic debilitating disease.

Hematocrit, urea and gender: The Hematocrit, Urea and GEnder formula for prognosing progressive renal failure in diabetic nephropathy - Corrected Proof

2011-11-21

Abstract: Objective: Diabetic nephropathy is a common cause of end stage renal disease. Notwithstanding, wide inter-individual variations in the speed of progression of diabetic nephropathy are frequent. We have used the score of the HUGE formula to predict progression of kidney disease in a group of diabetic nephropathy patients.Design and methods: The sample consisted of 84 type 2 diabetic patients. At treatment entry, the mean age was 62.1±12.5years and 59.5% were male. Blood pressure was measured at office at each visit. Serum creatinine, urea, hematocrit and 24h proteinuria were analyzed every 6months. HUGE score was calculated from gender, urea and hematocrit.Results: Mean HUGE score was 0.99±3.88. Using as cut off point 1.5, those patients who had a score equal or higher (n=31) showed a bigger increase in serum creatinine after one year (41.8±62.1%) than those subjects with score<1.5 (n=53) (18.7±38.6%, p=0.041). 5 patients with low HUGE score reached end stage renal failure (9.4%) and 10 patients in the high HUGE score group (32.3, p=0.008). When logistic regression analysis was performed only a HUGE score higher than 1.5 (p=0.003) and proteinuria higher than 2g/day (p=0.041) were independently associated to CRF progression (creatinine increment>25%).Conclusions: In diabetic nephropathy patients the HUGE equation may be useful to detect the subjects prone to progressive renal failure. Wider samples will be needed to confirm this finding and, most important, its applicability to other kinds of nephropathy.

Sleep disorders in morbid obesity - Corrected Proof

Morohunfolu E. Akinnusi, Ranime Saliba, Jahan Porhomayon, Ali A. El-Solh — 2011-11-21

Abstract: The increasing prevalence of obesity has lead to an increase in the prevalence of sleep disordered breathing in the general population. The disproportionate structural characteristics of the pharyngeal airway and the diminished neural regulation of the pharyngeal dilating muscles during sleep predispose the obese patients to pharyngeal airway collapsibility. A subgroup of obese apneic patients is unable to compensate for the added load of obesity on the respiratory system, with resultant daytime hypercapnia. Weight loss using dietary modification and life style changes is the safest approach to reducing the severity of sleep apnea, but its efficacy is limited on the long run. Although it has inherent risks, bariatric surgery provides the most immediate result in alleviating sleep apnea. Obesity has been linked also to narcolepsy. The loss of neuropeptides co-localized in hypocretin neurons is suggested as the potential mechanism. Poor sleep quality, which leads to overall sleep loss and excessive daytime sleepiness has also become a frequent complaint in this population. Identifying abnormal nocturnal eating is critically important for patient care. Both sleep related eating disorder and night eating syndrome are treatable and represent potentially reversible forms of obesity.

D-dimer levels in assessing severity and clinical outcome in patients with community-acquired pneumonia. A secondary analysis of a randomised clinical trial - Corrected Proof

2011-11-21

Abstract: Background: D-dimer levels are in several studies elevated in patients with CAP. In this study we assess the use of D-dimer levels and its association with severity assessment and clinical outcome in patients hospitalised with community-acquired pneumonia.Methods: In a subset of randomised trial patients with community-acquired pneumonia serial D-dimer levels was analysed. CURB-65 scores were calculated at admission.Results: A total of 147 patients were included. D-dimer levels at admission were higher in patients with severe CAP (2166±1258 versus1630±1197μg/l, p=0.03), with clinical failure at day 30 (2228±1512 versus 1594±1078μg/l, p=0.02) and with early failure (2499±1817μg/l versus 1669±1121μg/l, p=0.01). Non-survivors had higher D-dimer levels (3025±2105 versus 1680±1128μg/l, p=0.05). None of the 16 patients with D-dimer levels<500μg/l died. In multivariate analysis D-dimer levels were not associated with clinical outcome. D-dimer levels have poor accuracy for predicting clinical outcome at day 30 (AUC 0.62, 95% CI 0.51–0.73) or 30day mortality (AUC 0.71 (95% CI 0.51–0.91)). Addition of D-dimer levels to CURB-65 did not increase accuracy. No differences were observed in serial D-dimer levels between patients with clinical success or failure at day 30.Conclusion: D-dimer levels are elevated in patients with CAP. Significantly higher D-dimer levels are found in patients with clinical failure and with severe CAP. D-dimer levels as single biomarker or as addition to the CURB-65 have no added value for predicting clinical outcome or mortality. D-dimer levels<500μg/l may identify candidates at low risk for complications.

Mortality in Cushing's syndrome: A systematic review and meta-analysis - Corrected Proof

D. Graversen, P. Vestergaard, K. Stochholm, C.H. Gravholt, J.O.L. Jørgensen — 2011-11-16

Abstract: Context: Data on mortality associated with Cushing's disease (CD) and Cushing's syndrome (CS) are scarce.Objective: To perform a systematic review and meta-analysis of mortality studies in patients with CD and CS secondary to a benign adrenal adenoma.Data sources: A search was performed in seven electronic databases. Sixty-six articles were retrieved for analysis and 7 included in the final study. The main outcome measure was standardized mortality ratio (SMR).Study eligibility criteria, participants, and interventions: Studies reporting SMR for patients diagnosed with CD and/or CS. Outcomes were stratified by subtype of Cushing's syndrome.Study appraisal and synthesis methods: Studies were appraised by two authors and were synthesized using a weighted estimate based on the standard error of the SMR.Results: The weighted mean of SMR for patients with CD was 1.84 (95% confidence interval (CI): 1.28–2.65). CD patients with persistent disease after initial surgery had a SMR of 3.73 (95% CI: 2.31–6.01), whereas mortality of CD patients with initial remission did not differ significantly from the general population (SMR: 1.23 (95% CI: 0.51–2.97)). SMR for patients with a benign adrenal adenoma was 1.90 (95% CI: 0.93–3.91). Age, sex and observation time did not significantly impact mortality.Conclusions: CD as opposed to CS due to a benign adrenal adenoma is associated with an excess mortality, which is attributed to patients in whom initial surgical cure is not obtained. This underlines the importance of a rigorous and early follow-up of newly operated patients with CD.

The role of radix hedysari polysaccharide on the human umbilical vein endothelial cells induced by high glucose - Corrected Proof

2011-11-10

Abstract: Background: Diabetes mellitus can cause a wide variety of vascular complications and it is one of the major risk factors for cardiovascular diseases (CVD). High glucose can induce vascular endothelial cell apoptosis. In this study, we investigated the effect of radix hedysari polysaccharide (HPS) on the depression of apoptosis of human umbilical vein endothelial cells (HUVECs) induced by high glucose.Methods: HUVECs were treated with media containing 30mM glucose in the presence or absence of vitamin C or HPS. The level of intracellular reactive oxygen species (ROS) and apoptosis of HUVECs was measured with flow cytometry. Expression of c-Jun NH2-terminal kinase (JNK) and caspase-3 were testified by real-time quantitative RT-PCR and immunofluorescence.Results: High glucose was capable of eliciting the overexpression of JNK during the treatment procedure. Moreover, we found that the caspase-3 became overexpressed in apoptosis induced by high glucose; HPS could inhibit apoptosis under high glucose and suppress the generation of ROS and the overexpression of JNK and caspase-3. The effect of HPS on ROS quenching, inhibition of JNK and caspase-3 overexpression at the concentration of 100μg/ml was similar to that of vitamin C at the concentration of 100μM.Conclusion: The findings of the present study may suggest that HPS play a protection role on HUVECs against apoptosis induced by high glucose.

Sepsis-induced acute respiratory distress syndrome with fatal outcome is associated to increased serum transforming growth factor beta-1 levels - Corrected Proof

2011-11-07

Abstract: Background: TGF-β1 is a promoter of pulmonary fibrosis in many chronic inflammatory diseases. TGF-β1 circulating levels in patients with sepsis-induced Acute Respiratory Distress Syndrome (ARDS) have not been established.Methods: In this prospective pilot cohort study, serum bioactive TGF-β1 concentration, determined by sandwich ELISA, was analyzed in 52 patients who fulfilled criteria for septic shock at admission and on days 3 and 7.Results: Of the 52 patients enrolled in the study, 46.1% fulfilled the criteria for ARDS on admission. At ICU admission, there were not statistical differences in TGF-β1 concentrations between septic shock patients with or without ARDS. After 7days of follow-up in ICU, circulating TGF-β1 levels were significantly higher in patients with sepsis and ARDS than in those without ARDS [55.47 (35.04–79.48pg/ml) versus 31.65 (22.89–45.63pg/ml), respectively] (p=0.002). Furthermore, in septic shock associated ARDS patients, TGF-β1 levels were significantly higher in nonsurvivors than in survivors [85.23 (78.19–96.30pg/ml) versus 36.41 (30.21–55.47pg/ml), respectively] (p=0.006) on day 7 of ICU follow-up.Conclusions: In patients with septic shock, persistent ARDS is accompanied with increased circulating TGF-β1 levels. Furthermore, ARDS patients with fatal outcome show higher TGF-β1 concentrations than survivors. These results suggest the relevance of TGF-β1 levels found in the pathogenesis of persistent sepsis-induced ARDS.

Optimal drug therapy after aspirin-induced upper gastrointestinal bleeding - Corrected Proof

M. Struijk, D.F. Postma, S.A.C. van Tuyl, M.A. van de Ree — 2011-11-07

Abstract: Upper gastrointestinal bleeding is a common adverse effect of chronic aspirin treatment. Traditionally, most physicians might tend to discontinue aspirin therapy after related gastrointestinal bleeding. However, recent studies have shown that continuation of aspirin is beneficial because of a decrease of cardiovascular complications and only a relatively small increase of recurrent peptic ulcer bleeding when combined with a proton pump inhibitor. There might be individual cases where the burden of recurrent gastrointestinal complications outweighs the risk of vascular events. In these cases the physician needs to carefully consider other precipitating factors for the recurrent gastrointestinal symptoms. At the moment, alternative antiplatelet therapy does not lead to lower gastrointestinal risks. In the near future, therapies with a more favorable profile might emerge.

Can we use severity assessment tools to increase outpatient management of community-acquired pneumonia? - Corrected Proof

James D. Chalmers, Julia Rutherford — 2011-11-04

Abstract: Outpatient management of community-acquired pneumonia (CAP) has several potential advantages, including significant cost-savings, a reduction in hospital-acquired infections and increased patient satisfaction. Despite the benefits, it is often difficult to identify which patients may be managed in the community without compromising patient safety. CAP severity scores, such as the pneumonia severity index (PSI) and the British Thoracic Society CURB65/CRB65 scores are designed to identify groups of patients at low risk of mortality who may be suitable for outpatient care.This review discusses the strengths and weaknesses of severity scores for use in determining site of care for patients with pneumonia.Use of the PSI in emergency departments has been shown to increase the proportion of patients treated in the community without increasing patient mortality or hospital readmissions. The CURB65 and CRB65 scores are less complex alternatives to the PSI that have been shown to perform similarly for prediction of 30-day mortality.All 3 scores identify populations at low risk of mortality who may be eligible for outpatient care. Nevertheless, a number of factors not included in severity scores may prevent discharge of these patients, including social factors, co-morbidities and severity markers not captured by severity scores. The limitations of severity scores are discussed along with recent attempts to improve predictive tools, with the development of new biomarkers and alternative scoring systems.

Did Lind perform a clinical trial of scurvy in 1747? - Corrected Proof

Jeremy Hugh Baron — 2011-10-24

In their recent review article Magiorkinis, Beloukas and Diamantis were apparently unaware of three critical papers on James Lind's published trial on treatment of scurvy with oranges and lemons .

Prognostic value of low and high ankle-brachial index in hospitalized medical patients - Corrected Proof

2011-10-07

Abstract: Background: Peripheral arterial disease (PAD) is frequently underdiagnosed in the clinical practice, leading to a lack of opportunity to detect subjects at a high risk for cardiovascular (CV) death. The ankle-brachial pressure index (ABI) represents a noninvasive, objective tool to diagnose PAD and to predict adverse outcome.Methods: ABI was determined by means of Doppler velocimetry, in 707 patients, aged 50years or older, consecutively hospitalized in an internal medicine ward, who were followed-up for at least 12months in order to assess all-cause and CV mortality.Results: Symptomatic PAD affected 8% of the population while the prevalence of PAD, defined as ABI <0.90, was 29%; high ABI (>1.40) was found in 8% of the patients. After a mean follow-up period of 1.6years, both low and high ABI were independently associated with CV mortality with a hazard ratio of 1.99 (p=0.016) for low and 2.13 (p=0.04) for high ABI, compared with normal ABI (0.90–1.40). High ABI also independently predicted all-cause mortality with a hazard ratio of 1.77 (p=0.04).Discussion: ABI measurement reveals a large number of individuals with asymptomatic PAD among those hospitalized in an internal medicine department. An increased mortality was observed in patients with both low and high ABI. Hospital admission for any reason may serve as an opportunity to detect PAD and start appropriate preventive actions.

Residual pulmonary thromboemboli after acute pulmonary embolism - Corrected Proof

2011-09-12

Abstract: Background: After an acute pulmonary embolism (PE), the complete resolution of thromboemboli may not be routinely achieved. The rate of persistence may depend on the time and the diagnostic technique used for evaluation.Patients and methods: Patients were diagnosed with acute PE by means of computed tomography angiography (CTA). While they were receiving anticoagulant therapy, a second CTA was used to explore the rate of persistence of residual thromboemboli. During the initial episode, the plasma levels of Troponin I and natriuretic peptide, patient demographics, and hemodynamic and gas exchange data were evaluated as risk factors for persistence of pulmonary thromboemboli.Results: In this study 166 patients were diagnosed. A second CTA was not made in 46 (28%) patients for different reasons. In 120 (72%) patients a second CTA was made 4.5 [SD2.34] months after the initial episode (range 2–12months). Complete clearance of thrombi occurred in 89 (74%, 95% CI 65–81) patients. Residual thrombi remained in 31 (26%, 95% CI 18–34) patients. In 6%, 13% and 81% of the patients the size of the residual thrombi was greater, similar to and smaller than initially diagnosed, respectively.The risk factors for residual thrombi included the thrombotic burden (OR 1.95), the alveolar to arterial difference of oxygen (OR 1.64), and the clinical antecedents of venous thromboembolic disease (OR 0.65).Conclusions: After 4.5months of anticoagulant therapy, residual pulmonary thromboemboli persisted in 26% of the patients. The risk factors for residual thromboemboli include a greater initial thrombotic burden, a deeper gas exchange disturbation and a history of previous venous thromboembolism.

Low dose or high dose of proton pump inhibitor for ulcer bleeding? - Corrected Proof

Hwai-Jeng Lin — 2011-09-05

I am interested in one recent paper “Comparison of infusion or low-dose proton pump inhibitor treatments in upper gastrointestinal system bleeding” in the European Journal of Internal Medicine . Songür et al. conducted one trial and compared continuous infusion of esomeprazole (80mg bolus followed by 8mg/h continuous infusion for 72h) and low-dose esomeprazole (40mg twice daily IV) in GI bleeding patients and found that patients receiving both doses of PPI were similar in rebleeding rates, need of surgery and mortality.

Hypovitaminosis D: Don't forget dementia - Corrected Proof

Cédric Annweiler, Olivier Beauchet — 2011-09-01

Recently, Makariou et al. reported the results of an interesting literature review in which the “novel roles of vitamin D in disease” were studied. Based on a non-systematic method, the authors did an admirable effort to list the recently described links between vitamin D and several predefined outcomes including mortality, immunity and cardiovascular diseases. The key messages were that the vitamin D concentration decreases with the advance in age, and is associated with dysimmune diseases as well as with metabolic syndrome, hypertension, diabetes and stroke . The involvement of vitamin D in immune function and vascular health seems of particular importance in older adults since both these mechanisms are involved not only in the clinical complications cited by Makariou et al., but also in brain aging and cognitive decline , which is one of the main issue of aging.

Corrected Proof

2011-08-17

Reprint of: Diagnosis of Cushing's syndrome - Corrected Proof

J.W.F. Elte — 2011-08-16

The diagnosis of Cushing's syndrome (CS), including pituitary-dependent CS (Cushing's disease), adrenal CS (adenoma, carcinoma, hyperplasia), ectopic and iatrogenic CS, is easy as long as it presents in its classical and full-blown form. A description can be found in every textbook and the diagnosis is usually made “at first sight”. Specific clinical signs and symptoms include moon face, purple striae, central obesity, growth retardation in children, decreased libido, menstrual changes, hirsutism, hypertension, ecchymoses, depression, weakness, dorsal fat pad (buffalo hump), edema, abnormal glucose tolerance and osteopenia . However, CS is rare (0.1–1.2 per 100,000) and many of the individual symptoms and signs are rather non-specific . There are subgroups of patients in whom the prevalence of CS is higher, such as those with diabetes mellitus type 2 and obesity , but even then the diagnosis is made in a small minority .

Reprint of: Thiazolidinediones for the treatment of type 2 diabetes - Corrected Proof

J.W.F. Elte, J.F. Blicklé — 2011-08-16

Abstract: Thiazolidinediones (TZD), or glitazones, represent a new generation of antidiabetic drugs that have recently been introduced in Europe. They improve insulin resistance, one of the key anomalies involved in the pathogenesis of type 2 diabetes mellitus, by activating the nuclear peroxoxisome proliferator activated receptor-γ (PPAR-γ), leading to crucial metabolic alterations in adipose tissue. Rosiglitazone and pioglitazone have been shown to be active as monotherapy, in combination therapy with metformin or sulfonylureas, and even in triple therapy. They are generally well tolerated but can induce fluid retention. Cardiac failure is a contraindication for the use of TZDs, as is the concomitant administration of insulin. Aside from their effect on glycemic control, TZDs act on several cardiovascular risk factors and may protect pancreatic β cells from apoptosis. The cardiovascular protective effect of TZDs has recently been demonstrated with the results of the PROactive study, and long-term preservation of β-cell function is currently under further investigation.

Reprint of: Proposal for a multidisciplinary approach to the patient with morbid obesity: The St. Franciscus Hospital Morbid Obesity Program - Corrected Proof

2011-08-16

Abstract: Morbid obesity is a serious disease as it is accompanied by substantial co-morbidity and mortality. The prevalence is increasing to an alarming extent, in Europe as well as in the United States. In the past few decades, bariatric surgery has developed and gained importance. It currently represents the only long-lasting therapy for this group of patients, resulting in an efficient reduction in body weight and obesity-related medical conditions, mostly cardiovascular in nature. The importance of a standardized protocol, the use of selection criteria, and a multidisciplinary approach have been stressed but not yet described in detail. Therefore, in this article, the multidisciplinary approach and the treatment protocol that have been applied in our hospital for more than 20 years are set out in a detailed manner. The application of a strict protocol may help to select and follow-up motivated patients and to organize multidisciplinary research activities.

Reprint of: Peripheral arterial disease: A growing problem for the internist - Corrected Proof

2011-08-16

Abstract: The atherothrombotic conditions, coronary artery disease, cerebrovascular disease and peripheral arterial disease (PAD), together account for almost one-half of all deaths in Europe each year; however, perception of the specific risks associated with PAD is generally poor compared with its related conditions. PAD is not just a localised disease — it has serious systemic effects, and affected individuals have a higher risk of serious cardiovascular sequelae or death within 1 year of diagnosis compared with those with coronary artery or cerebrovascular disease. PAD, which currently affects approximately 16% of the general population aged over 55 years, is increasing because of the population aging and the continuing rise in cardiovascular risk factors. The management of PAD is a multi-disciplinary approach, and while this can have its advantages, it can also mean that responsibility for patient care is unclear. Globally, almost one-third of all patients with PAD are under internist care. Internists are ideally placed to identify patients at risk of PAD and initiate prompt risk factor management because of their role in the continued care of elderly patients and those with diabetes, hypertension, dyslipidaemia, and chronic renal disease. Multi-disciplinary guidelines for the clinical management of PAD, based on consensus among international specialists in a number of fields, have been developed to create an informed, unified and proactive approach to the treatment of PAD. They stress the continuity of care, the use of office-based ankle–brachial index testing to aid early diagnosis, and prompt and aggressive risk factor management.

Reprint of: The history of the (Young) AEMI(E) and the EFIM - Corrected Proof

Ugo E.F. Carcassi, Jan Willem F. Elte, Christopher Davidson — 2011-08-16

Abstract: The European Federation of Internal Medicine (EFIM) was formed in 1996 through a merger between the Association Européenne de Médicine Interne (d' Ensemble) (AEMI(E)) and the Forum of Presidents of National Societies of Internal Medicine (IM). It arose as a result of ideas from Carcassi (Rome/Cagliari) and Merino (Alicante) to transform the largely French-speaking and rather elitist AEMI into a more easily accessible and English-speaking federation of national societies. The founding meeting of the General Assembly of the EFIM took place in May 1996 in Paris. Since then, the EFIM has initiated many activities, some of them originating from the time of the AEMI(E).

Reprint of: Bone metastasis of a follicular thyroid carcinoma originated in a toxic multinodular goiter - Corrected Proof

T.S. Schmitt, J.W.F. Elte, A.P. Rietveld, H.C.T. van Zaanen, M. Castro Cabezas — 2011-08-16

Follicular thyroid carcinoma is the second most common thyroid malignancy, accounting for 5–15% of such tumours . Because physical examination does not differentiate between benign and malignant nodules, laboratory and cytological evaluation are usually warranted . When evaluating a thyroid nodule measuring serum thyrotropin (TSH) level is one of the first steps taken. If the serum TSH level is normal or elevated, the patient should undergo fine needle aspiration (FNA). However, if the serum TSH level is subnormal, a radionuclide thyroid scan may be performed prior to FNA in order to determine whether the nodule is hyper-, iso-, or non-functioning . Thyroid cancer generally presents as a single, cold thyroid nodule on a radionuclide scan. Thyroid cancer manifesting as a hot nodule is much less frequent, with a prevalence of 4–11% . It is unusual for this neoplasm to present early in its course as a single metastasis in the spine . We report a case of follicular thyroid carcinoma presenting as a spine metastasis which originated in a toxic multinodular goiter.

Reprint of: Detrimental action of thiazolidinediones on bone (rebuttal) - Corrected Proof

J.W.F. Elte, J.F. Blicklé — 2011-08-16

Dr. Mascitelli and colleagues raise an important problem. At the time our review was written and accepted, data on bone problems were not known to us. In Table 2 of our article, we adapted a table from Ovalle and Ovalle–Bérumen (our reference 62). “Less bone turnover” was included as a potentially beneficial effect, but we agree that this is highly questionable.

Reprint of: Differential diagnosis by laboratory medicine: a quick reference for physicians - Corrected Proof

J.W.F. Elte — 2011-08-16

This reference book is divided into four parts: Introduction to laboratory medicine; biochemical/laboratory parameters in biological materials; biochemical/laboratory findings in clinical units and conditions; and medicaments: interfering factors and reference ranges. In addition, it has a number of appendices that include SI conversion factors, cluster of differentiation (CD) molecules, and sampling rules, together with an extensive list of frequently used synonyms and an index.