Showing papers in "Netherlands Journal of Medicine in 2013"

Obesity-associated low-grade inflammation in type 2 diabetes mellitus: causes and consequences

Abstract: The epidemic of overweight and obesity is a major problem because of the plethora of health and economic issues that it induces. Key among these is the sharply increasing prevalence of type 2 diabetes (T2D) and cardiovascular disease. The development of T2D is characterised by two processes: 1) insulin resistance, resulting from impaired insulin signalling and leading to an increased demand for insulin, which must be met by increased insulin production by pancreatic β-cells (compensatory β-cell function); and 2) β-cell dysfunction, with T2D developing when the amount of insulin that is produced is insufficient to meet the demand. Overweight and obesity, especially in case of abdominal fat accumulation, are associated with systemic low-grade inf lammation. This low-grade inf lammation is characterised by, among other things, higher levels of circulating proinflammatory cytokines and fatty acids. These can interfere with normal insulin function and thereby induce insulin resistance, and have also been implicated in β-cell dysfunction. This review focuses on the known and emerging relations between inflammation and T2D. We first discuss current views on the effects of fat distribution on adipose tissue inflammation and adipose tissue dysfunction. Next we focus on the detrimental roles of proinflammatory cytokines and fatty acids on insulin signalling and β-cell function. In the last part of this review we provide some insight into novel players in (the initiation of) inflammation in overweight and obesity, and their effects on T2D and vascular dysfunction.

Smelling the diagnosis: a review on the use of scent in diagnosing disease.

Abstract: For centuries, our sense of smell has been used as a diagnostic tool in the practice of medicine, be it for recognising gas gangrene on the battle field or diabetic ketoacidosis in the emergency room. In recent decades, many scent detection studies have been performed with human, animal and electronic noses. The ability of humans to diagnose disease by smelling has only rarely been the subject of quantitative studies. Scent detection by animals, on the other hand, has been addressed in several diagnostic studies, which all suggest similar or even superior accuracy compared with standard diagnostic methods. Examples include, amongst many others, the use of dogs for the detection of lung cancer in breath samples, or rats for Mycobacterium tuberculosis detection in sputum. Studies using different types of electronic noses in conditions such as pulmonary disease and cancer have also shown promising results with high overall sensitivity and specificity. However, results of different types of noses are not easily generalisable and independent confirmation studies are generally lacking, which should be a focus for future research. In conclusion, scent detection by animals and electronic noses holds promise for the future and should receive higher priority in terms of research effort and funding.

The increasing incidence of anal cancer: can it be explained by trends in risk groups?

Abstract: Background Anal cancer incidence is gradually increasing. The cause of this increase is not exactly known. This systematic literature review aimed to investigate the trend in time of anal cancer incidence and to find an explanation for the supposed increase. Methods The TRIP database and PubMed were searched for trends in time in incidence of anal cancer in the general population, for risk factors and risk groups for anal cancer, and for incidence trends in time in these risk groups. Results Age-adjusted incidence rates have increased in all Western countries during the last decades, up to 2.2% per year. Infection with the oncogenic human papilloma virus is the most important aetiological factor. Besides increasing age, other risk factors have been identified: smoking, sexual practices, in particular receptive anal intercourse, and being human immunodeficiency virus (HIV) positive. The standardised incidence ratio (SIR) is significantly increased in HIV-positive men who have sex with men (MSM) (SIR 77.8), organ transplant recipients (SIR approx. 6) and women with a history of cervical cancer (SIR 6) or cervical intraepithelial neoplasia (SIR 16). Absolute numbers of HIV-positive MSM and organ transplant recipients have increased significantly in the last decades. Conclusion The increasing incidence of anal cancer can be partially explained by an increase in the incidence rate in and absolute number of the most important risk group: HIV-positive MSM. The increasing number of renal transplant recipients probably also contributes. Further studies should answer the question whether these risk groups would benefit from preventive screening for anal cancer.

Women with silicone breast implants and unexplained systemic symptoms: a descriptive cohort study.

Abstract: Background Since their introduction, the safety of silicone breast implants has been under debate. Although an association with systemic diseases was never established, women continuously blamed implants for their unexplained systemic symptoms. In 2011, a pattern of symptoms caused by systemic reactions to adjuvants (e.g. vaccines, silicone) was identified: 'autoimmune syndrome induced by adjuvants' (ASIA). Our aim was to collect a cohort of women with silicone breast implants and unexplained systemic symptoms to identify a possible pattern and compare this with ASIA. Methods Women with silicone breast implants and unexplained systemic symptoms were invited through national media to visit a special outpatient clinic in Amsterdam. All were examined by experienced consultant physicians and interviewed. Chest X-ray and laboratory tests were performed. Results Between March 2012 and 2013, 80 women were included, of which 75% reported pre-existent allergies. After a symptom-free period of years, a pattern of systemic symptoms developed, which included fatique, neurasthenia, myalgia, arthralgia and morning stiffness in more than 65% of women. All had at least two major ASIA criteria and 79% fulfilled ≥ 3 typical clinical ASIA manifestations. After explantation, 36 out of 52 women experienced a significant reduction of symptoms. Conclusions After excluding alternative explanations, a clear pattern of signs and symptoms was recognised. Most women had pre-existent allergies, suggesting that intolerance to silicone or other substances in the implants might cause their symptoms. In 69% of women, explantation of implants reduced symptoms. Therefore, physicians should recognise this pattern and consider referring patients for explantation.

Immunosuppressive drugs after solid organ transplantation.

Abstract: In recent years solid organ transplantation has been rapidly developed as a therapeutic intervention that is life-saving and greatly contributes to a better quality of life in organ recipients. The rapid development has been made possible because of a drastic expansion in the immunosuppressive repertoire. Unfortunately, the side effects of these drugs can be severe, which is one of the reasons that life expectancy of transplant patients still significantly falls short of that of the general population. In this review manuscript we will discuss current and future immunosuppressive strategies that are employed in solid organ transplantation. Expanding our understanding of the human immune system will hopefully provide us with newer, smarter drugs that promote immunotolerance without the side effects observed today.

The long-term outcome of the Kasai operation in patients with biliary atresia: a systematic review.

Abstract: Background Biliary atresia (BA) is a progressive inflammatory destructive process of the bile ducts occurring in about one of every 20,000 live births. If left untreated, biliary atresia can lead to liver failure. The only effective treatments for BA at the moment are the Kasai operation and liver transplantation. Kasai portoenterostomy increases the survival of children with BA and postpones subsequent liver transplantation. Because long-term survival is rare, there is not much known about the long-term efficacy of the Kasai operation. Methods The aim of this review was to study the outcome of patients with BA who survived more than 20 years on their native liver. We performed a systematic search on PubMed using MeSH terms for articles describing the long-term outcomes of patients with biliary atresia. We searched for patients who have lived at least 20 years with their native liver and we registered the number of complications. The endpoints identified in these articles were: death, cholangitis, portal hypertension and gastrointestinal bleeding. Results From 53 articles we included 14 articles for analysis. In total 184 patients were above the age of 20 years. Of these 162 patients, 88% (162/184) were still alive with their native liver and 60.5% (98/162) were suffering from liver-related complications. Conclusions It is possible for patients with biliary atresia to survive more than 20 years on their native liver after undergoing the Kasai operation during early infancy. However, 60.5% of the long-term survivors alive on their native liver end up suffering from progressive liver-related complications.

Vitamin B12 deficiency and the lack of its consequences in type 2 diabetes patients using metformin.

Abstract: Objectives: To study vitamin B-12 concentrations in patients with type 2 diabetes with and without metformin use and to identify risk factors and consequences of low vitamin B-12 concentrations. Research design and methods: This study had a cross-sectional design. During eight weeks all patients with type 2 diabetes visiting the diabetic outpatient clinic of the Isala Clinics in Zwolle were approached for participation. Participation included measurement of haemoglobin, mean corpuscular volume and vitamin B-12 levels. Data on neuropathy were retrospectively searched for in the patient records. Vitamin B-12 deficiency was defined as serum B-12 concentrations Results: In the total cohort (n=298), the overall prevalence of vitamin B-12 concentrations Conclusion: Among patients with type 2 diabetes using metformin, the prevalence of vitamin B-12 deficiency is higher than compared with patients not using metformin. However, metformin use did not predict the chance of having anaemia or neuropathy.

Chocolate/cocoa and human health: a review.

Abstract: Chocolate/cocoa has been known for its good taste and proposed health effects for centuries. Earlier, chocolate used to be criticised for its fat content and its consumption was a sin rather than a remedy, associated with acne, caries, obesity, high blood pressure, coronary artery disease and diabetes. Therefore, many physicians tended to warn patients about the potential health hazards of consuming large amounts of chocolate. However, the recent discovery of biologically active phenolic compounds in cocoa has changed this perception and stimulated research on its effects in ageing, oxidative stress, blood pressure regulation, and atherosclerosis. Today, chocolate is lauded for its tremendous antioxidant potential. However, in many studies, contradictory results and concerns about methodological issues have made it hard for health professionals and the public to understand the available evidence on chocolate's effects on health. The purpose of this review is to interpret research done in the last decade on the benefits and risks of chocolate consumption.

Red cell distribution width as predictor for mortality in critically ill patients.

Abstract: Background: The objective of this study was to evaluate whether the red cell distribution width (RDW) is a significant risk factor for hospital mortality in critically ill patients and to investigate whether RDW is a parameter indicating inflammation, or a risk factor independent of inflammation. Methods: We studied all patients admitted to a ten-bed mixed intensive care unit in the Netherlands between May 2005 and December 2011 for whom RDW was available, and who had not received a blood transfusion in the preceding three months. Inflammation was measured by C-reactive protein and leucocyte count. Analyses included correlation, logistic regression analysis, and receiveroperating characteristic (ROC) curves. Results: We included 2915 patients, of whom 387 (13.3%) did not survive to hospital discharge. In univariate analysis higher RDW values were associated with increased hospital mortality. In multivariate analysis RDW remained an independent risk factor for mortality after correction for APACHE II score, age, admission type and mechanical ventilation (odds ratio 1.04, 95% confidence interval 1.02-1.06, for each femtolitre of RDW). Adding RDW to APACHE II, however, increased the area under the ROC curve marginally (from 0.845 to 0.849, p<0.001). RDW was not correlated with C-reactive protein and leucocyte count, refuting the hypothesis that the association between RDW and outcome is mediated through inflammation. Conclusion: In critically ill patients, the RDW on ICU admission was an independent predictor of mortality. Since RDW was not correlated with inflammation, the underlying mechanism of this association warrants further investigation.

The aetiology of community-acquired pneumonia and implications for patient management.

Abstract: PURPOSE: Understanding which pathogens are associated with clinical manifestation of community-acquired pneumonia (CAP) is important to optimise treatment. We performed a study on the aetiology of CAP and assessed possible implications for patient management in the Netherlands. METHODS: Patients with CAP attending the emergency department of a general hospital were invited to participate in the study. We used an extensive combination of microbiological techniques to determine recent infection with respiratory pathogens. Furthermore, we collected data on clinical parameters and potential risk factors. RESULTS: From November 2007 through January 2010, 339 patients were included. Single bacterial infection was found in 39% of these patients, single viral infection in 12%, and mixed bacterial-viral infection in 11%. Streptococcus pneumoniae was the most frequently identified pathogen (22%; n=74). Infection with atypical bacteria was detected in 69 (20%) of the patients. CONCLUSION: Initial empirical antibiotics should be effective against S. pneumoniae, the most common pathogen identified in CAP patients. The large proportion of patients with infection with atypical bacteria points to the need for improved diagnostic algorithms including atypical bacteria, especially since these atypical bacteria are not covered by the first-choice antibiotic treatment according to the recently revised Dutch guidelines on the management of CAP.

Venous thromboembolism and prothrombotic parameters in Klippel-Trenaunay syndrome.

Abstract: Background In Klippel-Trenaunay syndrome (KTS), a congenital combined vascular (capillary, venous and lymphatic) malformation with localised disturbed growth, venous thromboembolisms (VTEs) are frequently reported in small cohorts. Design and methods We quantified the frequency of VTE by screening a large KTS-patient cohort with duplex compression ultrasonography. Additionally, we performed a case-control study to evaluate whether coagulation alterations were related to VTE and magnitude of vascular malformations as quantified by magnetic resonance imaging (MRI). Results Twenty-nine (39%) of 75 patients had signs of current or previous VTE, including superficial venous thrombosis, six (8%) of whom had a deep venous thrombosis or a pulmonary embolism. Compared with 105 controls, 54 adult patients (both: median age 33 years) had higher plasma levels of D-dimer, medians 266 (IQR 195-366) versus 457 (IQR 270-3840) mg÷l (p.

Course of HbA1c in non-diabetic pregnancy related to birth weight

Abstract: Background Despite good glycaemic control (according to the internationally accepted level of HbA1c Methods We determined HbA1c by high-performance liquid chromatography in 103 healthy pregnant women. The results were corrected with a method which was certified by the National Glycohaemoglobin Standardisation Program (NGSP) and standardised to the Diabetes Control and Complication trial reference assay. All women had a body mass index (BMI) Results In the first trimester mean ± SD (range) HbA1c (n=93) was 4.7 ± 1.25% (27.9 ± 13.7 mmol/mol) (3.9-5.4% (19.1-35.5 mmol/mol)), in the second trimester (n=86) 4.6 ± 1.33% (26.8 ± 14.6 mmol/mol) (3.7-5.7% (16.9-38.8 mmol/mol)) and in the third trimester (n=71) 4.9 ± 1.39% (30.1 ± 15.2 mmol/mol) (4.0-6.0% (20.2-42.1 mmol/mol)). The calculated upper reference HbA1c values for the three trimesters were 5.4, 5.5 and 5.8% (35.5, 36.6 and 39.9 mmol/mol), respectively, compared with 6.5% (47.5 mmol/mol) in non-pregnant women in our hospital. We found a significant correlation between the differences of the first and second trimester HbA1c values and the birth weight percentiles (r=-0.251; p=0.032). All 44 women with a decrease in the HbA1c value from the first to the second trimester had a birth weight percentile ≤ 90. In the 30 women with no change or an increase in the HbA1c value from the first to the second trimester there was no relation between HbA1c values and birth weight percentiles, but seven of the 30 (23.3%) had a birth weight percentile of > 90. Conclusions HbA1c is lower in all three trimesters of normal pregnancy compared with the level in non-pregnant women, and the change in HbA1c from the first to the second trimester predicts (the percentile of) birth weight. This could implicate that in order to prevent macrosomia in pregnant women with diabetes one should aim at lower HbA1c levels than the internationally accepted level, and at a decrease in HbA1c from the first to the second trimester.

Blood loss after cardiopulmonary bypass, standard vs titrated protamine: a meta-analysis.

Abstract: BACKGROUND The aim of this meta-analysis was to determine whether standard or titrated dosing of protamine is more effective in facilitating haemostasis after cardiac surgery with cardiopulmonary bypass (CPB). METHODS We searched MEDLINE, and Biomedical Central using the terms 'cardiopulmonary bypass and heparin and protamine'. Studies were included in the meta-analysis if they were randomised controlled trials (RCTs), controlled clinical studies, or cohort studies with designs comparing the postoperative volume of bleeding between the study group (titrated dose) and the control group (standard dose) for protamine reversal of surgical anticoagulation in CPB procedures. The primary outcome of interest was postoperative blood loss. RESULTS There were 219 studies identified in the initial search; four of these were included in the meta-analysis. All studies were RCTs, involving a total of 507 patients. Postoperative blood loss was lower in the study group (range: 625-839 ml) compared with the control group (range: 765-995 ml) in all four studies. Transfusion of packed red blood cells was also lower in the study group compared with the control group in all four studies. There was no evidence of significant heterogeneity in postoperative blood loss among the four studies (Q=4.224, I2=28.98%, p=0.238); hence, a fixed-effects model of analysis was used. The overall/combined standardised difference in means of postoperative blood loss volume significantly favoured study treatment over control treatment (-0.562±0.322, p<0.001). CONCLUSION These findings suggest that titrated protamine dosing is more effective than standard protamine dosing for reducing postoperative bleeding after CPB.

established and forthcoming drugs for the treatment of osteoporosis

Abstract: Nowadays, effective drugs are available to prevent fractures in patients at high risk for osteoporotic fractures. The generic bisphosphonates alendronate and risedronate are first choice, because of their effectiveness and tolerability in the majority of patients, while they also have a low cost price. However, the use of bisphosphonates can be associated with side effects: not only the well-known (upper) gastrointestinal side effects, but also (spontaneous) atypical fractures of the femur and aseptic necrosis of the jaw. Denosumab and zoledronic acid are both potent antiresorptive drugs that could be an attractive alternative for those patients who do not tolerate oral bisphosphonates. Strontium ranelate has both antiresorptive and anabolic effects, while teriparatide has primarily anabolic effects. The working mechanism of cathepsin K inhibitors and monoclonal antibodies against sclerostin, both currently under development, is exciting since the usually occurring coupling of bone resorption and bone formation has not been found so far.

Guideline adherence for empirical treatment of pneumonia and patient outcome. Treating pneumonia in the Netherlands.

Abstract: Introduction: According to the Dutch guidelines, severity of community acquired pneumonia (CAP) (mild, moderate-severe, severe) should be based on either PSI, CURB65 or a ` pragmatic' classification. In the last mentioned, the type of ward of admission, as decided by the treating physician, is used as classifier: no hospital admission is mild, admission to a general ward is moderate-severe and admission to an intensive care unit (ICU) is severe CAP. Empiric antibiotic recommendations for each severity class are uniform. We investigated, in 23 hospitals, which of the three classification systems empirical treatment of CAP best adhered to, and whether a too narrow spectrum coverage (according to each of the systems) was associated with a poor patient outcome (in-hospital mortality or need for ICU admission). Patients and methods: Prospective observational study in 23 hospitals. Results: 271 (26%) of 1047 patients with CAP confirmed by X-ray were categorised in the same severity class with all three classification methods. Proportions of patients receiving guideline-adherent antibiotics were 62.9% (95% CI 60.0-65.8%) for the pragmatic, 43.1% (95% CI 40.1-46.1%) for PSI and 30.5% (95% CI 27.8-33.3%) for CURB65 classification. 'Under-treatment' based on the pragmatic classification was associated with a trend towards poor clinical outcome, but no such trend was apparent for the other two scoring systems. Conclusions: Concordance between three CAP severity classification systems was low, implying large heterogeneity in antibiotic treatment for CAP patients. Empirical treatment appeared most adherent to the pragmatic classification. Non-adherence to treatment recommendations based on the PSI and CURB65 was not associated with a poor clinical outcome.

Recent advances towards the clinical application of DNA vaccines.

Abstract: DNA vaccination is an attractive method for therapeutic vaccination against intracellular pathogens and cancer. This review provides an introduction into the DNA vaccination field and discusses the pre-clinical successes and most interesting clinical achievements thus far. Furthermore, general attributes, mechanism of action and safety of DNA vaccination will be discussed. Since clinical results with DNA vaccination so far show room for improvement, possibilities to improve the delivery and immunogenicity of DNA vaccines are reviewed. In the coming years, these new developments should show whether DNA vaccination is able to induce clinically relevant responses in patients.

Current concepts in the management of diabetic nephropathy

Abstract: Although much progress has been made in slowing the progression of diabetic nephropathy, renal dysfunction and development of end-stage renal disease (ESRD) remain major concerns in diabetes. In addition, diabetic patients with microalbuminuria have an increased cardiovascular mortality. Therefore, new treatment modalities or strategies are needed to prevent or slow the progression of diabetic nephropathy and prevent cardiovascular disease in diabetes. In this review we describe current concepts in pathophysiology, treatment goals and we discuss future developments in the treatment of diabetic nephropathy. Common risk factors for diabetic nephropathy and its progression are longer duration, poor glycaemic control, hypertension and the presence of albuminuria. Available treatment options, especially renin-angiotensin aldosterone system (RAAS) blockade, but also better blood pressure and blood glucose control, decrease the incidence of cardiovascular disease and renal disease in diabetes. It is important that treatment goals are tailored to the individual patient with individual treatment goals of glycaemic control and blood pressure, depending on age, type of diabetes and diabetes duration. Aggressive treatment of glucose control and blood pressure might not always be best practice for every patient. Since the proportion of ESRD due to diabetic nephropathy remains high, optimisation of RAAS blockade is advocated and can be achieved by adequate sodium restriction and/or diuretic treatment. Moreover, aldosterone blockade might be a valuable strategy, which has potency to slow the progression of diabetic renal disease. Other possible future interventions are under investigation, but large clinical trials have to be awaited to confirm the safety and efficacy of these drugs.

Vascular manifestations of systemic lupus erythematosis.

Abstract: Systemic lupus erythematosus (SLE) is an autoimmune connective disease, where vascular lesions are one of the typical symptoms. The differentiation of the type of vascular complications in SLE is very difficult, sometimes impossible, and requires an in-depth immune and histopathological approach, and extensive clinical experience. It may play a key role in the choice of treatment strategy and prediction of patient prognosis. SLE is a prototype of a multisystem autoimmune connective tissue disease, marked by immune complex-mediated lesions of blood vessels in diverse organs. Therefore, awareness of the aetiology, pathophysiology, the clinical and histopathogical setting, and SLE-associated vascular complications is of great clinical significance. In this review, the spectrum of vascular abnormalities and the options currently available to treat the vascular manifestations of SLE are discussed.

No effect of atorvastatin and simvastatin on oxidative stress in patients at high risk for cardiovascular disease

Abstract: Background Statins are thought to have anti-atherogenic effects beyond cholesterol lowering. One such mechanism may involve reduction of oxidative stress. The aim of our study was to investigate and to compare the oxidative stress lowering capacity of atorvastatin with that of simvastatin in patients at high risk for cardiovascular disease using conventional markers and sensitive markers measured by highly specific techniques such as liquid chromatography tandem mass spectrometry. Methods We included 30 statin-naive patients with diabetes mellitus, and/or obesity, and/or hypertension (12 male, 18 female, mean age 44.8±11.1 years), and randomised them to receive either atorvastatin 10 mg or simvastatin 40 mg daily to obtain an equimolar cholesterol reduction. Blood and urine samples were obtained at baseline and at 1, 6 and 12 weeks. Results Low-density lipoprotein (LDL) cholesterol and coenzyme Q10 decreased significantly in both groups. Simvastatin caused a faster initial LDL cholesterol lowering than atorvastatin (p=0.01), but the overall effect after 12 weeks of atorvastatin and simvastatin was similar. Plasma myeloperoxidase and malondialdehyde did not change during the study period in the two groups. Urinary F2-isoprostanes decreased gradually and significantly in the atorvastatin group but not in the simvastatin group, but the between-group difference was not significant. Urinary 8-hydroxy-2-deoxyguanosine did not change in the two groups.

MiRNA s in oesophageal squamous cancer.

Abstract: Oesophageal cancer is a common cancer worldwide with a very poor prognosis. Oesophageal squamous cell carcinoma (OSCC) is the major subtype of oesophageal cancer but also one of the least studied cancers worldwide. Although the molecular genetics of OSCC have been widely studied, the molecular mechanism of OSCC carcinogenesis is not completely understood. MicroRNA (miRNA) is now essential to understanding the molecular mechanism of cancer progression. Recent findings include the following: 1) recent findings regarding the functions of miRNA; 2) some of the latest findings on expression profile of miRNA involved in OSCC; 3) miRNAs and their target genes and molecular mechanisms in OSCC; and 4) the therapeutic-clinical potential of miRNAs in OSCC. We can make full use of this knowledge to guide us to evaluate and improve the patient's condition and choose the most fitting medical treatment or explore new approaches to improve the survival ratio of OSCC patients.

Polyomavirus BK in the pathogenesis of bladder cancer.

Abstract: Polyomaviruses are able to drive malignant transformation in rodent models, and have been implicated in the aetiology of a variety of human malignancies. However, the reports on this association in humans are strongly conflicting. Here we describe a renal transplant (RT) recipient with ureteral stenosis against the background of polyomavirus BK (BKV) activity. Six and a half years after transplantation, this patient developed metastasised bladder cancer. Prior to the diagnosis of cancer, atypical cells were detected in the urine that were denoted as 'decoy cells': virally infected epithelial cells that are frequently seen in the urine of RT recipients with BKV (re)activation, which may morphologically resemble malignant cells. Intriguingly, the primary urothelial carcinoma, as well as the mesenterial and two intestinal metastases, stained positive with antibodies against polyomavirus virus large T antigen protein, whereas the adjacent healthy tissue did not. This case suggests a role for BKV in the pathogenesis of bladder cancer, at least in the context of immunodeficiency.

Iron deficiency before and after bariatric surgery: the need for iron supplementation.

Abstract: Hepcidin inhibits the iron export from duodenal cells and liver cells into the plasma and therefore plays a key role in controlling iron homeostasis. In obese patients, elevated cytokine production stimulates hepcidin synthesis, causing iron to be retained as ferritin in e.g. macrophages (functional iron deficiency). In addition, patients often develop iron deficiency after bariatric surgery due to malabsorption, which may cause anaemia and thereby lead to complaints such as fatigue. In these patients, the absorption of iron may be disrupted because the reduction of Fe3+ by gastric acid into Fe2+ (the form that is easily absorbed) is not so effective after stomach reduction. Iron absorption is further reduced after malabsorptive interventions as a result of bypassing the duodenum and the proximal part of the small intestine, where the absorption takes place. Oral iron supplements often have little effect after bariatric surgery. Intravenous supplements of iron can restore the iron status rapidly after bariatric surgery, resulting in fewer symptoms such as fatigue.

An observational cohort study on geriatric patient profile in an emergency department in the Netherlands.

Abstract: BACKGROUND: Currently, Dutch emergency care systems focus on rapid emergency department (ED) patient management with short completion times, which may not meet specific geriatric care needs. METHODS: Six-week observational study in patients aged ≥70 years, attending the ED of VU University Medical Center (VUmc, Amsterdam, the Netherlands) during weekday peak presentation times (10 AM - 10 PM). RESULTS: During six weeks, a total of 183 patients aged ≥70 years attended the ED, of which 117 (63.9%) presented during weekday peak hours. One hundred patients with a median age of 81 (min-max; 70-97 years) were prospectively observed. The majority presented with fall-related complaints (30%), multiple comorbidities (≥3 in 50.0%) and polymedication (≥5 in 53.7%). Mean ED length of stay was 175.8 (range 20-399) minutes (n=98). Of the patients discharged to their usual residence prior to the ED visit (n=58), 36.2% returned to our ED within 30 days; one in five of these patients had initially presented with a fall. CONCLUSION: In this study, fall-related injuries were the most frequent presenting complaint during weekday peak presentation times in 70-plus patients. Of these, one in five discharged from the ED returned within 30 days. Our emergency care system may not adequately cover comprehensive ED geriatric assessment, or provide sufficient outpatient care after ED home discharge. We believe that EPs should be more aware of the complex problems encountered in acute geriatric patients and address follow-up care pathways such as geriatric outpatient services, more often in frail elderly patients discharged home. Language: en

Dutch Guideline for the Management of Electrolyte disorders--2012 Revision

Abstract: Electrolyte disorders are common and often challenging in terms of differential diagnosis and appropriate treatment. To facilitate this, the first Dutch guideline was developed in 2005, which focused on hypernatraemia, hyponatraemia, hyperkalaemia, and hypokalaemia. This guideline was recently revised. Here, we summarise the key points of the revised guideline, including the major complications of each electrolyte disorder, differential diagnosis and recommended treatment. In addition to summarising the guideline, the aim of this review is also to provide a practical guide for the clinician and to harmonise the management of these disorders based on available evidence and physiological principles.

Bortezomib-induced polyneuropathy

Abstract: Background: Peripheral neuropathy is a frequent side effect of bortezomib chemotherapy. Relatively little is known about the clinical characteristics of this neuropathy, especially with respect to pain. Our aim was to describe the clinical characteristics and course of bortezomib-induced polyneuropathy. Methods: This is a retrospective cohort study of 39 patients diagnosed with bortezomib-induced polyneuropathy. Results: Pain is the most prominent symptom and 14 of 39 patients suffered from severe pain. More than 50% of our patients used analgesics due to moderate or severe pain. We found no correlation between severity of symptoms of bortezomib-induced polyneuropathy and cumulative dose or dose intensity of bortezomib. Nerve conduction studies did not correlate well with symptom severity. Dose reduction or discontinuation of treatment reduced severity in most cases. Conclusion: Painful polyneuropathy is a frequent, dose-limiting side effect of bortezomib with a relatively good prognosis. Careful neurological monitoring of symptoms and timely dose adjustment is important.

Intestinal cholesterol secretion: future clinical implications

Abstract: Together with the liver, the intestine serves as a homeostatic organ in cholesterol metabolism. Recent evidence has substantiated the pivotal role of the intestine in reverse cholesterol transport (RCT). RCT is a fundamental antiatherogenic pathway, mediating the removal of cholesterol from tissues in the body to the faeces. In humans, faecal cholesterol elimination via the RCT pathway is considered to be restricted to excretion via the hepatobiliary route. Recently, however, direct trans-intestinal excretion of plasma-derived cholesterol (TICE) was shown to contribute substantially to faecal neutral sterol (FNS) excretion in mice. TICE was found to be amenable to stimulation by various pharmacological and dietary interventions in mice, offering new options to target the intestine as an inducible, cholesterol-excretory organ. The relevance of TICE for cholesterol elimination in humans remains to be established. There is, however, emerging evidence for the presence of TICE in human (patho) physiology. This review discusses our current understanding of TICE and its novel therapeutic potential for individuals at increased risk of cardiovascular disease.

High-dose methylprednisolone-induced hepatitis in a patient with multiple sclerosis: a case report and brief review of literature

Abstract: Toxic hepatitis is a rare but serious complication of high-dose prednisolone treatment. We report a case of high-dose prednisolone-induced acute hepatitis in a 48-year-old woman suffering from multiple sclerosis that recurred after repeated administration. Timely recognition is paramount to avoid this complication. This report includes a brief review of the literature on methylprednisolone- induced hepatitis.

Bariatric surgery is an effective treatment for morbid obesity.

Abstract: The global obesity epidemic is also affecting the Netherlands, paralleled by a proportional increase in the number of morbidly obese persons. Bariatric surgery has been included as a treatment for morbid obesity in the Dutch Guideline for Obesity (2008). Nonetheless, bariatric surgery is applied in only a limited number of morbidly obese subjects in the Netherlands. Based on the most recent literature and Dutch statistics, this review provides a summary of current knowledge on the impact of obesity on health and health care and highlights the effective role of bariatric surgery in reducing this threat to public health.

Intestinal pseudo-obstruction as a complication of paragangliomas: Case report and literature review

Abstract: Intestinal pseudo-obstruction is a rare and relatively unknown complication of phaeochromocytoma÷ paraganglioma (PCC÷PGL). Its pathophysiology can be explained by the hypersecretion of catecholamines, which may reduce the peristaltic activity of the gastrointestinal tract. Clinically, this can result in chronic constipation, intestinal pseudo-obstruction or even intestinal perforation. We conducted a comprehensive literature search and retrieved 34 cases of pseudo-obstruction caused by either benign or malignant PCC÷PGL. We also included a case from our centre that has not been described earlier. We conclude that intestinal pseudo-obstruction is a rare but potentially life-threatening complication of PCC÷PGL. Intravenous administration of phentolamine is the most frequently described treatment when surgical resection of the PCC÷PGL is not feasible.

Primary symptomatic adrenal insufficiency induced by megestrol acetate.

Abstract: Megestrol acetate (MA) is a progestational agent for the treatment of metastatic breast cancer and endometrial cancer. MA has also been used to promote weight gain in malnourished elderly patients, in patients with immunodeficiency virus and in cancer-induced cachexia. In addition to thromboembolic disease, MA may induce hyperglycaemia, osteoporosis, suppression of the gonadal axis, and Cushing's syndrome. MA has also been shown to cause symptomatic suppression of the hypothalamic-pituitary-adrenal (HPA) axis owing to its intrinsic glucocorticoid-like effect. Three additional patients are presented who developed symptomatic adrenal insufficiency while they were receiving 160-320 mg MA daily. The patients were treated with cortisone acetate supplements, had clear evidence of HPA-axis suppression but recovered fully after MA was discontinued. Patients receiving MA might have an inadequate adrenal response during stressful conditions, possibly because 160-320 mg MA daily may not provide adequate protection to prevent the symptoms of adrenal insufficiency. The adverse MA effect on the HPA axis is probably not well recognised in clinical practice, and clinicians need an increased awareness of the endocrine complications secondary to MA treatment.