[A man with polyarthralgia]. / Een man met polyartralgie.

A 46-year old Ghanaian man presented with immobilizing arthralgias in all joints except the forefoot, with a periarticular swelling most pronounced around the wrists and ankles. He had erythema nodosum and hilar lymphadenopathy on chest radiograph. We diagnosed Löfgren syndrome. The polyarthralgia recovered quickly with prednisone treatment.

Systemic features of retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations: a monogenic small vessel disease.

BACKGROUND: Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL-S) is a small vessel disease caused by C-terminal truncating TREX1 mutations. The disease is typically characterized by vascular retinopathy and focal and global brain dysfunction. Systemic manifestations have also been reported but not yet systematically investigated. METHODS: In a cross-sectional study, we compared the clinical characteristics of 33 TREX1 mutation carriers (MC+) from three Dutch RVCL-S families with those of 37 family members without TREX1 mutation (MC-). All participants were investigated using personal interviews, questionnaires, physical, neurological and neuropsychological examinations, blood and urine tests, and brain MRI. RESULTS: In MC+, vascular retinopathy and Raynaud's phenomenon were the earliest symptoms presenting from age 20 onwards. Kidney disease became manifest from around age 35, followed by liver disease, anaemia, markers of inflammation and, in some MC+, migraine and subclinical hypothyroidism, all from age 40. Cerebral deficits usually started mildly around age 50, associated with white matter and intracerebral mass lesions, and becoming severe around age 60-65. CONCLUSIONS: Retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations is a rare, but likely underdiagnosed, systemic small vessel disease typically starting with vascular retinopathy, followed by multiple internal organ disease, progressive brain dysfunction, and ultimately premature death.

Optimization of the APOP screener to predict functional decline or mortality in older emergency department patients: Cross-validation in four prospective cohorts.

INTRODUCTION: Many screening instruments to predict adverse health outcomes in older patients visiting the emergency department (ED) have been developed, but successful implementation has been hampered because they are insufficiently validated or not tailored for the intended use of everyday clinical practice. The present study aims to refine and validate an existing screening instrument (the APOP screener) to predict 90-day functional decline or mortality in older ED patients. METHODS: Consecutive older patients (≥70 years) visiting the EDs of four hospitals were included and prospectively followed. First, an expert panel used predefined criteria to decide which independent predictors (including demographics, illness severity and geriatric parameters) were suitable for refinement of the model predicting functional decline or mortality after 90 days. Second, the model was cross-validated in all four hospitals and predictive performance was assessed. Additionally, a pilot study among triage nurses experiences and clinical usability of the APOP screener was conducted. RESULTS: In total 2629 older patients were included, with a median age of 79 years (IQR 74-84). After 90 days 805 patients (30.6%) experienced functional decline or mortality. The refined prediction model included age, gender, way of arrival, need of regular help, need help in bathing/showering, hospitalization the prior six months and impaired cognition. Calibration was good and cross-validation was successful with a pooled area under the curve of 0.71 (0.69-0.73). In the top 20% patients predicted to be at highest risk in total 58% (95%CI 54%-62%) experienced functional decline or mortality. Triage nurses found the screener well suited for clinical use, with room for improvement. CONCLUSION: In conclusion, optimization of the APOP screener resulted in a short and more simplified screener, which adequately identifies older ED patients at highest risk for functional decline or mortality. The findings of the pilot study were promising for clinical use.

Impaired cognition is associated with adverse outcome in older patients in the Emergency Department; the Acutely Presenting Older Patients (APOP) study.

Objective: to investigate whether cognitive impairment, measured early after Emergency Department (ED) arrival and irrespective of its cause, is independently associated with functional decline or mortality after 3 and 12 months in older ED patients. Design and setting: a prospective multi-centre cohort study in all Acutely Presenting Older Patients visiting the Emergency Department (APOP study) of three hospitals in the Netherlands. Participants: 2,130 patients, ≥70 years. Measurements: data on demographics, disease severity and geriatric characteristics were collected during the first hour of the ED visit. Cognition was measured using the 6-Item-Cognitive-Impairment-Test ('6CIT'). Cognitive impairment was defined as 6CIT ≥11, self-reported dementia or the inability to perform the cognition test. The composite adverse outcome after 3 and 12 months was defined as a 1-point decrease in Katz Activities of Daily Living (ADL), new institutionalisation or mortality. Multivariable regression analysis was used to assess whether cognitive impairment independently associates with adverse outcome. Results: of 2,130 included patients, 588 (27.6%) had cognitive impairment at baseline and 654 patients (30.7%) suffered from adverse outcome after 3 months. Cognitive impairment associated with increased risk for adverse outcome (adjusted odds ratio (OR) 1.72, 95%CI 1.37-2.17). After 12 months, 787 patients (36.9%) suffered from adverse outcome. Again, cognitive impairment independently associated with increased risk for adverse outcome (adjusted OR 1.89, 95%CI 1.46-2.46). ORs were similar for patients who were discharged home versus hospitalised patients. Conclusion: cognitive impairment measured during the early stages of ED visit, irrespective of the cause, is independently associated with adverse outcome after 3 and 12 months in older patients.

Optimising the ISAR-HP to screen efficiently for functional decline in older patients.

INTRODUCTION: The Identification of Seniors At Risk-Hospitalised Patients (ISAR-HP) has recently been included in guidelines as a frailty indicator to identify patients for comprehensive geriatric assessment. Previous studies showed that the conventional cut-off score incorrectly classifies a high percentage of patients as high risk. We aimed to optimise the predictive value of ISAR-HP by using different cut-offs in older acutely hospitalised patients. METHODS: A prospective follow-up study was performed in two Dutch hospitals. Acutely hospitalised patients aged ≥ 70 years were included. Demographics, illness severity parameters, geriatric measurements and the ISAR-HP scores were obtained at baseline. The primary outcome was a combined end point of functional decline or mortality during 90-day follow-up. RESULTS: In total 765 acutely hospitalised older patients were included, with a median age of 79 years, of whom 276 (36.1%) experienced functional decline or mortality. The conventional ISAR-HP cut-off of ≥ 2 assigned 432/765 patients (56.5%) as high risk, with a positive predictive value (PPV) of 0.49 (95%CI 0.45-0.54) and a negative predictive value of 0.81 (95%CI 0.76-0.85). Thus, 51% of those whom the ISAR-HP denoted as high risk did not experience the outcome of interest. Raising the cut-off to ≥ 4 assigned 205/765 patients (26.8%) as high risk, with a marginally increased PPV to 0.55 (95%CI 0.48-0.62). CONCLUSION: The ISAR-HP with the conventional cut-off of ≥ 2 incorrectly identifies a large group of patients at high risk for functional decline or mortality and raising the cut-off to 4 only marginally improved performance. Caution is warranted to ensure efficient screening and follow-up interventions.

Predicting adverse health outcomes in older emergency department patients: the APOP study.

BACKGROUND: Older patients experience high rates of adverse outcomes after an emergency department (ED) visit. Early identification of those at high risk could guide preventive interventions and tailored treatment decisions, but available models perform poorly in discriminating those at highest risk. The present study aims to develop and validate a prediction model for functional decline and mortality in older patients presenting to the ED. METHODS: A prospective follow-up study in patients aged ≥ 70, attending the EDs of the LUMC, the Netherlands (derivation) and Alrijne Hospital, the Netherlands (validation) was conducted. A baseline assessment was performed and the main outcome, a composite of functional decline and mortality, was obtained after 90 days of follow-up. RESULTS: In total 751 patients were enrolled in the Leiden University Medical Center of whom 230 patients (30.6%) experienced the composite outcome and 71 patients (9.5%) died. The final model for the composite outcome resulted in an area under the curve (AUC) of 0.73 (95% CI 0.67-0.77) and was experienced in 69% of the patients at highest risk. For mortality the AUC was 0.79 (95% CI 0.73-0.85) and 36% of the patients at highest risk died. External validation in 881 patients of Alrijne Hospital showed an AUC of 0.71 (95% CI 0.67-0.75) for the composite outcome and 0.67 (95% CI 0.60-0.73) for mortality. CONCLUSION: We successfully developed and validated prediction models for 90-day composite outcome and 90-day mortality in older emergency patients. The benefits for patient management by implementing these models with preventive interventions have to be investigated.

[Criteria for admitting patients with anorexia nervosa as inpatients to a general hospital; survey among internists]. / Criteria voor opname van volwassenen met anorexia nervosa op een interne afdeling van een algemeen ziekenhuis; enquête onder internisten.

BACKGROUND: Anorexia nervosa (an) is associated with a number of life-threatening complications. Sometimes there are good reasons for admitting an anorexia nervosa patient to a general hospital for treatment as an inpatient. Therefore, there needs to be optimal collaboration between psychiatrists treating the patient and the medical staff at the general hospital. AIM: To obtain insight into the admission criteria and other possible factors that play a role in the physician's decision to admit a patient with anorexia nervosa for inpatient treatment in a general hospital. METHOD: Internists and residents-internal medicine completed a questionnaire about admission criteria and, where applicable, about threshold values for these criteria. The physicians were also asked to judge two case vignettes. In addition, they were questioned about other factors that influenced their views on the admission of patients with anorexia nervosa to a general hospital and about their attitude to this patient-group, their experience of treating patients with anorexia nervosa and their awareness of a need for a guideline. The data were collected at the annual Dutch congress for internists at Maastricht. RESULTS: In total 78 congress attendees responded to the questionnaire; 47% were internist and 53% were resident-in-training. Agreement was greatest with regard to the following admission criteria (top 5): 1. serum potassium (threshold value <2.5 mmol/l was the criterion selected most); 2. arrhythmia; 3. hypoglycemia; 4. heart rate (threshold value <40 bpm was chosen most); 5. prolonged qt interval on an ECG. According to the two fictitious cases, the reason for admitting a patient with anorexia nervosa with milder symptoms was influenced by 'attitude'. Half of the respondents pointed out that the patient's cooperation plays a role in the decision to admit a patient with an eating disorder. CONCLUSION: Respondents reached a consensus regarding several admission criteria but the threshold values they gave varied substantially. Attitude towards the patient-group can sometimes influence the decision to admit a patient with anorexia nervosa to a general hospital. Internists and residents-in-training indicated they require detailed, carefully compiled guidelines which take into consideration the expected results and which emphasise the importance of obtaining the patient's cooperation.

A diagnostic difficulty: two cases of haemophagocytic syndrome in adults.

Haemophagocytic syndrome is a rare and life-threatening disease, which often goes unrecognised in adults, with high mortality as a consequence. Here we present two adult patients who were diagnosed with haemophagocytosis of distinct underlying causes which, despite treatment, led to fatal outcomes. Measuring ferritin is an easy and cheap resource in diagnosis.

Cardiovascular risk factors after bariatric surgery: Do patients gain more than expected from their substantial weight loss?

BACKGROUND: While it has been established that even limited weight loss (5-10%) improves obesity-associated cardiovascular risk factors, it is not known if considerable weight loss following laparoscopic adjustable silicone gastric banding (LASGB) results in a cardiovascular risk profile that is comparable, worse, or even better than that of matched control subjects. METHODS: Cardiovascular risk factors were compared in three groups of 24 women each: an index group that had lost considerable weight following LASGB for morbid obesity (BMI>40 kg/m(2)), a control group with the same BMI that the index group achieved after weight loss, and a pre-weight loss group of women with a BMI above 40 kg/m(2). Anthropometric measures, fasting serum glucose, insulin, lipids, C-reactive protein, and homocysteine levels were determined and insulin sensitivity was estimated using a homeostasis model assessment index (HOMA-IR). RESULTS: After bariatric surgery, the index group had a BMI of 32.0+/-0.8 kg/m(2). This resulted in a significantly better cardiovascular risk profile than that of the pre-weight loss group (BMI 42.8+/-0.6 kg/m(2)). Unexpectedly, after weight loss, the index group had significantly lower systolic blood pressure, fasting serum insulin, and HOMA-IR than the BMI-matched (32.8+/-0.9 kg/m(2)) control group. Although not significant, diastolic blood pressure, LDL-cholesterol, and CRP levels were also lower. CONCLUSION: Considerable weight loss following bariatric surgery leads to a greater improvement in cardiovascular risk factors than might be expected from the weight loss.

The metabolic syndrome: a vascular perspective.

The metabolic syndrome (MS) is a clustering of cardiovascular risk factors. Current definitions of MS use hypertension, waist circumference, fasting glucose, triglyceride and HDL-cholesterol levels as defining variables. The prevalence of MS is increasing in our society due to lifestyle changes that result in decreased physical activity and increased body weight. Patients with MS have a three times greater risk of coronary heart disease and stroke, and a two to four times greater risk of dying from atherosclerotic coronary heart disease than those without MS. Imaging studies have shown an increased burden and progression of atherosclerosis. Also, MS patients seem to be more vulnerable to events at comparable levels of atherosclerosis. First-line treatment for MS is therapeutic lifestyle intervention, including exercise and weight reduction. Medical intervention strategies using blood pressure-lowering medication, statins, fibrates and metformin seem the most appropriate to date. The effects of thiazolidinediones on cardiovascular endpoints have not been studied to a large extent in the setting of MS. Evidence regarding risk assessment and optimal medical strategies will be an important aspect of vascular research in the coming years.

Impact of meal timing and frequency on the twenty-four-hour leptin rhythm.

OBJECTIVE: To study the influence of changes in meal timing and frequency on the diurnal rhythm of leptin and on the 24-hour profile of insulin and glucose. PATIENTS AND METHODS: Five obese women were studied twice during a weight-maintaining diet in either 3 daily or 8 day and night equal portions. Blood was sampled for 24-hour profiles of leptin and insulin. RESULTS: During the 8-meal intervention, the 24-hour rhythm of leptin changed significantly: the amplitude decreased (p = 0.0089) and the acrophase was delayed by 168 min (p = 0.021). Also, 8 small insulin secretion peaks occurred instead of the 3 postprandial high insulin peaks. CONCLUSION: The dispersion of food intake over 24 h affects the diurnal leptin rhythm. These changes could not be attributed to changes in circadian timing or energy balance. Instead, changes in daily insulin secretion profiles might play a role.

Exophthalmos in obesity.

AIMS: To establish the relationship between exophthalmos and obesity. METHODS: A group of 19 obese patients (body mass index, BMI >/=30 kg/m(2)) was compared with a control group of 45 nonobese individuals (26 > BMI >/= 20 kg/m(2)). Both groups underwent Hertel's exophthalmometry, Goldmann applanation tonometry and measurement of the medial rectus muscle by echography. RESULTS: Obese patients had higher Hertel values and enlarged medial rectus muscle diameter (p < 0.05). Indeed, bilateral exophthalmos was observed in 33% of obese subjects. However, this did not cause any ocular morbidity. In some cases the difference in intraocular pressure was enlarged but together with the exophthalmos not statistically significant. CONCLUSIONS: Standard values for exophthalmometry and orbital echography may have to be adapted for obese individuals. In several cases the eye signs had a remarkable resemblance to patients with Graves' orbitopathy. So in each patient with bilateral exophthalmos and eye signs suspicious of Graves' orbitopathy obesity should be considered as a possible cause.

Effects of recombinant human leptin treatment as an adjunct of moderate energy restriction on body weight, resting energy expenditure and energy intake in obese humans.

We explored the effects of recombinant human leptin (rL) as an adjunct of mild energy restriction (2092 kJ/day less than needed) in the treatment of obese humans as part of a larger multicentre trial. In a double blind, randomised, placebo (P)-controlled design, the effects of 10 mg of rL once daily vs twice daily (rL OD/BID, by s.c. injection) upon body weight, resting energy expenditure (REE) and energy intake were compared. The study groups comprised 9 (P), 15 (rL OD) and 6 (rL BID) healthy subjects (body mass index 27.5-35 kg/m2). We observed in both groups treated with rL a decline of body weight. [2.8+/-1.1 kg (P), 5.2+/-0.9 kg (rL OD), 7.9+/-1.4 kg (rL BID), p < 0.035]. No significant effects of rL treatment upon energy intake or REE were observed. However, rL tended to reduce the decline of energy expenditure associated with energy restriction, whereas the tendency of energy intake to increase back to baseline levels in placebo-treated subjects was largely prevented in subjects treated with rL. Thus, rL appears to enhance the loss of body weight in obese humans in a dose-dependent fashion if prescribed as an adjunct of energy restriction. This effect might be mediated by rL ability to counteract the behavioural and metabolic adaptations that accompany weight loss attempts.

Renal clearance of endogenous leptin in hypertensive humans with or without renal artery stenosis.

In humans, the kidney is involved in leptin clearance from the body. The present study was performed to assess the renal extraction of leptin in hypertensive patients with or without renal artery stenosis. Sixty-five hypertensive subjects (39 males and 26 females) underwent catheterization of the renal artery and both renal veins with blood sampling for measuring leptin levels. Blood flow to both kidneys was measured by the xenon washout technique. From these data, renal leptin uptake and renal fractional extraction of leptin were calculated. Endogenous creatinine clearance ranged from 24 to 191 ml/min in the males and from 20 to 149 ml/min in the females. In 25 patients, radiological signs of renal artery stenosis were present. Total renal leptin uptake by both kidneys averaged 141 +/- 47 ng x min(-1) x 100 g(-1). No differences in leptin uptake were found between males and females or between patients with or without renal artery stenosis. The average renal extraction fraction of leptin was 6 +/- 2%. Renal leptin uptake and renal extraction fraction of leptin did not correlate with arterial leptin concentrations or with blood pressure, endogenous creatinine clearance, or the presence or absence of renal artery stenosis. In hypertensive patients with or without renal artery stenosis, the kidney removes only a small fraction of circulating leptin from the body within one passage. This fraction remains relatively constant despite wide variations in renal function or circulating leptin.

[Diagnostic image (40). Scurvy]. / Diagnose in beeld (40). Scorbuut.

In a 17-year-old woman with anorexia nervosa, scurvy was diagnosed as the cause of fatigue, abdominal pain, vaginal bleeding and several distinctive skin lesions.

Successful treatment of veno-occlusive disease of the liver with urokinase in a patient with non-Hodgkin's lymphoma.

A 38-year-old man with a non-Hodgkin's lymphoma of intermediate grade malignancy attained partial remission after three courses of CHOP (cyclophosphamide+hydroxydaunorubicin+vincristine+prednisolone). He was assigned to undergo autologous bone marrow transplantation (ABMT). The conditioning regimen consisted of cyclophosphamide and whole body irradiation. Two weeks later he developed veno-occlusive disease (VOD) of the liver. Doppler sonography confirmed the diagnosis showing a reversal of the blood flow in the portal vein. In addition a large thrombus was present in the inferior caval vein. Protein C level was strongly reduced (28%). Because of clinical deterioration intravenous urokinase was started. The transaminases normalised rapidly and the patient showed a dramatic clinical improvement. There were no major bleeding complications. Repeat Doppler sonography showed a normal antegrade flow in the portal vein. This case suggests that a coagulopathy in the hepatic vascular bed might contribute to the development of VOD and that patients with VOD are at risk for other thrombotic complications. Furthermore it shows that urokinase with platelet support can be given safely and effectively to a patient with VOD and severe thrombocytopenia.