Clinical factors associated with hyponatremia correction during treatment with oral Urea.

BACKGROUND AND HYPOTHESIS: Oral urea is being used more commonly to treat hyponatremia, but factors contributing to the correction rate are unknown. We hypothesized that clinically relevant factors can be identified to help guide hyponatremia correction with oral urea. METHODS: Retrospective study in two university hospitals including hospitalized patients with hyponatremia (plasma sodium < 135 mmol/L) treated with oral urea. Linear mixed-effects models were used to identify factors associated with hyponatremia correction. Rates of overcorrection, osmotic demyelination and treatment discontinuation were also assessed. RESULTS: We included 161 urea treatment episodes in 140 patients (median age 69 years, 46% females, 93% syndrome of inappropriate antidiuresis). Oral urea succeeded fluid restriction in 117 treatment episodes (73%), was combined with fluid restriction in 104 treatment episodes (65%) and was given as only treatment in 27 treatment episodes (17%). A median dose of 30 grams/day of urea for 4 days (interquartile range 2-7 days) increased plasma sodium from 127 to 134 mmol/L and normalized hyponatremia in 47% of treatment episodes. Older age (ß 0.09, 95%CI 0.02 to 0.16), lower baseline plasma sodium (ß -0.65, 95%CI -0.78 to -0.62), and higher cumulative urea dose (ß 0.03, 95%CI -0.02 to -0.03) were independently associated with a greater rise in plasma sodium. Concurrent fluid restriction was associated with a greater rise in plasma sodium only during the first 48 h of treatment (ß 1.81, 95%CI 0.40 to 3.08). Overcorrection occurred in 5 cases (3%), no cases of osmotic demyelination were identified, and oral urea was discontinued in 11 cases (11%) due to side-effects. CONCLUSION: During treatment with oral urea, older age, higher cumulative dose, lower baseline plasma sodium and initial fluid restriction are associated with a greater correction rate of hyponatremia. These factors may guide clinicians to achieve a gradual correction of hyponatremia with oral urea.

Role of knowledge and reasoning processes as predictors of resident physicians' susceptibility to anchoring bias in diagnostic reasoning: a randomised controlled experiment.

BACKGROUND: Diagnostic errors have been attributed to reasoning flaws caused by cognitive biases. While experiments have shown bias to cause errors, physicians of similar expertise differed in susceptibility to bias. Resisting bias is often said to depend on engaging analytical reasoning, disregarding the influence of knowledge. We examined the role of knowledge and reasoning mode, indicated by diagnosis time and confidence, as predictors of susceptibility to anchoring bias. Anchoring bias occurs when physicians stick to an incorrect diagnosis triggered by early salient distracting features (SDF) despite subsequent conflicting information. METHODS: Sixty-eight internal medicine residents from two Dutch university hospitals participated in a two-phase experiment. Phase 1: assessment of knowledge of discriminating features (ie, clinical findings that discriminate between lookalike diseases) for six diseases. Phase 2 (1 week later): diagnosis of six cases of these diseases. Each case had two versions differing exclusively in the presence/absence of SDF. Each participant diagnosed three cases with SDF (SDF+) and three without (SDF-). Participants were randomly allocated to case versions. Based on phase 1 assessment, participants were split into higher knowledge or lower knowledge groups. MAIN OUTCOME MEASUREMENTS: frequency of diagnoses associated with SDF; time to diagnose; and confidence in diagnosis. RESULTS: While both knowledge groups performed similarly on SDF- cases, higher knowledge physicians succumbed to anchoring bias less frequently than their lower knowledge counterparts on SDF+ cases (p=0.02). Overall, physicians spent more time (p<0.001) and had lower confidence (p=0.02) on SDF+ than SDF- cases (p<0.001). However, when diagnosing SDF+ cases, the groups did not differ in time (p=0.88) nor in confidence (p=0.96). CONCLUSIONS: Physicians apparently adopted a more analytical reasoning approach when presented with distracting features, indicated by increased time and lower confidence, trying to combat bias. Yet, extended deliberation alone did not explain the observed performance differences between knowledge groups. Success in mitigating anchoring bias was primarily predicted by knowledge of discriminating features of diagnoses.

Hyponatremia is associated with unfavorable outcomes after reperfusion treatment in acute ischemic stroke.

BACKGROUND AND PURPOSE: In patients with acute ischemic stroke, hyponatremia (plasma sodium < 136 mmol/L) is common and associated with unfavorable outcomes. However, data are limited for patients who underwent intravenous thrombolysis (IVT) and/or endovascular thrombectomy (EVT). Therefore, our aim was to assess the impact of hyponatremia on postreperfusion outcomes. METHODS: We analyzed data of consecutive patients who presented with acute ischemic stroke and were treated with IVT and/or EVT at Isala Hospital, the Netherlands, in 2019 and 2020. The primary outcome measure was the adjusted common odds ratio (acOR) for a worse modified Rankin Scale (mRS) score at 3-month follow-up. Secondary outcomes included symptomatic intracranial hemorrhage, in-hospital mortality, infarct core, and penumbra volumes. RESULTS: Of the 680 patients (median age = 73 years, 49% female, median National Institutes of Health Stroke Scale = 5), 430 patients (63%) were treated with IVT, 120 patients (18%) with EVT, and 130 patients (19%) with both. Ninety-two patients (14%) were hyponatremic on admission. Hyponatremia was associated with a worse mRS score at 3 months (acOR = 1.76, 95% confidence interval [CI] = 1.12-2.76) and in-hospital mortality (aOR = 2.39, 95% CI = 1.23-4.67), but not with symptomatic intracranial hemorrhage (OR = 1.17, 95% CI = 0.39-3.47). Hyponatremia was also associated with a larger core (17.2 mL, 95% CI = 2.9-31.5) and core to penumbra ratio (55.0%, 95% CI = 7.1-102.9). CONCLUSIONS: Admission hyponatremia in patients with acute ischemic stroke treated with IVT and/or EVT was independently associated with unfavorable postreperfusion outcomes, a larger infarct core, and a larger core to penumbra ratio. Future studies should address whether correction of hyponatremia improves the prognosis.

Overcorrection and undercorrection with fixed dosing of bolus hypertonic saline for symptomatic hyponatremia.

OBJECTIVE: Current guidelines recommend treating symptomatic hyponatremia with rapid bolus-wise infusion of fixed volumes of hypertonic saline regardless of body weight. We hypothesize that this approach is associated with overcorrection and undercorrection in patients with low and high body weight. DESIGN: Single-center, retrospective cohort study. METHODS: Data were collected on patients treated with ≥1 bolus 100 or 150 mL 3% NaCl for symptomatic hyponatremia between 2017 and 2021. Outcomes were overcorrection (plasma sodium rise > 10 mmol/L/24 h, > 18 mmol/L/48 h, or relowering therapy) and undercorrection (plasma sodium rise < 5 mmol/L/24 h). Low body weight and high body weight were defined according to the lowest (≤60 kg) and highest (≥80 kg) quartiles. RESULTS: Hypertonic saline was administered to 180 patients and caused plasma sodium to rise from 120 mmol/L to 126.4 mmol/L (24 h) and 130.4 mmol/L (48 h). Overcorrection occurred in 32 patients (18%) and was independently associated with lower body weight, weight ≤ 60 kg, lower baseline plasma sodium, volume depletion, hypokalemia, and less boluses. In patients without rapidly reversible causes of hyponatremia, overcorrection still occurred more often in patients ≤ 60 kg. Undercorrection occurred in 52 patients (29%) and was not associated with body weight or weight ≥ 80 kg but was associated with weight ≥ 100 kg and lean body weight in patients with obesity. CONCLUSION: Our real-world data suggest that fixed dosing of bolus hypertonic saline may expose patients with low and high body weight to more overcorrection and undercorrection, respectively. Prospective studies are needed to develop and validate individualized dosing models.

Serum sodium, cognition and incident dementia in the general population.

BACKGROUND: Low serum sodium may be associated with cognitive impairment and dementia in the general population, but the data remain inconclusive. Therefore, we aimed to determine the association of low serum sodium with cognitive function and incident dementia in the general population. METHODS: Participants from a prospective population-based cohort were eligible if data on serum sodium (collected between 1997 and 2008), dementia prevalence and dementia incidence were available (follow-up until 2018). Global cognitive function was assessed with the Mini-Mental State Examination (MMSE) and the general cognitive factor (G-factor, derived from principal component analysis of individual tests). Linear regression and Cox proportional-hazards models were used to assess associations of standardised continuous and categorised low serum sodium (mean - 1.96*SD: cut-off of 137 mmol/L) with overall cognitive function and incident dementia, respectively. RESULTS: In all, 8,028 participants free of dementia at baseline (mean age 63.6 years, 57% female, serum sodium 142 ± 2 mmol/L), including 217 participants with low serum sodium, were included. Cross-sectionally, continuous serum sodium and/or low serum sodium were not associated with the MMSE or G-factor. However, participants with low serum sodium performed worse on the Stroop and Purdue Pegboard tests. During a median follow-up of 10.7 years, 758 subjects developed dementia. Continuous serum sodium (hazard ratio (HR) 0.98, 95% confidence interval (CI) 0.92;1.05) and low serum sodium (HR 1.27, 95% CI 0.90;1.79) were not associated with a higher risk of incident dementia. CONCLUSION: We identified no significant associations of low serum sodium with overall cognitive functioning and risk of dementia. However, low serum sodium-including levels above the clinical cut-off for hyponatremia-was associated with impairments in selected cognitive domains including attention and psychomotor function.

Oral Glucose Tolerance Test for the Screening of Glucose Intolerance Long Term Post-Heart Transplantation.

Post-transplant diabetes mellitus (PTDM) is a frequent complication post-heart transplantation (HT), however long-term prevalence studies are missing. The aim of this study was to determine the prevalence and determinants of PTDM as well as prediabetes long-term post-HT using oral glucose tolerance tests (OGTT). Also, the additional value of OGTT compared to fasting glucose and glycated hemoglobin (HbA1c) was investigated. All patients > 1 year post-HT seen at the outpatient clinic between August 2018 and April 2021 were screened with an OGTT. Patients with known diabetes, an active infection/rejection/malignancy or patients unwilling or unable to undergo OGTT were excluded. In total, 263 patients were screened, 108 were excluded. The included 155 patients had a median age of 54.3 [42.2-64.3] years, and 63 (41%) were female. Median time since HT was 8.5 [4.8-14.5] years. Overall, 51 (33%) had a normal range, 85 (55%) had a prediabetes range and 19 (12%) had a PTDM range test. OGTT identified prediabetes and PTDM in more patients (18% and 50%, respectively), than fasting glucose levels and HbA1c. Age at HT (OR 1.03 (1.00-1.06), p = 0.044) was a significant determinant of an abnormal OGTT. Prediabetes as well as PTDM are frequently seen long-term post-HT. OGTT is the preferred screening method.

Safety, feasibility and efficacy of metformin and sitagliptin in patients with a TIA or minor ischaemic stroke and impaired glucose tolerance.

INTRODUCTION: Impaired glucose tolerance (IGT) is highly prevalent after stroke and is associated with recurrent stroke and unfavourable outcome. OBJECTIVES: We aimed to assess the feasibility, safety and effects on glucose metabolism of metformin or sitagliptin in patients with transient ischaemic attack (TIA) or minor ischaemic stroke and IGT. DESIGN: We performed a multicentre, randomised, controlled, open-label phase II trial with blinded outcome assessment. INTERVENTIONS: Patients were randomised in a 2:1:1 ratio to 'no medication', sitagliptin or metformin. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome measures were baseline adjusted differences of 2-hour postload glucose; secondary outcome measures fasting glucose, glycosylated haemoglobin 1c (HbA1c) levels, tolerability and safety of metformin and sitagliptin at 6 months. Patients on metformin or sitagliptin were contacted by telephone for recording of possible adverse events and to support continuation of treatment at 2 weeks, 6 weeks and 3 months after inclusion. These events were not analysed as outcome measures. RESULTS: Fifty-three patients were randomised to control group, 26 to metformin and 22 to sitagliptin. We found no significant differences in 2-hour postload glucose between patients on antidiabetic drugs and controls ((-0.04 mmol/L (95% CI -0.53 to 0.45)). Patients in the treatment arms had reduced fasting glucose: ((-0.21 mmol/L (95% CI -0.36 to -0.06)) and HbA1c levels ((-1.16 mmol/mol (95% CI -1.84 to -0.49)). Thirteen patients (50%) on metformin and 7 (32%) on sitagliptin experienced side effects. Sixteen patients (61%) in the metformin and 13 (59%) in the sitagliptin group were still on treatment after 6 months. CONCLUSIONS: Metformin and sitagliptin were both effective in reducing fasting glucose and HbA1c levels in patients with recent TIA or minor ischaemic stroke and IGT. However, the reduction of glucose levels and sample size was relatively small. The clinical relevance, therefore, needs to be tempered. A phase III trial is needed to investigate whether medical treatment, compared with lifestyle intervention or a combination of both, not only improves glucose metabolism in IGT, but also leads to reduction of recurrent TIA or ischaemic stroke in these patients. TRIAL REGISTRATION NUMBER: NL3048.

Prediction of Persistent Impaired Glucose Tolerance in Patients with Minor Ischemic Stroke or Transient Ischemic Attack.

BACKGROUND: Impaired glucose tolerance (IGT) in patients with ischemic stroke can return to normal, reflecting an acute stress response, or persist. Persistent IGT is associated with an increased risk of recurrent stroke, other cardiovascular diseases and unfavorable outcome after stroke. We aim to validate our previously developed model to identify patients at risk of persistent IGT in an independent data set, and, if necessary, update the model. METHODS: The validation data set consisted of 239 nondiabetic patients with a minor ischemic stroke or TIA and IGT in the acute phase (2-hour post-load glucose levels between 7.8 and 11.0 mmol/l). The outcome was persistent versus normalized IGT, based on repeated oral glucose tolerance test after a median of 46 days. The discriminative ability of the original model was assessed with the area under the ROC curve (AUC). The updated model was internally validated with bootstrap resampling and cross-validated in the development population of the original model. RESULTS: One-hundred eighteen of 239 (49%) patients had persistent IGT. The original model, with the predictors age, current smoking, statin use, triglyceride, hypertension, history of cardiovascular diseases, body mass index (BMI), fasting plasma glucose performed poorly (AUC .60). The newly developed model included only BMI, hypertension, statin use, atrial fibrillation, 2-hour post-load glucose levels, HbA1c, large artery atherosclerosis, and predicted persistent IGT more accurately (internally validated AUC 0.66, externally validated AUC .71). CONCLUSIONS: This prediction model with simple clinical variables can be used to predict persistent IGT in patients with IGT directly after minor stroke or TIA, and may be useful to optimize secondary prevention by early identification of patients with disturbed glucose metabolism.

[Reduced consciousness levels caused by hyperammonaemia]. / Bewustzijnsdaling door hyperammoniëmie.

Hyperammonaemia is an important cause of lethargy. In this article, we describe a lesser-known but potential fatal cause of hyperammonaemia. A 27-year-old woman presented with lethargy caused by hyperammonaemia. She was treated with the emergency regime that is used to treat hyperammonaemia in urea cycle defects. Although this effectively lowered the ammonia levels, the clinical situation of the patient initially deteriorated and she was transferred to the Intensive Care Unit and intubated. Urine culture identified Proteus mirabilis, a urea-splitting bacterium that caused the hyperammonaemia. Prompt and adequate treatment with antibiotics and adequate drainage of urine was started and she completely recovered. Although every patient can get hyperammonaemia caused by urinary tract infection with urea-splitting bacteria, patients with structural bladder abnormalities are at greater risk. Lethargy can be the only presenting symptom. When recognized early, it is quite treatable and has a good prognosis.

Use of monomeric and oligomeric flavanols in the dietary management of patients with type 2 diabetes mellitus and microalbuminuria (FLAVA trial): study protocol for a randomized controlled trial.

BACKGROUND: Patients with type 2 diabetes mellitus (T2D) are prone to micro- and macro-vascular complications. Monomeric and oligomeric flavanols (MOF) isolated from grape seeds (Vitis vinifera) have been linked to improved endothelial function and vascular health. The aim of this study is to determine the effect of a daily supplementation of 200 mg MOF on renal endothelial function of patients with T2D and microalbuminuria. METHODS/DESIGN: For this double-blind, placebo-controlled, randomized, multicenter trial 96 individuals (ages 40-85 years) with T2D and microalbuminuria will be recruited. Participants will be randomly assigned to the intervention group, receiving 200 mg of MOF daily for 3 months, or to the control group, receiving a placebo. The primary endpoint is the evolution over time in albumin excretion rate (AER) until 3 months of intervention as compared with placebo. Secondary endpoints are the evolution over time in established plasma markers of renal endothelial function-asymmetric dimethylarginine (ADMA), soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular cell adhesion molecule-1 (sICAM-1), interleukin-6 (IL-6), and von Willebrand Factor (vWF)-until 3 months of intervention as compared with placebo. Mixed modeling will be applied for the statistical analysis of the data. DISCUSSION: We hypothesize that T2D patients with microalbuminuria have a medically determined requirement for MOF and that fulfilling this requirement will result in a decrease in AER and related endothelial biomarkers. If confirmed, this may lead to new insights in the dietary management of patients with T2D. TRIAL REGISTRATION: Nederlands Trial Register, NTR4669 , registered on 7 July 2014.

Admission Glucose and Effect of Intra-Arterial Treatment in Patients With Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Hyperglycemia on admission is common after ischemic stroke. It is associated with unfavorable outcome after treatment with intravenous thrombolysis and after intra-arterial treatment. Whether hyperglycemia influences the effect of reperfusion treatment is unknown. We assessed whether increased admission serum glucose modifies the effect of intra-arterial treatment in patients with acute ischemic stroke. METHODS: We used data from the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands). Hyperglycemia was defined as admission serum glucose >7.8 mmol/L. The primary outcome measure was the adjusted common odds ratio for a shift in the direction of a better outcome on the modified Rankin Scale at 90 days, estimated with ordinal logistic regression. Secondary outcome variable was symptomatic intracranial hemorrhage. We assessed treatment effect modification of hyperglycemia and admission serum glucose levels with multiplicative interaction factors and adjusted for prognostic variables. RESULTS: Four hundred eighty-seven patients were included. Mean admission serum glucose was 7.2 mmol/L (SD, 2.2). Fifty-seven of 226 patients (25%) randomized to intra-arterial treatment were hyperglycemic compared with 61 of 261 patients (23%) in the control group. The interaction of either hyperglycemia or admission serum glucose levels and treatment effect on modified Rankin Scale scores was not significant (P=0.67 and P=0.87, respectively). The same applied for occurrence of symptomatic hemorrhage (P=0.39 for hyperglycemia, P=0.39 for admission serum glucose). CONCLUSIONS: We found no evidence for effect modification of intra-arterial treatment by admission serum glucose in patients with acute ischemic stroke. CLINICAL TRIAL REGISTRATION: URL: www.isrctn.com. Unique identifier: ISRCTN10888758.

Metformin and sitAgliptin in patients with impAired glucose tolerance and a recent TIA or minor ischemic Stroke (MAAS): study protocol for a randomized controlled trial.

BACKGROUND: Impaired glucose tolerance is present in one third of patients with a TIA or ischemic stroke and is associated with a two-fold risk of recurrent stroke. Metformin improves glucose tolerance, but often leads to side effects. The aim of this study is to explore the feasibility, safety, and effects on glucose metabolism of metformin and sitagliptin in patients with TIA or minor ischemic stroke and impaired glucose tolerance. We will also assess whether a slow increase in metformin dose and better support and information on this treatment will reduce the incidence of side effects in these patients. METHODS/DESIGN: The Metformin and sitAgliptin in patients with impAired glucose tolerance and a recent TIA or minor ischemic Stroke trial (MAAS trial) is a phase II, multicenter, randomized, controlled, open-label trial with blinded outcome assessment. Non-diabetic patients (n = 100) with a recent (<6 months) TIA, amaurosis fugax or minor ischemic stroke (modified Rankin scale ≤ 3) and impaired glucose tolerance, defined as 2-hour post-load glucose levels between 7.8 and 11.0 mmol/L after repeated standard oral glucose tolerance test, will be included. Patients with renal or liver impairment, heart failure, chronic hypoxic lung disease stage III-IV, history of lactate acidosis or diabetic ketoacidosis, pregnancy or breastfeeding, pancreatitis and use of digoxin will be excluded. The patients will be randomly assigned in a 1:1:2 ratio to metformin, sitagliptin or "no treatment." Patients allocated to metformin will start with 500 mg twice daily, which will be slowly increased during a 6-week period to a twice daily dose of 1000 mg. Patients allocated to sitagliptin will be treated with a daily fixed dose of 100 mg. The study has been registered as NTR 3196 in The Netherlands Trial Register. Primary outcomes include percentage still on treatment, percentage of (serious) adverse events, and the baseline adjusted difference in 2-hour post-load glucose levels at 6 months. DISCUSSION: This study will give more information about the feasibility and safety of metformin and sitagliptin as well as the effect on 2-hour post-load glucose levels at 6 months in patients with TIA or ischemic stroke and impaired glucose tolerance. TRIAL REGISTRATION NUMBER: NTR3196 , Date of registration: 15 December 2011.

Prediabetes in patients with stroke or transient ischemic attack: prevalence, risk and clinical management.

BACKGROUND: The prevalence of diabetes is emerging worldwide and is an important modifiable risk factor for stroke. People with prediabetes, an intermediate metabolic state between normal glucose metabolism and diabetes, have a tenfold increased risk of developing diabetes compared to those with a normal glucose metabolism. Prediabetes is comprised of impaired fasting glucose and/or impaired glucose tolerance and/or disturbed glycosylated hemoglobin levels. Prediabetes is highly prevalent in nondiabetic patients with transient ischemic attack (TIA) or ischemic stroke and nearly doubles their risk of stroke. This offers new options for secondary stroke prevention. SUMMARY: Several detection methods exist for identifying (pre)diabetes, including fasting plasma glucose, 2-hour postload glucose and glycosylated hemoglobin levels. The concordance between these tests is not 100%, and they seem to be complementary. Screening for (pre)diabetes after stroke with fasting plasma glucose levels alone is insufficient, and 2-hour postload glucose and/or glycosylated hemoglobin levels should be determined as well. The prevalence of prediabetes in previously nondiabetic patients with a recent TIA or stroke ranges from 23 to 53%. This high prevalence in the acute phase after stroke can be transient or persistent, representing undiagnosed abnormal glucose metabolism. Impaired fasting glucose and impaired glucose tolerance have different pathophysiological mechanisms, including hepatic insulin resistance and muscle insulin resistance, respectively. Prediabetes seems to be a modest predictor for stroke, but doubles the risk for recurrent stroke. The relation between prediabetes after stroke and functional outcome is still unknown. However, it is most likely that prediabetes is a risk factor for a poor clinical outcome after stroke. There is a growing recognition that patients with prediabetes should be treated more aggressively. Both lifestyle and pharmacological interventions are possible treatment strategies. They are at least equally effective in preventing progression to diabetes. Lifestyle changes are difficult to maintain over a long period. The evidence of pharmacological interventions on stroke or other cardiovascular diseases is limited though and is still subject of several clinical trials. CONCLUSIONS: As the prevalence of prediabetes is growing rapidly, prediabetes might become one of the most important modifiable therapeutic targets in both primary and secondary prevention.

Occurrence and predictors of persistent impaired glucose tolerance after acute ischemic stroke or transient ischemic attack.

BACKGROUND: Impaired glucose tolerance is often present in patients with a transient ischemic attack (TIA) or ischemic stroke and doubles the risk of recurrent stroke. This impaired glucose tolerance can be transient, reflecting an acute stress response, or persistent, representing undiagnosed impaired glucose metabolism possibly requiring treatment. We aimed to assess the occurrence of persistent impaired glucose tolerance after a stroke or TIA and to develop a prediction model to identify patients at risk of persistent impaired glucose tolerance. METHODS: Patients admitted to the stroke unit or TIA clinic of the Erasmus Medical Center with ischemic stroke or TIA and impaired glucose tolerance (2-hour postload glucose level of 7.8-11.0 mmol/L) were consecutively enrolled between July 2009 and June 2012. The oral glucose tolerance test was repeated after 3 months and patients were classified as having transient impaired glucose tolerance or persistent impaired glucose tolerance. We developed a prediction model by means of a multivariable logistic regression model. We calculated the area under the receiver operating characteristic curve (AUC) to quantify the performance of the model and the internal validity by bootstrapping. RESULTS: Of the 101 patients included, 53 (52%) had persistent impaired glucose tolerance or progression to diabetes. These patients were older and more often had hypertension and used statins. A prediction model including age, current smoking, statin use, triglyceride, hypertension, previous ischemic cardiovascular disease, body mass index, and fasting plasma glucose accurately predicted persistent impaired glucose tolerance (bootstrapped AUC, .777), with statin use, triglyceride, and fasting plasma glucose as the most important predictors. CONCLUSIONS: Half of the patients with impaired glucose tolerance after a TIA or ischemic stroke have persistent impaired glucose tolerance. We provide a prediction model to identify patients at risk of persistent impaired glucose tolerance, with statin use, triglyceride, and fasting plasma glucose as the most important predictors, which after external validation might be used to optimize secondary prevention.

Bilateral axillary arterial obstruction.

A 74-year-old patient with longstanding diabetes mellitus and hypertension presented with obstruction in both axillary arteries. Although atherosclerotic obstructive disease would have been the most likely diagnosis in this patient, clinical findings were highly suggestive of extracranial giant-cell arteritis. Prompt treatment with systemic corticosteroids resulted in an excellent clinical response, avoiding the risks of endovascular or surgical intervention.

Prevalence of prediabetes and newly diagnosed diabetes in patients with a transient ischemic attack or stroke.

BACKGROUND: Patients with a transient ischemic attack (TIA) or stroke and prediabetes or newly diagnosed diabetes are at high risk of recurrent stroke or cardiovascular events. This underlines the importance of accurate screening for impaired glucose metabolism in clinical practice. Fasting plasma glucose levels are currently the most commonly measured glycemic parameter to detect prediabetes or diabetes, even if 2-hour postload glucose and glycosylated hemoglobin levels can be used as well. We assessed the prevalence of prediabetes and newly diagnosed diabetes with different screening methods, including fasting plasma glucose, 2-hour postload glucose and glycosylated hemoglobin levels in consecutive patients with recent TIA, ischemic stroke or intracerebral hemorrhage admitted to the stroke unit or visiting the specialized TIA outpatient clinic in the Erasmus Medical Center, Rotterdam, The Netherlands. METHODS: We measured fasting plasma glucose, 2-hour postload glucose and glycosylated hemoglobin levels in 269 patients with a TIA, 374 with ischemic stroke and 57 with intracerebral hemorrhage, all without a history of diabetes mellitus. Prediabetes was defined as fasting plasma glucose levels of 5.6-6.9 mmol/l and/or 2-hour postload glucose levels of 7.8-11.0 mmol/l and/or glycosylated hemoglobin levels of 5.7-6.4%. Newly diagnosed diabetes was defined as fasting plasma glucose levels of ≥7.0 mmol/l and/or 2-hour postload levels of ≥11.1 mmol/l and/or glycosylated hemoglobin levels of ≥6.5%. The diagnosis was based on a one-time measurement. RESULTS: Based on fasting plasma glucose, 2-hour postload glucose and glycosylated hemoglobin levels combined, 365 patients (52%) were identified as prediabetics and 188 (27%) as having newly diagnosed diabetes. Patients with intracerebral hemorrhage had more often newly diagnosed diabetes compared with patients with an ischemic stroke or a TIA [27 (47%) and 161 (25%), respectively; p < 0.001]; the prevalence of prediabetes was similar. Newly diagnosed diabetes was identified more frequently by 2-hour postload glucose levels (n = 162; 23%) than by fasting plasma glucose (n = 49; 7%) or glycosylated hemoglobin levels (n = 36; 5%). About one third of the patients with normal fasting glucose levels has impaired glucose tolerance or elevated glycosylated hemoglobin levels. CONCLUSIONS: Prediabetes and newly diagnosed diabetes are highly prevalent in patients with a TIA or stroke. The majority of these patients would not have been identified by fasting plasma glucose levels alone. Both 2-hour postload glucose and glycosylated hemoglobin levels identify more patients with a disturbed glucose metabolism.

High antibody titer in an adult with Pompe disease affects treatment with alglucosidase alfa.

Clinical trials have demonstrated beneficial effects of enzyme replacement therapy (ERT) with alglucosidase alfa in infants, children and adults with Pompe disease. Recent studies have shown that high antibody titers can occur in patients receiving ERT and counteract the effect of treatment. This particularly occurs in those patients with classic-infantile Pompe disease that do not produce any endogenous acid α-glucosidase (CRIM-negative). It is still unclear to what extent antibody formation affects the outcome of ERT in adults with residual enzyme activity. We present the case of a patient with adult-onset Pompe disease. He was diagnosed at the age of 39years by enzymatic testing (10.7% residual activity in fibroblasts) and DNA analysis (genotype: c.-32-13T>G/p.Trp516X). Infusion-associated reactions occurred during ERT and the patient's disease progressed. Concurrently, the antibody titer rose to a similarly high level as reported for some CRIM-negative patients with classic-infantile Pompe disease. Using newly developed immunologic-assays we could calculate that approximately 40% of the administered alglucosidase alfa was captured by circulating antibodies. Further, we could demonstrate that uptake of alglucosidase alfa by cultured fibroblasts was inhibited by admixture of the patient's serum. This case demonstrates that also patients with an appreciable amount of properly folded and catalytically active endogenous acid α-glucosidase can develop antibodies against alglucosidase alfa that affect the response to ERT.

Low bone mass in Pompe disease: muscular strength as a predictor of bone mineral density.

UNLABELLED: Pompe disease is an inherited metabolic myopathy caused by deficiency of acid alpha-glucosidase. The introduction of enzyme replacement therapy as treatment for the disease may change prospects for patients and may require that more attention be paid to co-morbidities such as osteoporosis. METHODS: Bone mineral status was assessed in children and adults with Pompe disease and compared with reference values by means of dual energy X-ray absorptiometry (DXA) technology (GE Lunar DPX, GE Health Care). Bone mineral density (BMD) of the total body and the lumbar spine (L2-L4) was measured in adults and children; BMD of the femoral neck was measured in adults only. Exclusion criteria were: age<4 years, severe contractures, and inability to transfer the patient. RESULTS: 46 patients were enrolled in the study; 36 adults and 10 children. The BMD was significantly lower in Pompe patients than in healthy individuals. Sixty-seven percent of patients had a BMD Z-score below -1, 26% were classified as osteoporosis/low bone mass for chronological age (T-score<-2.5 in adults or Z-score<-2 in children), 66% had a BMD Z-score below -1 of the femoral neck, and 34% had a BMD Z-score below -1 for the lumbar spine. Osteoporosis/low bone mass for chronological age was more frequent in patients who were wheelchair-bound, but was also observed in ambulant patients. We found a significant correlation between proximal muscle strength and total body BMD. Of the 10 children, 8 (all four patients with the classic infantile form) had a low BMD. CONCLUSION: Low BMD is a frequent finding in patients with Pompe disease and may be causally related to decreased proximal muscle strength. BMD should be monitored at regular intervals. Children deserve specific attention.

Using heparin therapy to reverse protein-losing enteropathy in a patient with CDG-Ib.

BACKGROUND: A 22-year-old female presented with edema, diarrhea, hypoalbuminemia and pancytopenia. She had previously been diagnosed with congenital disorder of glycosylation type Ib, and had a history of congenital hepatic fibrosis, portal hypertension and esophageal varices. In the past she had refused mannose therapy because of associated diarrhea and abdominal pain. INVESTIGATIONS: Laboratory examinations, abdominal ultrasonography, bacterial and viral cultures of blood, urine and stools, double-balloon enteroscopy and fecal excretion test using 51Cr-labeled albumin. DIAGNOSIS: Protein-losing enteropathy. MANAGEMENT: Infusion of albumin followed by intravenous and subcutaneous therapy with unfractionated heparin.